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Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway

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Abstract

Previous studies demonstrated that penta-acetyl geniposide ((Ac)5GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac)5GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund’s adjuvant. (Ac)5GP (30, 60, 120 mg/kg) was given to AIA rats by intragastric administration. Paw swelling, polyarthritis index, serum pro-inflammatory cytokines levels, histological assessments of ankle joint, and proteoglycan expression were respectively measured to evaluate the therapeutic effect of (Ac)5GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac)5GP on AIA synoviocytes in vivo. Protein levels of Bcl-2, Bax, caspase 3, IκBα, p-IκBα, and NF-κB p65 in synovial tissues were detected by Western blot. We found that (Ac)5GP treatment could suppress secondary hind paw swelling, reduce polyarthritis index, decrease TNF-α and IL-1β serum levels, attenuate pathological damage of ankle joint, and promote proteoglycans expression. (Ac)5GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac)5GP (120 mg/kg) could significantly decrease Bcl-2 protein level, increase Bax and cleaved caspase 3 protein levels, and normalize the ratio of Bcl-2 to Bax. Moreover, (Ac)5GP (120 mg/kg) could inhibit the degradation and phosphorylation of IκBα and reduce NF-κB p65 protein level in nuclear extracts. In conclusion, (Ac)5GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues.

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Funding

This study was supported by the National Natural Science Foundation of China (81102273, 81201052), the Program for Outstanding Young Talents of Higher Education Institution of Anhui Province (gxyqZD2016045), and the Program for the Young and Middle-aged Academic Technology Leaders of Anhui Medical University (201309).

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  1. Li Cai and Chun-mei Li contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China

    Li Cai

  2. School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China

    Chun-mei Li, Wen-jian Tang, Ming-ming Liu, Wei-na Chen & Rong Li

  3. School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long Road, Macau, China

    Yuan-ye Qiu & Rong Li

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  1. Li Cai
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Cai, L., Li, Cm., Tang, Wj. et al. Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway. Inflammation 41, 2184–2195 (2018). https://doi.org/10.1007/s10753-018-0861-0

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