ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1592818
This article is part of the Research TopicBioactivities and Clinical Applications of Medicinal Plants in Promoting Wellness in AgingView all articles
Shengyu decoction ameliorates knee osteoarthritis by inhibiting endoplasmic reticulum stress via Piezo1 channels
Provisionally accepted
- 1The Second Hospital of Shandong University, Jinan, China
- 2Tianjin University of Traditional Chinese Medicine, Tianjin, China
- 3Shandong University, Jinan, Shandong Province, China
- 4Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 5Shandong Academy of Chinese Medicine, Jinan, Shandong Province, China
- 6Lunan Pharmaceutical Group Co. Ltd, Linyi, Shandong Province, China
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Background: Shengyu decoction (SYD) is a classic and excellent prescription of traditional Chinese Medicine (TCM). The innovative use of SYD by Chinese medical master Prof. Qi Shi in the treatment of knee osteoarthritis (KOA) has achieved considerable clinical outcomes. However, the current weakness is the lack of study on the active ingredients and mechanisms of SYD. Purpose: To evaluate the role of SYD in reducing KOA cartilage damage as well as to explore the active ingredients and mechanisms of SYD. Methods: The KOA rat model and chondrocyte model were established. This study employed various molecular biology techniques to clarify the role of SYD in vivo and in vitro. Furthermore, the active ingredients and mechanisms of SYD were analyzed through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), RNA sequencing, molecular docking and surface plasmon resonance (SPR) experiment. Finally, rescue experiments were conducted to verify the mechanisms.The results revealed that SYD could significantly reduce cartilage tissue lesions, inhibit inflammation and regulate proliferation-apoptosis balance.Transcriptome analysis showed an increase in the expression of Piezo1, Xbp1, Atf6 in KOA and SYD downregulated them. UPLC-Q-TOF-MS analysis revealed four bioactive compounds of SYD, which were further confirmed to directly interact with Piezo1 through molecular docking and SPR assays. Furthermore, SYD downregulated the calcium ion concentration, Piezo1 and ERS intensity. Meanwhile, in the rescue experiment, Yoda1, the agonist of Piezo1, antagonized the pharmacological effects of SYD.The present results provides strong evidence that SYD protected articular cartilage via inhibiting the Piezo1-mediated ERS signaling pathway. Overall, our work emphasizes the pivotal role of TCM in addressing medical challenges and 4 provides new ideas for the treatment of KOA.
Keywords: Shengyu Decoction, knee osteoarthritis, Traditional Chinese Medicine, Endoplasmic Reticulum Stress, Piezo1 Abbreviation: CXB, Celecoxib, EIC, the extracted ion chromatograms, ERS, endoplasmic reticulum stress, GO, gene ontology
Received: 13 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Song, Liu, Shen, Zhang, Kong, Chen, Sheng and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rong Sun, The Second Hospital of Shandong University, Jinan, China
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