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In vitro and in vivo evaluation of efficacy of berberine chloride: Phyto-alternative approach against Trypanosoma evansi infection
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2023-04-20 , DOI: 10.1016/j.molbiopara.2023.111562
Snehil Gupta 1 , Sukhdeep Vohra 1 , Khushboo Sethi 2 , Ruma Rani 2 , Surbhi Gupta 3 , Sanjay Kumar 2 , Rajender Kumar 2
Affiliation  

Current chemotherapy against the Surra organism, Trypanosoma evansi has several limitations in terms of efficacy, toxicity, availability and emerging resistance. These reasons make the search of new chemo-preventive and chemo-therapeutic agent with high potency and low toxicity. Alkaloid phyto-molecules, berberine has shown promising anti-kinetoplastid activity against T. cruzi, T. congolense, T. brucei, Leishmania donovani and L. tropica. However, till date, there is no investigation of therapeutic efficacy of berberine chloride (BC) against T. evansi. The IC50 value of BC for growth inhibition of T. evansi at 24 h of culture was calculated as 12.15 µM. The specific selectivity index (SSI) of BC was calculated as 19.01 and 10.43 against Vero cell line and Equine PBMC’s, respectively. Thirteen drug target genes affecting various metabolic pathways were studied to investigate the mode of trypanocidal action of BC. In transcript analysis, the mRNA expression of arginine kinase 1 remained refractory to exposure with BC, which provides metabolic plasticity in adverse environmental conditions. In contrary, rest all the drug target gene were down-regulated, which indicates that drug severely affect DNA replication, cell proliferation, energy homeostasis, redox homeostasis and calcium homeostasis of T. evansi, leading to the death of parasite in low concentrations. It is the first attempt to investigate in vitro anti-trypanosomal activity of BC against T. evansi. These data imply that phytochemicals as alternative strategies can be explored in the future as an alternative treatment for Surra in animal.



中文翻译:

氯化小檗碱功效的体外和体内评价:植物替代方法对抗伊氏锥虫感染

目前针对Surra生物体伊氏锥虫的化学疗法在功效、毒性、可用性和新出现的耐药性方面存在一些局限性。这些原因促使人们寻找新的高效低毒的化疗预防和化疗药物。生物碱植物分子,小檗碱已显示出对T. cruziT. congolenseT. bruceiLeishmania donovaniL. tropica有前景的抗动质体活性。然而,迄今为止,还没有关于氯化小檗碱 (BC) 对伊万丝虫的治疗效果的研究。BC 抑制生长的IC 50值T. evansi在 24 小时的文化中被计算为 12.15 µM。BC 针对 Vero 细胞系和马 PBMC 的特异性选择性指数 (SSI) 分别计算为 19.01 和 10.43。研究了影响各种代谢途径的十三个药物靶基因,以研究 BC 的锥虫杀作用模式。在转录本分析中,精氨酸激酶 1 的 mRNA 表达仍然难以暴露于 BC,这在不利的环境条件下提供了代谢可塑性。相反,其余所有药物靶基因均被下调,这表明药物严重影响伊氏木霉的DNA复制、细胞增殖、能量稳态、氧化还原稳态和钙稳态, 导致寄生虫在低浓度下死亡。这是首次尝试研究BC 对伊氏锥虫的体外抗锥虫活性这些数据意味着未来可以探索植物化学物质作为替代策略,作为动物Surra的替代疗法。

更新日期:2023-04-23
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