title: Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion.
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 (H2O2) 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 (PGE2). 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.
authors.affiliation: 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.
authors.forename: Amita
authors.initials: A
authors.lastname: Verma
authors.affiliation: Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Center for Advanced Research in Pharmaceutical Sciences, Jamia Hamdard, New Delhi, 110062, India.
authors.forename: Prakash Chandra
authors.initials: PC
authors.lastname: Bhatt
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaithwas
authors.affiliation: University Institute of Pharmacy, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India.
authors.forename: Nikunj
authors.initials: N
authors.lastname: Sethi
authors.affiliation: 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.
authors.forename: Mohd
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India.
authors.forename: Yashwant
authors.initials: Y
authors.lastname: Singh
authors.affiliation: 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.
authors.forename: Mahfoozur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Abbasi
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Firoz
authors.initials: F
authors.lastname: Anwar
authors.affiliation: 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. phvikas@gmail.com.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005290:Ferric Compounds / Q000633:toxicity; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D035322:Melastomataceae; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D005290:Ferric Compounds; D018836:Inflammation Mediators; D010936:Plant Extracts; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate
keywords: DEN; Fe-NTA; Inflammatory cytokines; Melastoma malabathricum