HERBAL MODULATION OF HYPERGLYCEMIA VIA AMPK ACTIVATION

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent hyperglycemia arising from insulin resistance and progressive β-cell dysfunction. Adenosine monophosphate-activated protein kinase (AMPK), a heterotrimeric serine/threonine kinase and central cellular energy sensor, has emerged as an attractive pharmacological target because its activation enhances peripheral glucose uptake, suppresses hepatic gluconeogenesis, promotes fatty-acid oxidation, and improves insulin sensitivity. A growing body of phytochemical research indicates that numerous medicinal plants and their bioactive constituents lower blood glucose, at least in part, by engaging this pathway. This review synthesizes current evidence on herbal AMPK activators relevant to hyperglycemia, and a broader catalog of emerging phenolic and terpenoid activators. Mechanistic data from cell-based, animal, and clinical studies are summarized, molecular docking and structure–activity findings are reviewed, and translational challenges relating to bioavailability, nanoformulation, extract standardization, polyherbal synergy, herb–drug interactions, and mechanistic specificity are discussed in depth. Herbal AMPK activators represent a promising, multi-target complement to conventional antidiabetic therapy, warranting rigorously designed clinical trials to establish optimal dosing, efficacy, and long-term safety.