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Zeitschrift für Naturforschung C

A Journal of Biosciences

Editor-in-Chief: Seibel, Jürgen

Editorial Board: Aigner , Achim / Boland, Wilhelm / Bornscheuer, Uwe / Hoffmann, Klaus


IMPACT FACTOR 2017: 0.882
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CiteScore 2017: 0.92

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Source Normalized Impact per Paper (SNIP) 2017: 0.448

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1865-7125
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Volume 71, Issue 7-8

Issues

Neem tree (Azadirachta indica) extract specifically suppresses the growth of tumors in H22-bearing Kunming mice

Zhenxiang He
  • Suzhou High-Tech Institute of Nanjing University, Suzhou 215123, China
  • State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
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/ Cuihua Jiang
  • Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, Nanjing 210028, China
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/ Jian Zhang
  • Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, Nanjing 210028, China
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/ Zhiqi Yin
  • Laboratory of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing 210009, China
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/ Zengfang Yin
  • College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210037, China
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/ Yunfeng Zhu
  • Corresponding author
  • The college of life sciences and bioengineering in Beijing Jiaotong University, Beijing 100044, China
  • The cancer center in Chinese PLA General Hospital, Beijing 100853, China
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/ Jie Fu
  • Corresponding author
  • School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Published Online: 2016-06-01 | DOI: https://doi.org/10.1515/znc-2014-4210

Abstract

Recently, neem tree (Azadirachta indica) extract (NTE) has been reported to have various antitumor activities against gastric, breast, prostate, and skin cancer, respectively. The current study was designed to evaluate the effect of NTE on hepatic cancer in a mouse model. The possible side effects elicited by NTE were also evaluated. The components in NTE were analyzed by liquid chromatography–mass spectrometry (LC-MS). H22 cells-bearing Kumming mice were generated by injecting H22 cells subcutaneously into the right forelimb armpit of the mice. Then the mice were treated daily for 27 days with NTE (150, 300, and 600 mg/kg body weight) by intragastric administration, using carboxymethyl cellulose (CMC, 1%) as blank control and cyclophosphamide (CTX, 20 mg/kg) as positive control. The antitumor effect of NTE was evaluated by assessment of survival rate, body weight, tumor volume and weight, tumor histology, thymus and spleen indexes, and liver histology. The tumor weight and volume in groups of NTE and CTX were significantly lower than those in the CMC group. The survival rate in the NTE group receiving the high dose (600 mg/kg) was significantly higher than that in the CTX and CMC groups. Compared with CTX, NTE was observed to have a tumor-specific cytotoxicity without impairing the normal liver tissue. Additionally, the higher indexes of thymus and spleen indicated that NTE could facilitate the growth of immune organs. The results indicate that NTE is a promising candidate for the antitumor treatment with high efficacy and safety.

This article offers supplementary material which is provided at the end of the article.

Keywords: Azadirachta indica; cyclophosphamide; H22-bearing mice; hepatic cancer

References

  • 1.

    Khaled M, Jiang ZZ, Zhang LY. Deoxypodophyllotoxin: A promising therapeutic agent from herbal medicine. J Ethnopharmacol 2013;149:24–34.Google Scholar

  • 2.

    Long AH, Fu J, Hu Y, Luo Y. Annphenone from Artemisia vestita inhibits HepG2 cell proliferation. Asian J Chem 2013;25: 9497–9502.Google Scholar

  • 3.

    Sunila ES, Kuttan G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol 2004;90:339–346.Google Scholar

  • 4.

    Dholwani KK, Saluja AK, Gupta AR, Shah DR. A review on plant-derived natural products and their analogs with anti-tumor activity. Indian J Pharmacol 2008;40:49–58.Google Scholar

  • 5.

    Mukherjee AK, Basu S, Sarkar N, Ghosh AC. Advances in cancer therapy with plant based natural products. Curr Med Chem 2001;8:1467–1486.Google Scholar

  • 6.

    Bose A, Chakraborty K, Sarkar K, Goswami S, Chakraborty T, Pal S, et al. Neem leaf glycoprotein induces perforin-mediated tumor cell killing by T and NK cells through differential regulation of IFN gamma signaling. J Immunother 2009;32:42–53.Google Scholar

  • 7.

    Sarkar K, Goswami S, Roy S, Mallick A, Chakraborty K, Bose A, et al. Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response. Int Immunopharmacol 2010;10:865–874.Google Scholar

  • 8.

    Atawodi SE, Atawodi JC. Azadirachta indica (neem): a plant of multiple biological and pharmacological activities. Phytochem Rev 2009;8:601–620.Google Scholar

  • 9.

    Gangar SC, Koul A. Histochemical, ultrastructural, and biochemical evidences for Azadirachta indica – Induced apoptosis in benzo(a)pyrene-induced murine forestomach tumors. J Environ Pathol Toxicol Oncol 2008;27:219–232.Google Scholar

  • 10.

    Vinothini G, Manikandan P, Anandan R, Nagini S. Chemoprevention of rat mammary carcinogenesis by Azadirachta indica leaf fractions: Modulation of hormone status, xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation and apoptosis. Food Chem Toxicol 2009;47:1852–1863.Google Scholar

  • 11.

    Mahapatra S, Karnes RJ, Holmes MW, Young CY, Cheville JC, Kohli M, et al. Novel molecular targets of Azadirachta indica associated with inhibition of tumor growth in prostate cancer. Aaps J 2011;13:365–377.Google Scholar

  • 12.

    Arora N, Koul A, Bansal MP. Chemopreventive activity of Azadirachta indica on two-stage skin carcinogenesis in murine model. Phytother Res 2011;25:408–416.Google Scholar

  • 13.

    Chakraborty K, Bose A, Pal S, Sarkar K, Goswami S, Ghosh D, et al. Neem leaf glycoprotein restores the impaired chemotactic activity of peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients by maintaining CXCR3/CXCL10 balance. Int Immunopharmacol 2008;8:330–340.Google Scholar

  • 14.

    Haque E, Baral R. Neem (Azadirachta indica) leaf preparation induces prophylactic growth inhibition of murine Ehrlich carcinoma in Swiss and C57BL/6 mice by activation of NK cells and NK-T cells. Immunobiology 2006;211:721–731.Google Scholar

  • 15.

    Zhou M, Higo H, Cai YQ. Inhibition of hepatoma 22 tumor by liquiritigenin. Phytother Res 2010;24:827–833.Google Scholar

  • 16.

    Chen S, Ju ML, Luo Y, Chen ZJ, Zhao CP, Zhou Y, et al. Hepatoprotective and antioxidant activities of the aqueous extract from the rhizome of Phragmites australis. Z Naturforsch (C) 2013;68:439–444.Google Scholar

  • 17.

    Efron B. Logistic regression, survival analysis, and the Kaplan-Meier curve. J Am Stat Assoc 1988;83:414–425.Google Scholar

  • 18.

    Fu J, Zhang XW, Liu K, Li QS, Zhang LR, Yang XH, et al. Hypolipidemic activity in Sprague–Dawley rats and constituents of a novel natural vegetable oil from Cornus Wilsoniana fruits. J Food Sci 2012;77:H160–H169.Google Scholar

  • 19.

    Anyaehie UB. Medicinal properties of fractionated acetone/water neem Azadirachta indica leaf extract from Nigeria: a review. Nigerian J Physiol Sci 2009;24:157–159.Google Scholar

  • 20.

    Manikandan P, Anandan R, Nagini S. Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and protective effects against H2O2-induced oxidative damage to pBR322 DNA and red blood cells. J Agr Food Chem 2009;57:6990–6996.Google Scholar

  • 21.

    Priyadarsini RV, Manikandan P, Kumar GH, Nagini S. The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radical Res 2009;43:492–504.Google Scholar

  • 22.

    Yogesh BP, Bhattacharya S, Das T, Roy M, Besra SE, Gomes A, et al. Anti-leukemic activity of sulfonoquinovosyldiacylglyceride (SQDG): a constituent of Azadirachta indica leaves. Med Chem Res 2013;22:22–27.Google Scholar

  • 23.

    Yao Z, Lu R, Jia J, Zhao PP, Yang J, Zheng MN, et al. The effect of tripeptide tyroserleutide (YSL) on animal models of hepatocarcinoma. Peptides 2006;27:1167–1172.Google Scholar

  • 24.

    Okano K, Yamamoto J, Kosuge T, Yamamoto S, Sakamoto M, Nakanishi Y, et al. Fibrous pseudocapsule of metastatic liver tumors from colorectal carcinoma – Clinicopathologic study of 152 first resection cases. Cancer 2000;89:267–275.Google Scholar

  • 25.

    Akudugu J, Gade G, Bohm L. Cytotoxicity of azadirachtin A in human glioblastoma cell lines. Life Sci 2001;68:1153–1160.Google Scholar

  • 26.

    Kumar GH, Priyadarsini RV, Vinothini G, Letchoumy PV, Nagini S. The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis. Invest New Drug 2010;28:392–401.Google Scholar

About the article

Received: 2014-12-05

Revised: 2016-05-02

Accepted: 2016-05-02

Published Online: 2016-06-01

Published in Print: 2016-07-01


Citation Information: Zeitschrift für Naturforschung C, Volume 71, Issue 7-8, Pages 201–208, ISSN (Online) 1865-7125, ISSN (Print) 0939-5075, DOI: https://doi.org/10.1515/znc-2014-4210.

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