Herbal medicine Huazhuo Tiaozhi granule ameliorates dyslipidemia via regulating DDX17 lactylation and miR-155-5p biogenesis

Abstract

Background Huazhuo Tiaozhi granule (HTG) is a herbal medicine prescription, which is widely used in clinical practice for hypolipidemic effect. However, the molecular mechanism in treating dyslipidemia has not been well elucidated. Results In the clinical trial, a significant reduction in the levels of TC and LDL-C was observed in serum of dyslipidemia patients after HTG treatment without disruption of the levels of AST, ALT, BUN and Cr. Dyslipidemia rat model was induced by high-fat diet and treated with Xuezhikang (0.14g/kg/d) and HTG (9.33g crude herb/kg/d) by gavage, respectively for 8 weeks. The body weight and liver index were markedly downregulated in dyslipidemia rats after the treatment of Xuezhikang and HTG. HTG markedly ameliorated hyperlipidemia by significantly decreasing the levels of TC and LDL-C in serum and hepatic lipid accumulation. In vitro, lipid accumulation in L02 cells was alleviated after 20% HTG medicated serum treatment. Moreover, HTG sustains glycolytic rate analyzed by Seahorse assay. However, high lactylation was observed in a total of 198 proteins including RNA binding protein DDX17(K121) lactylation, HDAC1 (K412, K438), H2B (K6) and H4(K80) lactylation, which inhibited the biogenesis of miR-155-5p in vitro. Conclusions This study demonstrates that HTG is an effective and safe formula in treating dyslipidemia, which promoted lactylation level in hepatocytes resulting in retardation of miR-155-5p biogenesis.