背景:旋毛虫病是由于食用未煮熟的肉类而感染动物和人类的公共卫生威胁。它由旋毛虫引起,具有广泛的耐药性,甚至制定了许多复杂的生存策略,这增加了从天然来源寻找新的驱虫药的需求。
方法:我们的目的是测试矢车菊BuOH压裂的体外和体内驱虫活性。,并使用UPLC-ESI-MS/MS表征其化学成分。除了对PreADMET特性进行预测的计算机分子对接研究。
结果:in双歧杆菌BuOH压裂的体外研究。,显示成虫和幼虫的严重破坏,明显的角质层肿胀,有囊泡的区域,气泡和环的损失。这通过体内研究得到了保证,显示平均成虫数量显着降低(P<0.05),功效为47.8%,而每克肌肉的平均幼虫数量显着降低(P<0.001),功效为80.7%。小肠和肌肉切片的组织病理学检查显示出明显改善。此外,免疫组织化学结果表明B.indicaBuOHfrac。抑制促炎细胞因子TNF-α的表达,明显被T.spiralis上调。BuOH压裂的精确化学研究。UPLC-ESI-MS/MS鉴定出13种齐墩果型三萜皂苷;齐墩果酸3-O-6'-O-甲基-β-D-葡糖醛酸-吡喃糖苷(1),四叶皂甙-IVa(2)及其甲酯(3),四叶皂甙IV(4)及其甲酯(5),莫莫丁-Ic(6)及其甲酯(7),betavulgaroside-I(8),-II(9)-IV(10),-X(11),甘草皂苷-C2(12)和-J2(13)。此外,又有6种酚类被鉴定为丁香树脂醇(14),3,4-二-O-咖啡酰基奎尼酸(15),3-O-咖啡酰基-4-O-二氢咖啡酰基奎尼酸(16),3,4-二-O-咖啡酰基奎宁酸丁酯(17),3,5-二-O-没食子酰基-4-O-二没食子酰基奎尼酸(18)和槲皮素3-O-(6'-阿魏酸)-槐苷(19)。使用靶向某些蛋白质受体(β-微管蛋白单体,肿瘤坏死因子α(TNF-α),半胱氨酸蛋白酶(Ts-CF1),钙网蛋白(Ts-CRT),所有对接的化合物(1-19)都符合活性口袋的结合位点,其结合亲和力比阿苯达唑显著。此外,ADMET属性,预测所有化合物的药物评分和药物相似性。
BACKGROUND: Trichinellosis is a public health threat infected both animals and humans as a result of eating undercooked meat. It caused by Trichinella spiralis that has widespread drug resistance and even developed many sophisticated strategies for their survival, this increases the demand in searching for new anthelmintic drugs from natural source.
METHODS: Our objectives were to test the in vitro and in vivo anthelmintic activity of Bassia indica BuOH frac., and to characterize its chemical composition using UPLC-ESI-MS/MS. Besides an in silico molecular docking
study with the prediction of the PreADMET properties.
RESULTS: In vitro investigation of B. indica BuOH frac., showed severe destruction of the adult worm and larvae, marked cuticle swelling, areas with vesicles, blebs and loss of annulations. This was assured via in vivo
study, which revealed a significant reduction (P < 0.05) in the mean adult worm count with efficacy of 47.8% along with a significant decrease (P < 0.001) in the mean larval count per gram muscle with efficacy 80.7%. Histopathological examinations of the small intestine and muscular sections showed marked improvement. In addition, immunohistochemical findings demonstrated that B. indica BuOH frac. depressed the proinflammatory cytokines expressions of TNF-α, which was obviously upregulated by T. spiralis. Precise chemical investigation of the BuOH frac. using UPLC-ESI-MS/MS resulted in the identification of 13 oleanolic type triterpenoid saponins; oleanolic acid 3-O-6´-O-methyl-β-D-glucurono-pyranoside (1), chikusetsusaponin-IVa (2) and its methyl ester (3), chikusetsusaponin IV (4) and its methyl ester (5), momordin-Ic (6) and its methyl ester (7), betavulgaroside-I (8), -II (9) -IV (10), -X (11), licorice-saponin-C2 (12) and -J2 (13). In addition, 6 more phenolics were identified as syringaresinol (14), 3,4-di-O-caffeoylquinic acid (15), 3-O-caffeoyl-4-O-dihydrocaffeoylquinic acid (16), 3,4-di-O-caffeoylquinic acid butyl ester (17), 3,5-di-O-galloyl-4-O-digalloylquinic acid (18) and quercetin 3-O-(6´´-feruloyl)-sophoroside (19). The auspicious anthelmintic activity was further ascertained using in silico molecular docking approach that targeted certain protein receptors (β-tubulin monomer, tumor necrosis factor alpha (TNF-α), cysteine protease (Ts-CF1), calreticulin protein (Ts-CRT)), all the docked compounds (1-19) fit into the binding site of the active pocket with binding affinities noteworthy than albendazole. In addition, ADMET properties, drug score and drug likeness were predicted for all compounds.