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Research ArticleEndocrine and Diabetes

Ginsenoside Ro Ameliorates High-Fat Diet–Induced Obesity and Insulin Resistance in Mice via Activation of the G Protein–Coupled Bile Acid Receptor 5 Pathway

Lin-shan Jiang, Wei Li, Tong-xi Zhuang, Jie-jing Yu, Shuai Sun, Zheng-cai Ju, Zheng-tao Wang, Li-li Ding and Li Yang
Journal of Pharmacology and Experimental Therapeutics June 2021, 377 (3) 441-451; DOI: https://doi.org/10.1124/jpet.120.000435
Lin-shan Jiang
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Wei Li
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Tong-xi Zhuang
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Jie-jing Yu
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Shuai Sun
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Zheng-cai Ju
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Zheng-tao Wang
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Li-li Ding
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Li Yang
Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica (L.J., W.L., T..Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.), and Institute of Interdisciplinary Integrative Medicine Research (L.J., J.Y., L.Y.), Shanghai University of Traditional Chinese Medicine, Shanghai, China; and Shanghai R&D Center for Standardization of Traditional Chinese Medicine, Shanghai, China (L.J., W.L., T.Z., J.Y., S.S., Z.J., Z.W., L.D., L.Y.)
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Abstract

Obesity, a well known risk factor in multiple metabolic diseases, is dramatically increasing worldwide. Ginsenosides extracted from ginseng have been reported against obesity and the associated metabolic disorders. As a subtype of ginsenoside, ginsenoside Ro is a critical constituent of ginseng. However, its specific effects on obesity remain unknown. G protein–coupled bile acid receptor 5 (TGR5) (also known as GPBAR1) is a bile acid membrane receptor, widely expressed in human tissues contributing to various metabolic processes to confer the regulations of glucose and lipid homeostasis. TGR5 has displayed potential as a therapeutic target for the treatment of metabolic disorders. Here, we explore the antiobesity effect of ginsenoside Ro with TGR5 activation screened by a library of natural products. Our results showed that the ginsenoside Ro (90mg/kg) treatment ameliorated body weight and lipid accumulation in multiple metabolic organs of high-fat diet–induced obese (DIO) mice without affecting food intake and improved oral glucose tolerance tests, intraperitoneal insulin tolerance tests, and fasting serum glucose. We also found that triglyceride and total cholesterol in serum and liver were significantly decreased after ginsenoside Ro treatment. Then we used Tgr5 knockout mice to explore the role of Tgr5 in the antiobesity effect of ginsenoside Ro. Our results further demonstrated that ginsenoside Ro promoted glucagon-like peptide 1 (GLP-1) secretion and energy expenditure in wild-type DIO mice. However, the stimulation of ginsenoside Ro on GLP-1 secretion and energy expenditure were restrained in the Tgr5 knockout mice. In conclusion, our findings demonstrated that ginsenoside Ro ameliorates obesity and insulin resistance in DIO mice via activating TGR5, indicating a potential therapeutic role of ginsenoside Ro to treat obesity and its associated metabolic diseases.

SIGNIFICANCE STATEMENT Obesity is dramatically increasing worldwide, and it contributes to multiple metabolic diseases. G protein–coupled bile acid receptor 5 (TGR5) is a potential therapeutic target for the treatment of metabolic disorders. Ginsenoside Ro, as an oleanane-type ginsenoside, ameliorates obesity and insulin resistance, promotes glucagon-like peptide 1 secretion, and increases energy expenditure via activating TGR5. Ginsenoside Ro could be a potential leading compound for treating obesity and its associated metabolic diseases.

Footnotes

    • Received November 24, 2020.
    • Accepted March 26, 2021.
  • ↵1 L.J. and W.L. contributed equally to this work.

  • This work is financially sponsored by Natural Science Foundations of China to Z.W. (81920108033) and L.D. (81773961), the Shanghai Pujiang Program (17PJ1408800) to L.D., and the National S&T Major Special Projects of China (2017ZX09309006) to L.Y. as well as China Postdoctoral Science Foundation (2020M681368) to W.L.

  • The authors declare that they have no conflicts of interest.

  • https://doi.org/10.1124/jpet.120.000435.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 377 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 3
1 Jun 2021
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Research ArticleEndocrine and Diabetes

Ginsenoside Ro Ameliorates Obesity via the TGR5 Pathway

Lin-shan Jiang, Wei Li, Tong-xi Zhuang, Jie-jing Yu, Shuai Sun, Zheng-cai Ju, Zheng-tao Wang, Li-li Ding and Li Yang
Journal of Pharmacology and Experimental Therapeutics June 1, 2021, 377 (3) 441-451; DOI: https://doi.org/10.1124/jpet.120.000435

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Research ArticleEndocrine and Diabetes

Ginsenoside Ro Ameliorates Obesity via the TGR5 Pathway

Lin-shan Jiang, Wei Li, Tong-xi Zhuang, Jie-jing Yu, Shuai Sun, Zheng-cai Ju, Zheng-tao Wang, Li-li Ding and Li Yang
Journal of Pharmacology and Experimental Therapeutics June 1, 2021, 377 (3) 441-451; DOI: https://doi.org/10.1124/jpet.120.000435
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