Unlocking the Antidiabetic and Antioxidant Potentials of Phyllanthus amarus Using In Vitro and In Silico Approaches

For centuries, medicinal plants have played a vital role in healthcare. Phyllanthus amarus is one such plant traditionally used to manage diabetes. This study combined computational modeling and laboratory experiments to evaluate the antidiabetic and antioxidant properties of its methanol extract (MEPa). MEPa exhibited notable in vitro antidiabetic activity by inhibiting key enzymes involved in glucose metabolism, with IC₅₀ values of 10.2 µg/mL (α-amylase) and 12.5 µg/mL (α-glucosidase), compared to acarbose (6.4 and 8.5 µg/mL). In RIN-5F insulinoma cells, MEPa improved cell viability (87.6% ± 2.6%), reduced reactive oxygen species (43.6% ± 4.2%), enhanced insulin secretion (155.6% ± 11.2%), and inhibited TNF-α release (55.1% ± 5.5%; IC₅₀ = 21.3 ± 2.8 µg/mL). The extract also showed high total polyphenol (153.2 ± 3.6 mg GAE/g) and flavonoid contents (114.5 ± 2.8 mg QE/g), contributing to strong antioxidant activity, including DPPH scavenging (IC₅₀ = 31.4 ± 0.7 µg/mL), FRAP (EC₅₀ = 37.2 ± 5.8 µg/mL), and lipid peroxidation inhibition (IC₅₀ = 5.8 ± 0.8 µg/mL). Computational analysis identified DL-α-tocopherol and γ-sitosterol as key bioactive compounds with strong binding affinities to α-amylase and Keap1, respectively, surpassing standard inhibitors. These findings highlight MEPa as a promising natural source for antidiabetic and antioxidant drug development.