Antidiabetic-relevant and differential Nrf2-modulatory activities of Uvaria valderramensis leaf extracts
摘要
Uvaria valderramensis, an endemic Philippine species, has not previously been evaluated for antidiabetic activity. This study evaluated the antidiabetic-relevant and Nrf2-modulatory activities of its leaf extracts using in vitro assays for α-glucosidase and α-amylase inhibition, antiglycation activity, and Nrf2 reporter modulation. Petroleum ether (UvP), dichloromethane (UvD), and methanol (UvM) extracts were obtained by cold percolation. UvM exhibited significant α-glucosidase inhibition (IC50 = 44.21 µg/mL), whereas none of the extracts inhibited α-amylase. UvP demonstrated moderate inhibition of advanced glycation end-product formation (IC50 = 333.6 µg/mL). In luciferase reporter assays, UvP increased Nrf2 activity in HaCaT keratinocytes (111.22% vs. DMSO control; p < 0.05), while UvP and UvM reduced Nrf2 activity in Huh7 hepatocellular carcinoma cells (24.7% and 67.6%, respectively; p < 0.05). The extracts also did not promote cytotoxicity. These findings demonstrate extract-specific bioactivities involving carbohydrate-digestive enzyme inhibition, antiglycation activity, and context-dependent Nrf2 modulation. This study provides the first in vitro evidence of antidiabetic-relevant and Nrf2-modulatory bioactivities of U. valderramensis leaf extracts and supports further chemical, mechanistic, cellular, and in vivo investigations.