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Ling Gui Zhu Gan decoction (LGZGD) is a traditional Chinese medicine (TCM) prescription that is widely used in cardiovascular disease clinical prevention and treatment with high efficacy. Recent studies have shown that LGZGD can also be used in hyperlipidemia (HL) intervention, but its pharmacodynamic material basis and its mechanisms remains unclear. This study aimed to reveal the protective effects of LGZGD on HL, elucidate the pharmacodynamic material basis. The hamster HL model was established by high-fat diet. Thereafter, non-targeted metabolomics and quantitative lipidomics were established for screening differential metabolites and pathways. Finally, the mechanisms were elucidated based on network pharmacology to screen for shared targets, which were computational selected by molecular docking. After four weeks of LGZGD administration, the TC, TG, and liver index levels decreased notably and hepatocyte injury was obviously reduced. The Multi-omics identified 62 differential metabolites and 144 differential lipids, respectively. The network pharmacology study predicted 343, 85, and 974 relevant targets from LGZGD components, HL, differential metabolites and lipids, respectively. Eventually, seven core targets were selected by molecular docking. Six key components in LGZGD, including genistein and naringenin, could play a therapeutic role in HL by regulating seven pathways, including HMGCR and PPARA. This comprehensive strategy provides a promising example and approach for further research on TCM for the treatment of lipid metabolic diseases.

Ling Gui Zhu Gan decoction (LGZGD) is a traditional Chinese medicine (TCM) prescription that is widely used in cardiovascular disease clinical prevention and treatment with high efficacy. Recent studies have shown that LGZGD can also be used in hyperlipidemia (HL) intervention, but its pharmacodynamic material basis and its mechanisms remains unclear. This study aimed to reveal the protective effects of LGZGD on HL, elucidate the pharmacodynamic material basis. The hamster HL model was established by high-fat diet. Thereafter, non-targeted metabolomics and quantitative lipidomics were established for screening differential metabolites and pathways. Finally, the mechanisms were elucidated based on network pharmacology to screen for shared targets, which were computational selected by molecular docking. After four weeks of LGZGD administration, the TC, TG, and liver index levels decreased notably and hepatocyte injury was obviously reduced. The Multi-omics identified 62 differential metabolites and 144 differential lipids, respectively. The network pharmacology study predicted 343, 85, and 974 relevant targets from LGZGD components, HL, differential metabolites and lipids, respectively. Eventually, seven core targets were selected by molecular docking. Six key components in LGZGD, including genistein and naringenin, could play a therapeutic role in HL by regulating seven pathways, including HMGCR and PPARA. This comprehensive strategy provides a promising example and approach for further research on TCM for the treatment of lipid metabolic diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)