Bryophyllum pinnatum methanolic extract and flavonoid-rich fraction regulate antioxidant/neurotransmitter levels in MSG-induced rat neurotoxicity

Introduction: Bryophyllum pinnatum (B. pinnatum/BP), a medicinal plant known for its diverse pharmacological properties, has been traditionally used for treating various ailments. This study investigated its potential therapeutic effects against MSG-induced oxidative stress and neurotoxicity in Wistar rats, employing both in vivo and in-silico approaches. Methods: Forty-eight adult Wistar rats (n=48) were divided into six groups: control group, MSG group, and treatment groups receiving BP extract and B.pinnatum flavonoid-rich fractions. Biochemical markers such as LDH, MDA, CAT, GST, and AChE were assessed. Neurotransmitter levels of glutamate and GABA were also measured. Molecular docking and MM GBSA analyses were conducted using Maestro 12.8v to evaluate the binding affinities of 10 B.pinnatum compounds with Nrf2 protein, NMDA receptor, and acetylcholinesterase. ADMET profiling was performed using SwissADME and ADMETlab 3.0. Results: MSG increased LDH and MDA levels significantly, while decreasing CAT, GST, and AChE levels, indicating oxidative stress and neurotoxicity. Treatment with B.pinnatum extracts and fractions mitigated these effects, restoring antioxidant enzymes/neurotransmitter levels and reducing lipid peroxidation. In silico studies showed B.pinnatum compounds exhibiting substantial binding affinities for Nrf2, NMDA receptor and acetylcholinesterase, correlating with their neuroprotective effects observed in vivo. ADMET profiling confirmed the drug-like properties of these compounds. Conclusions: B. pinnatum methanolic extract and its flavonoid-rich fraction demonstrated significant antioxidant and neuroprotective effects against MSG-induced toxicity in Wistar rats. There was significant difference in the activity levels of the flavonoid fractions as compared to the crude extract in LDH and AChE, however, the difference was only relative in MDA, CAT and GST.