Asanga Edet Effiong, Noah Kufre Uyo, Okokon Jude Efiom, Ekeleme Chinedum Martins, Udoh Imaobong Etima, Bassey Augustine, Anagboso Martin Osita, Inyang Aniekeme Ndisa
Department of Biochemistry, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria.
Department of Pharmacology and Toxicology, University of Uyo, Uyo, Akwa Ibom State, Nigeria.
BMC Complement Med Ther. 2025 Jun 4;25(1):200. doi: 10.1186/s12906-025-04941-8.
Hippocratea africana root is scientifically used in cardiotoxicity treatment; therefore, this study was designed to validate this claims through the evaluation of its cardioprotective activity, isolation, and characterization of its constituents, as well as in silico profiling of these ligands against antioxidant enzymes.
Standard protocols were followed in the extraction, fractionation, isolation, characterization, evaluation of cardio-protective activity (marker enzymes, oxidative stress markers, and histological section), retrieval of target proteins (SOD, CAT, GPx, and GSH), ADMET, and docking studies. Column and thin layer chromatography as well as GC/MS aided the isolation and characterization of compounds; SWISSADME and ADMET lab 2 enhanced the evaluation of pharmacokinetic properties; PyRx for docking analysis; Biovia discovery studio and PyMol software for 2D and 3D visualization of the ligand-protein interactions.
The root extract administration significantly (p < 0.05) reduced the serum levels of CK-MB, LDH, and troponin I that were elevated after doxorubicin administration; however, the levels of GSH, GST, SOD, GPx, and CAT that were decreased after doxorubicin administration were significantly (p < 0.05) elevated whereas the raised MDA level was reduced after treatment with the extract and fractions of the plant. Also, the histological sections in the extract-treated rats showed reductions in pathological features as compared with the negative control group. Moreover, the chemical pathological changes were consistent with histopathological observations suggesting marked cardio-protective potentials. Furthermore, the chromatographic analyses yielded bulked fractions {D3 (11 mg), E6 (25 mg), and E8 (21 mg)} and their GC/MS analyses revealed dihydroartemisinin; retinoic acid, methyl ester; α-thujene; α-terpinolene; 9,12,15-octadecatrienal; α-terpineol etc. with already reported antioxidant activities. These ligands (dihydroartemisinin; retinoic acid, methyl ester) obeyed Lipinski's criteria, had remarkable pharmacokinetic profiles, and their docking analyses revealed that they modulated antioxidant enzymes with better binding affinities than vitamin C.
Given the demonstrated antidotal and cardioprotective properties of the plant root, it presents a promising candidate for mitigating doxorubicin-induced toxicities and could be effectively utilized as a supportive therapy in such contexts.
非洲希波克拉底树的根在科学上被用于心脏毒性治疗；因此，本研究旨在通过评估其心脏保护活性、成分的分离与表征以及这些配体针对抗氧化酶的计算机模拟分析来验证这一说法。
在提取、分级分离、分离、表征、心脏保护活性评估（标记酶、氧化应激标记物和组织学切片）、靶蛋白（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽）检索、药物代谢动力学及药物毒性预测和对接研究中遵循标准方案。柱色谱和薄层色谱以及气相色谱/质谱联用辅助化合物的分离和表征；SWISSADME和ADMET lab 2增强了药物代谢动力学性质的评估；PyRx用于对接分析；Biovia discovery studio和PyMol软件用于配体 - 蛋白质相互作用的二维和三维可视化。
给予根提取物后，显著（p < 0.05）降低了阿霉素给药后升高的血清肌酸激酶同工酶、乳酸脱氢酶和肌钙蛋白I水平；然而，阿霉素给药后降低的谷胱甘肽、谷胱甘肽 - S - 转移酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶水平显著（p < 0.05）升高，而提取物和植物提取物处理后升高的丙二醛水平降低。此外，与阴性对照组相比，提取物处理大鼠的组织学切片显示病理特征减少。而且，化学病理变化与组织病理学观察结果一致，表明具有显著的心脏保护潜力。此外，色谱分析得到大量馏分{D3（11毫克）、E6（25毫克）和E8（21毫克）}，其气相色谱/质谱联用分析显示有双氢青蒿素；视黄酸甲酯；α - 侧柏烯；α - 松油烯；9,12,15 - 十八碳三烯醛；α - 松油醇等，这些成分已报道具有抗氧化活性。这些配体（双氢青蒿素；视黄酸甲酯）符合Lipinski规则，具有显著的药物代谢动力学特征，并且它们的对接分析表明，它们调节抗氧化酶的结合亲和力比维生素C更好。
鉴于已证明该植物根具有解毒和心脏保护特性，它是减轻阿霉素诱导毒性的有前途的候选物，并且在这种情况下可有效地用作支持性治疗。
