Frontiers in Pharmacology (Sep 2024)
Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II
- Dexin Li,
- Dexin Li,
- Dexin Li,
- Dexin Li,
- Dexin Li,
- Jingxin Zhang,
- Jingxin Zhang,
- Jingxin Zhang,
- Jingxin Zhang,
- Jingxin Zhang,
- Yuxin Jin,
- Yuxin Jin,
- Yuxin Jin,
- Yuxin Jin,
- Yuxin Jin,
- Yaoxuan Zhu,
- Yaoxuan Zhu,
- Yaoxuan Zhu,
- Yaoxuan Zhu,
- Yaoxuan Zhu,
- Xiaoqing Lu,
- Xiaoqing Lu,
- Xiaoqing Lu,
- Xiaoqing Lu,
- Xiaoqing Lu,
- Xinmei Huo,
- Xinmei Huo,
- Xinmei Huo,
- Xinmei Huo,
- Xinmei Huo,
- Chunshui Pan,
- Chunshui Pan,
- Chunshui Pan,
- Chunshui Pan,
- Lijun Zhong,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Lulu Yan,
- Lulu Yan,
- Lulu Yan,
- Lulu Yan,
- Ping Huang,
- Ping Huang,
- Ping Huang,
- Ping Huang,
- Quan Li,
- Quan Li,
- Quan Li,
- Quan Li,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Yin Li,
- Yin Li,
- Yin Li,
- Yin Li,
- Yin Li
Affiliations
- Dexin Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Dexin Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Dexin Li
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Dexin Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Dexin Li
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Jingxin Zhang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jingxin Zhang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jingxin Zhang
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Jingxin Zhang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jingxin Zhang
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Yuxin Jin
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Yuxin Jin
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Yuxin Jin
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Yuxin Jin
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Yuxin Jin
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Yaoxuan Zhu
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Yaoxuan Zhu
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Yaoxuan Zhu
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Yaoxuan Zhu
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Yaoxuan Zhu
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Xiaoqing Lu
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xiaoqing Lu
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xiaoqing Lu
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Xiaoqing Lu
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xiaoqing Lu
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Xinmei Huo
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xinmei Huo
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xinmei Huo
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Xinmei Huo
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xinmei Huo
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Chunshui Pan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Chunshui Pan
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Chunshui Pan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Chunshui Pan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Lijun Zhong
- Peking University Medical and Health Analysis Center, Peking University, Beijing, China
- Kai Sun
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Kai Sun
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Kai Sun
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Kai Sun
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Li Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Li Yan
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Li Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Li Yan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Lulu Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Lulu Yan
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Lulu Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Lulu Yan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Ping Huang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Ping Huang
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Ping Huang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ping Huang
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Quan Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Quan Li
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Quan Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Quan Li
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Jing-Yan Han
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Yan Han
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yan Han
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Yin Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Yin Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Yin Li
- The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine, Beijing, China
- Yin Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Yin Li
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- DOI
- https://doi.org/10.3389/fphar.2024.1435230
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.
Keywords
