New approaches to the treatment of metabolic dysfunction-associated steatotic liver with natural products

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread and potentially severe liver condition characterized by abnormal fat accumulation in the liver unrelated to alcohol consumption. According to the World Health Organization, MASLD is the most prevalent liver disease globally, it affects approximately 25% of the world’s population, nearly two billion individuals. This staggering prevalence underscores the urgent need for effective and safe therapeutic approaches to address this escalating global health concern. Natural products have emerged as promising candidates for preventing and treating MASLD in recent years because of their diverse bioactive compounds and minimal side effects. Well-known natural products such as curcumin, resveratrol, green tea polyphenols, and silymarin exhibit notable hepatoprotective effects by influencing lipid metabolism, mitigating oxidative stress, and reducing inflammation. Ongoing research highlights the potential of phytochemicals from traditional medicinal plants, such as Phyllanthus and Salvia, in ameliorating liver steatosis and fibrosis. These natural products demonstrate the capacity to impede fibrogenesis by interfering with hepatic stellate cell activation, which is pivotal in liver fibrosis development. Recent studies underscore the significance of natural products in modulating the gut–liver axis, where they restore balance to the gut microbiota and enhance intestinal barrier function, which slows the progression of MASLD. Moreover, advancements in nanotechnology facilitate the targeted delivery of natural product-derived compounds, which enhances their bioavailability and therapeutic efficacy. Harnessing the potency of natural products offers a promising avenue for developing novel, safer therapies for MASLD and addressing a critical global health concern with far-reaching implications for public well-being. Graphic Abstract: The role of natural compounds in treating MAFLD disease via different mechanistic approaches. SREBP-1c: Sterol regulatory element-binding protein-1c, Nrf2: Nuclear factor-erythroid 2-related factor 2, PPAR: Peroxisome proliferator-activated receptor, AMPK: AMP-activated protein kinase, SIRT: Sirtuin, NLRP3: NOD-like receptor family pyrin domain-containing 3, SAMC: S-ally mercapto cysteine, DADS: Diallyl disulfide, TLR-4: Toll like receptor 4, COX-2: Cyclooxygenase-2, EGCG: Epigallocatechin gallate, RCTs9: Randomized Controlled/Clinical Trial, TGF-β: transforming gr