M13, an anthraquinone compound isolated from Morinda officinalis alleviates the progression of the osteoarthritis via the regulation of STAT3.

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2024-12-15 DOI:10.1016/j.phymed.2024.156329
Baolin Zhang, Ya Xiao, Deying Su, Chuan Li, Shun Zhang, Jiahui Long, Ricong Weng, Hengyu Liu, Yingtong Chen, Zhiheng Liao, Xu Zhu, Junming Huang, Shuqing Chen, Taifeng Zhou, Yuan Ma, Caixia Xu
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Abstract

Background: Osteoarthritis (OA) is characterized by the progressive deterioration of articular cartilage, leading to joint pain and functional impairment. OA severely impacts quality of life and presents a substantial societal burden. Currently, effective treatment options remain limited. Morinda officinalis (MO), a traditional Chinese herb, is commonly used to treat rheumatoid arthritis and alleviate joint pain. M13, an anthraquinone extracted from MO, has shown significant anti-inflammatory properties, making it a promising candidate for the treatment of OA. However, its role in inhibiting OA progression and the mechanisms involved remain poorly understood.

Purpose: The objective of this study is to examine the impact of M13 on osteoarthritis and uncover the mechanisms.

Methods: The effects of M13 on OA were assessed using TNF-α induced chondrocyte models and mice with destabilization of the medial meniscus (DMM). Celecoxib was used as a positive control. We evaluated the expression of factors related to chondrocyte degeneration and inflammation through qRT-PCR, immunoblotting, and immunofluorescence. Chondrocyte viability was measured using CCK-8 assays, EdU staining, and flow cytometry. Molecular docking, molecular dynamics simulations and isothermal titration calorimetry (ITC) were performed to evaluate the binding efficacy of target proteins. Additionally, the therapeutic effects of M13 in OA mice were confirmed through in vivo experiments.

Results: In primary murine chondrocytes, M13 rescued TNF-α-induced matrix degradation and loss of vitality while suppressing ROS generation. Mechanistically, STAT3 was identified as a target protein of M13, through which M13 mitigated OA by inhibiting the STAT3 signaling pathway. Further in vivo experiments demonstrated that M13 reduced the scores of the Osteoarthritis Research Society International (OARSI), alleviating cartilage impairment. M13 enhanced levels of collagen II and aggrecan in cartilage tissue while decreasing the amounts of cartilage-degrading proteins ADAMTS-5 and MMP13.

Conclusion: This is the first study to validate that M13 mitigates the inflammation and damage in cartilage tissue by blocking the STAT3 signaling pathway. These findings hold promise for enhancing innovative clinical interventions targeting OA.

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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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