Crude triterpenoid saponins from Anemone flaccida (Di Wu) exert anti-arthritic effects on type II collagen-induced arthritis in rats.
Crude triterpenoid saponins from Anemone flaccida (Di Wu) exert anti-arthritic effects on type II collagen-induced arthritis in rats.
复制标题
地乌粗三萜皂苷对 II 型胶原诱导的大鼠关节炎具有抗关节炎作用
DOI：
10.1186/s13020-015-0052-y
复制
发表时间：
2015
期刊：
影响因子：
4.9
通讯作者：
Ye WC
中科院分区：
文献类型：
--
作者：
Liu Q;Zhu XZ;Feng RB;Liu Z;Wang GY;Guan XF;Ou GM;Li YL;Wang Y;Li MM;Ye WC
摘要背景黄花银莲花
。施密特(Ranunculaceae)用于治疗打击伤和类风湿性关节炎(RA)。然而，黄曲霉抗关节炎作用的活性成分和潜在的作用机制尚不清楚。本研究采用II型胶原(CII)诱导的大鼠关节炎(CIA)模型，研究黄花三萜皂苷(AFS)对类风湿关节炎(RA)的作用机制，并评价AFS的主要活性成分，即黄花皂苷II、安息香皂苷E、皂苷ST-I4a、牛血藤总皂苷B、长春花皂苷B、白花蛇舌草总皂苷B、白花蛇床子皂苷B、白花蛇舌草总皂苷B、白花蛇舌草总皂苷B的抗炎作用。和3-O-α-L-鼠李糖基(1-→-2)-β-d-吡喃葡萄糖齐墩果酸28-O-β-d-吡喃葡萄糖基(1-→-6)-β-d-吡喃葡萄糖酯。造模后灌胃给予AFS(200或400 mg/kg)和地塞米松30天。用体积计测量足爪体积来评估关节炎的严重程度。治疗30天后，取大鼠右后爪。用苏木精-伊红染色进行组织学分析，用微型计算机断层扫描进行放射成像。采用四甲基偶氮唑盐比色法检测AFS及其主要化合物对RAW264.7细胞的细胞毒作用。采用酶联免疫吸附测定试剂盒检测不同剂量黄花总皂苷及其主要成分对脂多糖刺激的RAW264.7细胞血清和培养上清液中白介素6、肿瘤坏死因子-α的影响。放射学和组织学检查表明，AFS治疗后炎症反应减轻。此外，与未治疗大鼠相比，AFS 200和400 mg/kg/d治疗组大鼠血清肿瘤坏死因子-α(P=0.001和P<0.01)和IL-6(P=0.0058和P=0.0087)均显著降低。黄连总皂甙及其主要成分白花蛇舌草总皂苷B、白花蛇舌草苷II和血藤总皂苷B分别显著抑制脂多糖诱导的RAW264.7细胞产生肿瘤坏死因子-α(P=0.0022，P=0.013，P=0.0015，P=0.016)和IL-6(P=0.0175，P=0.001，P=0.001，P=0.001)。
AbstractBackgroundAnemone flaccida Fr
. Schmidt (Ranunculaceae) (Di Wu in Chinese) is used to treat punch injury and rheumatoid arthritis (RA). However, the active compounds and underlying mechanism of action mediating the anti-arthritic effects of A. flaccida remain unclear. This study aims to evaluate the underlying action mechanism of A. flaccida crude triterpenoid saponins (AFS) on RA using a type II collagen (CII)-induced arthritis (CIA) rat model, and to assess the anti-inflammatory effects of the main active compounds of AFS, namely flaccidoside II, anhuienoside E, glycoside St-I4a, hemsgiganoside B, hederasaponin B, and 3-O-α-l-rhamnopyranosyl (1 → 2)-β-d-glucopyranosyl oleanolic acid 28-O-β-d-glucopyranosyl (1 → 6)-β-d-glucopyranosyl ester.MethodsMale Wistar rats (n = 50) were randomly separated into five groups (n = 10) and immunized by CII injection. AFS (200 or 400 mg/kg) and dexamethasone were orally administered for 30 days after establishing the model. The arthritis severity was assessed by paw volume using a plethysmometer. After 30 days of treatment, the right hind paws of the rats were obtained. Paw histology was analyzed by hematoxylin and eosin staining, and radiologic imaging was performed by micro-computed tomography. MTT assays were used to evaluate the cytotoxicity of AFS and its main compounds in RAW264.7 cells. Enzyme-linked immunosorbent assay kits were used to measure interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum and supernatants from AFS- and main AFS compound-treated RAW264.7 cells stimulated by lipopolysaccharide (LPS).ResultsAnemone flaccida crude triterpenoid saponins inhibited redness and swelling of the right hind paw in the CIA model. Radiological and histological examinations indicated that inflammatory responses were reduced by AFS treatment. Moreover, comparing with untreated rats, serum TNF-α (P = 0.0035 and P < 0.001) and IL-6 (P = 0.0058 and P = 0.0087) were lower in AFS-treated CIA rats at the dose of 200 and 400 mg/kg/day. AFS and its main compounds, including hederasaponin B, flaccidoside II, and hemsgiganoside B, significantly inhibited TNF-α (P = 0.0022, P = 0.013, P = 0.0015, and P = 0.016) and IL-6 (P = 0.0175, P < 0.001, P < 0.001, and P < 0.001) production in LPS-treated RAW264.7 cells, respectively.Conclusions