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The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the regulation of PTEN

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Abstract

Rheumatoid arthritis (RA) is a systemic immune disease characterized by joint inflammation and pannus. The nascent pannus contributes to synovial hyperplasia, cartilage, and tissue damage in RA. This study aims to explore the therapeutic effect and potential mechanism of Geniposide (GE) on RA angiogenesis, involving the participation of phosphate and tension homology deleted on chromosome ten (PTEN) and downstream pathways. Clinical manifestations, synovial pathomorphology, microvessel density, and the level of angiogenesis-related factors were used to evaluate the therapeutic effect of GE on adjuvant-induced arthritis (AA) rats. The proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) indicate the degree of angiogenesis in vitro. Lentivirus over-expression of PTEN was employed to elucidate the potential mechanism. The results showed that GE improved the degree of arthritis and angiogenesis in AA rats. The expression of PTEN was decreased significantly in vivo and in vitro, and over-expression of PTEN improved the biological function of HUVECs to inhibit angiogenesis. GE inhibited the proliferation, migration, and tubule formation of HUVECs and plays an anti-angiogenesis role in vitro. Mechanism study showed that PTEN expression was increased and p-PI3K and p-Akt expression was decreased with GE treatment. It suggests that GE up-regulated the expression of PTEN and inhibited the activation of PI3K-Akt signal, which plays a role in inhibiting angiogenesis in RA in vivo and in vitro.

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Data availability

The data generated in this study have been analyzed and included in this article, and unprocessed data will be available on request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No 81874360 and No 81073122) and the major projects of Natural Science Research in Anhui Universities (KJ2021ZD0060).

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Authors and Affiliations

  1. Key Laboratory of Xin’an Medicine, Ministry of Education, Hefei, 230012, China

    Yanhong Bu, Hong Wu, Ran Deng & Yan Wang

  2. College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road 1, Hefei, 230012, China

    Yanhong Bu, Hong Wu, Ran Deng & Yan Wang

  3. Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China

    Yanhong Bu, Hong Wu, Ran Deng & Yan Wang

  4. Anhui Province Key Laboratory of Research and Development of Chinese Medicine, Hefei, 230012, China

    Yanhong Bu, Hong Wu, Ran Deng & Yan Wang

Authors
  1. Yanhong Bu
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  2. Hong Wu
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  3. Ran Deng
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  4. Yan Wang
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Contributions

Participated in research design: YB and HW. Conducted experiments: YB, RD, and YW. Performed data analysis: YB, RD, and YW. Wrote or contributed to the writing of the manuscript: YB.

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Correspondence to Hong Wu.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval

All animal studies designed in this article have been approved by the experimental animal ethics committee of Anhui University of Traditional Chinese Medicine (No. ahucm-rates-2021049). It is considered that this study meets the requirements of animal ethics in animal species selection, quantity, feeding, and modeling.

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Bu, Y., Wu, H., Deng, R. et al. The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the regulation of PTEN. Inflammopharmacol 30, 1047–1062 (2022). https://doi.org/10.1007/s10787-022-00975-3

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  • DOI: https://doi.org/10.1007/s10787-022-00975-3

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