Protective effects of Yiqi Huoxue Huatan formula on atherosclerosis: An in vivo and in vitro study

IF 2.6 3区 医学 Q3 CHEMISTRY, MEDICINAL
Lu Li , Yu Gao , Lei Liao , Qiuling Wu , Yitong Hu , Zilong Zhang
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Abstract

Atherosclerosis (AS) is a significant pathological contributor to cardiovascular disease, marked by high rates of death and illness globally. Yiqi Huoxue Huatan formula (YHH), a Chinese traditional decoction, has been clinically validated as effective for patients with AS; however, its underlying mechanisms remain partially unexplained. The goal of this research is to understand the protective effects of YHH against AS and the mechanisms involved. In vivo, YHH was administered orally at 14.24 and 28.47 g/kg/day (raw medicinal herbs) to ApoE−/− mice on a high-fat diet (HFD) to model AS. In vitro, RAW264.7 macrophages were exposed to oxidized low-density lipoprotein (ox-LDL) and YHH-conducting serum. The therapeutic effects of YHH were assessed using biochemical assays, histopathological observations, and enzyme-linked immunosorbent assays. Mass spectrometry, network pharmacology analyses, molecular docking, and western blotting were used to identify the primary components and anti-AS mechanisms of YHH. YHH significantly reduced AS development, as evidenced by decreased aortic plaque and lower blood lipid levels in HFD-induced AS mice. Meanwhile, YHH significantly decreased the increase in inflammatory cytokines in the supernatant of macrophages induced by ox-LDL. Mechanistic studies revealed that YHH significantly downregulated protein levels of TLR4, p-NF-κB, and HIF-1α. Moreover, molecular docking showed that key active compounds in YHH, including Gardenin A, isosinensetin, alisol B, 3′,4′,5′,5,7-pentamethoxyflavanone, and scutellarein, exhibited strong binding activity to the core targets. YHH emerges as a promising agent in ameliorating AS by reducing inflammatory responses, achieved via the downregulation of TLR4/NF-κB/HIF-1α signaling pathways.

Abstract Image

益气活血化痰方对动脉粥样硬化的保护作用:体内外研究。
动脉粥样硬化(AS)是心血管疾病的重要病理因素,在全球范围内以高死亡率和发病率为特征。益气活血化痰方(YHH)是一种中药汤剂,已被临床证实对as患者有效;然而,其潜在机制仍部分无法解释。本研究的目的是了解YHH对AS的保护作用及其机制。在体内,以14.24和28.47 g/kg/天(生药材)剂量口服ApoE-/-小鼠,以高脂饮食(HFD)模型AS。在体外,RAW264.7巨噬细胞暴露于氧化低密度脂蛋白(ox-LDL)和yhh传导血清中。采用生化试验、组织病理学观察和酶联免疫吸附试验评估YHH的治疗效果。采用质谱分析、网络药理学分析、分子对接、western blotting等方法对其主要成分及抗as机制进行鉴定。hfd诱导的AS小鼠主动脉斑块减少,血脂水平降低,YHH显著降低AS的发展。同时,YHH显著降低ox-LDL诱导的巨噬细胞上清中炎症因子的升高。机制研究显示,YHH显著下调TLR4、p-NF-κB和HIF-1α的蛋白水平。此外,分子对接表明,栀子苷A、异皂苷、茜草醇B、3′、4′、5′、5,7-五甲基黄酮和黄芩苷等关键活性物质与核心靶点具有较强的结合活性。通过下调TLR4/NF-κB/HIF-1α信号通路,YHH成为一种有希望通过减少炎症反应来改善as的药物。
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来源期刊
Fitoterapia
Fitoterapia 医学-药学
CiteScore
5.80
自引率
2.90%
发文量
198
审稿时长
1.5 months
期刊介绍: Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.
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