Antidiabetic, Antioxidant, and Anti-Inflammatory Potential of Herbal Compounds: A Multi-Mechanistic Approach

Diabetes mellitus, oxidative stress, and chronic inflammation represent a triad of interrelated pathophysiological conditions responsible for considerable global morbidity and mortality. Conventional pharmacotherapies, while effective, are associated with dose-limiting side effects and therapeutic resistance, necessitating the exploration of safer, multi-target natural alternatives. The present study aimed to evaluate the antidiabetic, antioxidant, and anti-inflammatory properties of selected herbal compounds—curcumin, resveratrol, quercetin, berberine, and epigallocatechin gallate (EGCG) through a battery of standardised in vitro assays and molecular docking simulations. Antidiabetic activity was assessed using α-amylase and αglucosidase inhibitory assays. Antioxidant capacity was determined by DPPH radical scavenging, FRAP, and ABTS decolourisation methods. Anti-inflammatory potential was evaluated through COX-1/COX-2 inhibition and nitric oxide (NO) inhibition assays. Molecular docking was performed against key targets—human pancreatic α-amylase (PDB: 1SMD), αglucosidase (PDB: 3AJ7), COX-2 (PDB: 5IKT), and Keap1 (PDB: 4ZY3) using AutoDock Vina. Results: Berberine demonstrated the highest α-glucosidase inhibition (IC₅₀ 18.4 ± 0.9 µg/mL), while quercetin exhibited superior DPPH scavenging (IC₅₀ 6.2 ± 0.4 µg/mL) and COX-2 inhibition (IC₅₀ 22.1 ± 1.3 µg/mL). Molecular docking revealed that curcumin possessed the most favourable binding energy against COX-2 (−9.3 kcal/mol), while EGCG showed strong interactions with Keap1 (−8.7 kcal/mol). These findings collectively support the multi-mechanistic therapeutic potential of the studied phytochemicals in managing diabetes, oxidative damage, and inflammation. The concurrent modulation of insulin signalling, reactive oxygen species (ROS) scavenging, and inflammatory mediator suppression underscores the value of these compounds as leads for integrative therapeutic development.

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