- Basic Research
- Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats
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Weiyue Hu, Lingling Wang, Guizhen Du, Quanquan Guan, Tianyu Dong, Ling Song, Yankai Xia, Xinru Wang
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Diabetes Metab J. 2020;44(5):747-763. Published online May 11, 2020
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DOI: https://doi.org/10.4093/dmj.2019.0124
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Abstract
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Background
Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity.
Methods
We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol.
Results
We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 µg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW.
Conclusion
Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.
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Citations
Citations to this article as recorded by
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Jia Gu, Ya-Ning Shi, Neng Zhu, Hong-Fang Li, Chan-Juan Zhang, Li Qin Biomedicine & Pharmacotherapy.2023; 164: 114981. CrossRef - Tripterygium hypoglaucum extract ameliorates adjuvant-induced arthritis in mice through the gut microbiota
Jianghui HU, Jimin NI, Junping ZHENG, Yanlei GUO, Yong YANG, Cheng YE, Xiongjie SUN, Hui XIA, Yanju LIU, Hongtao LIU Chinese Journal of Natural Medicines.2023; 21(10): 730. CrossRef - Natural compounds as obesity pharmacotherapies
Xin‐Yuan Zhao, Ji‐Qiu Wang, G. Gregory Neely, Yan‐Chuan Shi, Qiao‐Ping Wang Phytotherapy Research.2023;[Epub] CrossRef - Health improvements of type 2 diabetic patients through diet and diet plus fecal microbiota transplantation
Lili Su, Zhifan Hong, Tong Zhou, Yuanyuan Jian, Mei Xu, Xuanping Zhang, Xiaoyan Zhu, Jiayin Wang Scientific Reports.2022;[Epub] CrossRef - Tripterygium hypoglaucum (Levl.) Hutch: A systematic review of its traditional uses, botany, phytochemistry, pharmacology, pharmacokinetics and toxicology
Jiangping Wei, Liyun Chen, Sijia Gao, Jirui Wang, Yunhong Wang, Zhiwei Zhang, Yuyu Zhang, Xiaomei Zhang, Yong Yang, Dajian Yang Pharmacological Research - Modern Chinese Medicine.2022; 3: 100094. CrossRef - Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms
Mengzhen Li, Faren Xie, Lu Wang, Guoxue Zhu, Lian-Wen Qi, Shujun Jiang Frontiers in Pharmacology.2022;[Epub] CrossRef - Celastrol inhibits the proliferation and migration of MCF-7 cells through the leptin-triggered PI3K/AKT pathway
Pingping Chen, Bin Wang, Meng Li, Chunxue Cui, Fei Liu, Yonggang Gao Computational and Structural Biotechnology Journal.2022; 20: 3173. CrossRef - Investigating Celastrol’s Anti-DCM Targets and Mechanisms via Network Pharmacology and Experimental Validation
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Si-wei Wang, Tian Lan, Fang Zheng, Hui Huang, Hang-fei Chen, Qi Wu, Feng Zhang Phytomedicine.2022; 104: 154316. CrossRef - Celastrol: A Promising Agent Fighting against Cardiovascular Diseases
Zhexi Li, Jingyi Zhang, Xulei Duan, Guoan Zhao, Min Zhang Antioxidants.2022; 11(8): 1597. CrossRef - Celastrol: A lead compound that inhibits SARS‐CoV‐2 replication, the activity of viral and human cysteine proteases, and virus‐induced IL‐6 secretion
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Xueping Yang, Fan Wu, Lingli Li, Ernest C. Lynch, Linglin Xie, Yan Zhao, Ke Fang, Jingbin Li, Jinlong Luo, Lijun Xu, Xin Zou, Fuer Lu, Guang Chen Phytotherapy Research.2021; 35(1): 297. CrossRef - Celastrol in metabolic diseases: Progress and application prospects
Shaohua Xu, Yaqian Feng, Weishen He, Wen Xu, Wei Xu, Hongjun Yang, Xianyu Li Pharmacological Research.2021; 167: 105572. CrossRef - The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism
Qijing Fan, Furong Xu, Bin Liang, Xiaoju Zou Frontiers in Pharmacology.2021;[Epub] CrossRef - Serum Metabolome Mediates the Antiobesity Effect of Celastrol-Induced Gut Microbial Alterations
Shaohua Xu, Liwei Lyu, Huaichang Zhu, Xiaoqiang Huang, Wei Xu, Wen Xu, Yaqian Feng, Yong Fan Journal of Proteome Research.2021; 20(10): 4840. CrossRef - Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger
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