Cell Discovery
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2025
·Vol. 11
·期 1
·1-21
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IF 12.5
Li Lingru,Li Tianxing,Liang Xue,Zhu Linghui,Fang Yini,Dong Ling,Zheng Yi,Xu Xiaoxue,Li Mingrui,Cai Tianqi,Zhao Fufangyu,Xin Meiling,Shao Mingyan,Guan Yuanyuan,Liu Meiyi,Li Fangli,Zhang Chenhong,Wang Qi,Sun Wenlong,Zheng Yanfei
According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.
研究领域:
中医药学
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微生物学
·
代谢生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Honghua Zhang,Yunting Sun,Yuqing Zou,Cheng Chen,Shuling Wang
Ethnopharmacological relevance Banxia baizhu tianma decoction (BBTD) originated from the Qing Dynasty Chinese medicine book “Medical Xinwu”, which has a clinical application history of more than 300 years. It's a classic prescription for expelling phlegm, extinguishing wind, strengthening the spleen (traditional Chinese medicine, ie, TCM, refers to the spleen channel) and dissipating excessive fluid based on TCM theory. BBTD is particularly effective in the treatment of excessive phlegm-dampness hypertension. However, the precise pharmacological effect of each herb of BBTD on hypertension treatment is not yet fully understood. Aim of the study To investigate the pharmacological effects of each herb in BBTD on hypertension treatment and to explore the mechanisms behind them. Materials and methods A high-fat-diet fed animal model was developed to evaluate the efficacy of different groups of drugs in BBTD for the treatment of hypertension. Untargeted metabolism was used to detect the metabolic changes after modeling and drug intervention. Then, Stigmasterol (STI) and gastrodin (GAS), major components of Pinellia Ternate Makino and Gastrodia elata Blume, were selected for treatment on HepG2 cell steatosis model. Real-time quantitative polymerase chain reaction and Western blotting were used to detect changes of corresponding gene and protein after drug intervention to explore the exam anti-hyperlipidemia mechanism of STI and GAS combination. Results The weight gain, elevated blood pressure and increased blood lipids induced by high-fat-diet were significantly decreased ( p < 0.05) after each prescription medicine intervention in a dose-dependent manner. In addition, 28 differential metabolites (DMs) were detected after modeling and were regulated to normal at varying degrees after each drug group treatment. In addition, eight of the 28 DMs were significantly different from the model group after the full prescription drug intervention, primarily related to four metabolic pathways, while only two metabolites were significantly different from the model group after the unprincipled drug intervention, related to one metabolic pathway. In HepG2 hyperlipidemia cell model, STI, GAS and their combination significantly decreased TC , TG levels and lipid accumulation ( p < 0.05), and decreased sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1) and their protein expressions ( p < 0.05), increased adenosine monophosphate-activated protein kinase (AMPK) and it's protein expression ( p < 0.05). The two drugs work better in combination than alone. Conclusion BBTD has been shown to be effective in reducing lipid accumulation in a high-fat rat model, as well as in restoring the model-induced abnormal metabolites to normal levels in a dose-dependent manner. Pinellia ternata Makino and Gastrodia elata Blume, the main components of BBTD, may regulate lipid metabolism through fatty acid biosynthesis, arginine and proline metabolism. Their main active agents, STI and GAS, effectively reduce lipid accumulation and lipid content in cells and regulate the expression levels of genes and proteins associated with lipid metabolism. These results suggest that BBTD may regulate lipid metabolism via AMPK/SREBP-1c pathway.
研究领域:
药理学
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中医
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代谢组学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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