Network Pharmacology and Experimental Validation to Investigate the Effects of Huatan Huoluo Decoction on Enhancing Lipid Metabolism Mechanism.

Abstract

Introduction: Hyperlipidemia (HLP) is a disorder of lipid metabolism, and dyslipidemia represents a major risk factor for Atherosclerosis (AS) and cardiovascular diseases. HuaTan HuoLuo (HTHL) Decoction, a Chinese herbal formulation, has demonstrated significant therapeutic efficacy in the clinical management of HLP. Nevertheless, the underlying molecular mechanisms by which HTHL exerts its lipid-lowering effects remain poorly understood.

Methods: A combined strategy integrating network pharmacology analysis and experimental validation was employed to investigate the active components, key targets, and potential mechanisms of HTHL in the treatment of HLP. Body weight, liver index, and serum biochemical parameters were assessed. Histopathological alterations in the liver, kidney, heart, and aorta were evaluated using hematoxylin and eosin (H&E) staining. Furthermore, the pharmacological effects and molecular mechanisms of HTHL in hyperlipidemia (HLP) Sprague-Dawley (SD) rats were examined using Western blotting (WB), Reverse transcription-quantitative PCR (RTqPCR), immunofluorescence, and immunohistochemistry.

Results: Network pharmacology analysis effectively identified 273 active components in HTHL Decoction and 121 potential therapeutic targets associated with HLP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 186 signaling pathways. The experimental results indicated that the anti-HLP effects of HTHL may be closely linked to key targets such as AKT1. Following HTHL administration, serum total cholesterol (TC) levels decreased to 1.69 ± 0.30 mmol/L, while Triglyceride (TG) levels decreased to 0.41 ± 0.13 mmol/L. WB revealed that HTHL significantly downregulated the expression of PI3K, AKT, phosphorylated AKT (p-AKT), and phosphorylated PI3K (p-PI3K). Immunofluorescence analysis showed that HTHL suppressed the expression of phosphorylated mTOR (p-mTOR), while immunohistochemical analysis indicated a marked reduction in PTEN expression.

Discussion: Given the increasing global prevalence of metabolic disorders, elucidating the therapeutic efficacy and molecular mechanism of HTHL Decoction in HLP provides an important experimental basis and potential translational value for clinical application.

Conclusion: This study suggests HTHL Decoction improves lipid metabolism, potentially through modulation of the PI3K-AKT signaling pathway.