β-Elemene induces apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes via reactive oxygen species-dependent activation of p38 mitogen-activated protein kinase

Zou, Shibo; Wang, Changyin; Cui, Zhengjun; Guo, Pengfei; Meng, Qingnan; Shi, Xun; Gao, Ya; Yang, Gaoyuan; Han, Zhaofeng

doi:10.1016/j.pharep.2015.06.004

Cited by 52 publications

(33 citation statements)

References 30 publications

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“…have reported that p38 MAPK can be activated by serum amyloid A, which is highly expressed in autoimmune disease, to be involved in the angiogenic process of RA. Meanwhile, Zou et al . has reported that activated p38 MAPK can induce β‐elemene to induce mitochondrial apoptosis of RA fibroblast‐like synoviocytes.…”

Section: Discussionmentioning

confidence: 99%

Identifying key genes in rheumatoid arthritis by weighted gene co‐expression network analysis

Lv²,

Teng

et al. 2017

Int J of Rheum Dis

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Section: Discussionmentioning

confidence: 99%

Identifying key genes in rheumatoid arthritis by weighted gene co‐expression network analysis

Lv²,

Teng

et al. 2017

Int J of Rheum Dis

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“…[110]. β-Elemene (30) is a known natural sesquiterpene compound, treatment with β-Elemene (10-200 µg/mL) can improve the phosphorylation level of p38 and promote cell apoptosis in RA-FLS, and p38 inhibitors can significantly reverse the pro-apoptotic effect of β-Elemene, consequently these results suggested that the MAPK pathway is closely involved in the pro-apoptotic effects of β-Elemene on RA-FLS [111].…”

Section: Mapk Mediated Apoptotic Pathwaymentioning

confidence: 91%

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

et al. 2019

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Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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“…HFLSs participate in the development and progression of RA by producing cytokines and proteases that contribute to cartilage destruction (18). Apoptosis of HFLSs is currently considered as a potential therapeutic target for RA (19,20). Our study observed that IL-17 inhibited HFLSs apoptosis, while lncRNA CASC2 promoted HFLSs apoptosis by inhibiting IL-17.…”

Section: Discussionmentioning

confidence: 57%

lncRNA CASC2 downregulation participates in rheumatoid arthritis, and CASC2 overexpression promotes the apoptosis of fibroblast‑like synoviocytes by downregulating IL‑17

et al. 2020

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lncrna cancer susceptibility candidate 2 (caSc2) is a recently identified oncogenic lncRNA in different types of cancers. Our preliminary microarray data showed that lncRNA CASC2 was downregulated in the plasma of patients with rheumatoid arthritis (RA), indicating the involvement of this lncRNA in RA. In the present study, lncRNA CASC2 and IL-17 in plasma were detected by reverse transcription-quantitative PCR and ELISA, respectively. Diagnostic analyses were performed using receiver operating characteristic curves. Flow cytometry was performed to evaluate cell apoptosis. The effects of lncRNA CASC2 on IL-17 expression were determined via western blotting. lncRNA CASC2 was found to be downregulated, while IL-17 was upregulated in the plasma of RA patients when compared with these levels in the plasma of healthy controls. Plasma levels of lncRNA CASC2 and IL-17 were significantly and inversely correlated in both RA patients and healthy controls. Altered plasma levels of lncRNA CASC2 and IL-17 were able to differentiate RA patients from healthy controls. Overexpression of lncRNA CASC2 promoted, while treatment with IL-17 inhibited the apoptosis of human fibroblast-like synoviocytes (HFLSs) isolated from RA patients. Overexpression of lncRNA CASC2 inhibited IL-17 expression in HFLS, while treatment with IL-17 did not significantly affect the expression of lncRNA CASC2. Therefore, downregulation of lncRNA CASC2 is involved in RA and lncRNA CASC2 overexpression may promote the apoptosis of HFLS by downregulating IL-17.

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β-Elemene induces apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes via reactive oxygen species-dependent activation of p38 mitogen-activated protein kinase

Abstract: Taken together, β-elemene is effective in inducing mitochondrial apoptosis of RA-FLS, which is mediated through induction of ROS formation and p38 MAPK activation. β-Elemene may thus have therapeutic benefits for RA.

Cited by 52 publications

References 30 publications

Identifying key genes in rheumatoid arthritis by weighted gene co‐expression network analysis

Identifying key genes in rheumatoid arthritis by weighted gene co‐expression network analysis

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

lncRNA CASC2 downregulation participates in rheumatoid arthritis, and CASC2 overexpression promotes the apoptosis of fibroblast‑like synoviocytes by downregulating IL‑17

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