关键词: Aluminium-chloride-induced-hepatotoxicity BALB/c mice In-silico M. acuminata peels Pharmacokinetic Therapeutic-potential

来  源:   DOI:10.1007/s40203-024-00216-1   PDF(Pubmed)

Abstract:
East Africa (Musa spp.), notably Musa acuminata, \"Matooke\" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds\' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker\'s function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells\' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE\'s chronic or intermittent use to ascertain its safety in whole organism systems.
摘要:
东非(Musaspp。),尤其是Musaacuminata,“Matooke”是该地区的主食和经济上重要的食物。这里,研究了12种选定的M.acuminata果皮提取物(MAPE)生物活性化合物在成年BALB/c小鼠中氯化铝诱导的肝毒性中的肝保护潜力。GC-MS分析用于鉴定MAPE的活性成分。在药代动力学的计算机模拟估计中,将GCMS鉴定的化合物的毒性谱和分子对接与标准(辛伐他汀)药物进行比较。使用MAPE处理的氯化铝诱导肝毒性,随后进行生化和组织病理学检查。12种生物活性化合物2,2-二氯苯乙酮(72870),环辛硅氧烷18993663),7-羟基-6,9a-二甲基-3-亚甲基-十氢-偶氮并[4,5-b]呋喃-2,9-二酮(534579),全反式-α-胡萝卜素(4369188),环硅氧烷(53438479),3-氯-5-(4-甲氧基苯基)-6,7a-二甲基-5,6,7,7a-四氢-4H-呋喃并[2,3-c]吡啶-2-酮(536708),新戊酸(6417),10,13-十八碳二烯酸(54284936),亚油酸乙酯(5282184),油酸(5363269),Tirucalol(101257),通过GC-MS鉴定了obtusifoliol(65252)。其中,七个成功地与靶蛋白对接。该化合物具有不抑制CYP450同工型生物转化的药物相似性潜力。所有对接的化合物都对AMES毒性具有化学保护作用,hERGI,hERGII和肝毒性。动物模型揭示了MAPE对肝脏标志物功能的保护作用,而组织学研究表明,胆管迷失方向层的再生并改善了AlCl3诱导的肝细胞的细胞/组织结构。结果表明,MAPE改善了AlCl3诱导的肝功能,改善了肝细胞的细胞或组织结构。需要进一步的研究来阐明MAPE的慢性或间歇性使用的机制作用和毒理学评估,以确定其在整个生物体系统中的安全性。
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