Mufti Afoua, Feriani Anouar, Ouchari Wafae, Mandour Yasmine M, Tlili Nizar, Ibrahim Mohammed Auwal, Mahmoud Mona F, Sobeh Mansour
Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University of Gafsa, Gafsa, Tunisia.
AgroBioSciences Program, College for Sustainable Agriculture and Environmental Science, Mohammed VI Polytechnic University, Ben Guerir, Morocco.
Front Pharmacol. 2023 Aug 1;14:1221486. doi: 10.3389/fphar.2023.1221486. eCollection 2023.
Herein, we explored the protective effect of (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their - and -glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.
在此，我们探究了（Burm.f.）Iwarsson地上部分提取物（LO）对顺铂（CP）诱导的大鼠肾毒性的保护作用，并分析了其植物成分。通过液相色谱-串联质谱法鉴定出了总共31种属于有机和酚酸及其糖苷以及黄酮类及其β-和γ-糖苷的化合物。二苯基苦味酰基自由基（DPPH）和铁还原抗氧化能力（FRAP）测定表明该提取物具有强大的抗氧化性能。结果表明，与顺铂组相比，连续30天给予LO提取物（40和80mg/kg体重）通过降低肌酐（仅高剂量）和尿酸水平，显著改善了改变的肾损伤标志物。顺铂对肾氧化应激标志物（谷胱甘肽、丙二醛、超氧化物歧化酶和过氧化氢酶）的有害作用也通过LO预处理得到缓解。炎症标志物（白细胞介素-6）的降低以及DNA片段化的抑制，突出了LO在肾组织中的预防作用。分子对接随后进行100纳秒的分子动力学模拟分析表明，在LO中鉴定出的31种化合物中，绿原酸和咖啡酰苹果酸与白细胞介素-6的结合最稳定。组织病理学观察进一步证实了肾保护作用，其显示顺铂诱导的超微结构变化有所改善。观察到的结果强化了这样的结论，即LO提取物具有肾保护特性，这可能与其抗氧化和抗炎活性有关。需要进一步研究来确定治疗剂量和合适的给药时间。
