Journal of ethnopharmacology · 2026
Clematis tangutica extract alleviates hyperlipidemia: an integration of network pharmacology, molecular docking, molecular dynamics and experimental verification.
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Zhang Xiu, Ren Qidong, Guo Xu, Chen Yingying, Sun Shutao, Wang Muxuan, Ren Xia, Liu Chao, Zhang Mengqi
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is a major risk factor for cardiovascular diseases. Clematis tangutica (Maxim.) Korsh. (CT), a commonly used Tibetan medicine for cardiovascular disorders, has rarely been reported for its lipid-lowering efficacy and mechanism.
AIM OF THE STUDY: To evaluate CT's lipid-lowering effect and clarify its action site and molecular mechanism.
MATERIAL AND METHODS: Lipid-lowering activity of CT total extract (Total) was assessed via pancreatic lipase inhibition, oleic acid-induced high-fat cell model, and high-fat diet-fed hyperlipidemic animal model. CT was fractionated into aqueous (H2O), ethyl acetate (EA), and petroleum ether (PE) fractions. Network pharmacology, molecular docking, and molecular dynamics simulations were used to identify and verify targets of the most active EA fraction, with in vitro/in vivo validation of target protein expression.
RESULTS: Total extract and EA fraction significantly reduced lipid accumulation, improved serum/liver lipid profiles. EA fraction had 47 hyperlipidemia-related overlapping targets, stably interacting with key HIF-1 pathway proteins and the independent target ESR2. It normalized p-EGFR, p-AKT2, PAI-1, INSR, HIF-1 (HIF-1 pathway) and ESR2 expression in vivo, and modulated ESR2 in vitro.
CONCLUSION: CT's EA fraction ameliorates hyperlipidemia potentially by regulating key HIF-1 pathway targets, providing a scientific basis for developing lipid-lowering therapeutics from CT.
AIM OF THE STUDY: To evaluate CT's lipid-lowering effect and clarify its action site and molecular mechanism.
MATERIAL AND METHODS: Lipid-lowering activity of CT total extract (Total) was assessed via pancreatic lipase inhibition, oleic acid-induced high-fat cell model, and high-fat diet-fed hyperlipidemic animal model. CT was fractionated into aqueous (H2O), ethyl acetate (EA), and petroleum ether (PE) fractions. Network pharmacology, molecular docking, and molecular dynamics simulations were used to identify and verify targets of the most active EA fraction, with in vitro/in vivo validation of target protein expression.
RESULTS: Total extract and EA fraction significantly reduced lipid accumulation, improved serum/liver lipid profiles. EA fraction had 47 hyperlipidemia-related overlapping targets, stably interacting with key HIF-1 pathway proteins and the independent target ESR2. It normalized p-EGFR, p-AKT2, PAI-1, INSR, HIF-1 (HIF-1 pathway) and ESR2 expression in vivo, and modulated ESR2 in vitro.
CONCLUSION: CT's EA fraction ameliorates hyperlipidemia potentially by regulating key HIF-1 pathway targets, providing a scientific basis for developing lipid-lowering therapeutics from CT.