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巴旦木种皮通过改变多种分子途径的临床前肾化学保护潜力。

Preclinical renal chemo-protective potential of Prunus amygdalus Batsch seed coat via alteration of multiple molecular pathways.

机构信息

a Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences , Sam Higginbottom University of Agriculture, Technology & Sciences , Allahabad , India.

b Centre for Advanced Research in Pharmaceutical Sciences, Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.

出版信息

Arch Physiol Biochem. 2018 Feb;124(1):88-96. doi: 10.1080/13813455.2017.1364773. Epub 2017 Aug 24.

Abstract

Prunus amygdalus Batsch (almond) is a classical nutritive traditional Indian medicine. Along with nutritive with anti-oxidant properties, it is, clinically, used in the treatment of various diseases with underlying anti-oxidant mechanism. This study is an effort to scrutinise the renal protective effect of P. amygdalus Batsch or green almond (GA) seed coat extract and its underlying mechanism in animal model of Ferric nitrilotriacetate (Fe-NTA) induced renal cell carcinoma (RCC). RCC was induced in Swiss Albino Wistar rats by intraperitoneal injection of Fe-NTA. The rats were then treated with ethanolic extract of GA (25, 50 and 100 mg/kg per oral) for 22 weeks. Efficacy of GA administration was evaluated by change in biochemical, renal, macroscopical and histopathological parameters and alterations. Additionally, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inflammatory mediator including prostaglandin E2 (PGE), nuclear factor-kappa B (NF-κB) were also observed to explore the possible mechanisms. The oral administration of GA significantly (p < .001) altered the Fe-NTA induced RCC in rats by inhibition of renal nodules, decolourisation of tissues, tumour promoter marker including thymidine [H] incorporation, ornithine decarboxylase, renal parameters and anti-oxidant parameters in serum. Additionally, GA treatment significantly (p < .001) down-regulated the IL-6, IL-1β, TNF-α, inflammatory mediators PGE and NF-κB in a dose-dependent manner. Histopathology observation supported the renal protective effect of GA by alteration in necrosis, size of Bowman capsules and inflammatory cells. Hence, it can be concluded that GA possesses observable chemo-protective action and effect on Fe-NTA induced RCC via dual inhibition mechanism one by inhibiting free radical generation and second by inhibiting inflammation.

摘要

巴旦杏仁(扁桃)是一种经典的营养性传统印度药物。除了具有抗氧化特性外,它还在临床上用于治疗各种具有抗氧化机制的疾病。本研究旨在探讨巴旦杏仁(GA)种皮提取物的肾保护作用及其在铁氮三乙酸(Fe-NTA)诱导的肾细胞癌(RCC)动物模型中的潜在机制。通过腹腔注射 Fe-NTA 诱导瑞士白化 Wistar 大鼠 RCC。然后,大鼠用 GA 的乙醇提取物(25、50 和 100mg/kg 口服)治疗 22 周。通过生化、肾脏、宏观和组织病理学参数以及变化来评估 GA 给药的疗效。此外,还观察了白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素 1β(IL-1β)和包括前列腺素 E2(PGE)在内的炎症介质以及核因子-kappa B(NF-κB),以探讨可能的机制。GA 的口服给药通过抑制肾结节、组织褪色、胸苷 [H]掺入、鸟氨酸脱羧酶、肾脏参数和血清抗氧化参数显著(p<.001)改变了 Fe-NTA 诱导的大鼠 RCC。此外,GA 治疗以剂量依赖性方式显著(p<.001)下调了 IL-6、IL-1β、TNF-α、炎症介质 PGE 和 NF-κB。组织病理学观察通过改变坏死、鲍曼囊大小和炎症细胞,支持了 GA 的肾保护作用。因此,可以得出结论,GA 通过抑制自由基生成和抑制炎症的双重抑制机制,对 Fe-NTA 诱导的 RCC 具有明显的化学保护作用和效果。

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