Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan.
Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman.
J Ethnopharmacol. 2020 Apr 24;252:112558. doi: 10.1016/j.jep.2020.112558. Epub 2020 Jan 9.
Drug induced liver damage remains a prevalent concern in healthcare and may reduce the effectiveness of therapy by compromising therapeutic regimens. Many Commiphora species are known for their medicinal properties, and some of them are used traditionally for hepatoprotective effect. In the course of our drugs discovery from natural sources, phytosterols (lophenol (Lop) and lathosterol (Lat)), isolated from Commiphora kua were studied to evaluate their hepatoprotective effects in acetaminophen (APAP) induced hepatotoxicity in mice.
To evaluate the hepatoprotective effects of phytosterols isolated from C. kua using in vivo experimental model.
Mice of either sex were divided into 7 groups: Vehicle, silymarin (SLY), acetaminophen (APAP), Lop 25, Lop 50, Lat 25, Lat 50 (n = 5). Vehicle group received only vehicle (0.1% DMSO solution) for 7 days, APAP group received single dose of acetaminophen on day 7 and SLY group received silymarin for 7 days. Lop 25 and Lop 50 received low and high doses of Lop (25 μg/kg BW and 50 μg/kg BW), respectively, for 7 days, while Lat 25 and Lat 50 received low and high doses of Lat (25 μg/kg BW and 50 μg/kg BW) for 7 days. On day 7, all animals except Vehicle group kept fasted for 18 h and received APAP i. p. 400 mg/kg BW. After 20 h of APAP administration, the animals anesthetized with light chloroform and scarified by cervical decapitation. The blood serum and liver tissue samples were collected for biochemical and histopathological analysis. Liver function tests (LFTs) including lactate deydrogenase (LDH), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and direct bilirubin) were used as biochemical parameters. While catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) were taken as anti-oxidant enzymes.
Significant increase in levels of ALT, AST, ALP, LDH and direct bilirubin, and significant decrease in concentration of anti-oxidant enzymes (SOD, CAT and GSH) was observed in APAP-treated group. Similarly, histological slides showed obvious signs of damage to liver cells, reflecting acetaminophen induced hepatotoxicity. Treatment of test animals with phytosterols resulted in significant recovery of LFTs profile and concentration of anti-oxidant enzymes. Similarly, significant improvement of liver tissues was noted in histological analysis.
Both phytosterols possessed hepatoprotective potential and should be further evaluated for acute toxicity studies and pharmacokinetics/pharmacodynamics profile.
药物性肝损伤仍然是医疗保健中的一个普遍关注问题，可能会通过损害治疗方案来降低治疗效果。许多角茴香属植物因其药用特性而闻名，其中一些传统上用于保护肝脏。在我们从天然来源发现药物的过程中，从角茴香属植物中分离出的植物甾醇（lophenol（Lop）和麦角甾醇（Lat））被研究用于评估它们在对乙酰氨基酚（APAP）诱导的小鼠肝毒性中的保肝作用。
使用体内实验模型评估从 C.kua 中分离出的植物甾醇的保肝作用。
将雌雄小鼠分为 7 组：载体、水飞蓟素（SLY）、对乙酰氨基酚（APAP）、lop 25、lop 50、lat 25、lat 50（n=5）。载体组仅给予载体（0.1% DMSO 溶液）7 天，APAP 组第 7 天给予单次对乙酰氨基酚，SLY 组给予水飞蓟素 7 天。lop 25 和 lop 50 分别给予低剂量和高剂量 lop（25μg/kg BW 和 50μg/kg BW）7 天，而 lat 25 和 lat 50 分别给予低剂量和高剂量 lat（25μg/kg BW 和 50μg/kg BW）7 天。第 7 天，除载体组外，所有动物禁食 18 小时，并腹腔内给予 400mg/kg BW 的对乙酰氨基酚。给予对乙酰氨基酚 20 小时后，动物用轻氯仿麻醉并断头处死。收集血清和肝组织样本进行生化和组织病理学分析。肝功能试验（LFTs）包括乳酸脱氢酶（LDH）、碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和直接胆红素，作为生化参数。而过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）被用作抗氧化酶。
APAP 处理组的 ALT、AST、ALP、LDH 和直接胆红素水平显著升高，抗氧化酶（SOD、CAT 和 GSH）浓度显著降低。同样，组织学切片显示肝细胞明显受损，反映出对乙酰氨基酚诱导的肝毒性。用植物甾醇治疗实验动物可显著恢复 LFT 谱和抗氧化酶浓度。同样，在组织学分析中也观察到肝脏组织的显著改善。
两种植物甾醇均具有保肝潜力，应进一步评估其急性毒性研究和药代动力学/药效学特征。
