ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1571884
The Eucommia ulmoides -Achyranthes bidentata pair and their active monomers exert synergistic therapeutic potential for osteoarthritis through the PI3K-AKT pathway
Provisionally accepted
Leilei Bao1,2*
Chun Chen1Lei Lv1Yueying Huang1Mingzhu Gao1Sailiang Zeng1,2Zijun Wang1,2Xue Jiang1Yangyang Zhan1*- 1the third affiliation hospital of naval medical university, Shanghai, China
- 2Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China
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Osteoarthritis (OA) is characterized by articular cartilage degradation, involving inflammation-mediated chondrocyte apoptosis and extracellular matrix destruction.Eucommia ulmoides (EU) and Achyranthes bidentata (AB) constitute a classic herbal pair for OA treatment, yet their combinatorial effects and molecular mechanisms remain unelucidated.The EU-AB extract was prepared via aqueous decoction. An LPS-induced ATDC5 chondrocyte inflammatory model and an MIA-induced rat OA model were established.Therapeutic efficacy was evaluated using Lequesne scores, ELISA, Western blotting, and immunohistochemistry. Bioactive components were identified by HPLC-TOF/MS, while RNA-seq and molecular interaction analyses validated underlying mechanisms.The EU-AB extract significantly suppressed the expression of matrix metalloproteinases (MMP-3/13) and inflammatory cytokines (NO, TNF-α, IL-6, IL-1β) in both ATDC5 cells and rat serum (P<0.05). Concurrently, it reduced Lequesne scores and joint swelling in MIA-induced OA rats (P<0.05) while ameliorating histopathological cartilage damage. Among 35 compounds identified by HPLC-TOF/MS, pinoresinol diglucoside (PIN) from EU and chikusetsusaponin Ⅳa (CHI) from AB demonstrated synergistic effects, downregulating pro-apoptotic proteins (Caspase-3/9, Bax) through activation of the PI3K-Akt pathway and promotion of Akt phosphorylation.The herbal pair aqueous extract suppresses osteoarthritis via the bioactive component group CHI-PIN, demonstrating synergistic anti-inflammatory effects in MIA rats, likely mediated by PI3K-Akt-regulated apoptosis.
Keywords: Drug pair, Osteoarthritis, synergies, Pi3k-akt, Apoptosis
Received: 06 Feb 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 Bao, Chen, Lv, Huang, Gao, Zeng, Wang, Jiang and Zhan. 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:
Leilei Bao, the third affiliation hospital of naval medical university, Shanghai, China
Yangyang Zhan, the third affiliation hospital of naval medical university, Shanghai, China
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