Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain

injury via gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 signaling pathway

Citation: Wang, Y. et al. Rhein and rhubarb similarly protect the blood-brain barrier after experimental
traumatic brain injury via gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 pathway. Sci. Rep. 6,
37098; doi: 10.1038/srep37098 (2016).

Traumatic brain injury transpires when an outside mechanical force causes brain dysfunction. This is
typically caused by a violent blow or bump to the head or body. Among all types of injury, those to the
brain are among the most likely to effect in death or permanent disability. Traumatic brain injury (TBI)
is a leading cause of disability in the entire expanse of the globe. The worldwide incidence rate of TBI is
estimated at 200 per 100 000 people per year; however, this rate is doubtful and a likely undervalue.
Hence, as stated in the paper, traumatic brain injury (TBI) is a silent epidemic because humanity is
largely ignorant of the extent of this problem. Addressing diseases that kills and disables a number of
people is as important as finding the cure to cancer.

A key characteristic of TBI is the disruption of the blood brain barrier. Due to the increase in the
permeability of the damaged endothelium following blood brain barrier breakdown, the ensuing brain
edema is the most probable cause of up to half of all observed mortality and morbidity. For that reason,
safeguarding of BBB integrity to assuage brain edema is a key aim of TBI treatments. Over the years,
understanding of these molecular and cellular mechanisms of TBI has progressed however strategies to
protect the brain have failed to develop into a distinct successful treatment; thus, the need to identify
novel chemical entities and drugs to treat TBI.

When everything else fails, scientists turn back to nature to look for answers. Herbal medicines have been
a major source of new drugs. One herbal medicine has been shown to protect the blood brain barrier from
breakdown i.e., rhubarb. This study answered the probable mechanism behind the neuroprotective
activity of rhein, the anthraquinone component of rhubarb able to cross the blood brain barrier.
Wang et al (2016), has found that rhein provides similar neuroprotection to rhubarb by inhibiting
the gp91phox subunit of the NADPH oxidase/ROS/ERK/MMP-9 signaling pathway and then
minimizing BBB disruption in response to TBI, hence implying that rhein is indeed the bioactive
component of rhubarb responsible for BBB protection. This finding further implies that rhein may
be a successful compound for development as a prospective therapeutic agent to maintain the
integrity of BBB following TBI.