Drug Advances in NAFLD: Individual and Combination Treatment Strategies of Natural Products and Small-Synthetic-Molecule Drugs

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 140 - 140

Published: Jan. 17, 2025

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress been made in understanding pathogenesis of NAFLD, identifying multiple therapeutic targets providing new directions drug development. This review summarizes advances focusing on mechanisms action natural products, small-synthetic-molecule drugs, combination therapy strategies. aims to provide insights treating NAFLD.

Language: Английский

Identification of a Novel NPC1L1 Inhibitor from Danshen and Its Role in Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2793 - 2793

Published: March 20, 2025

Danshen, a well-known traditional Chinese medicine (TCM), has gained increasing attention for its protective effects on nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying these remain to be elucidated. Niemann-Pick C1-like 1 (NPC1L1), key transporter mediating intestinal cholesterol absorption, emerged as critical target NAFLD treatment. This study aimed screen NPC1L1 inhibitors from Danshen and investigate their therapeutic NAFLD. We established high-throughput screening platform using stable Caco2 cell lines expressing human (hL1-Caco2) discovered that tanshinones (Tans), liposoluble components of inhibited NPC1L1-mediated absorption in hL1-Caco2 cells. Additionally, Tans treatment reduced hepatic steatosis high-fat diet (HFD)-fed mice. To identify active compounds Tans, activity-oriented separation was performed by integrating two-dimensional chromatographic techniques. Ultimately, cryptotanshinone (CTS) identified novel inhibitor significantly decreased HFD-fed Molecular docking dynamics simulation showed CTS stably bound with NPC1L1, where TRP383 acted amino acid. Taken together, this demonstrates, first time, CTS, compound is inhibitor. Our findings suggest inhibitory effect against may potential mechanism, contributing alleviation

Language: Английский

Gut microbiota-mitochondrial crosstalk in obesity: novel mechanistic insights and therapeutic strategies with traditional Chinese medicine

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 22, 2025

Obesity rates are rising globally and have become a major public health issue. Recent research emphasizes the bidirectional communication between gut microbiota mitochondrial function in obesity development. Gut regulates energy metabolism through metabolites that impact processes, such as oxidative phosphorylation, biogenesis, autophagy. In turn, alterations homeostasis. Traditional Chinese medicine (TCM), which encompasses TCM formulas of botanical drugs, employs holistic integrative approach shows promise regulating microbiota–mitochondrial crosstalk. This review systematically explores intricate interactions function, underscoring their crosstalk critical mechanistic axis pathogenesis. Furthermore, it highlights potential developing innovative, targeted interventions, paving way for personalized approaches treatment precise modulation interactions, offering more effective individualized therapeutic options.

Language: Английский