J Ethnopharmacol. 2021 Mar 26 ;274:114025. Epub 2021 Mar 26. PMID: 33775804
Prevention of MEK-ERK-1/2 hyper-activation underlines the neuroprotective effect of Glycyrrhiza glabra L. (Yashtimadhu) against rotenone-induced cellular and molecular aberrations.
ETHNOPHARMACOLOGICAL RELEVANCE: Yashtimadhu choorna (powder) is prepared from the dried root of Glycyrrhiza glabra L., commonly known as licorice. The Indian Ayurvedic system classifies Yashtimadhu as a Medhya Rasayana that can enhance brain function, improves memory, and possess neuroprotective functions, which can be used against neurodegenerative diseases like Parkinson’s disease (PD).AIM OF THE STUDY: We aimed to decipher the neuroprotective effects of G. glabra L., i.e., Yashtimadhu, in a rotenone-induced PD model.MATERIALS AND METHODS: Retinoic acid-differentiated IMR-32 cells were treated with rotenone (PD model) and Yashtimadhu, and were assessed for cellular toxicity, live-dead staining, cell cycle, oxidative stress, protein abundance, and kinase phosphorylation.RESULTS: Yashtimadhu conferred protection against rotenone-induced cytotoxicity, countered cell death, reduced expression of pro-apoptotic proteins (cleaved-caspases-9, and 3, cleaved-PARP, BAX, and BAK) and increased anti-apoptotic protein, BCL-2. Rotenone-induced cell cycle re-entry (G2/M transition), was negated by Yashtimadhu and was confirmed with PCNA levels. Yashtimadhu countered rotenone-mediated activation of mitochondrial proteins involved in oxidative stress, cytochrome-C, PDHA1, and HSP60. Inhibition of rotenone-induced ERK-1/2 hyperphosphorylation prevented activation of apoptosis, which was confirmed with MEK-inhibitor, highlighted the action of Yashtimadhu via ERK-1/2 modulation.CONCLUSIONS: We provide the evidence for neuroprotection conferred by G. glabra L. (Yashtimadhu) and its mechanism via inhibiting MEK-ERK-1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights Yashtimadhu as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.