6th Edition of Neurology World Conference 2026

Abstract

Nearly 1 out of 8 individuals in the United States is affected by diabetes mellitus (DM), of which approximately 90-95% of cases are attributed to Type 2 (T2DM), a major metabolic disorder resulting from impaired insulin production and/or reduced insulin sensitivity. T2DM causes chronic hyperglycemia and dysregulated energy metabolism, ultimately contributing to long-term cellular and tissue damage across multiple organ systems. Diabetic neuropathy, characterized by progressive neuronal damage and pain, is among the most debilitating complications. Gymnema sylvestre, an anti-diabetic medicinal plant traditionally used in Ayurvedic medicine for glucose regulation, has emerged as a potential neuroprotective candidate. Previous studies conducted in our laboratory demonstrated the neuroprotective potential of Gymnemic Acid-I (GA-1), a major bioactive constituent of Gymnema sylvestre, in undifferentiated SH SY5Y cells. Building upon these findings, the present study provides a mechanistic evaluation of GA-1 in differentiated neuronal SHSY5Y cells, thereby offering a more physiologically relevant in vitro model for investigating diabetic neuropathy. To further validate the therapeutic potential of GA-1, its cytotoxic profile and neuroprotective efficacy were evaluated in differentiated SH-SY5Y neuronal cells. GA-1 (10µM-80µM) exhibited no significant decrease in cell viability, confirming the absence of inherent toxicity. Neurotoxicity was induced using 6-hydroxydopamine (6-OHDA) and streptozotocin (STZ), which model oxidative stress-mediated neuronal damage and diabetic neuropathy, respectively. The IC50 value for 6-OHDA was determined to be 40 µM and that of STZ was 3.5 nM with statistical significance (p<0.05) through One-Way ANOVA. Considering the established role of GA-1 in glucose homeostasis, insulin production was investigated as a potential mechanism using an insulin ELISA initially in undifferentiated SH-SY5Y cells. GA-1 treatment groups did not exhibit insulin levels above control, indicating that GA-1's neuroprotection is not insulin-mediated in this cell line. Consequently, this investigation was not extended to differentiated SH-SY5Y cells. Current studies are focused on evaluating oxidative stress and the involvement of the advanced glycation end products (RAGE) signaling pathway. These studies aim to further elucidate the molecular mechanisms underlying the neuroprotective effects of GA-1 in differentiated SH-SY5Y neuronal cells and its potential therapeutic relevance in diabetic neuropathy