Biochemistry Discipline, School of Sciences, Indira Gandhi National Open University, New Delhi, India.
Department of Biochemistry, Bundelkhand University, Jhansi, Uttar Pradesh, India.
J Ethnopharmacol. 2024 May 23;326:117922. doi: 10.1016/j.jep.2024.117922. Epub 2024 Feb 24.
Kidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties.
This study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats.
The leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography-Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney.
The LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity.
The results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy.
肾脏问题在全球范围内变得越来越普遍,并且被认为是现代世界的一个主要健康问题,具有很高的死亡率。多花山竹子(Sonn.)Thwaites 是一种热带民族药用植物,用于治疗各种疾病,如糖尿病、高血压和泌尿系统疾病,并具有抗氧化和抗炎特性。
本研究旨在研究 70%乙醇叶提取物 Polyalthia longifolia(Sonn.)Thwaites(PL)的植物化学成分,并评估其对顺铂诱导的 Wistar 大鼠肾毒性的肾脏保护作用。
采用 70%乙醇提取 PL 叶,采用液相色谱-质谱联用(LC-MS)进行植物化学成分分析。PL 叶提取物以三个剂量(150、300 和 600mg/kg,po)进行为期 14 天的治疗,以评估其对顺铂毒性(16mg/kg,ip,一次)的肾脏保护作用。对雄性 Wistar 大鼠进行血清中肾功能标志物和脂质谱标志物、肾组织中氧化应激标志物以及体重和肾脏重量指数的测定,并进行肾脏组织学分析。
LC-MS 图谱证实了 PL 叶提取物中存在各种植物化合物,包括 N-甲基赫那金(阿朴啡生物碱)、4-乙酰氨基丁酸(γ-氨基酸)和胆碱等。顺铂(16mg/kg,ip,仅一次)暴露于动物体内,显著提高了血清中肾功能标志物(即血清尿素、尿酸、肌酐)和脂质标志物(甘油三酯和总胆固醇)的水平,同时降低了血清白蛋白水平,而 PL 叶提取物(150、300 和 600mg/kg)的治疗则以剂量依赖性方式逆转了这一水平。顺铂处理组的体重和肾脏重量的改变也被 PL 叶提取物的治疗所恢复。PL 叶提取物通过恢复组织谷胱甘肽、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还原酶的水平,以及剂量依赖性降低顺铂诱导的肾氧化应激中的脂质过氧化,有效地改善了肾脏的抗氧化防御系统。组织病理学观察还表明,与顺铂毒性组相比,PL 治疗后细胞形态有显著恢复。PL 叶提取物的最高剂量 600mg/kg 显示出更明显的肾脏恢复(p<0.001),其次是其他两个剂量,这与水飞蓟素治疗组(参考药物)对肾毒性的作用相似。
本研究结果表明,PL 叶对顺铂诱导的肾毒性具有肾脏保护作用,可通过逆转生化标志物水平、减轻氧化应激以及改善肾脏组织结构来实现。PL 的这种肾脏保护作用可能是由于其植物成分的协同作用和抗氧化作用。