苦木总生物碱的化学成分分析及其对大鼠胶原诱导性关节炎的作用

Chemical constituents of total alkaloids from Picrasma quassioides and its effects on collagen induced arthritis in rats

研究苦木总生物碱对大鼠胶原诱导性关节炎的作用。采用酸提碱沉法制备苦木总生物碱(TAPQ),并通过HPLC-Q-TOF-MS/MS对苦木总生物碱进行定性分析,分析得到14个生物碱化合物,并通过HPLC对其中的3个成分进行了定量分析。以地塞米松为阳性对照,考察了苦木总生物碱对脂多糖(LPS)诱导的RAW264.7抗炎活性;并建立牛Ⅱ型胶原诱导性关节炎SD大鼠模型。苦木总生物碱尾静脉注射0.907或1.814 mg/kg,连续给药18 d,记录大鼠足跖肿胀的关节炎分数以及足跖体积变化,相对于模型组,苦木总生物碱能够显著降低给药组大鼠的足跖肿胀程度(P<0.001);大鼠处死后,检测血清中炎症因子的含量,苦木总生物碱能够显著降低给药组大鼠血清TNF-α(P<0.01)和IL-6(P<0.001)的含量;关节组织经HE染色观察病理改变情况,结果表明苦木总生物碱抗炎活性良好,给药组大鼠关节受损程度明显降低。

This study aimed to investigate the effects of total alkaloids from Picrasma quassioides(TAPQ) on collagen-induced arthritis(CIA) in rats.TAPQ were prepared by acid extraction and alkali precipitation.The qualitative analysis of TAPQ by HPLC-Q-TOF-MS/MS was carried out.Fourteen alkaloids were obtained and three of them were quantitatively analyzed by HPLC.The anti-inflammatory activity of TAPQ was investigated on RAW264.7 induced by LPS.Dexamethasone was used as a positive control.The model of bovine type II collagen-induced rheumatoid arthritis in SD rats was established.Daily tail intravenous injection of 0.907 or 1.814 mg/kg of TAPQ was administered for 18 days continuously,using dexamethasone as a positive control.The changes of mean arthritis scores in the paw of the rats and the volume of the paw were measured every day.Compared with the model group,the TAPQ significantly reduced the degree of paw swelling(P<0.001).After the rats were sacrificed,the levels of TNF-α and IL-6 in the serum were measured.The TAPQ could significantly reduce the level of TNF-α(P<0.01) and IL-6(P<0.001).The pathological changes of the joints were observed by HE staining,the anti-inflammatory activity of TAPQ was good,and the degree of joint damage in rats was obviously reduced.