Bidens biternata (Lour.) Merr. & Sherff improves liver lipid metabolism disorders in type 2 diabetic mice by activating mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Bidens biternata (Lour.) Merr. et Sherff (JZYP), a congener of the well-studied hypoglycemic herb Bidens pilosa L, remains pharmacologically underexplored despite shared traditional use for metabolic disorders. While Bidens pilosa L. demonstrates validated anti-diabetic and hepatoprotective properties, this study pioneers the mechanistic investigation of JZYP's therapeutic potential in type 2 diabetes mellitus (T2DM).

AIM OF THE STUDY: The aim of this study was to elucidate the anti-steatotic effects of JZYP on T2DM-associated hepatic lipid accumulation and investigate the underlying mechanisms.

MATERIALS AND

METHODS

JZYP extract was prepared and analyzed by UPLC-Q-TOF/MS. HFD-fed ob/ob mice were used to establish a model of T2DM with hepatic lipid metabolic dysfunction and then administered with JZYP (3.9, 7.8 g/kg) for 6 weeks. Biochemical lipid parameter were analysis alongside Hematoxylin-eosin (HE) and Oil Red O staining. Western blotting was used to evaluate hepatic lipid metabolism-related proteins. Liver metabolomic profiling were used to explore the metabolome changes and subsequent pathway. The occurrence of mitophagy was detected using fluorescence co-localization, and the real-time quantitative (RT-qPCR) and immunohistochemistry (IHC) were utilized to quantify the mitophagy-associated gene and protein expressions.

RESULTS

245 chemical constituents were identified in JZYP, with 88 detected in positive ion mode, and 157 negative ion mode. It effectively alleviated metabolic disorders, reduced hepatic pathological damage, and down-regulated the expression of lipid-related proteins in the livers of HFD.-fed mice. The study further identified 47 significantly altered lipid compounds, most of which were enriched in Glycerophospholipid metabolism. The JZYP group showed elevated level of PC/PE compared to the model group. Immunofluorescence analysis of TOM20 and LC3 demonstrated a strong correlation, suggesting the activation of mitophagy. PCR and IHC confirmed that JZYP activated the mitophagy pathway.

CONCLUSIONS

This study demonstrated that beneficial effects of JZYP on ameliorating hepatic lipid accumulation in T2DM mice, potentially through enhancing mitophagy and suppressing de novo lipogenesis. These findings positions JZYP as a promising botanical candidate for managing metabolic syndrome-related hepatopathies.