PMID- 35469160 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2022 DP - 2022 TI - Network Pharmacology-Based Prediction and Verification of the Potential Targets of Pinoresinol Diglucoside for OA Treatment. PG - 9733742 LID - 10.1155/2022/9733742 [doi] LID - 9733742 AB - OBJECTIVE: This study aimed to explore the effects and related mechanisms of pinoresinol diglucoside (PDG) on osteoarthritis (OA) via a combination of pharmacology and animal experiments. METHODS: Traditional Chinese Medicine Database and Analysis Platform (TCMSP) Drugbank, Online Mendelian Inheritance in Man, and GeneCards databases were used to predict the putative targets of PGD against OA. A protein protein interaction (PPI) network was constructed in STING database to analyze the interaction network of these targets. Enrichment analysis was performed with DAVID database. The OA model was built by anterior cruciate ligament transection and then injected with PDG for 5 weeks. Hematoxylin and eosin (HE) staining and safranin-fixed green staining were used to evaluate the pathological change. ELISA was applied to measure the serum levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Immunohistochemistry was employed to detect the protein levels of kinase B (AKT), BAX, Bcl2, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and phosphatidylinositol 3 kinase (PI3K) in knee cartilage tissues. RESULTS: Seventy-one key targets were identified, including AKT1, epidermal growth factor receptor, SRC, estrogen receptor 1 (ESR1), and MMP9. Enrichment analysis revealed a series of pathway related to cancer, PI3K-Akt signaling pathway, and proteoglycans in cancer. Animal experiments showed that PDG alleviated the abnormal histomorphological changes of OA; suppressed TIPM, serum IL-1beta, IL-6, and TNF-alpha levels, and PI3K and AKT activation; and increased MMP-1 expression and Bcl2/Bax ratio. CONCLUSION: PDG has a cartilage-protecting effect associated with PI3K/AKT signaling pathway in rabbit with OA and therefore might serve as a potential agent for the treatment of this disease. CI - Copyright (c) 2022 Hongkan Lou et al. FAU - Lou, Hongkan AU - Lou H AUID- ORCID: 0000-0001-8241-6832 AD - Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Ningbo 315012, China. FAU - Zhang, Yang AU - Zhang Y AD - Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310000, China. FAU - Fang, Jianli AU - Fang J AD - Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Ningbo 315012, China. FAU - Jin, Yong AU - Jin Y AUID- ORCID: 0000-0003-2586-7594 AD - Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Ningbo 315012, China. LA - eng PT - Journal Article DEP - 20220416 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC9034917 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/04/27 06:00 MHDA- 2022/04/27 06:01 PMCR- 2022/04/16 CRDT- 2022/04/26 05:30 PHST- 2021/10/26 00:00 [received] PHST- 2022/03/16 00:00 [revised] PHST- 2022/03/17 00:00 [accepted] PHST- 2022/04/26 05:30 [entrez] PHST- 2022/04/27 06:00 [pubmed] PHST- 2022/04/27 06:01 [medline] PHST- 2022/04/16 00:00 [pmc-release] AID - 10.1155/2022/9733742 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2022 Apr 16;2022:9733742. doi: 10.1155/2022/9733742. eCollection 2022.