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齐墩果酸通过抑制 P13K/AKT 信号通路对Ⅱ型胶原诱导的关节炎大鼠的保护作用。

Protective effect of lupeol on arthritis induced by type II collagen via the suppression of P13K/AKT signaling pathway in Sprague dawley rats.

机构信息

Department of Orthopaedic Trauma Joint Ward 1, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, China.

Department of Surgery, People's Liberation Army, Xi'an, China.

出版信息

Environ Toxicol. 2022 Jul;37(7):1814-1822. doi: 10.1002/tox.23529. Epub 2022 Apr 21.

Abstract

To explore the therapeutic value of lupeol on collagen-induced arthritis (CIA) in rats, a rheumatoid arthritis model. Lupeol is well known pentacyclic triterpene found in various plant sources, which possess anti-inflammatory and antioxidant actions. The current study was assessed the anti-arthritic potential of lupeol and its molecular mechanisms as compared with indomethacin (Indo) in collagen-induced arthritis CIA rats. The rats were randomly alienated into five groups: Control, CIA alone, CIA + lupeol (10 mg/kg bw), CIA + Indomethacin (3 mg/kg bw), and lupeol (10 mg/kg bw) alone. The paw volume, biochemical, hematological parameters, inflammatory enzymes, and cytokines were measured. As well protein expression of apoptotic proteins, and histopathological of ankle joint were examined. Inflammatory markers, cytokines, histological changes, paw volume, and inflammation were intensely reduced and enhanced apoptosis by lupeol. Alterations in hematological parameters, rheumatoid factor, C-reactive protein, and ceruloplasmin in arthritis were reverted by lupeol. Protein expressions of Bcl-2, and P13K/Akt signaling were declined, whereas the Bax, caspssae-3, and caspase-9 were elevated. These results highlighted that lupeol suppresses P13K/Akt signaling and has a promising anti-arthritic potential for collagen-induced rheumatic arthritis treatment. Hence lupeol would be suggested as an alternative natural source with potent anti-inflammatory and apoptotic actions for chronic inflammatory disorders.

摘要

为了探索羽扇豆醇(lupeol)对胶原诱导性关节炎(CIA)大鼠模型(一种类风湿关节炎模型)的治疗价值,我们评估了羽扇豆醇与吲哚美辛(Indo)在胶原诱导性关节炎 CIA 大鼠中的抗关节炎潜力及其分子机制。将大鼠随机分为五组:对照组、CIA 组、CIA+lupeol(10mg/kg bw)组、CIA+Indo(3mg/kg bw)组和 lupeol(10mg/kg bw)组。测量爪体积、生化、血液学参数、炎症酶和细胞因子。还检查了踝关节的凋亡蛋白和组织病理学的蛋白表达。羽扇豆醇强烈减少了炎症标志物、细胞因子、组织学变化、爪体积和炎症,增强了细胞凋亡。关节炎中血液学参数、类风湿因子、C 反应蛋白和铜蓝蛋白的改变被 lupeol 逆转。Bcl-2 和 P13K/Akt 信号的蛋白表达下降,而 Bax、caspase-3 和 caspase-9 则升高。这些结果表明,lupeol 抑制了 P13K/Akt 信号通路,具有治疗胶原诱导性风湿性关节炎的潜在的抗关节炎作用。因此,lupeol 可能被建议作为一种具有强大抗炎和促凋亡作用的替代天然来源,用于治疗慢性炎症性疾病。

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