Modulation of pancreatic β-cell function by adaptogens: Emerging evidence and integrative therapeutic potential

Pancreatic β-cells are vulnerable to glucotoxicity, lipotoxicity, oxidative and endoplasmic reticulum stress, chronic inflammation, sustained secretory demand, and loss of cellular identity. This narrative review critically evaluates the mechanistic, preclinical, and translational evidence for Panax ginseng, Curcuma longa, Withania somnifera, and Rhodiola rosea as modulators of β-cell function. A focused search of PubMed, Scopus, Web of Science, and Google Scholar prioritized studies that used β-cell lines, isolated islets, pancreatic tissue, and diabetic animal models, and that reported clinical outcomes related to glycemic control and β-cell function. The available evidence remains predominantly preclinical. Ginseng provides pancreas-level evidence for islet preservation and endocrine-cell remodeling; curcumin shows the strongest evidence for pancreatic and isolated-islet cytoprotection, although its translational relevance is limited by poor and formulation-dependent bioavailability. In a 9-month trial, curcumin reduced progression from prediabetes to type 2 diabetes, but HOMA-β remained an indirect endpoint. Salidroside has direct MIN6 and isolated-islet evidence supporting AMPK-dependent preservation of β-cell function, whereas ashwagandha is supported mainly by pancreatic findings in diabetic animals and by systemic metabolic or neuroendocrine outcomes. PI3K/Akt-, Nrf2-, NF-κB-, JNK-, UPR-, and incretin-related mechanisms have been reported, but their confirmation in β-cells is uneven and often derives from non-pancreatic models. Evidence for prevention of β-cell dedifferentiation, clinically relevant DPP-IV inhibition, and synergistic adaptogen combinations remains limited or hypothetical. Overall, these phytochemicals provide biological plausibility as adjunctive strategies, but standardized extracts, clinically achievable dosing, pharmacokinetic assessment, and β-cell-centered clinical endpoints are required before therapeutic conclusions can be established.