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多花山竹子对化学诱导的大鼠肾癌发生的化学调节作用:通过减轻炎症、氧化应激和肿瘤扩展的早期标志物来实现。

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion.

作者信息

Verma Amita, Bhatt Prakash Chandra, Kaithwas Gaurav, Sethi Nikunj, Rashid Mohd, Singh Yashwant, Rahman Mahfoozur, Al-Abbasi Fahad, Anwar Firoz, Kumar Vikas

机构信息

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences (Deemed to be University), Allahabad, 211007, Uttar Pradesh, India.

Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Center for Advanced Research in Pharmaceutical Sciences, Jamia Hamdard, New Delhi, 110062, India.

出版信息

Inflammopharmacology. 2016 Oct;24(5):233-251. doi: 10.1007/s10787-016-0276-1. Epub 2016 Sep 14.

DOI:10.1007/s10787-016-0276-1
PMID:27628241
Abstract

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC-MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (HO) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC-MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.

摘要

毛稔(Melastoma malabathricum Linn,MM)因其商业价值而备受重视。印度市场(东北部)对这种植物有很大需求,由于其抗炎作用,它作为传统家庭疗法的用途也得以扩展。在本研究中,我们仔细研究了毛稔对二乙基亚硝胺(DEN)和次氮基三乙酸铁(Fe-NTA)诱导的大鼠肾癌发生、肾脏过度增殖及氧化应激的治疗和保护作用。采用液相色谱 - 质谱联用(LC-MS)技术鉴定植物成分。给予DEN通过增加肿瘤发生率证实了肾癌发生的起始。腹腔注射Fe-NTA可增强抗氧化酶(I相),即超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPx)以及II相酶,即醌还原酶(QR)和谷胱甘肽 - S - 转移酶(GST)。它还增加了肾脏脂质过氧化(LPO)、过氧化氢(HO)的含量,同时降低了谷胱甘肽(GSH)的含量。它还增加了肾脏生化和非生化参数。它还证实了胸腺嘧啶核苷[3H]掺入肾脏DNA的水平、鸟氨酸脱羧酶(ODC)活性增加,以及促炎因子(TNF-α、IL-6和IL-β)和炎症介质(PGE)生成增加。我们还分析了肾脏组织的大体和组织学情况。此外,对毛稔提取物的植物成分作用进行了计算机模拟评估,并测定了其对DPPH和ABTS自由基的清除活性。LC-MS证实毛稔提取物中槲皮素含量大于没食子酸。用毛稔(100、250和500mg/kg)治疗肾癌大鼠证实了其具有显著(P < 0.001)的保护作用,可通过剂量依赖性方式降低抗氧化(I相和II相)酶、生化参数,并恢复促炎和炎症介质水平。毛稔改变了肾脏DNA中的ODC和胸腺嘧啶核苷活性。毛稔的化学保护作用通过降低肾脏肿瘤发生率得到证实,这一点通过大体和组织病理学观察得到了确认。因此,我们的结果表明,毛稔是一种有效的化学保护剂,可抑制DEN + Fe-NTA诱导的Wistar大鼠肾癌发生、炎症反应和氧化应激损伤。

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