Ononin induces cell apoptosis and reduces inflammation in rheumatoid arthritis fibroblast-like synoviocytes by alleviating MAPK and NF-κB signaling pathways

Abstract

As a kind of chronic inflammatory diseases, Rheumatoid arthritis (RA) has a low cure rate and easy recurrence. It has widely reported that abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways are associated with the development of RA inflammation. Blocking the inflammatory signaling pathways of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) can delay the development of RA. Ononin is a natural isoflavone glycoside and plays a key role in modulating inflammation related signaling pathways. However, whether Ononin exerts anti-inflammatory effects on RA inflammation remains unknown. In this study, we evaluated the therapeutic effect of Ononin on RA by establishing a tumor necrosis factor α (TNF-α)-induced RA-FLS cell model. Our data confirmed that Ononin could alleviate TNF-α-induced RA-FLS and MH7A cells viability, increase cell apoptosis, decrease the production of pro-inflammatory cytokines like interleukin-1β (IL-1β) and interleukin 6 (IL-6), and further inhibit the abnormal activation of NF-κB and MAPK pathways. Our results suggested that Ononin could be a potential therapeutic agent for RA.

Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

“…Meng et al. ( 21 ) mentioned that ononin treatment showed effective in vitro antiarthritic activity. Pan et al.…”

Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1β-induced osteoarthritis by downregulating the MAPK and NF-κB pathways

“…Ononin, a natural isoflavone, is widely distributed in Astragalus membranaceus, Glycyrrhiza uralensis, Hedysarum and Pueraria lobata [ 25 , 26 ]. Based on previous studies, ononin has anti-inflammatory and apoptotic effects [ 18 , 27 , 28 ]. In this study, we used IL-1β (10 ng/ml)-induced chondrocytes as an OA model in vitro and hypothesized that ononin mediated inflammation during OA through targets or signalling pathways.…”

“…Recent studies have widely reported that curcumin and resveratrol are potential therapeutic drugs for OA that inhibit the inflammatory response and oxidative stress in chondrocytes [ 31 , 32 ]. Studies have also shown that ononin can protect LPS-induced RF inflammatory cells and RAW 264.7 cells from damage [ 18 , 27 ]. In our study, ononin significantly inhibited the IL-1β-mediated enhancement of the inflammatory factors TNF-α and IL-6 in rat chondrocytes.…”

“…Ononin has a neuroprotective effect on acute cerebral ischaemia through inhibiting autophagy, apoptosis, and inflammation [ 17 ]. Meng et al [ 18 ] confirmed that ononin could alleviate damage in rheumatoid arthritis (RA) by curbing the production of proinflammatory cytokines and inhibiting the NF-κB and MAPK inflammation pathways. These studies showed that ononin has therapeutic effects on inflammatory diseases.…”

Clinical Evidence-Guided Anti-rheumatoid Arthritis Study of Shuji Tablet in Adjuvant-Induced Arthritis Rats and Mechanism Exploration via Network Pharmacological Approach

“…The results of UHPLC-QTOF-MS showed that Betaine, Albflorin, D-Tetrandrine, Ononin, Bergapten, Ligustilide, 3-butyl-1(3H)-Isobenzofuranone, 3-butylidene-1(3H)-Isobenzofuranone, Columbianetin, Levistilide A, Stigmasterol, Glycerin fatty acid ester, Dioctyl phthalate, Rutin, Liquiritin, Quercitrin, Glycyrrhizic acid were the major ingredients in SJT. Among them, D-Tetrandrine ( Li et al, 2018 ), Ononin ( Meng et al, 2021 ), Stigmasterol ( Ahmad et al, 2020 ), Rutin ( Sun et al, 2017 ), Liquiritin ( Zhai et al, 2019 ) were reported to have an anti-RA function in previous research, which suggested that SJT had the potential property of treating RA.…”