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Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study

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Abstract

Osteoarthritis (OA), a common degenerative joint disease, is characterized by the progressive degradation of articular cartilage and inflammation. Hederagenin (HE) is a pentacyclic triterpenoid saponin extracted from many herb plants. It has anti-inflammatory, anti-lipid peroxidative, anti-cancer, and neuroprotective activities. However, its effect on OA has not been investigated. Our study found that HE may be a potential anti-OA drug. In vitro, HE could suppress extracellular matrix (ECM) degradation via up-regulating aggrecan and Collagen II levels as well as downregulating MMPs and ADAMTS5 levels. It could also reduce proinflammatory and inflammatory cytokines or enzymes production, including TNF-α, IL-6, iNOS, COX-2, NO, and PGE2. Besides, HE markedly reduced IL-1β-induced C28/I2 cell apoptosis and ROS accumulation. Mechanistically, HE exerted chondroprotective and anti-inflammatory effects by partly inhibiting JAK2/STAT3/MAPK signalling pathway and the crosstalk of the two pathways. Also, HE exhibited anti-apoptotic and anti-oxidative effect via targeting Keap1-Nrf2/HO-1/ROS/Bax/Bcl-2 axis. In vivo, HE significantly reduced monosodium iodoacetate (MIA) induced cartilage destruction of rats with a lower OARSI score and inflammatory cytokine levels, further demonstrating its protective effects in OA progression. These results suggest that HE is a potential compound for the development of drugs to treat OA.

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DATA AVAILABILITY

The data used to support the current study are available from the corresponding author on reasonable request.

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ACKNOWLEDGEMENTS

We sincerely thank Professor Jinghong Chen (Xi’an Jiaotong University, Xi’an) for providing C28/I2 cells.

Funding

This work was supported by the Natural Science Foundation of China (No. 81872971) and Key R&D Program of Science and Technology Bureau of Chengdu (No. 2019-YFYF-00002-SN).

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Author notes

  1. Yue Shen and Li Teng contributed equally to this article.

Authors and Affiliations

  1. Key Laboratory of Drug-Targeting and Drug Delivery System of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, China

    Yue Shen, Yuehui Huang, Yi Peng & Qiang Fu

  2. School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China

    Li Teng, Yuhan Qu & Min Tang

Authors
  1. Yue Shen
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  2. Li Teng
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  6. Min Tang
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  7. Qiang Fu
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Contributions

Yue Shen participated in writing-original draft, methodology, and data analysis; Li Teng participated in acquisition, analysis, and interpretation of data; Yuhan Qu participated in conceptualization and data analysis; Yuehui Huang participated in methodology; Yi Peng took charge of data analysis; Min Tang participated in conceptualization. Qiang Fu provided concept and design, administrative, technical, and material support. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Qiang Fu.

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Ethics Approval and Consent to Participate

This study was approved by the Institutional Animal Care and Use Committee (IACUC) of Chengdu University (Permit Number: 2018–35).

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All authors have approved the manuscript and agree with submission.

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The authors declare no competing interests.

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Shen, Y., Teng, L., Qu, Y. et al. Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study. Inflammation 46, 655–678 (2023). https://doi.org/10.1007/s10753-022-01763-5

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