Gypenosides and capsaicinoids in combination ameliorates high-fat-diet- induced rat hyperlipidemia via the PPARγ-LXRα-ABCA1/ABCG1 pathway

ABCA1 高脂血症 非酒精性脂肪肝 内科学 内分泌学 ABCG1公司 药理学 脂质代谢 过氧化物酶体增殖物激活受体 胆固醇 生物 脂肪肝 化学 生物化学 受体 运输机 医学 糖尿病 疾病 基因
作者
Fangbo Zhang,Liqing Yu,Weijuan Xin,Lifang Wang,Yi Zhang,He Xu,Hongjie Wang,Haiyu Zhao,Hongjun Yang,Nan Si,Baolin Bian
出处
期刊:Journal of Functional Foods [Elsevier]
卷期号:108: 105714-105714 被引量:2
标识
DOI:10.1016/j.jff.2023.105714
摘要

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease characterized by excessive fat accumulation, and is the major risk for cardiovascular and metabolic disorders. We explored the therapeutic effect of gypenosides (Gyps) in combination with capsaicinoids (Caps) against high-fat-diet (HFD)-induced rat hyperlipidemia and oxidized low-density lipoprotein (ox-LDL)-treated Raw264.7 cells. Network pharmacology analysis predicted that the potential molecular mechanism of Gyps/Caps combination against hyperlipidemia was mainly associated with steroid metabolism, lipid synthesis and inflammatory response. Animal experiment demonstrated that Gyps/Caps combination lowered the liver weight, liver index, serum lipid profile and hepatic cholesterol content, improved liver function by reducing the serum markers of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thereby relieving the hepatic injury. Moreover, Gyps/Caps combination inhibited oxidative stress by decreasing the lactic dehydrogenase (LDH) activity and increasing the superoxide dismutase (SOD) activity. Western blotting result suggested that Gyps/Caps combination could upregulate the expressions of peroxisome proliferator-activated receptors γ (PPARγ), liver X receptor α (LXRα), ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) in the liver tissue. Cellular experiment revealed that the combination treatment protected RAW264.7 cells from ox-LDL induction through inhibiting apoptosis, lipid-decreasing and anti-inflammation, and caused the dramatic enhancement on PPARγ expression. Notably, the combined use of Gyps and Caps did not influence the pharmacological outcomes of each other, but significantly enhanced the overall therapeutic effect in ameliorating HFD-induced hyperlipidemia. Our research provided an experimental basis for advanced research and clinical application of Gyps/Caps combination. Importantly, our cumulative data indicated that combination use of Gyps and Caps may be an effective therapeutic strategy for alleviating hyperlipidemia-induced NAFLD.
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