Aminu Suleiman, Ibrahim Mohammed Auwal, Dada Chechet Gloria, Onyike Elewechi
Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria.
Chem Biol Drug Des. 2022 Jun;99(6):908-922. doi: 10.1111/cbdd.14048. Epub 2022 Apr 8.
Trypanosoma congolense is a pathogenic African animal trypanosome species causing devastating conditions leading to death of an infected host. The drawbacks of the existing trypanocidal drugs have led to the search for new drug candidates. In this study, β-ionone at 15 and 30 mg/kg body weight (BW) was orally administered to T. congolense infected rats for 14 days followed by an assessment of anemia, organ damages, and the expression of T. congolense trans-sialidase gene variants. A significant decrease in parasitemia (p < .05) was observed in the animals treated with 15 mg/kg BW β-ionone besides increased animal survival rate. A trypanosome-induced decrease in packed cell volume (PCV) and histopathological changes across tissues was significantly (p < .05) ameliorated following treatment with both doses of β-ionone. This is in addition to reversing the parasite-induced upsurge in free serum sialic acid (FSA) and expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3, and TconTS4). Correlation analysis revealed a positive correlation (p > .05) between FSA with the TconTS gene expressions. In addition, the compound inhibited partially purified T. congolense sialidase and phospholipase A via mixed inhibition pattern with inhibition binding constants of 25.325 and 4.550 µM, respectively, while molecular docking predicted binding energies of -5.6 kcal/mol for both enzymes. In conclusion, treatment with β-ionone suppressed T. congolense proliferation and protected the animals against some of the parasite-induced pathologies whilst the effect on anemia development might be due to inhibition of sialidase and PLA activities as well as the expression levels of TconTS3 and TconTS4.
刚果锥虫是一种致病性非洲动物锥虫物种,会引发严重疾病,导致受感染宿主死亡。现有杀锥虫药物的缺点促使人们寻找新的候选药物。在本研究中,以15和30毫克/千克体重(BW)的剂量给感染刚果锥虫的大鼠口服β-紫罗兰酮,持续14天,随后评估贫血、器官损伤以及刚果锥虫转唾液酸酶基因变体的表达。除了提高动物存活率外,在用15毫克/千克体重β-紫罗兰酮治疗的动物中观察到寄生虫血症显著降低(p < 0.05)。在用两种剂量的β-紫罗兰酮治疗后,锥虫引起的红细胞压积(PCV)降低和各组织的组织病理学变化均得到显著改善(p < 0.05)。这还包括逆转寄生虫引起的游离血清唾液酸(FSA)升高以及刚果锥虫转唾液酸酶基因变体(TconTS1、TconTS3和TconTS4)的表达。相关性分析显示FSA与TconTS基因表达之间存在正相关(p > 0.05)。此外,该化合物通过混合抑制模式部分抑制了纯化的刚果锥虫唾液酸酶和磷脂酶A,抑制结合常数分别为25.325和4.550微摩尔,而分子对接预测这两种酶的结合能均为-5.6千卡/摩尔。总之,用β-紫罗兰酮治疗可抑制刚果锥虫增殖,并保护动物免受一些寄生虫引起的病理影响,而对贫血发展的影响可能是由于抑制了唾液酸酶和PLA活性以及TconTS3和TconTS4的表达水平。