Herbal medicine formula Huazhuo Tiaozhi granule ameliorates dyslipidaemia via regulating histone lactylation and miR-155-5p biogenesis

Abstract

Background Huazhuo Tiaozhi granule (HTG) is a herbal medicine formula widely used in clinical practice for hypolipidaemic effects. However, the molecular mechanisms underlying dyslipidaemia treatment have not been well elucidated. Results A significant reduction in the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was observed in the serum of patients with dyslipidaemia after HTG treatment, without disruption in the levels of aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine (Cr). The dyslipidaemia rat model was induced by a high-fat diet and treated with Xuezhikang (0.14 g/kg/d) or HTG (9.33 g crude herb/kg/day) by gavage for 8 weeks. Body weight and liver index were markedly decreased in dyslipidaemic rats after treatment with Xuezhikang or HTG. HTG administration markedly ameliorated hyperlipidaemia by decreasing the levels of TC and LDL-C in serum and hepatic lipid accumulation. In vitro, lipid accumulation in LO2 and HepG2 cells was alleviated by serum treatment with HTG. High lactylation was observed in 198 proteins, including lactylation of histone H2B (K6), H4 (K80). Deep sequencing of microRNAs showed that miR-155-5p was significantly downregulated. Conclusions This study demonstrates that HTG is an effective and safe formula for treating dyslipidaemia, which promotes lactylation in hepatocytes, and the retardation of miR-155-5p biogenesis. Graphical abstract

Lactylation Modification in Cardiometabolic Disorders: Function and Mechanism

“…Yin et al demonstrated that lactylation was observed in 198 proteins after HTG treatment, including histone H2B (K6) and H4 (K80) lactylation. HTG promoted lactylation in hepatocytes, further validating lactylation modification as one of the important targets for regulating lipid metabolism [166].…”

Comparative Proteome Profiling of Extracellular Vesicles from Three Growth Phases of Haematococcus pluvialis under High Light and Sodium Acetate Stresses

“…To acquire insight into the proteomic profile of HpEVs, the identified proteins were screened in several databases and analyzed using bioinformatics methods, as described in previous reports [57][58][59][60]. Briefly, hierarchical clustering analysis was carried out using the R Package pheatmap (v.2.0.3 https://cran.r-project.org/web/packages/cluster/, accessed on 3 March 2020), and the heat map was produced by a dendrogram depicting the extent of similarity in the protein expression among samples.…”