Background:
Cerebral stroke is one of the leading disease-causing death and disability in a large number of patients globally. Brain damage in ischemic stroke is led by a complex cascade of events. The Rho-associated kinase-2 (ROCK2) has a significant role in cerebral vasospasm, vascular remodeling, and inflammation. It is activated in cerebral ischemia and its inhibition led to a neuroprotective effect.
Objective:
The present study is designed to identify potential inhibitors of ROCK2 using a molecular docking approach.
Method:
We docked phytochemicals of Withania somnifera (WS) into the catalytic site of ROCK2 and compared results with inhibitor Y-27632. ADME and drug-likeness properties of WS phytochemicals were also analyzed.
Results:
Results suggest that 11 phytochemicals exhibited higher binding affinity toward the ROCK2 catalytic domain compared to the Y-27632 inhibitor. Among these phytochemicals, Withanolide G formed H-bonding and established hydrophobic contacts with key catalytic domain residues of ROCK2.
Conclusion:
Our findings suggest that Withanolide G has the potential to inhibit the action of ROCK2 and can be developed as a neurotherapeutic agent to combat cerebral ischemic insult.
Neurodegenerative disease refers to the progressive deterioration of
neurologic function which leads to loss of speech, vision, hearing, and movement. It is
also associated with seizures, eating difficulties, and memory impairment. Natural
products have emerged as potential neuroprotective agents for the treatment of
neurodegenerative diseases due to the enormous adverse effects associated with
pharmacological drugs. Withania somnifera (Ashwagandha) is a traditional Ayurvedic
medicine, used in India as a general tonic. It contains withanolides, and phytochemicals
that may have adaptogenic properties. Studies show that W. somnifera is a
neuroprotective agent and can protect the brain from oxidative stress and inflammation.
This explains its ability to protect from mood disorders. In this review, we have
reviewed the available evidence of W. somnifera and its phytochemicals for
neurodegenerative disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.