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Scutellariae Radix and Coptidis Rhizoma improve NAFLD via regulation of SIRT6/ACSL5 pathway and SCD1
Yuanye Jiang1, Jiaqi Zhang2, Wangzhenzu Liu3
1Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200062, China.
Ethnopharmacological Relevance:
The herbal pair Scutellariae Radix-Coptidis Rhizoma (SR-CR) has been widely used in Traditional Chinese Medicine (TCM) for treating metabolic disorders, including nonalcoholic fatty liver disease (NAFLD) -related conditions. Its traditional use highlights its potential in addressing the multifaceted pathogenesis of NAFLD, though the underlying mechanisms remain unclear.
Aim Of The Study:
To evaluate the therapeutic efficacy of the SR-CR herbal pair in alleviating NAFLD and to elucidate its mechanisms of action, with a specific focus on lipid metabolism pathways.
Materials And Methods:
The therapeutic effects of SR-CR were assessed using a high-fat diet (HFD)-induced NAFLD rat model and HepG2 cell model. Multi-omics analyses were employed to identify molecular targets and pathways, while affinity ultrafiltration-mass spectrometry characterized bioactive constituents. Findings were validated in vivo and in vitro via Western blot and immunofluorescence. Protein-constituent interactions were further characterized by surface plasmon resonance and molecular docking.
Results:
SR-CR significantly alleviated NAFLD symptoms in HFD-fed rats by reducing hepatic lipid accumulation, inflammation, and hepatocyte ballooning while normalizing biochemical indicators. Mechanistic studies revealed that SR-CR regulates the SIRT6/ACSL5 pathway and SCD1, both critical to lipid metabolism. Scutellariae Radix (SR) and its major constituent, baicalin, enhanced ACSL5 activity via SIRT6-mediated deacetylation, promoting fatty acid oxidation and intracellular lipid utilization. Coptidis Rhizoma (CR) and its primary component, berberine, inhibited SCD1, thereby reducing de novo lipogenesis. These complementary effects synergistically enhanced energy expenditure and reduced lipid synthesis.
Conclusion:
The SR-CR herbal pair effectively alleviates HFD-induced NAFLD by synergistically modulating lipid metabolism, enhancing energy expenditure, and reducing de novo lipogenesis through the regulation of the SIRT6/ACSL5 pathway and SCD1. These findings provide molecular evidence for the traditional use of SR-CR in treating metabolic disorders and highlight its potential as a plant-based therapeutic for NAFLD.
