A New Vista of Opportunity in Diabetes Management: Natural Product‐Based β ‐cell Preservation

ABSTRACT A defining characteristic of diabetes is β ‐cell failure, in which β ‐cells cannot modulate insulin secretion to compensate for escalating insulin resistance, pushing forward disease development. However, functional β ‐cell preservation is implicated in maintenance/restoration of β ‐cell mass (survival/proliferation), identity, maturity, insulin synthesis/secretion, and resistance to cell death. Targeting these related processes is a promising approach for treating and curing diabetes. This review provides a comprehensive overview of a natural product‐based β ‐cell‐centric approach to diabetes treatment, focusing on molecular mechanisms, natural inhibitors, and clinical potential. Relevant publications from 2002 to 2025 were retrieved through a systematic database search of PubMed, Web of Science, and Google Scholar. As a result of the search, 16 natural compounds, belonging to 5 major structural classes, polyynes, (iso)flavonoids, alkaloids, aliphatic amino alcohols, and phenolics, were chosen for discussion in this review based on their β ‐cell‐modulatory properties. In parallel, thirteen β ‐cell‐relevant molecular targets are identified and discussed: positive regulators of β ‐cells (PI3K, NKX6.1, PDX1, P2RY1, S1P receptors, P2Y1 receptors, antioxidant enzymes, TEAD1 and SIRT1), and negative regulators (MST1, BACH2, PHLPP1 and PDIA4). Furthermore, key challenges, use dosage, treatment duration and specificity, target identification, and likely side effects of the above compounds are discussed. Thistle, Ophiocordyceps sinensis , Peganum harmala , Bidens pilosa , Curcuma longa , vegetables, fruits, soybean, teas, coffee, cocoa, wines, and their compounds (silymarin, quercetin, genistein, harmine, polyyynes, phenolics, curcumin, and epigallocatechin 3‐gallate) are generally recognized as safe for human consumption. Further studies, including in‐depth animal models and human studies in compounds, are presented along with an assessment of efficacy and safety. A combination of β ‐cell‐modulatory nutraceuticals, phytocompounds, and/or drugs may represent a futuristic approach to treating diabetes by preserving β cells, offering new anti‐diabetic remedies. In conclusion, the natural compounds discussed in this review are readily available in everyday life and show promise as new nutraceuticals and/or pharmaceuticals for achieving β ‐cell homeostasis and glycemic control in diabetes management.