Dataset Information

Fengshi Gutong Capsule Attenuates Osteoarthritis by Inhibiting MAPK, NF-?B, AP-1, and Akt Pathways.

ABSTRACT: Background and purpose: Fengshi Gutong capsule (FSGTC), a traditional herbal formula, has been used clinically in China for the treatment of arthritis. However, the mechanism underlying the therapeutic effects of FSGTC on osteoarthritis (OA) has not been elucidated. The present study investigated the function and mechanisms of FSGTC in rat OA model and interleukin (IL)-1?-stimulated synovial cells. Materials and methods: Rat OA model was established by intra-articular injection containing 4% papain. IL-1?-induced SW982 cells were used as an OA cell model. Safranin-O-Fast green (S-O) and hematoxylin-eosin (HE) stainings were used to observe the changes in cartilage morphology. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qPCR) detected the expression of inflammatory cytokines. In addition, molecular mechanisms were analyzed by Western blot in the OA cell model. Results: FSGTC treatment significantly relieved the degeneration of cartilage and reduced the contents of tumor necrosis factor-? (TNF-?) and IL-6 in the serum in papain-induced OA rats. FSGTC also reduced the protein and mRNA levels of IL-6 and IL-8 in IL-1?-stimulated SW982 cells. Moreover, it inhibited the phosphorylation levels of ERK (extracellular signal-related kinase), JNK (c-Jun N-terminal kinase), p38, Akt (protein kinase B), and c-Jun. It also decreased the extent of I?B? degradation and p65 protein translocation into the nucleus. Conclusion: The current data confirmed the protective effects of FSGTC in the rat and OA cell models. The results suggested that FSGTC reduced the production of inflammatory mediators via restraining the activation of mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-?B), activator protein-1 (AP-1), and Akt.

SUBMITTER: Gao YX

PROVIDER: S-EPMC6107711 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Fengshi Gutong Capsule Attenuates Osteoarthritis by Inhibiting MAPK, NF-κB, AP-1, and Akt Pathways.

Gao Yao-Xin YX Yu Hao-Heng HH He Chuan C Li Ming M Guo Dan-Dan DD Lian Jun-Jiang JJ Yang Hai-Jie HJ Wang Mian M Wang Lei L Feng Zhi-Wei ZW Cheng Bin-Feng BF

Frontiers in pharmacology 20180817

<b>Background and purpose:</b> Fengshi Gutong capsule (FSGTC), a traditional herbal formula, has been used clinically in China for the treatment of arthritis. However, the mechanism underlying the therapeutic effects of FSGTC on osteoarthritis (OA) has not been elucidated. The present study investigated the function and mechanisms of FSGTC in rat OA model and interleukin (IL)-1β-stimulated synovial cells. <b>Materials and methods:</b> Rat OA model was established by intra-articular injection con ...[more]

PMID: 30174601

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Project description:BackgroundTo investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development.MethodsTen-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages.ResultsFargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling.ConclusionsThis study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

Dataset Information

Fengshi Gutong Capsule Attenuates Osteoarthritis by Inhibiting MAPK, NF-?B, AP-1, and Akt Pathways.

Publications

Fengshi Gutong Capsule Attenuates Osteoarthritis by Inhibiting MAPK, NF-κB, AP-1, and Akt Pathways.

Similar Datasets

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