2. Academic Validation
  3. Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes

Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes

  • J Orthop Surg Res. 2023 Mar 2;18(1):154. doi: 10.1186/s13018-023-03645-4.
Jieyun Jiang # 1,  Jin Li # 2,  Chenwei Xiong 3 4,  Xindie Zhou 5 6 7,  Ting Liu 8 9
Affiliations

Affiliations

  • 1 Medical Development Department, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China.
  • 2 Department of Orthopedic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China.
  • 3 Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, China.
  • 4 Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China.
  • 5 Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, China. zhouxindie@njmu.edu.cn.
  • 6 Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China. zhouxindie@njmu.edu.cn.
  • 7 Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture, 811800, Qinghai Province, China. zhouxindie@njmu.edu.cn.
  • 8 Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, China. 1418583360@qq.com.
  • 9 Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China. 1418583360@qq.com.
  • # Contributed equally.
PMID: 36864518 DOI: 10.1186/s13018-023-03645-4
Abstract

Context: Osteoarthritis is a common degenerative disease, the cause of it is still unknown, and the treatment mainly focuses on improving symptoms. Studies have found that Isorhynchophylline (Isorhy) has antioxidant, anti-inflammatory, antiproliferative and neuroprotective effects.

Objective: This study investigates the role and mechanism of Isorhy in OA.

Methods: The destabilized medial meniscus model was used to mimic OA. Fifteen male Sprague Dawley rats were partitioned into three portions: Normal group, OA group (surgery; normal saline treatment) and OA + Isorhy group (surgery; 50 μM Isorhy treatment) were performed on the first day of every week from the 5th to the 8th week after surgery. After 4 weeks of drug treatment, the rats have been processed without debridement of the knee specimens and fixed using 4% paraformaldehyde for two days. The morphological analysis was performed by H&E, Safranin O-Fast green staining and micro-CT analysis. The specimens were researched employing Micro-CT. In the part of the aggregate methods that were evaluated by qRT-PCR and western blot of the following proteins LC3II/LC3I, Beclin-1, ATG5, Atg7, MMP3 andMMP13. Akt/PI3K signaling related proteins (p-AKT, Akt, p-PI3K, PI3K, p-mTOR, mTOR) were detected by Western blot. Beclin1 and MMP3 were detected by Immunofluorescence assay.

Results: In this present research, it was proved that autophagy-related and cartilage matrix-related proteins in osteoarthritis could be regulated by Isorhynchophylline treatment. The transcriptome Sequencing results suggested the regulation was closely associated with PI3K/Akt/mTOR pathway, thereby alleviating osteoarticular inflammation. In-depth study showed that Isorhy could also affect OA in rat OA models, that was indicated by H&E, Safranin O-Fast green staining, and also micro-CT analysis.

Conclusion: Our findings indicated that Isorhy could be regarded as a prospective candidate for OA treatment.

Keywords

Autophagy; Chondrocytes; Isorhynchophylline; Osteoarthritis; PI3K/AKT/mTOR signaling.

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