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()对乙酰氨基酚诱导的小鼠肝毒性的保护作用:通过分子对接方法研究和表征生物活性化合物。

Hepatoprotective Activity of () on Acetaminophen-Induced Toxicity in Mice: Study and Characterization of Bioactive Compounds through Molecular Docking Approaches.

机构信息

Laboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454 Ngaoundere, Cameroon.

Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaounde I, P.O. Box 812 Yaounde, Cameroon.

出版信息

Biomed Res Int. 2020 Aug 31;2020:3807234. doi: 10.1155/2020/3807234. eCollection 2020.

Abstract

MATERIALS AND METHODS

Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME.

RESULTS

APAP administration significantly increased ( < 0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly ( < 0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels ( < 0.05) and increased those of GSH, SOD, and CAT ( < 0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant ( < 0.001) decrease of TNF levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNF, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase.

CONCLUSION

Based on these results, could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties.

摘要

材料与方法

从该植物中提取了各种水提取物,并在 APAP 给药前 3 小时经口给予白化病小鼠,每天一次,共一周。正常组动物仅给予蒸馏水,而阴性对照组仅给予 APAP 250mg/kg。治疗后,处死小鼠,收集肝脏进行组织病理学分析,并测量不同的生化标志物(丙氨酸氨基转移酶(ALT)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、丙二醛(MDA)和肿瘤坏死因子-α(TNF))。采用 HPLC/UV 分析提取物的含量。采用 iGEMDOCK 软件进行分子对接,采用 Swiss ADME 评价药物相似性和药代动力学特征。

结果

与正常对照组相比,APAP 给药后显著增加(<0.001)肝匀浆中 ALT,而 250mg/kg 的茎煎剂可显著(<0.001)降低该活性,使其恢复至与 50mg/kg 的水飞蓟素相当的正常水平,优于叶和根提取物。此外,与阴性对照组相比,250 和 500mg/kg 的茎煎剂还可显著降低 MDA 水平(<0.05),并增加 GSH、SOD 和 CAT 水平(<0.001)。该提取物治疗后可观察到 TNF 水平和白细胞浸润显著降低。煎剂的 HPLC/UV 分析显示,存在二羟香豆素、奎宁和东莨菪内酯,保留时间分别为 2.6、5.1 和 7.01min。研究表明,奎宁和二羟香豆素具有成为口服药物的巨大潜力,并且与 TNF、TNF 受体、环氧化酶-2、诱导型一氧化氮合酶、细胞色素 P450 2E1 和谷胱甘肽还原酶具有很强的结合亲和力。

结论

基于这些结果,可认为该植物是具有抗氧化和抗炎特性的有前途的肝保护化合物的来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/7482022/118400cf749f/BMRI2020-3807234.001.jpg

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