Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway

Yao, Minjun; Zhang, Caihua; Ni, Lingzhi; Ji, Xiaoxiao; Hong, Jianqiao; Chen, Yazhou; Wang, Jie; Li, Congsun; Lin, Jiyan; Lu, Tingting; Sheng, Yihao; Sun, Menghao; Shi, Mude; Zhou, Chenhe; Cai, Xun-Zi

doi:10.3389/fphar.2022.854239

Cited by 10 publications

(5 citation statements)

References 64 publications

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“…In addition, for assessment of the NF-κB signalling pathway, chondrocytes were pretreated with 10 nM or 25 nM of omaveloxolone for 2 h and then incubated with 10 ng/ml IL-1β for another 1 h ( Xian et al, 2022 ; Yao et al, 2022 ). The results of Western blotting analysis showed that 10 and 25 nM of omaveloxolone reduced the p-P65/P65 and p-IκBα/IκBα ratio, indicating that omaveloxolone could suppress the NF-κB signalling pathway in chondrocytes exposed to IL-1β ( Figure 5J -L).…”

Section: Resultsmentioning

confidence: 99%

Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo

Jiang

Lü

et al. 2022

Front. Pharmacol.

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Osteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects. The present study aims to determine whether omaveloxolone has a therapeutic effect on OA. Chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model in vitro. Indicators of cell viability, oxidative stress, inflammation, cell apoptosis and extracellular matrix (ECM) degradation were investigated. Proteins related to the Nuclear factor erythroid derived-2-related factor 2 (Nrf2)/antioxidant response element (ARE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways were assessed using Western blotting. A destabilized medial meniscus surgery-induced OA rat model was used in vivo. Gait analysis, microcomputed tomography analysis, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of omaveloxolone on attenuating osteoarthritis in vivo. The results showed that omaveloxolone exerts antioxidative, anti-inflammatory, antiapoptotic and anti-ECM degradation effects via activation of the Nrf2/ARE signalling pathway and inhibition of the NF-κB signalling pathway in chondrocytes in vitro and attenuates OA progression in vivo, suggesting that omaveloxolone may be a potential therapeutic agent for OA.

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Section: Resultsmentioning

confidence: 99%

Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo

Jiang

Lü

et al. 2022

Front. Pharmacol.

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“…Concurrently, the anti-inflammatory property of CEP enables its use in the treatment of cerebral ischemia/reperfusion injury, wherein CEP inhibits NLRP3 signaling, and caspase-1, thereby suppressing the overproduction of IL-1β and IL-18, thus attenuating cerebral ischemia/reperfusion injury [ 44 ]. Moreover, CEP ameliorates chondrocytic inflammation and osteoarthritis by regulating the MAPK/NF-κB-autophagy pathway [ 45 ]. CEP also inhibited NF-κB activation, IκBα degradation, and ERK, JNK, and p38 phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells in vitro and lipopolysaccharide-induced lung injury model in a dose-dependent manner [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

Chen¹,

Li²,

Liu³

et al. 2023

Molecules

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Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.

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“…TNF, IL-1β, IL-6, and IL-15 are cytokines related to inflammation, and NF-κB, MAPK, and AMPK are common signal pathways to induce the inflammatory response. Some studies have found that regulating NF-κB/SIRT1/AMPK and MAPK/NF-κB signaling pathways can affect the inflammatory response and ultimately affect the pathological process of OA ( 35 ) ( 36 ). In addition, Hypoxia can also aggravate inflammatory reaction by affecting macrophages, T cells and neutrophils ( 37 ).…”

Section: Mechanism Of Pathological Changes In Osteoarthritismentioning

confidence: 99%

Mechanism of HIFs in osteoarthritis

Zhang

Kong

2023

Front. Immunol.

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Osteoarthritis (OA) is a common disabling disease which has a high incidence rate in the elderly. Studies have found that many factors are involved in the pathogenesis of OA. Hypoxia-inducible factors (HIFs) are core regulators that induce hypoxia genes, repair the cellular oxygen environment, and play an important role in the treatment of OA. For example, HIF-1α can maintain the stability of the articular cartilage matrix, HIF-2α is able to cause chondrocyte apoptosis and intensify in-flammatory response, and HIF-3α may be the target gene of HIF-1α and HIF-2α, thereby playing a negative regulatory role. This review examines the mechanism of HIFs in cartilage extracellular matrix degradation, apoptosis, inflammatory reaction, autophagy and then further expounds on the roles of HIFs in OA, consequently providing theoretical support for the pathogenesis of OA and a new target for OA treatment.

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Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis via Regulating the MAPK/NF-κB-Autophagy Pathway

Cited by 10 publications

References 64 publications

Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo

Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

Mechanism of HIFs in osteoarthritis

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