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Review

Ayurvedic drug discovery


Premalatha Balachandran & Rajgopal Govindarajan
University of Mississippi, National Center for Natural Products Research,
Research Institute of Pharmaceutical Sciences, School of Pharmacy, MS, 38677, USA

1. Introduction Ayurveda is a major traditional system of Indian medicine that is still being
2. Modern drug discovery versus successfully used in many countries. Recapitulation and adaptation of the
ayurvedic products-based older science to modern drug discovery processes can bring renewed
drug discovery interest to the pharmaceutical world and offer unique therapeutic solutions
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3. Ayurvedic drug discovery:


for a wide range of human disorders. Eventhough time-tested evidences
essential considerations vouch immense therapeutic benefits for ayurvedic herbs and formulations,
and requirements several important issues are required to be resolved for successful imple-
mentation of ayurvedic principles to present drug discovery methodologies.
4. Ayurvedic medicine: what
Additionally, clinical examination in the extent of efficacy, safety and
it can offer?
drug interactions of newly developed ayurvedic drugs and formulations are
5. Ayurvedic literature
required to be carefully evaluated. Ayurvedic experts suggest a reverse-
6. Recent developments in pharmacology approach focusing on the potential targets for which
ayurvedic medicine ayurvedic herbs and herbal products could bring tremendous leads to
7. Development of new ayurvedic drug discovery. Although several novel leads and drug molecules
therapeutic compounds from have already been discovered from ayurvedic medicinal herbs, further
medicinal plants of Ayurveda scientific explorations in this arena along with customization of present
8. Mechanism of action of technologies to ayurvedic drug manufacturing principles would greatly
For personal use only.

ayurvedic drug compounds facilitate a standardized ayurvedic drug discovery.


9. Reverse pharmacology: a road
Keywords: Ayurveda, ayurvedic discovery, ayurvedic leads, drug discovery, medicinal plants,
to ayurvedic drug discovery
traditional medicine
10. Ayurvedic drug discovery:
possible present and Expert Opin. Drug Discov. (2007) 2(12):1631-1652
future directions
11. Tools and methodologies
1. Introduction
in ayurvedic drug discovery
Ayurveda is a traditional Indian system of medicine that includes medical
12. Selection criteria for herbs practices and beliefs as it relates to the prevention and treatment of diseases,
and herbal preparations health, well-being and spiritual healing, in which all have evolved as a part of the
13. Major challenges in ayurvedic indigenous culture. ayurvedic medicinal products are time-tested over centuries
drug discovery and together with recent extensive research on the medicinal chemistry, pharma-
14. Ayurvedic drug development cology and clinical aspects of many of these herbal products, their beneficial
in India: government and properties are continuously proving to be useful [1]. The components used in
private sectors ayurvedic medicine provide an attractive basis for the development of novel
pharmaceutical products that can either act as active single-molecule medications
15. Conclusion
by themselves or as components of multimodel (combination of western and
16. Expert opinion ayurvedic medicines) therapeutic regimens [1]. The ultimate objective in drug
discovery is to manufacture safe and effective remedies, especially with the
immense solutions already put forth by the traditional Indian (ayurvedic, sidhha,
unani) and Chinese medicines drug discovery from herbalplant products always
remained a compelling approach [2]. Ayurvedic plants or its proven herbal
formulations could platform a foundation step for standard drug discovery
methodologies with close guidance from ayurvedic principles. Indeed, pharma-
ceutical companies in many countries, including those in developed countries, are
finding it promising to adopt strategies for therapeutic channels from what have
been long known as merely traditional remedies [3]. Ayurvedic drug discovery
cannot only offer renewal interest to the pharmaceutical world [101], but also benefits
to patients by bringing closer-to-nature (by virtue of its source-material) and

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Ayurvedic drug discovery

cheaper (by cutting down the conventional drug-manufacturing medical utilities, especially by researching on the extent of
costs) forms of therapy. Although the potential benefits effectiveness and safety of their medicinal products [14],
envisaged from ayurvedic drug discovery are numerous, the could offer newer and extremely valuable directions to drug
radical changes required for implementing them into leads. Although some pharmaceutical companies have already
pre-existing standardized approaches of drug discovery pose marched significant strides from traditional medicinal
immense challenges [4]. products, complete recapitulation of the older sciences like
Ayurveda in accordance to modern drug standards are
2.Modern drug discovery versus ayurvedic difficult, if not impossible. Nevertheless, continued and
products-based drug discovery renewed enthusiasm on traditional medical resources is
anticipated to bring more unique and successful remedies in
Drug discovery involves multi-disciplinary research efforts the near future.
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to identify active molecules with desirable biological effects.


Major steps in drug discovery include synthesis, identification, 3.Ayurvedic drug discovery: essential
screening and assaying of chemical compounds. Drug considerations and requirements
development also demands a multi-disciplinary approach,
but with a focused track to develop a single drug molecule. Standardized ayurvedic drug discovery process necessitates
It involves testing the lead molecules identified in drug the consideration of several factors, which can be broadly
discovery processes against precisely defined target grouped under two major categories. First, it demands
molecule(s). Through a range of preclinical and clinical incorporation of alternative steps in addition to present drug
trials, drug compounds are eventually evaluated for their development processes to establish a more versatile ayurvedic-
therapeutic utilities against specific diseases in humans [5]. library screen [102] rather than a limiting chemical-library
The present trend in the drug discovery methodology has screen. The prospects of this wide-screening approach could
gotten its roots or origin from simple resources, such as be numerous, but essentially allow the characterization of
plant and mineral sources, as well as from many accidental extremely diverse chemical compounds to successfully
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discoveries. Although innumerable examples of such successful identify druggable ayurvedic leads with defined biochemical
drug compounds can be readily identifiable (e.g., paclitaxel, specificities [7]. Also, it has recently been reported that
statins, quinine, vinblastine), the sustained enthusiasm on natural products-based extract libraries, as opposed to existing
the use of herbal-based resources for newer drug discovery chemical libraries, comprise predominantly (> 90%)
has only gotten dampened lately (since the early 1980s) [6,7]. compounds whose structure follows Lipinskis rule-of-five
This is because of several reasons that accompany the properties [15], which are ideal for oral administrations. Such
pace and focus of modern technological advancements in chemical characteristics can only be found in drug molecules
drug discovery, the streamlined screening processes of that have already made their entry to the market [7]. Second,
compound libraries, the molecular understanding on disease ayurvedic drug discovery mandates the inclusion of existing
processes and desirability for target-specific therapeutic knowledge on ayurvedic medicines and the blending of
solutions [8]. Without doubt, scientific milestones, such as known principles of ayurvedic science with modern drug
the human genome sequencing and ultra-high-throughput development technologies for more successful investigational
screening, have revolutionized present-day drug discovery drugs. Based on these requirements, ayurvedic practitioners
methodologies [9-11]. However, despite these advents and and researchers have recently proposed many effective, yet
transformations in drug discovery, it becomes important to feasible, methods that could facilitate detailed experimenta-
note that new drug discovery continues to act as a challenge tion on ayurvedic herbs and products for eventual imple-
and successful outcomes occur only at a very slow rate mentation of standardized ayurvedic drug discovery
(10 years per drug on average) with extreme use of man-hours methodologies [1,16,17]. In this review, a broad outline on the
and funding (a few billion US dollars per drug) [12]. Newer scientific aspects and resources available on ayurvedic
diseases emerge all the time and existing diseases (such as medicine, and its pertinence to present and potential future
cancer, AIDS, diabetes etc.) still pose life-threatening drug development strategies, along with the major scientific
dangers. In the light of all of these situations, considering challenges to be faced, are discussed. Mechanistic aspects on
alternative forms of medicines, especially from those ayurvedic plant actions and biochemical evidences on
scientific roots that are the initial basis of todays modern ayurvedic formulations, reviewed in other recent
drug discovery and matured independently into valuable articles [1,2,18], are excluded.
medical disciplines by themselves, should prove to be highly
beneficial. Recent understanding on the human genome and 4. Ayurvedic medicine: what it can offer?
the structural characterization of human proteins are
beginning to offer clearer views by which diverse chemical The ayurvedic system of medicine in India dates back
structures in plant products are acting on precise biological to 3000 BC and prescribes remedies for a wide range of
targets [13]. Reinforcing further active efforts on alternate disorders, diseases and conditions [17]. Ayurvedic classic

1632 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

texts, Charak Samhita and Sushrut Samhita, describe > 700 kvath, curn, guggulu, grita, taila, dravak, kshara, lepa, vati,
medicinal plants [1] of therapeutic value against both gutika, rasayana, parpati, bhasma, mandura, rasa yoga and
infectious and non-infectious disease conditions. These herbs lauha). It also includes 27 single drugs of animal origin,
are categorized based on their appearance, taste, digestive 42 single drugs of mineral origin, 271 single drugs of plant
effects, safety, efficacy, dosage and therapeutic benefits [7]. In origin accompanied with disease indication indices [104].
India, 3000 plants of proven medicinal value are found [19], The ayurvedic pharmacopeia of India includes in-depth
and > 6000 plants are known to be used in traditional, folk details on 326 ayurvedic plants, such as botanical names
and herbal medicines [19]. An overwhelming number of and identification criteria, standard measures for various
pharmaceuticals companies in India (a total of 7000) parts of the plants, physical tests and determinations, quan-
manufacture Ayurvedic medicines along with two other tradi- titative data for vegetable drugs, limits for chlorides, sulfates,
tional forms of medicines, the siddha medicines (revitalizing sulfated ash, arsenic, mercury, iron, lead and other heavy
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and rejuvenating form of medicine developed by ancient metals present in the drugs with complete official testing
sages [Siddhars] for subsequent future generations) and the methodologies [104]. A total of three volumes of ayurvedic
unani medicines (a system of medicine based on the balance pharmacopeia have been published by the Indian govern-
of the elements in the body that originated 980 AD in ment, with a total of 258 monographs. A total of 80
Persia, but was popularized in India) [20]. These indigenous monographs were published in the volume I, 78 mono-
medical practices continue to prove beneficial for millions of graphs in the volume II and 100 monographs in the
people in India, Sri Lanka and Nepal, despite the significant volume III. The work on remaining single drugs of
prevalence and accessibility of western medicine. The impor- plant, animal, mineral/metal and marine origin and
tance of ayurvedic medicine is not only reflected in its multi-ingredients formulations is presently being carried
successful influence on other traditional systems. such as out in 30 different ayurvedic and other scientific
unani, Chinese and Tibetan medicine, but also its present research institutions [103].
modern applications in Pakistan, Bangladesh, China and The Materia Medica of Ayurveda consists of an extremely
Tibet. Traditional plant medications are estimated to fulfill rich armamentarium of natural drugs, derived from the
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nearly three quarters of all the medicinal needs of the plants, minerals, animals and marine sources. These drugs
people in developing countries [19], and some form of other are used as monotherapies or in simple combinations, which
alternative medicines are used for therapeutic, food-additive are otherwise referred to as polypharmaceuticals. The forms
and cosmetic benefits by millions in developed countries. in which these are used are varied, such as extracted juices,
In spite of these proven track records of traditional decoctions, infusions, distillates, powders, tablets, pills,
medicines, a statistical analysis indicates only a poor confections, syrups, fermented liquids, medicated oil,
representation of its value in the global market and its bhasmas (resultant of incineration) and many more.
commonly held perception of unconventionality compared The Materia Medica of Ayurveda is an exhaustive publication
with modern medicines [21]. that describes simple, safe and proven remedies including
remedies for common ailments [103].
5. Ayurvedic literature The Treatise on Indian medicinal plants, edited by
A Chatterjee and SC Pakrashi (1991), is a five volume
Ayurveda offers extensive information about the herbal drug treatise with each volume containing 180 325 pages.
products and their therapeutic uses. The ayurvedic know- These books contain > 800 medicinal plants. It also served
ledge has been spread over 100 books containing > 100,000 as a search engine for many scientific studies and clinical
recipes documented by ayurvedic physicians and scholars. trials conducted on ayurvedic therapies during the last five
Besides these major resources (described later), there exist a decades [104]. A recent book on the scientific basis of
even larger number of recipes that are being used on a daily ayurvedic therapies, edited by LC Mishra, also summarizes
basis, but are unpublished. Although the documented many of these findings [22].
ayurvedic knowledge chiefly assists ayurvedic practitioners, The Compendium of Indian medicinal plants, edited by
by virtue of its utility they can also be used as a resource for R Rastogi and BN Mehrotra, is a total of five volumes
scientific research and drug discovery processes. Some of the published so far with 518 1016 pages per volume [103].
most commonly used reference materials for ayurvedic drugs The Indian herbal pharmacopeia (2002) contains
and products are given in this section. 52 monographs on widely used medicinal plants in India
The ayurvedic formulary of India, published by the with scientific evidences on therapeutic effects.
government of India, contains a total of 636 compound In addition, the Pharmacopeia of India (1996) covers
formulations with the volume I containing 444 formula- additional botanical monographs on clove, guggul, opium,
tions, the volume II containing 192 formulations and the mentha, senna and ashwagantha. Several other lifetime
volume III containing 192 formulations [103]. Ayurvedic works of many eminent pharmacologists could be found
formulae and preparations include aqueous liquids, oils, in different ayurvedic and natural product-based scientific
powders, tablets, pills and others (Asava, arishta, ark, avaleh, institutions of India. For example, the experimental

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Ayurvedic drug discovery

pharmacology research works on indigenous drugs of India 8.Mechanism of action of ayurvedic


conducted by Sir RN Chopra (considered as the father of drug compounds
Indian pharmacology) can be found at the Regional Research
Laboratory (RRL), Jammu-Tawi [17]. Ayurvedic system of medicine is founded on the principle
that disease occurs due to the derangement of the functional
6.Recent developments in vital energies in the body (vata [air + ether] or the kinetic
ayurvedic medicine energy; pitta [fire] or the thermal energy and kapha
[earth + water] or the potential energy), as well as the loss
Ayusoft (2004) is a recently developed, interactive software of mutual coordination between them. ayurvedic drugs are
that chiefly assists ayurvedic practitioners. It contains several formulated to rejuvenate the deranged state to a healthy
databases on various ayurvedic drugs along with the network state so to restore the harmony between body and nature.
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of diet patterns, lifestyles, diseases and treatment principles. The extreme chemical diversity of compounds in ayurvedic
This software acts as a quick reference guide or index for drug formulations simultaneously targets most systems
practitioners to aid in the diagnostic and treatment aspects. of the body, resulting in an array of potent and diverse
The software is based on the prakruthi (ayurvedic disease biochemical outcomes. Many scientific studies corroborate
diagnosis) section of the ayurvedic texts [105]. ayurvedic principles and the basis for ayurvedic drug action
Ayugenomics [23] is a body of literature aimed at have been extensively reviewed recently [18,22,26,27]. Based on
understanding the ayurvedic concepts of Prakruthi from a the scientific literature published so far, it also becomes evident
pharmacogenomics perspective. It offers a basis for that some of the components used in ayurvedic formula-
inter-individual variations in diagnosis, drug efficacy tions or multi-herb extracts do not possess major biological
and toxicity, hence the development of customized activities by themselves, but instead act as potentiators or
therapeutic approaches. moderators of the efficacy and toxicity effects of the major
Herboprint [24] uses three-dimentional HPLC and active principles. For example, non-therapeutic components,
attempts to develop tools for activity-based standardization such as milk and ghee, are added to Semecarpus anacardium
For personal use only.

of botanicals. formulations to moderate its hot, acrid and dry nature [28,106].
Similarly in amalaki (Emblica officinalis)-based rejuvenators,
7.Development of new therapeutic such as chyavnan prasha avaleha, although amalaki is the main
compounds from medicinal plants of Ayurveda ingredient, the formulation contains > 25 herbs that are
added for synergistic and counter-balancing effects. In
The phytochemical analytical studies of ayurvedic medicinal addition to that, a sweetener, such as raw sugar or honey
plants is an area of thrust and significant investigation as it that has no biological activity, has been added to moderate
offers a direct path for the emergence of newer therapeutic its pungent taste. The herbs in this preparation insure that
agents. Furthermore, when the structures of the active the sweet is properly digested and cause no adverse
principles are identified, it provides a platform for synthetic reaction [107]. Triphala, another ayurvedic formulation, is a
and medicinal chemists to alter the efficacy or toxicity combination of amla (Emblica officinalis), bibhitaki
properties or even create analogs with similar or varied phar- (Terminalia belerica) and haritaki (T. chebula), in which all
macological actions. So far, among a list of frequently used these three herbs act synergistically as laxative and helps
ayurvedic medicinal plants, 43% of it has undergone human digestion [108]. Thus, multi-ingredient herbal compounds in
clinical trials studies and 62% of it has been subjected to ayurvedic sciences are rendered both effective and safe in
animal studies [25]. Ayurvedic drugs, such as guggul, brahmi, treating human ailments. Although these principles have
ashwangantha, amlaki, guduchi, kutki, shatavari and shunthi, been shown to successfully offer prevention and treatment
have also shown clinical promises for therapeutic usage [25]. of many diseases, it also reminds the confounding issues of
In relevance to future ayurvedic drug discovery, one could new drug discovery from ayurvedic herbs (standardization
categorize ayurvedic plants as follows: and precise utilization of various herbal components in the
Those on which sufficient leads are available and their generation of active drug formulations) [14].
biological targets are known. Some well-known ayurvedic
leads and their molecular targets for cancer therapy are 9.Reverse pharmacology: a road to
discussed in detail in a recent review by Aggarwal et al. [18] ayurvedic drug discovery
and a summary of ayurvedic plants and their biological
targets are listed in Table 1. Although conventional drug discovery starts with lead
Those with proven medicinal value and with considerable identification and optimization followed by in vivo
availability of scientific evidences (Table 2 and 3). preclinical studies (Phase I) and human clinical trials
Those with significant potentials to offer novel drugs, (Phase II and Phase III), ayurvedic drug discovery
but for which substantial experimentation needs to be was recently proposed [29] to preferably work in a reverse
performed (see Section 12). pharmacology direction with stages described in Figure 1.

1634 Expert Opin. Drug Discov. (2007) 2(12)


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Table 1. Successful lead compounds (see Figure 2) isolated from Ayurvedic plant products, their biological targets and therapeutic effects.

Plant name Ayurvedic Lead compound Biological targets/mechanism of action Therapeutic effects
name (Structures are
given in the figure)

Adhatoda vasica Vasaka Vasicine Inhibition of histamine release, clearance of Bronchodilator and expectorant
airway passages. Uterine stimulant
Allium sativum Lasuna Allicin Inhibition of cysteine protease and alcohol Antimicrobial
dehydrogenase enzymes
Andrographis paniculata Kalamegha Andrographolide Inhibits NO synthesis in macrophages by reducing Antiinflammatory
of iNOS protein expression
Bacopa monniera Brahmi Bacosides Repair of damaged neurons by enhancing kinase activity, Cognitive function enhancer
neuronal synthesis, and restoration of synaptic activity, and
ultimately nerve impulse transmission
Bergenia ligulata Pashanbhedi Gallic acid NF-B inhibitor, TNF- induced p65 nuclear translocation Anti-inflammatory, anti-allergic
Boswellia serrata Shallaki Boswellic acid By non-redox inhibition of pro-inflammatory enzyme, Anti-inflammatory, anti-arthritic
5-lipoxygenase, inhibition of NF-B
Commiphora mukul Guggulu Guggulsterone Bile acid receptor antagonist, COX-2 inhibition, Hypolipidemic agents,

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NF-B inhibition anti-inflammatory, promotes
cardiovascular health
Curcuma longa Haridra Curcumin Regulation of Aryl hydrocarbon receptors, cytochrome P450 Cancer, inflammation, diabetes and
enzymes, GST kinases, COX, iNOS, MMP, chemoprevention
p53 signalling, NF-B inhibition, apoptosis inducer
Eugenia caryophyllus Lavangaha Eugenol Antibacterial activity through membrane disruption Toothache
Glycyrrhiza glabra Madhu yasti Glycyrrhizin P21CIP1/WAF1 inhibitor Constipation, body ache, etc.
Mucuna pruriens Kapikachhu L-dopa Production of dopamine Parkinsons disease, nerve tonic
GST: Glutathione-S-transferase; MMP: Matrix metalloprotease.

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Balachandran & Govindarajan
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Ayurvedic drug discovery

Table 1. Successful lead compounds (see Figure 2) isolated from Ayurvedic plant products, their biological targets and therapeutic effects (continued).

Plant name Ayurvedic Lead compound Biological targets/mechanism of action Therapeutic effects
name (Structures are
given in the figure)

Picrorhiza kurroa Kutki Kutkoside Stimulate the action of nucleolar polymerase A, resulting Hepatoprotective against
in ribosomal protein synthesis and, thus stimulates jaundice, hepatitis
the regenerative ability of the liver and formation of
new hepatocytes
Piper longum Pipalli Piperin Unknown Bioenhancer
Punica granatum Dadima Ellagic acid NF-B inhibition, COX-2 inhibition Anti cancer, anti-inflammatory
Rauwolfia serpentina Sarpagandha Reserpine Disrupts norepinephrine vesicular storage, Adrenergic Antihypertensive, adrenergic
blocking, inhibition of the ATP/Mg2+ pump located in the uptake inhibitor, used for snake bites
presynaptic neuron
Semecarpus anacardium Bhallataka Biflavonoids Inhibition of NF-B Anticancer, anti-inflammatory
Tinospora cordifolia Guduchi Tinocordifolin COX-2 inhibition, cytokine modulator, NF-B translocation Asthma, rheumatism,

Expert Opin. Drug Discov. (2007) 2(12)


immune stimulant
Vitis vinifera Draksa Resveratrol NF-B Inhibition, inhibition of the CYP1A1, Anticancer
COX-2 enzymes
Withania somnifera Aswagantha Withaferin A Inhibition of IB kinase , NF-B Anti-inflammatory
Zingiber officinale Sunthi Gingerols Capsaicin-activated VR1 (vannilloid) receptors agonists Antipyretic, analgesic,
antitussive, sedative
GST: Glutathione-S-transferase; MMP: Matrix metalloprotease.
Balachandran & Govindarajan

Table 2. List of Ayurvedic botanicals with potential for drug discovery [103].

Botanical name Ayurvedic/ Common Disease conditions


Name

Acorus calamus Vacha Obesity, hypertension, speech disorders, sedative, transquilizer, mental distress
Adhatoda zeylanica Vasa Bronchiolar constriction
Anethum sowa Soya Appetiser, carminative
Asparagus racemosus Shatavari Aphrodisiac, dysuria, galactogogue, leucorrohea, peptie ulcer
Azadirachta indica Nimba Gastritis, bleeding piles, wounds, fumigative, disinfectant against
bacterial and viral infections
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Berberis aristata Daruharidra Liver disorders, conjuctivitis, dysentery, anti-pyretic,


antiperidoic, diaphoretic
Boerhaavia diffusa Punarnava Eye diseases, diabetes, anti-diuretic, hepatoprotective, inflammation
Crataeva nurvala Varuna Erysipelas, lymphadenopathy, urolithiasis
Cassia augustifolia Rechani, markhandi Severe constipation
Centella asiatica Mandukparni Neurological problems
Commiphora wightii Balsamodendron mukul Arthritis
Emblica officinalis Amalaki (Amla) Anaemia, jaundice, haemorrhage, acidity, immune stimulant
Eugenia jambolana Jamboo Diabetes
Ferula foetida Hingu (Heeng) Septic conditions, digestive stimulant, expectorant, carminative
Mallotus philippinensis Kampillak (Kamila) Anthelminthic, aphrodisiac
For personal use only.

Moringa oleifera Shigru (Sehanjana) Abcess, septic conditions, wound healing, piles, inflammation,
neuritis, joint diseases
Myristica fragrans Jaiphal Nausea and vomiting, diarrhea, leucorrhoea
Nelumbo nucifera Kamal beej/Kamal Gatta Hypoglycemic
Piper longum (root) Pippalimool Malaria, insomnia, worms, piles
Phyllanthus emblica amla Anti-ageing
Psoralea corylifolia Bakuchi Vitiligo, bronchial asthma
Saraca asoca Ashok Meno-metrorrhagia, neurological disorders, spasmogenic, uterine infections
Terminalia arjuna Arjun Cardiac disorders
Terminalia chebula Haritaki (harad) Laxative
Trachyspermum ammi Yavani Anthelminthic, spasmogenic carminative
Tribulus terrestris Goksura (Gokkru) Diuretic, aphrodisiac, lithontriptic

The advocation of reverse pharmacology in ayurvedic based on reverse-pharmacology and their respective directors
sciences was initiated by eminent vaidyas, including have detailed the prospects of this approach in national
Mahamahopadhyaya Gananath Sen [17], and since then has and international forums [109] for future drug discoveries.
evolved as a powerful scientific approach for newer drug Some of the plants that have been successfully analyzed
discovery. The reverse pharmacology approach is described by this approach include Mucuna pruriens for Parkinsons
by Ashok DB Vaidya as a newer academic discipline that disease, Zingiber officinale for nausea/vomiting, Picrorhiza
integrates documented clinical and experimental hits with kurroa for hepatitis, Curcuma longa for oral cancer,
leads by trans-disciplinary exploratory studies. The further Panchavalkal spp. for burns and wounds and Azadirachta
development of leads into drug candidates is triggered indica for malaria.
by experimental and clinical research. Thus, ayurvedic
drug discovery follows a retrogressive path based on clinical 10. Ayurvedic drug discovery: possible
observations noted with herbal products. present and future directions
The Indian Council of Scientific and Industrial Research
(CSIR) and the Indian Council for Medical Research Recent trends indicate that ayurvedic drug discovery and
(ICMR) have successfully conducted many clinical trials therapeutics can take several possible reverse-pharmacology

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Ayurvedic drug discovery

Table 3. Classification of botanicals according to their efficacy towards various diseases.

Health disorders Botanicals with scientific evidence

Allergies [52] Cleodendrum seratum, Benincasa hispida, Aquilaria agallocha, Albizzia lebbeck, Curcuma longa,
Inula racemosa, Galphimia glauca, Picrorhiza kurroa, Adhatoda vasica
Alzhemiers disease [53] Bacopa monniera, Centella asiatica, Convolvulus pluricaulis, Eugenia caryophyllus,
Glycyrrhiza glabra, Hydrocotyl asiatica, Lawsonia inermis, Nardostachys jatamansi, Poenia emodi,
Pongamia pinnata, Tinospora cordifolia, Withania somnifera
Antimutagens [54] Terminalia arjuna/chebula/bellerica, Ocimum sanctum, Glycyrrhiza glabra, Semecarpus anacardium,
Embilica officinalis, Cinnamomum cassia, Withania somnifera, Centella asiatica
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Arthritis [55] Vanda roxburghii, Commiphora mukul, Semecarpus anacardium, Crataeva nurvala,
Hemidesmus indicus, Andrographis paniculata, Aglaia roxburghiana
Bronchial asthma [56] Picrorrhiza kurroa, Solanum spp, Tylophora indica, Boswellia serrata
Cancer Withania somnifera, Aloe vera, Coleus forskohlii, Andrographis paniculata, Santalum album,
(benign and malignant) [57] Picrorrhiza kurroa, Semecarpus anacardium, Ocimum sanctum, Calotrophis procera,
Plumbago rosea, Nigella sativa, Embilica officinalis
Colon diseases [58] Zingiber officinale, Acorus calamus, Aegle marmelos, Withania somnifera, Bacopa monniera
Constipation [59] Aloe vera, Plantago ovata, Cassia senna, Rheum officinale, Prunus persica, Terminalia chebula,
Cassia fistula, Mallotus philippinensis, Ricinus communis
Dermatophytes [60] Cassia tora, Hydnocarpus laurifolia, Pongamia pinnata, Argemone mexicana, Ricinus communis,
Plumbago zeylanica, Psoralea corylifolia
Diabetes mellitus [61] Momordica charantia, Trigonella foenum, Coccinia indica, Pterocapus marsupium, Ficus bengalensis
Diarrhea and dysentery [62] Holarrhena antidysenterica, Myristica fragrans, Dioscorea oppositifolia, Psidium guajava,
For personal use only.

Musa paradisiaca, Nelumbo nucifera, Ficus bengalensis, Acorus calamus, Clerodendrum phlomidis,
Piper nigrum, Berberis aristata, Punica granatum, Tinospora cordifolia, Calotrophis procera,
Valeriana officinalis
Emetics [63] Azadirachta indica, Randia dumatorum, Cucumis sativus, Luffa echinata, Embelia ribes,
Salix caprea, Toddalia asiatica, Pongamia pinnata
Enema [63] Randia dumatorum, Holarrhena antidysenterica, Saussurea costus, Luffa echinata,
Acorus calamus, Aegle marmelose
Epilepsy [64] Withania somnifera, Semecarpus anacardium
Gastroduodenal ulcers [65] Musa sapientum, Bacopa monniera, Eclipta alba, Abies pindrow, Benincasa hispida,
Centella asiatica, Convolvulus pluricaulis, Pongamia pinnata, Garcinia indica, Zingiber officinale,
Asparagus racemosus, Aegle marmelos
Gynecological disorders [66] Saraca indica, Aloe vera, Glycyrrhiza glabra, Curcuma longa, Nardostachys jatamansi, Zingiber officinale,
Commiphora mukul, Withania somnifera, Tinospora cordifolia, Asparagus racemosus
Heart diseases [67] Terminalia arjuna, Aloe vera, Coleus forskohlii, Inula racemosa, Andrographis paniculata,
Centella asiatica, Piper longum, Picrorhiza kurroa, Commiphora mukul
Hepatic disorders [68] Andrographis paniculata, Annona atemoya, Boerhavia diffusa, Eclipta alba, Terminalia chebula,
Semecarpus anacardium, Phyllanthus niruri/amarus, Picrorrhiza kurroa, Podophyllum hexandrum,
Tinospora cordifolia
Thyroid dysfunction Azadirachta indica, Momordica charantia, Convolvulus pluricaulis, Emblica officinalis,
(hyperthyrodism) [69] Ocimum sanctum, Piper betel, Rauwolfia serpentina, Trigonella foenum, Moringa oleifera,
Lithospermum officinale, Lithospermum ruderale, Allium sativum, Nelumbo nucifera, Aloe vera,
Aegle marmelos
Thyroid dysfunction Bauhinia variegata, Echhornia crassipes, Bauhinia purpurea, Commiphora mukul,
(hypothyroidism) [69] Withania somnifera, Achyranthes aspera, Saussurea lappa
Hyperacidity [70] Embilica officinalis, Glycyrrhiza glabra, Asparagus racemosus, Eclipta alba, Trichosanthes dioica,
Adhatoda vasica, Cocos nucifera
Immune modulation [71] Terminalia chebula, Embilica officinalis, Piper longum, Gycyrrhiza glabra, Allium sativum,
Commiphora mukul, Tinospora cordifolia, Withania sominifera, Aloe vera
Indigestion [72] Zingiber officinale, Foeniculum vulgare, Curcuma longa, Mentha piperita

1638 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

Table 3. Classification of botanicals according to their efficacy towards various diseases (continued).

Health disorders Botanicals with scientific evidence

Male reproductive disorders [73] Asparagus racemosus, Cynomorium coccineum, Mucuna pruriens, Piper longum,
Tribulus terrestris, Trichopus zeylanicus, Vanda tessellata, Withania somnifera, Zingiber officinale
Obesity [74] Commiphora mukul, Terminalia chebula, Terminalia belerica, Embilica officinalis,
Picrorrhiza kurroa, Curcuma longa, Plantago ovata
Parkinsons disease [75] Withania somnifera, Bacopa monniera, Centella asiatica, Sida cordifolia,
Mucuna pruriens
Psychiatric disorders [76] Withania somnifera, Ocimum sanctum, Bacopa monniera, Convolvulus pluricaulis,
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Centella asiatica
Purgatives [63] Picrorrhiza kurroa, Ricinus communis, Terminalia chebula, Terminalia belerica,
Embilica officinalis, Euphorbia neriifolia, Indigofera tinctoria, Cassia fistula
Sciatica [77] Commiphora mukul, Vitex negundo, Ricinus communis, Pluchea lanceolata,
Sida cordifolia, Tinospora cordifolia
Urolithiasis [78] Crateva nurvala, Tribulus terrestris, Bergenea ligulata

Experiential stage
Diagnosis
Documentation
Follow-up
For personal use only.

Exploratory stage
Tolerability studies
Clinical observations Doseresponse studies
Druginteraction studies
In vitro and In vivo assays
for Safety and Efficacy

Experimental stage
Molecular targets
Signaling pathways
Receptor pathways
Structure elucidation and
Crystallization of drug-target
complexes

Figure 1. Reverse pharmacology approach for ayurvedic drug discovery.


Reverse pharmacology concept adapted from Patwardhan et al. (2004) [1] and Vaidya (2002) [29].

tracks, with overlapping steps with each other. The following This method is quite feasible in countries where ayurvedic
are three major tracks that are anticipated to progress at an medicines are commonly practiced and where there is a
increased pace in the near future. drive for more use of natural medicines in place of conven-
i) New drug discovery, or more particularly widespread tional medicines that are either less effective or ineffective
use of known ayurvedic drugs, could result as a natural for a given problem. Such an approach would also be
direction when ayurvedic medications with proven abilities ideal for promising ayurvedic formulations that are not
are further subjected to well-designed and analyzed human amenable for standardized in vitro biological assays (e.g., cell
clinical trials. In this approach, ayurvedic formulations per se culture-based) and other laboratory-based exploratory studies.
are scrutinized for the extent of efficacy and toxicity using However, whenever the use of in vivo methodologies (such
precise biological and clinical end point assays, critical as whole-animal studies) that have traditionally been used
drug interactions and inter-individual variability measures. to test ayurvedic products are possible, they should be

Expert Opin. Drug Discov. (2007) 2(12) 1639


Ayurvedic drug discovery

O
O
OH
O E
N SR S O
S R
OH
N R
R S H
O OH
Vascine RH R
R
S HO O
R R S R
S HO OH
S RH HR HO OH
O O OH OH OH
Allicin Boswellic acid Andrographolide Bacoside A
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OH Z O O
O E E
HO
S O
O S HS
HO
HO RH R H HO OH
OH O O O
Gallic acid Guggulosterone Curcumin Eugenol

O HO O
OH
O OH
O SS
OH HO H R S
OH O R
HO S E E O OH
O O O
HO N OH
NH2 O H
HO O O OH
O
HS HS SRS
L-dopa Ellagic acid Piperine O SS
For personal use only.

OH OH
R R
H R
O S R S HO O
S

Glycyrrhizin

OH
H H
N
S O N
R S O H RH
O S S S
O S OH O
H H SH
E OH O SRR O
O S O
O R SS R O
O
S SR H S O O
HO OH O
OH O O
Kutkoside Tinocordifolin Reserpine

H
OH R O OH O OH
O O
HO E H S S 6
O R 4
S HS S
HO HO
RH SH O O
OH S
S
O
O
Reservatol Withaferin A 8-Gingerol 6-Gingerol

Figure 2. Structures of Ayurvedic leads.

1640 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

adequately used to validate ayurvedic products before higher probability of identifying single-molecule active
escalating to human clinical trials. compounds from designated ayurvedic herbs (e.g., curcumin
ii) Ayurvedic medications per se are subjected to a in turmeric, guggulosterone from guggul), it also suffers
higher level of (more rigorous analysis than the previous) the selective disadvantage of not taking into account
scientific exploratory studies comprising both in vitro/ex vivo the supplemental benefits offered by trace-levels compounds
components (metabolic and activity evaluation assays) and additionally present in those herbal plants (as opposed to
in vivo (preclinical and clinical) components. Heterogeneous original ayurvedic preparations). Such an approach is also
crude extracts containing a mixture of compounds feasible in any part of the world provided the resources,
(2 100 compounds) are subjected to biological activity- infrastructure and methodology are available.
based (e.g., whole animal model testing for response The first two processes are shot-gun approaches to make
elicitations) or assay-based screening (e.g., antimicrobial an extensive use of the known properties on the ayurvedic
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challenge studies) and fractionation methods. These response- plants and medications and bring ayurvedic formulations
based studies narrows down complex mixtures to single- to the market in a relatively shorter period. It encompasses
molecule or fewer-combination (2 10 compounds) optimistic approaches to find superior ayurvedic formula-
mixtures. The subsequent validation of these refined prepa- tions and drug products among the existing herbal
rations for efficacy and toxicity studies by human clinical preparations or even to develop new drug compounds.
trials for the diseases originally targeted by the ayurvedic Multi-ingredient mixtures are also gaining significance in
formulations should be conducted. Identification and the drug discovery field because they yield drug preparations
isolation procedures in this approach would probably involve of superior clinical value compared with monotarget drugs.
several rounds of chemical purification as well as synthesis However, in the light of the lack of available data on the
measures to scale-up drug compounds. Approximately, lower successful use of ayurvedic products in different ethnic
milligram (1 10 mg) levels of active compounds are population, metabolic enzymes involved in detoxifying
required for bio-assaying and at least a few grams (1 10 g) ingredients and toxicity issues need to be carefully considered.
of pure or semipure compounds are required for lead The last approach uses the pharmacognostic sources of
For personal use only.

identification [30]. Such an approach is suitable for both ayurvedic drugs for streamlined drug discovery approaches,
proven and potential forms of Ayurveda therapeutic beginning with the identification of the active compounds
formulations and can be conducted at any place where the from ayurvedic plants. Even though this approach is intensely
quantity and quality of the authentic ayurvedic drug time consuming, relatively expensive and requires major
products is not a problem. Difficulties in this approach modifications in the early drug discovery methodologies, it
could arise when more than one compound at varying orders has a higher probability of identifying novel drug molecules
of concentration is responsible for a desired biological or a or chemical structures for experimentation on directed
therapeutic response, which is many a time the case with structural alterations and lead optimizations.
ayurvedic herbs. In that case, even extensive end point
characterizations (such as Ki or IC50 values for a potential 11. Tools and methodologies in
enzyme inhibitor) of many of the active components in a ayurvedic drug discovery
mixture may not sufficiently identify discernible clues for a
therapeutically effective few-compound mixture. The evaluation of ayurvedic herbs (or products) lays out
iii) The last track is the elementary analysis of ayurvedic several stages that demand the use of modern analytical
herbs (and not ayurvedic products) that are described in tools for compound screening and analysis. The mixture of
ayurvedic texts and pharmacopeias, for identification and compounds in multi-ingredient formulations or in ayurvedic
isolation of active single-molecule drugs. Being an exhaus- plants often requires to be simplified into simple and pure
tive venture for identifying active and potent single mole- (or semipure) single- or fewer-combination molecules. This
cules, the procedure becomes quite complex for certain plant is achieved by preparing concentrated ayurvedic plant
compounds that tend to occur as bonded complexes with extracts and fractionating and purifying them into sufficient
similarly structured and often inactive compounds. If the quantities for assaying purposes. Recent high-resolution
molecular profiling of active ingredients is successful, then separation technologies, such as HPLC and tandem mass
these catalogued compounds can be subsequently subjected spectrometry have indeed revolutionized compound
to conventional drug discovery steps. The beginning step, separation and fractionation procedures in a relatively
which extensively use combinatorial screening library of time-conserving manner. The HPLC effluents can be directly
compounds from ayurvedic plant extracts is excepted. As ionized (electrospray ionization or atmospheric pressure
mentioned in the previous approach, overcoming difficulties ionization) and can be further analyzed by mass spectrometry
posed by the multi-active ingredients that are present at techniques [31] (e.g., Fourier transform ion cyclotron
varying orders of concentrations (and contributing to resonance mass spectrometry) for a precise determination of
different levels of therapeutic benefits) need to be molecular masses and other relevant compound parameters.
carefully considered. Even though this approach has On the other hand, high-resolution NMR spectroscopy

Expert Opin. Drug Discov. (2007) 2(12) 1641


Ayurvedic drug discovery

analysis could greatly facilitate analysis or even could help the 13. Major challenges in ayurvedic
elucidation of the structure of novel ayurvedic compounds. drug discovery
An array of sophisticated analytical techniques [32] (e.g.,
ultra-pressure liquid chromatography, supercritical fluid Ayurvedic drug discovery beginning with elementary
chromatography, capillary electrophoresis), combinatorial analysis of ayurvedic plants is one of the main approaches
techniques (e.g., high-resolution mass spectroscopy with that have received significant attention so far in new
two-dimensional NMR) and high-throughput online assays drug discovery. Even with this approach, the time consumed
(continuous-flow enzymatic analysis) that are presently from compound analysis and cataloging of ingredients to
used in conventional drug discovery processes can also be manufacturing final drug products is enormous. Many
customized for ayurvedic drug discovery processes. Although a time, enthusiasm in this approach weakens when the
these modern instruments will surely facilitate the chemical multi-component beneficial activity of herbal medicines can-
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analysis of ayurvedic compounds at an incredibly rapid pace not be closely or even nearly reproduced by single-molecule
and with lower amounts (nanogram or lower microgram or fewer-combination drugs. Compared with this approach,
levels of pure compounds), chemical derivatizations guided other proposed approaches for developing modern medica-
by structureactivity relationships and traditional medicinal tions from ayurvedic formulations lag behind even in terms
chemistry approaches can also be used wherever scaling-up of clinical initiatives. Much of this is because of the inherent
becomes a factor. For compounds exhibiting absolute technical difficulties in understanding and implementing the
difficulties for the purification from ayurvedic plant matrices, ayurvedic theories to present drug manufacturing and drug
circumventing measures could be taken to assay and market delivery practices. The lack of expertise to develop and
them as fractionated or semipurified complexes. produce these formulations on a large scale basis and
successful fitting of available ayurvedic resources to present
12.Selection criteria for herbs and high-through screening methodologies, creates additional
herbal preparations hindrances [33]. In addition, difficulties in conducting the
pharmacokinetic, pharmacodynamic and bioequivalence
For personal use only.

One of the major points, which often also becomes an studies with specialized ayurvedic formulations also signifi-
issue that has to be carefully considered in ayurvedic drug cantly retard new drug discovery ideas. Moreover, the lack
discovery, is the nature of the source materials. The selection of precise pharmacological end points of multi-ingredient
of potential herbal leads would essentially depend on several formulations and massive interferences by fluorescent and
selection criteria. These include relevance to disease preva- light-scattering compounds in ayurvedic formulations, bring
lence and thrust areas of present research where therapeutic daunting difficulties in assay developments. Furthermore,
alternatives are not available, easy availability of ingredients the lack of characterized animal models for preclinical
and raw materials, necessity for single- or multi-ingredient examination of ayurvedic formulations poses a new type of
formulations, modes of compound extractions and purifica- challenges. One other general limitation is the failure of
tions, desirability for wide-spectrum benefits within a ayurvedic disease descriptions and treatment modalities to
range of disorders, innovativeness in the material used, comply with perfect curative paths in the present days
shelf-life required for the newer ayurvedic formulations, scenarios. This is because of differences in the disease forms
extent of efficacy and toxic side effects, scope for commercial- described in ayurvedic texts as opposed to the present-world
ization and availability of previous preclinical and clinical disease presentations. The complexities in understanding the
data [110] on those ayurvedic compounds. Additional older nomenclatures, disease descriptions, and their correla-
factors that have to be considered in ayurvedic drug tion to modern disease symptoms and courses also pose
discovery, but not necessarily in conventional drug discovery inconveniences. The changes in the properties of the
processes, are the use of appropriate plant parts (e.g., leaves, medicinal plants due to alterations in soil conditions,
barks, dried roots), the preparatory forms (powders, enriched climatic factors and other environmental reasons over time
extracts, tender shoot extracts etc.) and the processing also complicate the ayurvedic drug discovery issues. Studies
methods and durations (shade-dried leaves, freshly harvested on the Saraca asoca plant, which was broadly described in
seed-pods etc.). ayurvedic texts as an effective herb for menorrhagia and
Several workshops and conferences are now conducted in other uterine problems, had only shown to be therapeuti-
different parts of India for an active implementation of cally effective against ovulatory dysfunctional uterine bleeding
research and clinical validations of ayurvedic plants described in recent clinical trials and not for other types of uterine
in ayurvedic texts. A recently held National Innovative dysfunctions [34,35]. Although the multiple factors described
Foundation workshop on ayurvedic drugs (2004) has above could very well contribute to such inaccuracies, finely
concluded that the selective herbs listed in Table 4 should be tuned recharacterizations of the ayurvedic plants for precise
used for various disease conditions [110]. In concurrence to therapeutic effects and outcome become a major necessity.
that, several Indian scientific research institutes have agreed Although the above-mentioned factors definitely create
to conduct clinical trials on these medicinal plants. hurdles in handling the ayurvedic sources for drug discovery,

1642 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

Table 4. Selective herbs that should be used for various disease conditions, as concluded by the Indian National
Innovative Foundation workshop on ayurvedic drugs (2004) [110].

Disease/disorder Medicinal plant

Gastrointestinal and hepatic Peptic ulcer Murraya koenigi (leaf)


diseases and disorders Aristolocehia bracteata
Hyperacidity Ricinus communis
Constipation Aeglemarmelos + Cynodon dactylon + Eclipta alba
Diarrhoea Abutilon indicum
Asparagus racemosus + rice grain
Solanum tilobatum
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Zingiber officinale
Liver damage Cassia sophora
Jaundice Justicia gendurussa
Cascaria esculenta + Phyllanthus fraternus
Citrus limon + Ervattamia heyneana
Pergularia daemia + rice grain
Coccinia indica
Gymnosporia spinosa
Dermal problems (including burn Heritiera littoralis
injury, sepsis, eczema, herpes Ervattamia heyneana
infection and leucoderma) Azadirachta indica
Maytenus emarginatus
Piper betel
Euphorbia hirta + Madhuca indica
Aneilema nudiflora + Aquilaria agallocha + Citrus limon
Lawsonia inermis + Santalum album
For personal use only.

Azadirachta indica
Cyclea peltata+ Cocos nucifera
Allium sativum + Musa sp. + Nicotiana sp.
Andrographis alata
Semecarpus anacardium + Ricinus communis
Vernonia cineria
Diabetes Holarrhena pubescens
Ficus racemosa + Prosopis juliflora + Sapindus laurifoius +
Bougainvillea spectabilis
Ficus glomerata
Aristolochia bracteata
Odema and urinary infections Oedema of legs Daemia extensa
Urinary infection Dracena terniflora
Miscarriages and infertility Abortion prevention Citrus limon + Ixora nigricans
Aegle marmelos + Putranjiva roxburghi
Frequent miscarriage Aristolochia bracteata
Respiratory disorders and Cough Cuminum cyminum + Piper nigrum + Zingiber officinale
miscellaneous diseases Allium sativum + Cissus quadrangularis + Piper nigrum
Adhatoda vasica + Cuminum cyminum + Coriandrum sativum
Cough and asthma Piper betel + Zingiber officinale
Infant cough Aegle marmelos + Zingiber officinale
Asthma Allium sativum + Chenopodium album + Cuminum cyminum +
Piper longum + Sachharum officinarum + Syzygium aromaticum +
Zingiber officinale
Cinnamomum verum + Curcuma longa + Elettaria cardamomum +
Syzygium aromaticum + Zingiber officinale

Expert Opin. Drug Discov. (2007) 2(12) 1643


Ayurvedic drug discovery

Table 4. Selective herbs that should be used for various disease conditions, as concluded by the Indian National
Innovative Foundation workshop on ayurvedic drugs (2004) [110] (continued).

Disease/disorder Medicinal plant

Bronchial asthma Acorus calamus + Glycyrrhiza glabra + Sida stipulata +


Trigonella foenum-graceum
Dry cough and asthma Arum sp. + Piper nigrum + Nigella sativa + Zingiber officinale
Bronchitis Curcuma longa + Rubia cordifolia + Zingiber officinale
Ear pain and tooth ache Pongamia pinnata
Ear pain Azadirachta indica + Hemidesmus indicus + Vitex negundo
Acorus calamus + Allium sativum + Azadirachta indica +
Ferula asafoetida
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Cold Ocimum sanctum + Piper nigrum


Ocimum sanctum + Zingiber officinale

none of it necessarily poses a complete technical impasse for differences within a plant type (variability factors within a
ayurvedic drug discovery. However, there are few immediate species) [2]. Recent developments in molecular characteriza-
and practical challenges, viz availability of the ayurvedic tion studies not only greatly facilitate the understanding of
source materials, clinical evaluation of efficacy and safety of the species and genetic variability in medicinal plants,
ayurvedic medicines, problems on ayurvedic drug formula- but also help in dissecting finer plant properties including
tions and ayurvedic drugdrug interactions, which would contraindications and quality-control measures [11]. In this
require more serious considerations for ayurvedic drug devel- regard, Indian drug manufacturers generally follow the
opment initiatives. These critical issues are discussed at World Health Organization guidelines for identifying heavy-
length in the following sections, along with some possible metal and mycotoxin contamination, adulterations in plant
For personal use only.

alternatives to overcome such shortcomings. products and for processing techniques including harvesting
and storage requirements [20].
13.1Availability of raw materials for an Distinct plant breeding strategies for conservation of nearly
ayurvedic discovery path extinct medicinal plants, large-scale cultivation of medicinal
Any drug discovery process mandates availability of source plants for bulk production, understanding of habitats role
raw materials that are adequately and qualitatively sufficient (climatic, soil and other environmental influence) on the
to obtain enough active principles both for initial clinical composition and content of medicinal plants, incorporation of
evaluation and for further scaling up processes to meet the modern processing and storage methods and implementing
market demand. The major source for ayurvedic drug strict quality-control standardization methods are some
discovery is the medicinal plants described in ayurvedic of the efforts needed to generate quality raw materials
texts. Clear shortage of required raw materials is one of the from rare ayurvedic plants showing promise for new
major reasons why reverse-pharmacology approaches are less drug discovery. Cross-breeding and plant biotechnology
commonly practiced in drug discovery processes. Technical techniques (genetic transformation, micropropagation
limitations to produce desired amounts of active components tissue culture, cryopreservation) could also diversify the
even when medicinal plants are adequately available pose medicinal value of well-studied ayurvedic plants [4]. Selective
another key issue for the ayurvedic pharmaceutical industries. enrichment of desired plant components or reduction
Naturally, this constraint is carried on as a failure to meet of toxic plant components by genetic engineering
required market demand even when the drug product proves techniques should also be practiced for better
to be therapeutically effective in clinical trials. Alternate resource managements.
initiatives that could circumvent inadequacy problems
include either synthetic or semisynthetic development of the 13.2Clinical evaluation of efficacy and
plant drug compounds [36,37]. Guggul, an antichloesetrol safety of ayurvedic medicines
drug isolated from Commiphora mukul, is one of the The ayurvedic drug formulations are based on medicinal
best examples for such synthetic versions developed in plant extracts and products that have been safely used for
circumventing inadequacy or supply problems [7]. thousands of years. For most part, this assures a time-tested
Although the availability of the resource for some medicinal selection process for various plant drugs available in the
plants is not a problem, heavy metal contaminations and ayurvedic pharmacopeias. However, ayurvedic medicinal
alterations in ingredients due to other environmental preparations (liquid kashayams [aqueous or oily extracts]
pollutants can make them difficult or unsuitable for drug or powders) often use extremely low concentrations of
development [38,39]. Additional issues include segregation active ingredients and many of these ingredients have
of phenotypically identical plants and identification of been shown to operate in conjunction (by covalent or

1644 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

non-covalent bonding) with other natural substances (e.g., (fine powders), ghrithams (ghee preparations), lehyams
tannins, carbohydrates, minerals) in the body. The key goal (jaggary syrup preparations), lepam (ointments), panakam
in ayurveda-based drug discovery is the development of a (aqueous extracts), thailam (medicated oils), bhasma
single-molecule or a fewer-combination drug formulations (incinerated metals or minerals), sinduram (drugs prepared
that faithfully represents the drug actions noticed in tradi- by sublimation) etc. On the contrary, modern drugs require
tional multi-ingredient ayurvedic formulations. Although convenient formulations mainly in the form of tablets,
ayurvedic texts mention that multi-ingredient formulation capsules, injectables or oral-liquid (syrups) preparations.
can overcome key therapeutic drug delivery issues, such A heavy-metal content of ayurvedic medicine has been
as low bioavailability, and less potency, it can also pose another hot topic of concern for its consumers, especially
serious disadvantages including susceptibility to toxicities after the publication of reference [38] in the Journal of
(hepatotoxicity and nephrotoxicity) and drugbotanical American Medical Association. In ayurveda, there is a class
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interactions especially in the light of present-day diet, of medicine called rasaushadha (herbo-mineral/metallic
environment and lifestyle patterns. Also, the active formulations) that contains minerals and metals in the
parent-drug molecules and the metabolites of each of these form of bhasmas (incinerated metals) in addition to herbs.
parent drug compounds complicate the pharmacokinetic Ayurveda clearly recognized and established all the symptoms
understanding of multi-ingredient formulations, which of heavy metal toxicity at least 3000 years ago, and
would become easier when single or fewer-combination has advocated stringent standards to use the metals
drug molecules are developed. Sometimes the isolated new therapeutically only after eliminating its toxic effects by
compounds may not completely comply with original processing [111]. Rasa shastra is the section which describes
ayurvedic descriptions and, hence, it might become essential the use of metals, gems, minerals in formulations to treat
to revalidate their efficacy and safety by in vitro/in vivo incurable chronic diseases. These non-herbal ingredients are
studies and clinical evaluations. Although extensive first purified and then burnt several times and converted
clinical evaluation as used in conventional drug discovery into ash (bhasma). Some of the metals are burnt up to
(such as randomized clinical trials) may not be feasible 100 times to nullify their toxic effects. These ultra-fine
For personal use only.

all the time for ayurvedic drug products, a carefully particles should be able to float on water, which indicates
designed case-study process could help addressing if activity the non-existence of heavy metals in the preparation.
and safety are attained within measurable parameters. Case Although modern chemical testing may give positive result
study trials essentially evaluate the traditional uses of a for the presence of heavy metals, according to Ayurveda,
drug in the existing clinical settings and have also been these metals have been converted to non-toxic form, which
recommended by the NIH and the National Center for is safe for internal use, and it could even not be possible to
Complementary and Alternative Medicine [40] for ayurvedic recover metals from such preparations [41]. These trans-
practitioners. The knowledge available from ayurvedic formed forms of metals acts as carriers and catalysts, helping
literature can guide the usual ethical considerations and the herbs to reach their desired site of action and also
dose and dosage forms. For all new (single) molecular increase their bioavailability. The proper dose and duration
entities identified from ayurvedic plants, the dose and of intake of these medicines are extremely important and
dosing-regimens are evaluated based on therapeutic they should only be prescribed and taken under the
concentrations, elimination pathways and pharmacokinetic guidance of ayurvedic practitioners who are experts in this
parameters (bioavailability, clearance, volume of distribution, particular field of medicine [42,112].
half-life, plasma-protein binding, AUC). These processes The manufacture of many ayurvedic drugs in tablets or in
closely follow and parallel conventional drug pipeline a capsule forms require fine grounding and processing
assays as well as help to consolidate resources in a manufac- of crude herbs and its products. Particle sizes alter herbal
turing unit. In cases and diseases (e.g., cancer) where properties due the physical and chemical alterations in plant
single-molecule compounds fail to offer adequate therapeu- compounds that occur during the blending, compression
tic solutions and where ayurvedic theories firmly and filling processes. Such dosage forms are not found to
support multi-drug treatment modalities [26], further clinical be successful for ayurvedic products due to problems
evaluation for potency and toxicity studies could be encountered by therapeutic efficacy and compliance issues [4].
planned in the presence of one or more secondary However, these problems could be largely avoided when
active ingredients. single active molecules are developed from ayurvedic plant
products. Iwu, in his book Ethno-medicine as drug discovery,
13.3Problems on ayurvedic drug formulations, discussed the solubility issues in drugs discovery in detail
dosage and delivery, and their evaluation and these issues seem to be fit for ayurvedic drug products
Ayurvedic formulations are often dispensed in specialized as well. Although the active constituents predominantly
preparations, such as arka (saturated aqueous solutions occur naturally as soluble salts or organic complexes with
prepared by distillation), asava (non-boiled fermentation solubility-enhancing matrices, the extraction processes often
products), arishta (boiled fermentation products), churnams lead to the dissociation of these organic compounds from

Expert Opin. Drug Discov. (2007) 2(12) 1645


Ayurvedic drug discovery

the water-soluble components, resulting in production of the -glutamyl-S-alkylcyteines are completely hydrolyzed to
insoluble extractives [43]. Meticulous experimentation or mainly S-allylcysteine and S-1-propenylcysteine with no
customization of present drug delivery techniques would presence of volatile sulfides in aged garlic preparation.
help in handling some of the first-pass and bioavailability Allicin, the major active component in garlic, is also converted
issues with ayurvedic drug products. to a concentrate of allylic mono-, di- and tri-sulfides in
dispersed oil during steam-distillation process of garlic oil
13.4 Drugbotanical interactions generation. Allicin is also the major ingredient responsible
Plant product-based drug interactions are alarmingly rising for lowering blood cholesterol levels that possibly inhibits
in countries where traditional plant medicines act as health- key enzymatic reactions in the cholesterol biosynthetic
care component (e.g., India and China) as well as in others pathway. Depending on the form of garlic preparation, the
regions of the world where herbal supplemental drugs are extent and magnitude of cholesterol-lowering effects of
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extensively used (e.g., US). The occurrences and reporting garlic products would vary distinctly to a measurable extent.
on the drugbotanical interaction are also anticipated to Garlic powder and aged garlic are also known to have
reach far more heights in the near future because of antithrombolytic activity that may contribute to additional
the worldwide market for herbal medicine expecting to cardiovascular effects. Earlier clinical studies on garlic
reach a tune of $26 billion by the year 2011 [113]. Drug supplements and HIV-1 protease inhibitors (saquinavir)
interactions often result in pharmacokinetic (e.g., increased showed distinct pharmacokinetic alterations and CYP3A
clearance or reduced half-life) or pharmacodynamic altera- involvement [46], whereas other follow-up studies with
tions (e.g., increased blood-clotting time or reduced glucose different CYP3A substrates (midazolam, alprazolam) did not
levels) or, more frequently, in some level of both. show any CYP3A-based drug interactions [47,48]. This
Drugbotanical interactions mainly occur because of herbal suggests multiple factors including the form of garlic supple-
components inducing or inhibiting (or acting as a substrate) ments and substrate dependence in interaction with CYP3A
the drug-metabolizing cytochrome P450 (CYP) enzymes might be important in understanding garlic-based drug
(e.g., CYP3A4, CYP2D6, CYP2C9) and/or drug-transporting interaction. Garlic products have also been shown to signifi-
For personal use only.

proteins, such as P-glycoprotein, breast cancer resistance cantly decrease CYP2E1 activity [47], but not CYP2D6 and
protein and organic anion transporting peptides. Although CYP1A2 activities [48]. Although the content of active
the predominant mechanisms of induction or inhibition are components in herbal extracts with respect to both composi-
thought to be due to modulation of the levels of the tion and uniformity is a major issue in understanding
transcription factors, such as pregnane-X-receptor and drugherb interactions, patient compliance and other related
constitutive androstane receptor that control the mRNA issues also creates distinct challenges in managing drugherb
expression levels of these genes, a number of other mecha- interactions. Missing reports or misreports of patients usage
nistic possibilities for drug interactions are only yet to be of herbal products to their healthcare providers, significant
discovered. Although plants products, such as St. Johns lack of prospective studies available with plant products
Wort extract and grapefruit (or cranberry) juices are exten- especially in a disease context (as opposed to studies in
sively studied at the moment for their interactions [44,45], the healthy volunteers), lack of governmental regulations
majority of ayurvedic plant products are not yet completely resulting in large variation in the quality of commercial
evaluated for their interaction with other prescription drugs. products and magnitudes of herbdrug interactions as well
Some of the well-assessed and available reports on drug as inability to extrapolate or predict results from one
interactions with ayurvedic products are summarized in herbal product to another, still remain prominent issues
Table 5. Guggul or guggulipid, an antihyperlipidemic and to address.
antiarthritis ayurvedic drug, is reported to interact with
azathiopurine, statins and a number of anticancer agents. 14. Ayurvedic drug development in India:
Laxative herbs (e.g., Aloe) have been found to cause a serious government and private sectors
hypokalemic cardiac effect when co-administered with
potassium-lowering drugs. Bitter melon can induce severe The Indian government agencies, such as the Department of
hypoglycemic effects when co-administered with other anti- Biotechnology, the Ministry of Health and Family Welfare,
diabetic agents. For some plant compounds, the constituents ICMR and CSIR, have brought significant initiatives for
and the proportions of those constituents, depending on ayurvedic drug discovery and development. The Department
the type and form of plant products administered, largely of Biotechnology initiated the network program on
determine the presence or the extent of the interaction. bio-prospecting of biological wealth using biotechnological
For example, garlic (Allium sativum) is commonly used tools and this includes bio-prospecting of molecules and
as dehydrated garlic powder, garlic oil or aged garlic genes for product development. As mentioned earlier,
preparations. Although dehydrated garlic powder contains the CSIR and the ICMR have successfully implemented
two main groups of organo-sulfur constituents, that is, a reverse-pharmacology approach in many of their drug
S-alkylcysteine (mostly allicin) and -glutamyl-S-alkylcyteines, discovery processes. The CSIR has adopted this new path

1646 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

Table 5. Ayurvedic herbdrug interactions.

Ayurvedic medicine Drugs Symptoms of interactions

Evolvulus alsinoides [79] Phenytoin Co-administration reduces anti-epileptic activity


(Shankhapushpi syrup) and serum levels of phenytoin
Withanolides from Withania somnifera [80] Digoxin assay Falsely lowers digoxin values with MEIA assay
Guggul lipid from Commiphora mukul [115] Aspirin Increase the activity of aspirin leading to
bleeding problems
Areca catechu [81] Prednisone and salbutamol Inadequate control of asthma
Allium sativum [82] Warfarin Increased INR
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Momoridica charantia [83] Chlorpropamide Less glucosuria


Glycyrrhiza glabra [84] Prednisolone Increase plasma concentrations
Tamarindus indica [85] Aspirin Increase availability of aspirin
Trigonella foenum-graecum Warfarin Increased INR
(Fenugreek) [86]
Camellia sinensis (Green tea) [87] Warfarin Increased INR
Foeniculum vulgare (Fennel) [88] Enalapril Cough suppression
Zingiber officinale (Ginger) [89] NSAIDS No effect of NSAIDS
Citrus paradisi (Grapefruit juice) [90] Fluoxedine and trazodone Serotonin syndrome
INR: International normalized ratio; MEIA: Microparticle enzyme immunoassay; NSAID: Nonsteroidal anti-inflammatory drug.
For personal use only.

through the New Millenium Indian Leadership Initiative Welfare has also established a traditional-knowledge
and this team has a network of 19 CSIR laboratories digital library that will particularly aid in traditional
along with several research and development institutions, knowledge resource classification (TKRC) [51]. The TKRC is
as a multi-disciplinary approach. It is aimed at studying similar to and in accordance with the international patent
and researching various diseases, such as diabetes, arthritis classification system that acts as a bridge between the
and hepatitis, paving the way for new hits and leads. ayurvedic knowledge and patent examiners. This would
The government of India has framed good manufacturing promote accuracies in granting research patents on ayurvedic
practice regulations to improve the standard and quality of drug formulations [50].
manufactured ayurvedic drugs. New rules delineating the Private pharmaceutical companies in India have also
essential infrastructure, manpower and quality-control immensely renewed their interest in favor of ayurvedic
requirements came into force during the year 2000 and drug discovery and development. Indian pharmaceutical
reinforced as part of the Drugs and Cosmetics act of companies, such as Himalaya Drug Company (HDC),
1940 [49]. As a result, ayurvedic medicine-manufacturing Emami, Aswini, Ayur, Dabur India Limited and Cholayil
firms are obligated to comply with these rules and use Pharma, have already patented many of their herbal and
only the ingredients from the recommended resource ayurvedic products both in India and others parts of
materials. For any type of newer formulations, documented the world. The ayurvedic products manufactured by HDC
safety and efficacy data are necessitated for further develop- are exported to as many as 60 countries all over the world
ment as a drug product [50]. An exclusive department and its herbal laxative preparation has been recently
called AYUSH was also established by the Indian govern- patented in the US. HDCs ayurvedic products are also
ment in 1995 to specifically promote the indigenous registered as a pharmaceutical specialty in many countries
medicinal system. Prioritized areas include standardization (e.g., Switzerland). Dabur India Limited, considered as
of drugs, enhancement of availability of raw materials, one of the leading Indian pharmaceutical companies, owns
research and development, information communication, about 30 patents in the US alone. It is also one of the
education and awareness as well as larger involvement of only two pharmaceutical companies in the world to
the national system in delivering healthcare. The Indian introduce Paclitaxel, an anticancer drug. Daburs research
government also established several new laboratories exclu- foundation also possesses the infrastructure for unique
sively for traditional Indian medicine drug testing, and eco-friendly drug extracting and processing procedures
is preesemtly upgrading existing laboratories to test from plant resources. Zandu Indian Pharmaceuticals
herbal medicines for safety and quality requirements for manufactures about 300 health-promoting ayurveda-based
licensing purposes [50]. To protect the intellectual property products using hundreds of medicinal herbs and
rights of ayurvedic drugs, the Ministry of Health and Family herb extracts [114].

Expert Opin. Drug Discov. (2007) 2(12) 1647


Ayurvedic drug discovery

Despite significant strides in herbal pharmaceuticals, diabetes, jaundice, renal failure, chicken pox, herpes
Indias present share is only of $1 billion out viral infections etc. Furthermore, multiherbal ayurvedic
of US$62 billion in the global herbal market (< 2% of formulatory drugs have been clearly identified to possess
the global market share), ranking only in the third position. much lesser side effects or toxicities compared with the
China seems to do better than India by holding 30% modern drug-based monotherapy used in treating diseases
of the global herbal market share, ranking second overall. such as cancer. Despite much of its clinical success in
However, it is widely considered that a huge opportunity developing countries, there is a significant backlog in
is still awaiting the Indian pharmaceutical companies and the standardized ayurvedic drug discovery efforts to go
institutions by way of new innovations, patents and beyond what has slowly emerged so far. Furthermore, as
trademarks. Incorporation of modern pharmaceutical, the global use of ayurvedic knowledge is strikingly
biotechnological and chemical tools is firmly believed to minimal, ayurvedic medicine is still stigmatized as one of
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bring a new leverage in ayurvedic drug discovery by way of the unconventional forms of medicine in many parts of
fusion of traditional and modern medicines [114]. the world.
Ayurvedic drug discovery incorporating modern trends in
15. Conclusion compound identification and clinical screening would help
in the widespread use of ayurvedic drugs, uncovering
The mechanistic basis of action of medicinal herbs used in potentials and benefits described in ayurvedic classics. In
ayurvedic Indian medicine, especially in the context of order to successfully compete for a significant stake in
understanding disease processes in molecular terms, is pav- the global market, there is a pressing need for ayurvedic
ing the way for identifying new drug compounds as well as practitioners and scientists to systematically evaluate the
new drug targets. At the same time, the present and increased therapeutic potentials of ayurvedic products as per standard-
prevalence of diseases that are not completely amenable to ized regulations (e.g., World Health Organization guide-
therapeutic control by modern medicines is creating a surge lines). Although the word systematic research may inspire
in the interest of pharmaceutical companies in developing images of large and expensive clinical trials, case-study trials
For personal use only.

new solutions from therapeutic principles put forth by tradi- suggested by the Office of Alternative Medicine at the
tional medicines. These trends suggest that drug discovery NIH [40] is a simplistic research design with a multitude of
efforts from natural products and specifically from those advantages. It is less expensive and particularly suited
described in traditional medicines, will undoubtedly offer for ayurvedic practitioners in a smaller clinical setting.
more significant drug leads for future development. This The essential elements include maintenance of records of
review presents ayurvedic drug discovery approaches diagnosis, pre-treatment and examination schedules, docu-
suggested by ayurvedic experts in the context of new drug mentation of treatment details including clinical status of
discovery as well as the practical challenges connecting the patients, documentation of clinical observations includ-
traditional ayurvedic resources to present drug discovery ing side effects and drug responses and inter-individual
methodologies. Conformation of ayurvedic drug discovery variations in treatment responses. These studies form the
to modern drug standards and regulations requires signifi- initial basis for reverse-pharmacology approaches in drug
cant customization and up-scaling efforts besides the stan- discovery and provide valuable contributions to the existing
dardized drug discovery steps. Careful evaluation of ayurvedic body of knowledge on a given subject of interest. In
herbs and herb products in accordance to present-day addition to triggering new drug discovery interests, further
practice of drug evaluation and pre-clinical trials is standardizations, dose determinations, toxicity profile
anticipated to bring more successful therapeutic outcomes to identifications and quality-control measurements will
the worlds medicine. also help to identify safe and effective ayurvedic drugs
and formulations.
16. Expert opinion Ayurvedic extract libraries and resources for drug
screening procedures can tremendously favor novel
Ayurvedic drugs are used by Indian populations as drug identification. In particular, high demand exists for
mainstream, alternative, complementary or integrative forms alternative-medicines in treating chronic and degenerative
of medicines. Several joint-ventures of western and ayurvedic type of ailments (e.g., Alzheimers disease, rheumatoid
medical specialty centers are successfully being initiated in arthritis). Although recent genomic understanding provides
India (e.g., Mohans diabetes specialty center and Arya a better picture on the biological targets for ayurvedic
Vaidyas pharmacy in Chennai) to offer multimodal drug products, recategorizing ayurvedic herbs and products
treatment options incorporating advantages put forth by based on the current molecular understanding of disease
both medical streams. Moreover, it is also common to notice processes would highly facilitate a focused search for
medical practitioners suggesting the incorporation of natural new drug leads. This, along with substantial inputs in
medicine-based procedures and medications in the regularly terms of innovation, customization, infrastructure and
prescribed modern drugs to handle disorders such as technology, would clearly facilitate standardized drug

1648 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

discovery procedures from ayurvedic resources. Critical Acknowledgements


challenges described earlier, but not limited to, are required
to be meticulously addressed for productive outcomes in The authors would like to thank Li Liu, Department of
ayurvedic drug discovery. Although this is the case for Pharmaceutics, University of Washington, for her critical
well-studied ayurvedic plants, rigorous scientific experimen- comments on the manuscript.
tations are still required for a number of other medicinal
herbs for which understanding on their biochemical basis Declaration of interest
of cellular action remains less understood. Considering
these major issues and bringing specializations from The authors state no conflict of interest and have received
different streams under one roof, ayurvedic drug no payment in preparation of this manuscript. The views
discovery could be pushed forward to shed light on novel and opinions expressed in this article are those of the authors
Expert Opin. Drug Discov. Downloaded from informahealthcare.com by University of Notre Dame Australia on 06/22/13

therapeutic interventions. only and not necessarily of the organizations they work for.

Bibliography 11. JOSHI K, CHAVAN PE, WARUDE D, 21. PATWARDHAN B, CHOPRA A,


1. PATWARDHAN B, VAIDHYA ADB, PATWARDHAN B: Molecular markers in VAIDHYA ADB: Herbal remedies and
CHORGHADE M: Ayurveda and natural herbal drug technology. Curr. Sci. (2004) the bias against Ayurveda. Curr. Sci.
products drug discovery. Curr. Sci. 87:159-165. (2003) 84:1165-1166.
(2004) 86:789-799. 12. RANG HP: The development of the 22. MISHRA LC: Scientific Basis for Ayurvedic
2. MUKHERJEE PK, RAI S, KUMAR V, pharmaceutical industry. In: Drug Discovery Therapies, CRC Press, Florida (2003).
MUKHERJEE K, HYLANDS PJ, and Development: Technology in Transition. 23. PATWARDHAN B: Ayugenomic:
HIDER RC: Plants of Indian origin in Rang HP (Ed.), Elsevier, Philadelphia, integration of customized medicine.
drug discovery. Expert Opin. Drug Discov. USA (2006):3-18. Indian J. Nat. Products (2003) 19:16-23.
(2007) 2:633-657. 13. CRAGG GM, NEWMANN DJ: 24. VIJAYAKUMAR D, RAGHAVAN KV:
3. ROUHI AM: Rediscovering natural International collaboration in drug Novel chromatographic fingerprinting
For personal use only.

products. Chem. Eng. News discovery and development from method for standardization of single
(2003) 81:104-107. natural sources. Pure Appl. Chem. (2005) medicines and formulations. Indian
77:1923-1942. Institute of Chemical Technology,
4. JACHAK SM, SAKLANI A:
Challenges and opportunities in drug 14. KAR A: Ayurveda: where are we? Hyderabad, WO 0246739-EP2 0000991
discovery from plants. Curr. Sci. (2007) Curr. Sci. (2007) 92:159. 991-263397?CSIR C01N30-88 (2002).
92:1251-1256. 15. LIPINSKI CA, LOMBARDO F, 25. KHAN S, BHALICK MJ: Therapeutic
5. RANG HP: Drug discovery process: DOMINY BW, FEENEY PJ: plants of Ayurveda: a review of selected
general principles and some case histories. Experimental and computational clinical and other studies for 166 species.
In: Drug Discovery and Development: approaches to estimate solubility and J. Altern. Complement Med. (2001)
Technology in Transition. Rang HP (Ed.), permeability in drug discovery and 7:405-515.
Elsevier, Philadelphia, USA (2006):45-56. development settings. Adv. Drug Deliv. Rev. 26. BALACHANDRAN P,
(1997) 23:3-25. GOVINDARAJAN R: Cancer an
6. KUHRT LM: Successful but often
unconventional: the continued and 16. MASHELKAR RA: Chitrakoot Declaration, ayurvedic perspective. Pharmacol. Res.
long-term contribution of natural products National Botanical Research Institute (2005) 51:19-30.
to healthcare. Expert Opin. Drug Discov. convention (2003). 27. HANKEY A: The scientific value of
(2007) 2:305-311. 17. VAIDHYA ADB: Reverse pharmacological Ayurveda. J. Altern. Complement Med.
7. PADMA TV: Ayurveda. Nature (2005) correlates of ayurvedic drug actions. (2005) 11:221-225.
436:486. Ind. J. Pharmacol. (2006) 38:311-315. 28. PREMALATHA B: Semecarpus anacardium
8. STOUGHTON RB, FRIEND SH: 18. AGGARWAL BB, ICHIKAWA H, Linn. nuts a boon in alternative
How molecular profiling could GARODIA P et al.: From traditional medicine. Indian J. Exp. Biol. (2000)
revolutionize drug discovery. Nat. Rev. ayurvedic medicine to modern medicine: 38:1177-1182.
Drug Discov. (2005) 4:345-350. identification of therapeutic targets for 29. VAIDHYA A: Reverse Pharmacolgy
suppression of inflammation and approach, CSIR NMITLI Herbal Drug
9. LEVINE H, RANG HP: The role of
cancer. Expert Opin. Ther. Targets (2006) Development Programme (2002).
genomics and bioinformatics. In: Drug
10:87-118.
Discovery and Development: Technology in 30. POTOSKI J: Timely synthetic support
Transition. Rang HP (Ed.), Elsevier, 19. RAJASEKHARAN PE: Herbal medicine. for medicinal chemists. Drug Discov. Today
Philadelphia, USA (2006):77-98. In: World of Science, Employment News, (2005) 10:115-120.
(21 27 November 2002):3.
10. STOECKLI K, HAAG H: 31. SURYAWANSHI S, MEHROTRA N,
High-throughput screening. In: Drug 20. DUBEY NK, KUMAR R, TRIPATHI P: ASTHANA RK, GUPTA RC:
Discovery and Development: Technology in Global promotion of herbal medicine: Liquid chromatography/tandem mass
Transition. Rang HP (Ed.), Elsevier, Indias opportunity. Curr. Sci. (2004) spectrometric study and analysis of
Philadelphia, USA (2006):99-120. 86:37-41. xanthone and secoiridoid glycoside

Expert Opin. Drug Discov. (2007) 2(12) 1649


Ayurvedic drug discovery

composition of Swertia chirata, a in literature. Ind. J. Pharmacol. (2007) Mishra LC (Ed.), CRC Press, Florida, USA
potent antidiabetic. Rapid Commun. 39:129-139. (2003):273-306.
Mass Spectrom. (2006) 20:3761-3768. 46. PISCITELLI SC, BURSTEIN AH, 58. MITRA SK, RANGESH PR: Irritable
32. WHO Publication: Quality Control WELDEN N, GALLICANO KD, colon. In: Scientific Basis for Ayurvedic
Methods for Medicinal Plant Materials. FALLOON J: The effect of garlic Therapies. Mishra LC (Ed.), CRC Press,
Geneva, Switzerland (1998). supplements on the pharmacokinetics Florida, USA (2003):355-370.
33. WALTERS, WP, NAMCHUK M: of saquinavir. Clin. Infect. Dis. (2002) 59. MITRA SK, RANGESH PR:
Designing screens: how to make yours 34:234-238. Constipation. In: Scientific Basis for
hits a hit. Nat. Rev. Drug Discov. (2003) 47. GURLEY BJ, GARDNER SF, Ayurvedic Therapies. Mishra LC (Ed.),
2:259-266. HUBBARD MA et al.: Cytochrome P450 CRC Press, Florida, USA (2003):323-338.
34. CHOPRA RN: Indigenous Drugs of India. phenotypic ratios for predicting 60. RAI MK, CHIKHALE NJ,
Expert Opin. Drug Discov. Downloaded from informahealthcare.com by University of Notre Dame Australia on 06/22/13

Academic Publishers, Calcutta, India herbdrug interactions in humans. CHOUKHANDE MJ, DUDHANE MN:
(1994). Clin. Pharmacol. Ther. (2002) 72:276-287. Raktaja krimis. In: Scientific Basis for
35. SHRINGI M, GALVANKAR P, 48. MARKOWITZ JS, DEVANE CL, Ayurvedic Therapies. Mishra LC (Ed.),
VAIDYA R et al.: Therapeutic profile of CHAVIN KD, TAYLOR RM, RUAN Y, CRC Press, Florida, USA (2003):479-490.
an ayurvedic formulation Ashotone in DONOVAN JL: Effects of garlic 61. MISHRA LC, ADRA T: Diabetes mellitus
dysfunctional uterine bleeding (DUB). (Allium sativum L.) supplementation on (Madhumeha). In: Scientific Basis for
Ind. Practitioner (2003) 53:193-198. cytochrome P450 2D6 and 3A4 activity in Ayurvedic Therapies. Mishra LC (Ed.),
healthy volunteers. Clin. Pharmacol. Ther. CRC Press, Florida, USA (2003):101-132.
36. LEY SV, BAXENDALE IR: New tools
(2003) 74:170-177.
and concepts for modern organic synthesis. 62. MITRA SK, RANGESH PR: Diarrhea and
Nat. Rev. Drug Discov. (2002) 1:573-586. 49. SHARMA DC: India raises standards dysentry. In: Scientific Basis for Ayurvedic
for traditional drugs. Lancet (2000) Therapies. Mishra LC (Ed.), CRC Press,
37. FEDERSEL HJ: Logistics of process R&D:
356:231. Florida, USA (2003):371-392.
transforming laboratory methods to
manufacturing scale. Nat. Rev. Drug Discov. 50. PATWARDHAN B, WARUDE D, 63. SHARMA AK: Panchakarma therapy in
(2003) 2:654-664. PUSHPANGADAN P, BHATT N: ayurvedic medicine. In: Scientific Basis for
For personal use only.

Ayurvedic and traditional Chinese Ayurvedic Therapies. Mishra LC (Ed.),


38. SAPER RB, KALES SN, PAQUIN J et al.:
medicine: a compartive overview. ECAM CRC Press, Florida, USA (2003):43-62.
Heavy metal content of ayurvedic herbal
(2005) 2:465-473.
medicine products. J. Am. Med. Assoc. 64. BHATT JA, GOGTAY NJ, DALVI SS,
(2004) 292:2868-2873. 51. GANGULI P: Patents and patent KSHIRSAGAR NA: Epilepsy. In: Scientific
information in 1979 and 2004: Basis for Ayurvedic Therapies. Mishra LC
39. ERNST E: Toxic heavy metals and
a perspective from India. World Patent Inf. (Ed.), CRC Press, Florida, USA
undeclared drugs in Asian herbal
(2004) 26:61-62. (2003):427-438.
medicines. Trends Pharmacol. Sci. (2002)
23:136-139. 52. MISHRA LC: Allerigic reaction. 65. SAIRAM K, BATCHU SV:
In: Scientific Basis for Ayurvedic Therapies. Gastroduodenal ulcers. In: Scientific Basis
40. OAM. Office of alternative medicine
Mishra LC (Ed.), CRC Press, Florida, for Ayurvedic Therapies. Mishra LC (Ed.),
workshop on the collection of clinical
USA (2003):203-208. CRC Press, Florida, USA (2003):393-410.
research data relevant to alternative
medicine and cancer. Office of Alternative 53. VOHORA DS, MISHRA LC: Alzhemiers 66. VINJAMURY M, NAGASHAYANA N,
Medicine, Bethesda, USA (1994). disease In: Scientific Basis for Ayurvedic VINJARMURY S, SINGH BB:
Therapies. Mishra LC (Ed.), CRC Press, Gynecological diseases. In: Scientific Basis
41. CHARAK SAMHITA:
Florida, USA (2003):411-426. for Ayurvedic Therapies. Mishra LC (Ed.),
BHAGAVAN DASH, SHARMA BK
(Eds): Chaukhamba Sanskrit Series Office, 54. KAUR S: Antimutagenic effect of ayurvedic CRC Press, Florida, USA (2003):551-574.
Varanasi, India (2001). therapies. In: Scientific Basis for Ayurvedic 67. GAUTHAMAN K, MISHRA LC:
Therapies. Mishra LC (Ed.), CRC Press, Ischemic heart disease. In: Scientific Basis
42. BHUSHAN B, DNYANESHWAR W,
Florida, USA (2003):255-272. for Ayurvedic Therapies. Mishra LC (Ed.),
GIRISH T: Heavy metals and Ayurveda.
Curr. Sci. (2005) 88:1535-1536. 55. MISHRA LC: Rhematoid arthritis, CRC Press, Florida, USA (2003):511-534.
osteoarthritis and gout. In: Scientific Basis 68. BALACHANDRAN P,
43. IWU MM: Introduction:
for Ayurvedic Therapies. Mishra LC (Ed.), GOVINDARAJAN R: Hepatic disorders.
therapeutic agents from ethnomedicine.
CRC Press, Florida, USA (2003):167-184. In: Scientific Basis for Ayurvedic Therapies.
In: Ethnomedicine and Drug Discovery.
Iwu, MM, Wootton JC (Eds), Elsevier, 56. LODHA R, KABRA SK: Bronchial Mishra LC (Ed.), CRC Press, Florida,
Amsterdam, Netherlands (2002):1-23. asthma. In: Scientific Basis for Ayurvedic USA (2003):231-254.
Therapies. Mishra LC (Ed.), CRC Press, 69. KAR A, PANDA S: Ayurvedic therapies
44. BERMAN AF: Herb-drug interactions.
Florida, USA (2003) :209-230. for thyroid dysfunction. In: Scientific Basis
Lancet (2000) 355:134-138.
57. SAHU M, MISHRA LC: Benign growths, for Ayurvedic Therapies. Mishra LC (Ed.),
45. GOHIL KJ, PATEL JA: Herbdrug
cysts and malignant tumors. In: Scientific CRC Press, Florida, USA (2003):133-148.
interactions: a review and study based on
Basis for Ayurvedic Therapies. 70. MITRA SK, RANGESH PR: Hyperacidity.
assessment of clinical case reports
In: Scientific Basis for Ayurvedic Therapies.

1650 Expert Opin. Drug Discov. (2007) 2(12)


Balachandran & Govindarajan

Mishra LC (Ed.), CRC Press, Florida, USA 82. DE SMET PAGAM, DARCY PF: Theoretical and Scientific knowledge
(2003):339-354. Drug interactions with herbal and other of AMI (2002).
71. MUNGANTIWAR AA, PHADKE AS: non-toxic remedies. In: Mechanisms of 105. http://ayusoft.cdac.in
Immunomodulation: therapeutic strategy Drug Interactions. DArcy PF, McElnay JC, Ayusoft a decision support system for
through Ayurveda. In: Scientific Basis for Welling PG (Eds), Springer-verlag, Berlin, Ayurveda. C-DAC, Pune. Project
Ayurvedic Therapies. Mishra LC (Ed.), Germany (1996). sponsored by Ministry of Communication
CRC Press, Florida, USA (2003):63-82. 83. LEATHERADALE BA, PANESAR RK, and Information Technology, Government
72. MITRA SK, RANGESH PR: Indigestion SINGH G et al.: Improvement in glucose of India (2005).
In: Scientific Basis for Ayurvedic Therapies. tolerance due to Momoridica charantia. 106. http://www.jstor.org/view/0041977x/
Mishra LC (Ed.), CRC Press, Florida, BMJ (1981) 282:1823-1824. ap020143/02a00010/0
USA (2003):307-322. 84. CHEN MF, SHIMADA F, KATO H et al.: Baladhur (Marking nut): a popular medieval
Expert Opin. Drug Discov. Downloaded from informahealthcare.com by University of Notre Dame Australia on 06/22/13

73. AKBARSHA MA, SUBRAMONIAM A, Effect of glycyrrhizin on the drug for strengthening memory (1996).
MADHAVACHANDRAN VS: Male pharmacokinetics of prednisolone following 107. http://books.google.com/books?
reproductive dysfunction. In: Scientific Basis low dosage of predinisolone hemisuccinate. id = j5KNwRn7BKUC&pg =
for Ayurvedic Therapies. Mishra LC (Ed.), Endocrinol. Jpn (1990) 37:331-341. PA169&lpg = PA169&dq =
CRC Press, Florida, USA (2003):459-478. 85. MUSTAPHA A, YAKASAI IA, metals+herbs+synergistic+ayurved&
74. VAIDYA ADB, VAIDYA RA, JOSHI BA, AGUYE IA: Effect of Tamarindus indica source = web&ots = F1w3aI6w9N&
NABAR NS: Obesity in Ayurveda. L. on the bioavailability of aspirin in sig = uNDrl1NmDbgFt6bfikXjsu
In: Scientific Basis for Ayurvedic Therapies. healthy human volunteers. Eur. Drug 9CmCU Prakriti
Mishra LC (Ed.), CRC Press, Florida, Metab. Pharmacokinet. (1996) 21:223-226. Your ayurvedic Constitution (1998).
USA (2003):149-166. 86. LAMBERT JP, CORMIER A: 108. http://www.ayurvediccure.com/triphala_
75. MISHRA LC, SINGH RH: Parkinsons Potential interaction between warfarin benefits.htm
disease. In: Scientific Basis for Ayurvedic and boldo-fenugreek. Pharmacotherapy Benefits of Triphala.
Therapies. Mishra LC (Ed.), CRC Press, (2001) 21:509-512. 109. http://www.expresspharmaonline.
Florida, USA (2003):453-458. 87. TAYLOR JR, WILT VM: Probable com/20060930/research03.shtml
For personal use only.

76. SINGH RH, MISHRA LC: Psychiatric antagonism of warfarin by green tea. Express Pharma: Pharmacology at
disorders. In: Scientific Basis for Ayurvedic Ann. Pharmacother. (1999) 33:426-428. reverse (2006).
Therapies. Mishra LC (Ed.), CRC Press, 88. ARYA SC: Controlling 110. http://www.nifindia.org/events/herbal_
Florida, USA (2003):439-452. angiotensin-converting-enzyme-inhibtior workshop.doc (word document) [or]
77. SINGH S: Ayurvedic therapies of Sciatica. induced cough by fennel fruit. http://72.14.209.104/search?q = cache:
In: Scientific Basis for Ayurvedic Therapies. Indian J. Pharmacol. (1999) 31:1999. VqnyvATIjpEJ:www.nifindia.org/events/
Mishra LC (Ed.), CRC Press, Florida, 89. SRIVATSAVA KC, MUSTAFA T: herbal_workshop.doc+National+innovation+
USA (2003):185-202. Ginger (Zingiber officinales) and foundation+workshop+validation&hl =
rheumatic disorders. Med. Hypothesis en&ct = clnk&cd = 1&gl = us
78. SRIDEVI V, LAKSHMI R, RAO SI:
(1989) 29:25-28. National Innovative Foundation. Minutes
Urolithiasis (Mutrashmari) In: Scientific
of the workshop on Building network for
Basis for Ayurvedic Therapies. Mishra LC 90. DREIR JP, ENDRES M: Stain associated
validation and value addition to Traditional
(Ed.), CRC Press, Florida, USA rhabdomyolysis triggered by grapefruit
herbal practices of Medicine, Held on
(2003):535-550. consumption. Neurology (2004) 62:670.
March 3, 2004 at IIM, Ahmedabad.
79. DANDEKAR UP, CHANDRAN RS, Organized by National Innovation
DALVI S et al.: Analysis of clinically Websites Foundation (2004).
important interactions between phenytoin 101. http://www.itmonline.org/arts/ayurind.htm 111. http://ayurveda-foryou.com/heavy_metals/
and shankhapuship, an ayurvedic The ayurvedic medicine industry in India ayurvedahm1.html
preparation. J. Ethnopharmacol. (1992) (2007). Ayurveda medicines and heavy metals.
35:285-288.
102. http://www.pharmabiz.com/article/ 112. http://ayurveda-foryou.com/heavy_metals/
80. DASGUPTA A, REYES MA: Effect of detnews.asp?articleid = 26819&sectionid = heavy_metals1.html
Brazilian, Indian, Siberian, Asian, and 50Ayurvedic research Modern approach by Ayurvedic metallic medicines are not fatal.
North American ginseng on serum digoxin Gangadharan GG (2005).
measurement by immunoassays and 113. http://www.marketresearch.com/product/
103. http://indianmedicine.nic.in/html/pharma/ display.asp?productid = 1378188&g = 1
binding of digoxin-like immunoreactive
apmain.htm Plant-Derived Drugs: Products,
components of ginseng with Fab
Department of Ayurveda, Technology, Applications (2006).
fragment of antidigoxin antibody
Yoga & Naturopathy, Unani, Siddha and
(Digibind). Am. J. Clin. Pathol. (2005) 114. http://www.ipfrontline.com/depts/article.
Homeopathy: ayurvedic Pharmacopeia
124:229-236. asp?id = 6775&deptid = 6
and formulary (2007).
81. TAYLOR RFH, AL-JARAD N, iPrex Intellectual Property Solutions,
104. http://www.aapra.com/sources.htm M Qaiser, and P Mohan Chandran,
JOHN LME: Betel nut chewing and
American Association of Practitioners and ipfrontline.com. What is Indian Pharmas
asthma. Lancet (1992) 339:1134-1136.
Researchers of Ayurveda: Sources of next move (2005).

Expert Opin. Drug Discov. (2007) 2(12) 1651


Ayurvedic drug discovery

115. http://nccam.nih.gov/health/ayurveda/
What is ayurvedic Medicine. NCCAM
Backgrounder (2007).

Affiliation
Premalatha Balachandran1 PhD &
Rajgopal Govindarajan2 PhD
Author for correspondence
1University of Mississippi,

National Center for Natural Products Research,


Research Institute of Pharmaceutical Sciences,
Expert Opin. Drug Discov. Downloaded from informahealthcare.com by University of Notre Dame Australia on 06/22/13

School of Pharmacy,
MS 38677, USA
Tel: +1 662 915 3463; Fax: +1 662 915 7062;
E-mail: prembala@olemiss.edu
2University of Washington,

Department of Pharmaceutics,
School of Pharmacy,
Seattle, WA 98195, USA
For personal use only.

1652 Expert Opin. Drug Discov. (2007) 2(12)