Objective: To explore the neuroprotective mechanisms of T. cordifolia ethanolic extract against Rotenone (ROT)-intoxicated mouse model through proteomics approach.

Background: The death of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc)is the primary cause of Parkinson’s disease (PD). PD is the slow-progressive neurodegenerative disease, affecting about 2% of the global population over the age of 65. Tinospora cordifolia, a traditional medicinal plant, possess strong biological activities

Method: Adult swiss albino mice were divided into four groups six in each. Group-I: treated with normal saline (0.9% NaCl, orally), Group-II: treated with ROT (2mg/kg body wt. for 35 days, subcutaneous), Group-III: pretreated for a week with T. cordifolia ethanolic extract (200 mg/kg body wt., orally), followed by simultaneous administration of T. cordifolia ethanolic extract, and ROT, Group IV: T. cordifolia ethanolic extract (200 mg/kg body wt., for 21 days, orally). Mice were sacrificed, and the nigrostriatal region of the brain was isolated for label free quantification (LFQ), and to identify differentially expressed protein (DEPs) in comparative groups. A systematic bioinformatics analysis was then performed to explore the molecular pathway, cellular location, molecular function of DEPs.

Results: In the current study, 800 DEPs in control vs. PD and 133 in PD vs. Treatment group has been reported. Significant enrichment of DEPs with biochemical and molecular pathways has been demonstrated by in silico. The in silico study showed that mitochondrial gene expression, hypothetical network for drug addiction, TGF-β signaling, odorant GPCRs, and chemokine signaling pathway, played role in PD progression.

Conclusion: The current study demonstrates that T. cordifolia ethanolic extract exerts the therapeutic effects through the regulation of TGF-β signaling, and other pathways to protect DAergic neurons.

References: 1.Birla H1, Rai SN1, Singh SS1, Zahra W1, Rawat A1, Tiwari N1, Singh RK1, Pathak A2, Singh SP3. Tinospora cordifolia Suppresses Neuroinflammation in Parkinsonian Mouse Model. Neuromolecular Med. 2019 Mar;21(1):42-53. doi: 10.1007/s12017-018-08521-7. 2. Jantas, D., et al., Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP (+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state. Neuropharmacology, 2014. 83: p. 36-53.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tinospora-cordifolia-protects-against-rotenone-induced-degeneration-of-dopaminergic-neurons-in-mouse-model-of-parkinsons-disease/