Silymarin in type 2 diabetes – Targeting adipose tissue dysfunction and pancreatic β-cell damage: A review

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and progressive pancreatic β-cell dysfunction, processes strongly influenced by adipose tissue inflammation, oxidative stress, and dysregulated lipid metabolism. Silymarin, a flavonolignan complex derived from Silybum marianum, has attracted interest as a potential adjunctive agent because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This review summarizes experimental and clinical evidence on the effects of silymarin and its major bioactive constituent, silibinin, on adipose tissue dysfunction and pancreatic β-cell injury in T2DM. Available evidence was narratively synthesized with emphasis on adipogenesis, lipid accumulation, inflammatory signaling, insulin signaling, oxidative stress, and β-cell survival. Experimental studies indicate that silymarin may reduce adipogenesis and lipid accumulation through modulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), and activation of AMP-activated protein kinase (AMPK). Silymarin may also attenuate pro-inflammatory cytokine production, enhance antioxidant defenses, and protect pancreatic β-cells from glucotoxicity-, lipotoxicity-, and cytokine-induced apoptosis. Limited clinical data suggest potential improvements in glycemic control, insulin resistance, lipid parameters, and systemic inflammation. Overall, silymarin shows promise as an adjunctive strategy for metabolic dysfunction in T2DM; however, standardized formulations and well-designed randomized clinical trials are needed to confirm its efficacy, safety, and clinical relevance.