Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process

Context Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.Objective Our study aimed to elucidate the underlying mechanism of apigenin on preventing athero...

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Main Authors: Zixuan Hu, Yuting Li, Nan Yao, Haining Gan, Qiaohuang Zeng, Xuejun Huang, Dane Huang, Dake Cai, Yuxing Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Pharmaceutical Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/13880209.2025.2509020
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author Zixuan Hu
Yuting Li
Nan Yao
Haining Gan
Qiaohuang Zeng
Xuejun Huang
Dane Huang
Dake Cai
Yuxing Chen
author_facet Zixuan Hu
Yuting Li
Nan Yao
Haining Gan
Qiaohuang Zeng
Xuejun Huang
Dane Huang
Dake Cai
Yuxing Chen
author_sort Zixuan Hu
collection DOAJ
description Context Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.Objective Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.Materials and methods ApoE−/− mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.Results In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.Discussion and conclusions The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.
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spelling doaj-art-677203dc89dd4a7aa29afa361b26b4e22025-08-20T03:08:50ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162025-12-0163138740110.1080/13880209.2025.2509020Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT processZixuan Hu0Yuting Li1Nan Yao2Haining Gan3Qiaohuang Zeng4Xuejun Huang5Dane Huang6Dake Cai7Yuxing Chen8Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaThe Fifth Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaSchool of Traditional Chinese Medicine and Health, Nanfang College · Guangzhou, Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaGuangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, ChinaContext Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.Objective Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.Materials and methods ApoE−/− mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.Results In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.Discussion and conclusions The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.https://www.tandfonline.com/doi/10.1080/13880209.2025.2509020Apigenindyslipidemia in atherosclerosisselective autophagy/lipophagyreverse cholesterol transport
spellingShingle Zixuan Hu
Yuting Li
Nan Yao
Haining Gan
Qiaohuang Zeng
Xuejun Huang
Dane Huang
Dake Cai
Yuxing Chen
Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
Pharmaceutical Biology
Apigenin
dyslipidemia in atherosclerosis
selective autophagy/lipophagy
reverse cholesterol transport
title Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
title_full Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
title_fullStr Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
title_full_unstemmed Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
title_short Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process
title_sort apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy lipophagy and promoting rct process
topic Apigenin
dyslipidemia in atherosclerosis
selective autophagy/lipophagy
reverse cholesterol transport
url https://www.tandfonline.com/doi/10.1080/13880209.2025.2509020
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