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Tianyu Dong  (Dong T) 1 Article
Basic Research
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Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats
Weiyue Hu, Lingling Wang, Guizhen Du, Quanquan Guan, Tianyu Dong, Ling Song, Yankai Xia, Xinru Wang
Diabetes Metab J. 2020;44(5):747-763.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2019.0124
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  • 16 Web of Science
  • 17 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Natural compounds as obesity pharmacotherapies
    Xin‐Yuan Zhao, Ji‐Qiu Wang, G. Gregory Neely, Yan‐Chuan Shi, Qiao‐Ping Wang
    Phytotherapy Research.2024; 38(2): 797.     CrossRef
  • Celastrol functions as an emerging manager of lipid metabolism: Mechanism and therapeutic potential
    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
  • 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
    Rui Xi, Yongxin Wan, Lihong Yang, Jingying Zhang, Liu Yang, Shuai Yang, Rui Chai, Fengchen Mu, Qiting Sun, Rui Yan, Zhifang Wu, Sijin Li, Zhijun Liao
    BioMed Research International.2022; 2022: 1.     CrossRef
  • Celastrol inhibits TXNIP expression to protect pancreatic β cells in diabetic mice
    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
    Carlos A. Fuzo, Ronaldo B. Martins, Thais F. C. Fraga‐Silva, Martin K. Amstalden, Thais Canassa De Leo, Juliano P. Souza, Thais M. Lima, Lucia H. Faccioli, Débora Noma Okamoto, Maria Aparecida Juliano, Suzelei C. França, Luiz Juliano, Vania L. D. Bonato,
    Drug Development Research.2022; 83(7): 1623.     CrossRef
  • In vitro activity of celastrol in combination with thymol against carbapenem-resistant Klebsiella pneumoniae isolates
    Mahmoud Saad Abdel-Halim, Momen Askoura, Basem Mansour, Galal Yahya, Amira M. El-Ganiny
    The Journal of Antibiotics.2022; 75(12): 679.     CrossRef
  • Celastrol alleviates metabolic disturbance in high‐fat diet‐induced obese mice through increasing energy expenditure by ameliorating metabolic inflammation
    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
    Francesco Caruso, Manrose Singh, Stuart Belli, Molly Berinato, Miriam Rossi
    International Journal of Molecular Sciences.2020; 21(23): 9266.     CrossRef

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