PMID- 37788787 OWN - NLM STAT- MEDLINE DCOM- 20231122 LR - 20231122 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 319 IP - Pt 1 DP - 2024 Jan 30 TI - Network pharmacology integrated with experimental validation revealed the mechanism of Fengshi Gutong Capsule in the treatment of osteoarthritis. PG - 117261 LID - S0378-8741(23)01131-5 [pii] LID - 10.1016/j.jep.2023.117261 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Fengshi Gutong Capsule (FSGTC) is a commonly used Chinese medicine for the treatment of joint pain caused by osteoarthritis (OA). However, the mechanism of action of FSGTC for OA remains unclear. AIM OF THE STUDY: This study aimed to explore the alleviating effects and potential mechanisms of action of FSGTC for OA through data mining, network pharmacology, and in vitro experiments. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was performed to establish the fingerprints of FSGTC and detect the components of FSGTC absorbed in the blood. The effects of FSGTC on inflammation, immunity, and liver and kidney functions in patients with OA were evaluated by mining clinical data. The potential targets and pathways of FSGTC were screened using network pharmacology. Subsequently, CCK-8 assay, flow cytometry, western blotting, RT-qPCR, ELISA, and immunofluorescence were performed in IL-1beta-stimulated chondrocytes for further validation. RESULTS: Eighty-seven common peaks and 10 components were identified using the HPLC fingerprints of 12 batches of samples, and the similarity was in the range of 0.973-0.998. Retrospective clinical analysis demonstrated a significant reduction in inflammatory response levels among patients with OA who received FSGTC treatment. Network pharmacology analysis revealed that FSGTC potentially targeted processes related to inflammation, oxidative stress, and apoptosis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), The nuclear factor-kappaB (NF-kappaB), and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways were predicted to be the main pathways involved in the therapeutic effects of FSGTC in OA. In vitro, FSGTC-containing serum aided the proliferation of chondrocytes stimulated by IL-1beta, while concurrently mitigating apoptosis, suppressing the expression of inflammatory cytokines and oxidative molecules, and inhibiting the degradation of the chondrocyte extracellular matrix (ECM). CONCLUSIONS: FSGTC alleviates the inflammatory response in patients with OA. This therapeutic effect was attributed to its anti-inflammatory and antioxidant properties, and its ability to promote IL-1beta-induced chondrocyte proliferation, inhibit apoptosis, and prevent the degradation of extracellular matrix. These favorable results were associated with the inhibition of the PI3K/AKT, NF-kappaB, and JAK2/STAT3 signaling pathways. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Sun, Yanqiu AU - Sun Y AD - Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230038, Anhui Province, China; Institute of Rheumatology, Anhui Academy of Chinese Medicine, Hefei, 230012, Anhui Province, China. Electronic address: 1007900836@qq.com. FAU - Liu, Jian AU - Liu J AD - Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230038, Anhui Province, China; Institute of Rheumatology, Anhui Academy of Chinese Medicine, Hefei, 230012, Anhui Province, China. Electronic address: liujianahzy@126.com. FAU - Wang, Jue AU - Wang J AD - Sinopharm Group Jingfang (Anhui) Pharmaceutical Co., Ltd, Xuancheng City, 242000, Anhui Province, China. Electronic address: 383958096@qq.com. FAU - He, Mingyu AU - He M AD - Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230038, Anhui Province, China; Institute of Rheumatology, Anhui Academy of Chinese Medicine, Hefei, 230012, Anhui Province, China. Electronic address: 2217135737@qq.com. FAU - Chen, Xiaolu AU - Chen X AD - Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230038, Anhui Province, China; Institute of Rheumatology, Anhui Academy of Chinese Medicine, Hefei, 230012, Anhui Province, China. Electronic address: 18709828532@qq.com. FAU - Chen, Li AU - Chen L AD - Pharmaceutical Department, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230038, Anhui Province, China. Electronic address: 46784412@qq.com. LA - eng PT - Journal Article DEP - 20231001 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (NF-kappa B) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - 0 (Interleukin-1beta) SB - IM MH - Humans MH - *Proto-Oncogene Proteins c-akt/metabolism MH - NF-kappa B/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Network Pharmacology MH - Retrospective Studies MH - *Osteoarthritis/drug therapy MH - Inflammation/drug therapy MH - Chondrocytes MH - Phosphatidylinositol 3-Kinase/metabolism MH - Interleukin-1beta/metabolism OTO - NOTNLM OT - Chondrocytes OT - Fengshi Gutong Capsule OT - Network pharmacology OT - Osteoarthritis OT - Traditional Chinese medicine COIS- Declaration of competing interest 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- 2023/10/04 00:42 MHDA- 2023/11/22 06:43 CRDT- 2023/10/03 19:15 PHST- 2023/06/21 00:00 [received] PHST- 2023/09/28 00:00 [revised] PHST- 2023/09/29 00:00 [accepted] PHST- 2023/11/22 06:43 [medline] PHST- 2023/10/04 00:42 [pubmed] PHST- 2023/10/03 19:15 [entrez] AID - S0378-8741(23)01131-5 [pii] AID - 10.1016/j.jep.2023.117261 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117261. doi: 10.1016/j.jep.2023.117261. Epub 2023 Oct 1.