Lu Li , Yu Gao , Lei Liao , Qiuling Wu , Yitong Hu , Zilong Zhang
{"title":"益气活血化痰方对动脉粥样硬化的保护作用:体内外研究。","authors":"Lu Li , Yu Gao , Lei Liao , Qiuling Wu , Yitong Hu , Zilong Zhang","doi":"10.1016/j.fitote.2025.106849","DOIUrl":null,"url":null,"abstract":"<div><div>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. <em>In vivo</em>, YHH was administered orally at 14.24 and 28.47 g/kg/day (raw medicinal herbs) to ApoE<sup>−/−</sup> mice on a high-fat diet (HFD) to model AS. <em>In vitro</em>, 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 <em>via</em> the downregulation of TLR4/NF-κB/HIF-1α signaling pathways.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"186 ","pages":"Article 106849"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective effects of Yiqi Huoxue Huatan formula on atherosclerosis: An in vivo and in vitro study\",\"authors\":\"Lu Li , Yu Gao , Lei Liao , Qiuling Wu , Yitong Hu , Zilong Zhang\",\"doi\":\"10.1016/j.fitote.2025.106849\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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. <em>In vivo</em>, YHH was administered orally at 14.24 and 28.47 g/kg/day (raw medicinal herbs) to ApoE<sup>−/−</sup> mice on a high-fat diet (HFD) to model AS. <em>In vitro</em>, 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 <em>via</em> the downregulation of TLR4/NF-κB/HIF-1α signaling pathways.</div></div>\",\"PeriodicalId\":12147,\"journal\":{\"name\":\"Fitoterapia\",\"volume\":\"186 \",\"pages\":\"Article 106849\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fitoterapia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0367326X25004757\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fitoterapia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0367326X25004757","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Protective effects of Yiqi Huoxue Huatan formula on atherosclerosis: An in vivo and in vitro study
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.
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.