Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication <i>via</i> Inflammation and Fibrosis Inhibition in Mice

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease with increased cardiovascular disease risk. Liquiritigenin (LG) is a triterpene with anti-inflammatory properties. Our study aimed to explore the effect of LG on RA and the cardiac complication. Collagen-induced arthritis (CIA) mice with LG treatment exhibited obvious alleviation in histopathological changes, accompanied by the decreased expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A in synovium and serum. LG attenuated cartilage destruction by reducing matrix metalloproteinase (MMP)-3 and MMP-13 expression in the synovium of CIA mice. The echocardiography results proved the alleviation of cardiac dysfunction in CIA mice. The electrocardiogram, biochemical, and histochemical analysis proved the cardioprotection effect of LG against RA. The decreased expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and fibrotic markers (fibronectin, Collagen I, and Collagen III) in cardiac tissues of CIA mice further corroborated the attenuation of myocardial inflammation and fibrosis by LG. Mechanistic studies showed that LG could inhibit transforming growth factor β-1 (TGF-β1) and phos-Smad2/3 expression in cardiac tissues of CIA mice. Our study suggested that LG could relieve RA and its cardiac complication probably by inhibiting the TGF-β1/Smad2/3 pathway. All these suggested that LG might be a potential candidate for RA and its cardiac complication therapy.

Therapeutic potential of Coptis chinensis for arthritis with underlying mechanisms

“…However, the types of arthritis treated with these targets are not completely clear. Targets, β2-adrenergic receptor (ADRB2), AHR, CRP, IRF1, prostaglandin G/H synthase 1 (PTGS1), SPP1 and other targets, exert key effects in the pathogenesis of arthritis, but role of them in the treatment of arthritis with CC has not been confirmed ( Table 3 ) ( Xu et al, 2004 ; Koskela et al, 2012 ; Ko et al, 2013 ; Li et al, 2013 ; Xue et al, 2014 ; Song et al, 2016 ; Trzybulska et al, 2018 ; Bonelli et al, 2019 ; Chu et al, 2019 ; Lin et al, 2019 ; Sun et al, 2020 ; Orecchini et al, 2020 ; Yang et al, 2020 ; Nalesso et al, 2021 ; Tang et al, 2021 ; Xu and Xu, 2021 ; Zou et al, 2021 ; Balasundaram et al, 2022 ; Cai et al, 2022 ; Liu et al, 2022 ; Wang et al, 2022 ; Zhang et al, 2022 ; Zhang et al, 2022 ; Han et al, 2022 ; Man et al, 2022 ; Nguyen et al, 2022 ; Qian et al, 2022 ; Tavallaee et al, 2022 ; Zhuang et al, 2022 ; Afnan et al, 2023 ; Baggio et al, 2023 ; Sun et al, 2023b ; Zhou et al, 2023 ; Fan et al, 2023 ; Huang et al, 2023 ; Ning et al, 2023 ; Qin et al, 2023 ; Skougaard et al, 2023 ; Tu et al, 2023 ; Xie et al, 2023 ; Yan et al, 2023 ; Yu et al, 2023 ; Zhao et al, 2023 ). We have elaborated on the role of targets such as MMP-3, IL-1β, MAPK, IL-6, ADRB2, AHR, CRP, CAV1, CXCL2, SPP1 and other targets in treating arthritis, explored the potential targets and mechanisms of CC in treating arthritis, analyzed the feasibility of CC as an anti-arthritis drug, and provided a theoretical basis for subsequent research.…”

“…However, the types of arthritis treated with these targets are not completely clear. Targets, β2adrenergic receptor (ADRB2), AHR, CRP, IRF1, prostaglandin G/H synthase 1 (PTGS1), SPP1 and other targets, exert key effects in the pathogenesis of arthritis, but role of them in the treatment of arthritis with CC has not been confirmed (Table 3) (Xu et al, 2004;Koskela et al, 2012;Ko et al, 2013;Li et al, 2013;Xue et al, 2014;Song et al, 2016;Trzybulska et al, 2018;Bonelli et al, 2019;Chu et al, 2019;Lin et al, 2019;Sun et al, 2020;Orecchini et al, 2020;Yang et al, 2020;Nalesso et al, 2021;Tang et al, 2021;Zou et al, 2021;Balasundaram et al, 2022;Cai et al, 2022;Liu et al, 2022;Zhang et al, 2022;Zhang et al, 2022;Han et al, 2022;Man et al, 2022;Nguyen et al, 2022;Qian et al, 2022;Tavallaee et al, 2022;Zhuang et al, 2022;Afnan et al, 2023;Baggio et al, 2023;Sun et al, 2023b;Zhou et al, 2023;Fan et al, 2023;Huang et al, 2023;Ning et al, 2023;Qin et al, 2023;Skougaard et al, 2023;Tu et al, 2023;Xie et al, 2023;…”