Diabetes is a chronic metabolic disease, whereas α-glucosidases are key enzymes involved in the metabolism of starch and glycogen. There is a long history of the use of mulberry leaf (the leaf of Morus alba) as an antidiabetic herb in China, and we found that chalcomoracin, one of the specific Diels–Alder adducts in mulberry leaf, had prominent α-glucosidase inhibitory activity and has the potential to be a substitute for current hypoglycemic drugs such as acarbose, which have severe gastrointestinal side effects. In this study, chalcomoracin was effectively isolated from mulberry leaves, and its α-glucosidase inhibition was studied via enzymatic kinetics, isothermal titration (ITC) and molecular docking. The results showed that chalcomoracin inhibited α-glucosidase through both competitive and non-competitive manners, and its inhibitory activity was stronger than that of 1-doxymycin (1-DNJ) but slightly weaker than that of acarbose. ITC analysis revealed that the combination of chalcomoracin and α-glucosidase was an entropy-driven spontaneous reaction, and the molecular docking results also verified this conclusion. During the binding process, chalcomoracin went into the “pocket” of α-glucosidase via hydrophobic interactions, and it is linked with residues Val544, Asp95, Ala93, Gly119, Arg275 and Pro287 by hydrogen bonds. This study provided a potential compound for the prevention and treatment of diabetes and a theoretical basis for the discovery of novel candidates for α-glycosidase inhibitors.

Cili (Rosa roxburghii Tratt) fruit is a nutrient-rich edible plant known for its antioxidant and hepatoprotective properties. However, conventional extraction methods often lead to the degradation of its bioactive compounds. In this study, we developed a low-temperature homogenate-assisted high-pressure disruption extraction (HHPD) method to obtain a phytochemically enriched cili fruit extract (HHPD-CFE). The chemical characterization of the HHPD-CFE showed that it contained higher levels of polyphenols, polysaccharides, and superoxide dismutase (SOD) than those in conventional squeeze extraction. The hepatoprotective effects of the HHPD-CFE were evaluated in oxidative stress-induced liver injury and hepatic fibrosis models. The HHPD-CFE mitigated oxidative damage by reducing malondialdehyde while enhancing SOD and glutathione activity. Additionally, the HHPD-CFE inhibited the activation of hepatic stellate cells (HSC-T6) and reduced collagen deposition, suggesting a protective role against liver fibrosis. These findings support that the HHPD-CFE is a promising botanical extract with enriched bioactive compounds and liver-protective properties. This study supports the potential application of optimized extraction techniques to preserve thermosensitive compounds and improve the efficacy of functional foods for liver health.

Background: Cili (Rosa roxburghii Tratt) is a unique fruit native to China’s Yunnan–Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili’s hepatoprotective properties are reported, the bioactive components and underlying mechanisms remain poorly defined. Methods: We enriched proanthocyanidins from cili using column chromatography, identified their components via UPLC-Q-TOF-MS/MS, and validated their anti-liver fibrosis effects through in vitro and in vivo experiments. Results: Herein, we developed a novel proanthocyanidin-rich cili fruit extract (PACs-CFE) containing 84.2% total proanthocyanidins, comprising catechins, epicatechins, and diverse B-type dimers, trimers, tetramers, and gallate esters, as characterized by UPLC-Q-TOF-MS/MS. PACs-CFE inhibited LX-2 activation, suppressed collagen III and α-SMA expression, and induced ferroptosis via mitochondrial injury, reactive oxygen species accumulation, and GPX4/ferritin downregulation. In vivo, PACs-CFE ameliorated liver fibrosis, restored hepatic architecture, and improved serum alanine aminotransferase, aspartate aminotransferase, and bilirubin profiles. Moreover, PACs-CFE modulated the TGF-β1/Smad3 signaling pathway and beneficially reshaped the gut microbiota, enriching anti-inflammatory and hepatoprotective genera while reducing pathogenic taxa. Conclusions: Our findings show that PACs-CFE exerts multi-targeted anti-fibrotic effects through hepatic stellate cell inactivation, ferroptosis induction, TGF-β1/Smad3 suppression, and gut–liver axis modulation. This study provides useful insight into the hepatoprotective potential of cili fruit and supports its development as standardized functional ingredients for liver health.