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

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Journal of Functional Foods Pub Date : 2023-09-01 DOI:10.1016/j.jff.2023.105714

Fangbo Zhang , Yu Li , Weijuan Xin , Lifang Wang , Yi Zhang , He Xu , Hongjie Wang , Haiyu Zhao , Hongjun Yang , Nan Si , Baolin Bian

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Abstract

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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绞股蓝皂苷和辣椒素通过PPARγ-LXRα-ABCA1/ABCG1途径联合改善高脂饮食诱导的大鼠高脂血症

非酒精性脂肪性肝病(NAFLD)是最常见的慢性肝脏疾病，其特征是脂肪过度积累，是心血管和代谢紊乱的主要危险因素。我们探讨了绞股蓝皂苷(Gyps)联合辣椒素(Caps)对高脂饮食(HFD)诱导的大鼠高脂血症和氧化低密度脂蛋白(ox-LDL)处理的Raw264.7细胞的治疗作用。网络药理学分析预测，Gyps/Caps联合抗高脂血症的潜在分子机制主要与类固醇代谢、脂质合成和炎症反应有关。动物实验表明，Gyps/Caps组合可降低肝脏重量、肝脏指数、血脂和肝脏胆固醇含量，并通过降低血清谷丙转氨酶(ALT)和天冬氨酸转氨酶(AST)指标改善肝功能，从而减轻肝损伤。此外，Gyps/Caps组合通过降低乳酸脱氢酶(LDH)活性和提高超氧化物歧化酶(SOD)活性来抑制氧化应激。Western blotting结果显示，Gyps/Caps联合可上调肝组织中过氧化物酶体增殖物激活受体γ (PPARγ)、肝脏X受体α (LXRα)、atp结合盒转运蛋白A1 (ABCA1)和atp结合盒转运蛋白G1 (ABCG1)的表达。细胞实验表明，联合处理可通过抑制细胞凋亡、降脂和抗炎症等作用保护RAW264.7细胞免受ox-LDL诱导，并可显著增强PPARγ的表达。值得注意的是，Gyps和Caps联合使用对彼此的药理学结果没有影响，但在改善hfd诱导的高脂血症方面显著提高了整体治疗效果。本研究为Gyps/Caps联合用药的深入研究和临床应用提供了实验基础。重要的是，我们的累积数据表明，联合使用Gyps和Caps可能是缓解高脂血症诱导的NAFLD的有效治疗策略。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.