PMID- 36973772
OWN - NLM
STAT- MEDLINE
DCOM- 20230329
LR  - 20230330
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 18
IP  - 1
DP  - 2023 Mar 27
TI  - Daurisoline attenuates H(2)O(2)-induced chondrocyte autophagy by activating the 
      PI3K/Akt/mTOR signaling pathway.
PG  - 248
LID - 10.1186/s13018-023-03717-5 [doi]
LID - 248
AB  - BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease 
      characterized by cartilage degeneration and intra-articular inflammation. 
      Daurisoline (DAS) is an isoquinoline alkaloid isolated from Rhizoma Menispermi, 
      whose antitumor and anti-inflammatory pharmacological effects have been 
      demonstrated, but the effects of DAS on OA have rarely been researched. In this 
      study, we aimed to explore the potential role of DAS in OA and its partial 
      mechanism. MATERIALS AND METHODS: The cytotoxicity of H(2)O(2) and DAS toward 
      chondrocytes was detected by the Cell Counting Kit-8 assay. Safranin O staining 
      was used to detect chondrocyte phenotype changes. Cell apoptosis was measured by 
      both flow cytometry and quantitative analysis of the protein levels of the 
      apoptosis-related factors Bax, Bcl-2 and cleaved caspase-3 by western blot. 
      Western blotting and immunofluorescence were used to assess the expression of the 
      autophagy-related proteins LC3, Beclin-1 and p62. In addition, key signal pathway 
      targets and matrix-degrading indicators were measured by western blot. RESULTS: 
      Our results indicated that H(2)O(2) induced human chondrocyte apoptosis and 
      activated autophagy in a dose-dependent manner. DAS treatment dose-dependently 
      reversed the expression of apoptosis-related proteins (Bax, Bcl-2 and cleaved 
      caspase3) and the apoptosis rate induced by H(2)O(2). Western blot and 
      immunofluorescence analyses showed that DAS decreased the H(2)O(2)-induced 
      upregulation of the autophagy marker Beclin-1 and the LC3 II/LC3 I ratio and 
      upregulated the p62 protein level. Mechanistically, DAS inhibited autophagy 
      through the activation of the classical PI3K/AKT/mTOR signaling pathway and 
      protected chondrocytes from apoptosis. In addition, DAS alleviated the 
      H(2)O(2)-induced degradation of type II collagen and the high expression of 
      matrix metalloproteinase 3 (MMP3) and MMP13. CONCLUSION: Our research 
      demonstrated that DAS alleviated chondrocyte autophagy caused by H(2)O(2) through 
      activation of the PI3K/AKT/mTOR signaling pathway and protected chondrocytes from 
      apoptosis and matrix degradation. In conclusion, these findings suggest that DAS 
      may serve as a promising therapeutic strategy for OA.
CI  - (c) 2023. The Author(s).
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Department of Orthopaedics, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, People's 
      Republic of China.
FAU - Liu, Wenguang
AU  - Liu W
AD  - Department of Orthopaedics, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, People's 
      Republic of China.
FAU - Liu, Zhonghao
AU  - Liu Z
AD  - Department of Orthopaedics, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, People's 
      Republic of China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Orthopaedics, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, People's 
      Republic of China. liuyiys@163.com.
LA  - eng
GR  - ZR2020QH076/Liu Yi/
PT  - Journal Article
DEP - 20230327
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (Beclin-1)
RN  - 70553-76-3 (daurisoline)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 2.7.1.1 (MTOR protein, human)
SB  - IM
MH  - Humans
MH  - *Chondrocytes/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Hydrogen Peroxide/toxicity
MH  - bcl-2-Associated X Protein/metabolism
MH  - Beclin-1/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Osteoarthritis/genetics
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Autophagy/genetics
MH  - Apoptosis/genetics
PMC - PMC10041752
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Daurisoline
OT  - Osteoarthritis
OT  - PI3K/AKT/mTOR signaling pathway
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/03/28 06:00
MHDA- 2023/03/29 06:05
PMCR- 2023/03/27
CRDT- 2023/03/27 23:40
PHST- 2023/02/18 00:00 [received]
PHST- 2023/03/15 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/03/27 23:40 [entrez]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/27 00:00 [pmc-release]
AID - 10.1186/s13018-023-03717-5 [pii]
AID - 3717 [pii]
AID - 10.1186/s13018-023-03717-5 [doi]
PST - epublish
SO  - J Orthop Surg Res. 2023 Mar 27;18(1):248. doi: 10.1186/s13018-023-03717-5.