Table of Contents Author Guidelines Submit a Manuscript
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 7382506, 11 pages
http://dx.doi.org/10.1155/2016/7382506
Review Article

Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, P.O. Box 6699, Buraidah, Saudi Arabia

Received 6 October 2015; Revised 7 January 2016; Accepted 11 January 2016

Academic Editor: Luciana Dini

Copyright © 2016 Mohammad A. Alzohairy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Zong, H. Cao, and F. Wang, “Anticancer polysaccharides from natural resources: a review of recent research,” Carbohydrate Polymers, vol. 90, no. 4, pp. 1395–1410, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Efferth and E. Koch, “Complex interactions between Phytochemicals. The Multi-Target Therapeutic concept of Phytotherapy,” Current Drug Targets, vol. 12, no. 1, pp. 122–132, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. M. I. Al-Bukhari and S. Al-Bukhari, The Collection of Authentic Sayings of Prophet Mohammad (Peace Be upon Him), Division 71 on Medicine, Hilal Yayinlari, Ankara, Turkey, 2nd edition, 1976.
  4. G. Brahmachari, “Neem—an omnipotent plant: a retrospection,” ChemBioChem, vol. 5, no. 4, pp. 408–421, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Y. Ketkar and C. M. Ketkar, “Various uses of neem products,” in The Neem Tree, H. Schmutterer, Ed., pp. 518–525, John Wiley & Sons, Weinheim, Germany, 2004. View at Publisher · View at Google Scholar
  6. T. R. Govindachari, G. Suresh, G. Gopalakrishnan, B. Banumathy, and S. Masilamani, “Identification of antifungal compounds from the seed oil of Azadirachta indica,” Phytoparasitica, vol. 26, no. 2, pp. 109–116, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. N. Singh and M. S. Sastry, “Antimicrobial activity of Neem oil,” Indian Journal of Pharmacology, vol. 13, pp. 102–106, 1997. View at Google Scholar
  8. A. Kher and S. C. Chaurasia, “Antifungal activity of essential oils of three medical plants,” Indian Drugs, vol. 15, pp. 41–42, 1997. View at Google Scholar
  9. U. Bandyopadhyay, K. Biswas, A. Sengupta et al., “Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer,” Life Sciences, vol. 75, no. 24, pp. 2867–2878, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Sultana, F. Anwar, and R. Przybylski, “Antioxidant activity of phenolic components present in barks of Azadirachta indica, Terminalia arjuna, Acacia nilotica, and Eugenia jambolana Lam. trees,” Food Chemistry, vol. 104, no. 3, pp. 1106–1114, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. P. E. Ebong, I. J. Atangwho, E. U. Eyong, and G. E. Egbung, “The antidiabetic efficacy of combined extracts from two continental plants: Azadirachta indica (A. Juss) (Neem) and Vernonia amygdalina (Del.) (African Bitter Leaf),” The American Journal of Biochemistry and Biotechnology, vol. 4, no. 3, pp. 239–244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Paul, M. Prasad, and N. K. Sah, “Anticancer biology of Azadirachta indica L (neem): a mini review,” Cancer Biology and Therapy, vol. 12, no. 6, pp. 467–476, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. K. Biswas, I. Chattopadhyay, R. K. Banerjee, and U. Bandyopadhyay, “Biological activities and medicinal properties of neem (Azadirachta indica),” Current Science, vol. 82, no. 11, pp. 1336–1345, 2002. View at Google Scholar · View at Scopus
  14. K. Girish and S. B. S. Neem, “A green treasure,” Electronic Journal of Biology, vol. 4, pp. 102–111, 2008. View at Google Scholar
  15. A. Ali, Textbook of Pharmacognosy, Publication and Information Directorate, New Delhi, India, 1993.
  16. M. A. Hossain, M. D. Shah, and M. Sakari, “Gas chromatography–mass spectrometry analysis of various organic extracts of Merremia borneensis from Sabah,” Asian Pacific Journal of Tropical Medicine, vol. 4, no. 8, pp. 637–641, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. C. Kokate, A. P. Purohit, and S. B. Gokhale, Pharmacognosy, Nirali Prakashan, Maharashtra, India, 2010.
  18. A. J. Mordue (Luntz) and A. J. Nisbet, “Azadirachtin from the neem tree Azadirachta indica: its action against insects,” Anais da Sociedade Entomológica do Brasil, vol. 29, no. 4, pp. 615–632, 2000. View at Publisher · View at Google Scholar
  19. W. C. Sarmiento, C. C. Maramba, and M. L. M. Gonzales, “An in vitro study on the antibacterial effect of neem (Azadirachta indica) leaf extracts on methicillin-sensitive and methicillin-resistant Staphylococcus aureus,” PIDSP Journal, vol. 12, no. 1, pp. 40–45, 2011. View at Google Scholar
  20. M. A. Hossain, W. A. S. Al-Toubi, A. M. Weli, Q. A. Al-Riyami, and J. N. Al-Sabahi, “Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem,” Journal of Taibah University for Science, vol. 7, no. 4, pp. 181–188, 2013. View at Publisher · View at Google Scholar
  21. P. X. Nunes, S. F. Silva, R. J. Guedes, and S. Almeida, “Biological oxidations and antioxidant activity of natural products,” in Phytochemicals as Nutraceuticals—Global Approaches to Their Role in Nutrition and Health, InTech, 2012. View at Google Scholar
  22. A. H. Rahmani and S. M. Aly, “Nigella sativa and its active constituents thymoquinone shows pivotal role in the diseases prevention and treatment,” Asian Journal of Pharmaceutical and Clinical Research, vol. 8, no. 1, pp. 48–53, 2015. View at Google Scholar · View at Scopus
  23. A. K. Ghimeray, C. W. Jin, B. K. Ghimire, and D. H. Cho, “Antioxidant activity and quantitative estimation of azadirachtin and nimbin in Azadirachta indica A. Juss grown in foothills of Nepal,” African Journal of Biotechnology, vol. 8, no. 13, pp. 3084–3091, 2009. View at Google Scholar
  24. P. Sithisarn, R. Supabphol, and W. Gritsanapan, “Antioxidant activity of Siamese neem tree (VP 1209),” Journal of Ethnopharmacology, vol. 99, no. 1, pp. 109–112, 2005. View at Publisher · View at Google Scholar
  25. R. V. Priyadarsini, P. Manikandan, G. H. Kumar, and S. Nagini, “The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis,” Free Radical Research, vol. 43, no. 5, pp. 492–504, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Nahak and R. K. Sahu, “Evaluation of antioxidant activity of flower and seed oil of Azadirachta indica A. juss,” Journal of Applied and Natural Science, vol. 3, no. 1, pp. 78–81, 2011. View at Google Scholar
  27. M. Kiranmai, M. Kumar, and M. Ibrahim, “Free radical scavenging activity of neem tree (Azadirachta indica A. Juss Var., Meliaceae) root barks extract,” Asian Journal of Pharmaceutical and Clinical Research, vol. 4, pp. 134–136, 2011. View at Google Scholar
  28. P. Sithisarn, R. Supabphol, and W. Gritsanapan, “Antioxidant activity of Siamese neem tree (VP1209),” Journal of Ethnopharmacology, vol. 99, no. 1, pp. 109–112, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. A. H. Rahmani, M. A. Alzohairy, M. A. Khan, and S. M. Aly, “Therapeutic implications of black seed and its constituent thymoquinone in the prevention of cancer through inactivation and activation of molecular pathways,” Evidence-Based Complementary and Alternative Medicine, vol. 2014, Article ID 724658, 13 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Le Marchand, “Cancer preventive effects of flavonoids—a review,” Biomedicine and Pharmacotherapy, vol. 56, no. 6, pp. 296–301, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. G. H. Kumar, R. Vidya Priyadarsini, G. Vinothini, P. Vidjaya Letchoumy, and S. Nagini, “The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis,” Investigational New Drugs, vol. 28, no. 4, pp. 392–401, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. G. Harish Kumar, K. V. P. Chandra Mohan, A. Jagannadha Rao, and S. Nagini, “Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells,” Investigational New Drugs, vol. 27, no. 3, pp. 246–252, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Arumugam, P. Agullo, T. Boopalan et al., “Neem leaf extract inhibits mammary carcinogenesis by altering cell proliferation, apoptosis, and angiogenesis,” Cancer Biology and Therapy, vol. 15, no. 1, pp. 26–34, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Subapriya, R. Kumaraguruparan, and S. Nagini, “Expression of PCNA, cytokeratin, Bcl-2 and p53 during chemoprevention of hamster buccal pouch carcinogenesis by ethanolic neem (Azadirachta indica) leaf extract,” Clinical Biochemistry, vol. 39, no. 11, pp. 1080–1087, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Subapriya, V. Bhuvaneswari, and S. Nagini, “Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3,” Asian Pacific Journal of Cancer Prevention, vol. 6, no. 4, pp. 515–520, 2005. View at Google Scholar
  36. E. Cohen, G. B. Quistad, and J. E. Casida, “Cytotoxicity of nimbolide, epoxyazadiradione and other limonoids from neem insecticide,” Life Sciences, vol. 58, no. 13, pp. 1075–1081, 1996. View at Publisher · View at Google Scholar · View at Scopus
  37. S. C. Gupta, S. Reuter, K. Phromnoi et al., “Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen species- and ERK-dependent up-regulation of death receptors, p53, and Bax,” The Journal of Biological Chemistry, vol. 286, no. 2, pp. 1134–1146, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Li, C. Yen, D. Liaw et al., “PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer,” Science, vol. 275, no. 5308, pp. 1943–1947, 1997. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Khan, T. Kumagai, J. Vora et al., “PTEN promoter is methylated in a proportion of invasive breast cancers,” International Journal of Cancer, vol. 112, no. 3, pp. 407–410, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Rahmani, M. Alzohairy, A. Y. Babiker, M. A. Rizvi, and H. G. Elkarimahmad, “Clinicopathological significance of PTEN and bcl2 expressions in oral squamous cell carcinoma,” International Journal of Clinical and Experimental Pathology, vol. 5, no. 9, pp. 965–971, 2012. View at Google Scholar · View at Scopus
  41. F. Othman, G. Motalleb, S. L. Tsuey Peng, A. Rahmat, S. Fakurazi, and C. Pei Pei, “Extract of Azadirachta indica (Neem) leaf induces apoptosis in 4T1 breast cancer BALB/c mice,” Cell Journal, vol. 13, no. 2, pp. 107–116, 2011. View at Google Scholar · View at Scopus
  42. S. Kumar, P. K. Suresh, M. R. Vijayababu, A. Arunkumar, and J. Arunakaran, “Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3),” Journal of Ethnopharmacology, vol. 105, no. 1-2, pp. 246–250, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. K. S. Chitta, A. N. H. Khan, N. Ersing et al., “Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells,” Leukemia and Lymphoma, vol. 55, no. 3, pp. 652–661, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Schumacher, C. Cerella, S. Reuter, M. Dicato, and M. Diederich, “Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway,” Genes and Nutrition, vol. 6, no. 2, pp. 149–160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. R. V. Priyadarsini, R. S. Murugan, P. Sripriya, D. Karunagaran, and S. Nagini, “The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells,” Free Radical Research, vol. 44, no. 6, pp. 624–634, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Mahapatra, C. Y. F. Young, M. Kohli et al., “Antiangiogenic effects and therapeutic targets of azadirachta indica leaf extract in endothelial cells,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 303019, 14 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. L. P. B. Lavanya Uppuluri, V. N. Garge, and V. J. Kadam, “Evaluation of anti-angiogenesis activity of neem root using zebra fish model,” International Journal of Pharmaceutical Sciences and Research, vol. 6, no. 6, pp. 2437–2440, 2015. View at Google Scholar
  48. F. Othman, G. Motalleb, S. Lam Tsuey Peng, A. Rahmat, R. Basri, and C. Pei Pei, “Effect of neem leaf extract (Azadirachta indica) on c-Myc oncogene expression in 4T1 breast cancer cells of BALB/c mice,” Cell Journal, vol. 14, no. 1, pp. 53–60, 2012. View at Google Scholar · View at Scopus
  49. D. N. Gunadharini, P. Elumalai, R. Arunkumar, K. Senthilkumar, and J. Arunakaran, “Induction of apoptosis and inhibition of PI3K/Akt pathway in PC-3 and LNCaP prostate cancer cells by ethanolic neem leaf extract,” Journal of Ethnopharmacology, vol. 134, no. 3, pp. 644–650, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. P. Elumalai, D. N. Gunadharini, K. Senthilkumar et al., “Ethanolic neem (Azadirachta indica A. Juss) leaf extract induces apoptosis and inhibits the IGF signaling pathway in breast cancer cell lines,” Biomedicine and Preventive Nutrition, vol. 2, no. 1, pp. 59–68, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Raja Singh, R. Arunkumar, V. Sivakamasundari et al., “Anti-proliferative and apoptosis inducing effect of nimbolide by altering molecules involved in apoptosis and IGF signalling via PI3K/Akt in prostate cancer (PC-3) cell line,” Cell Biochemistry and Function, vol. 32, no. 3, pp. 217–228, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Sen and D. Baltimore, “Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism,” Cell, vol. 47, no. 6, pp. 921–928, 1986. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Veeraraghavan, M. Natarajan, P. Lagisetty, V. Awasthi, T. S. Herman, and N. Aravindan, “Impact of curcumin, raspberry extract, and neem leaf extract on rel protein-regulated cell death/radiosensitization in pancreatic cancer cells,” Pancreas, vol. 40, no. 7, pp. 1107–1119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Kavitha, R. Vidya Priyadarsini, P. Anitha et al., “Nimbolide, a neem limonoid abrogates canonical NF-κB and Wnt signaling to induce caspase-dependent apoptosis in human hepatocarcinoma (HepG2) cells,” European Journal of Pharmacology, vol. 681, no. 1–3, pp. 6–14, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. R. R. Chattopadhyay, “Possible biochemical mode of anti-inflammatory action of Azadirachta indica A. Juss. in rats,” Indian Journal of Experimental Biology, vol. 36, no. 4, pp. 418–420, 1998. View at Google Scholar · View at Scopus
  56. A. S. M. Mosaddek and M. M. U. Rashid, “A comparative study of the anti-inflammatory effect of aqueous extract of neem leaf and dexamethasone,” Bangladesh Journal of Pharmacology, vol. 3, no. 1, pp. 44–47, 2008. View at Publisher · View at Google Scholar
  57. G. Kaur, M. Sarwar Alam, and M. Athar, “Nimbidin suppresses functions of macrophages and neutrophils: relevance to its antiinflammatory mechanisms,” Phytotherapy Research, vol. 18, no. 5, pp. 419–424, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Arora, A. Koul, and M. P. Bansal, “Chemopreventive activity of Azadirachta indica on two-stage skin carcinogenesis in murine model,” Phytotherapy Research, vol. 25, no. 3, pp. 408–416, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. K. Biswas, I. Chattopadhyay, R. K. Banerjee, and U. Bandyopadhyay, “Biological activities and medicinal properties of Neem (Azadirachta indica),” Current Science, vol. 82, no. 11, pp. 1336–1345, 2002. View at Google Scholar · View at Scopus
  60. S. Kumar, D. Agrawal, J. Patnaik, and S. Patnaik, “Analgesic effect of neem (Azadirachta indica) seed oil on albino rats,” International Journal of Pharma and Bio Sciences, vol. 3, no. 2, pp. P222–P225, 2012. View at Google Scholar · View at Scopus
  61. M. R. Naik, A. Bhattacharya, R. Behera, D. Agrawal, S. Dehury, and S. Kumar, “Study of anti-inflammatory effect of neem seed oil (Azadirachta indica) on infected albino rats,” Journal of Health Research and Reviews, vol. 1, no. 3, pp. 66–69, 2014. View at Publisher · View at Google Scholar
  62. K. Ilango, G. Maharajan, and S. Narasimhan, “Anti-nociceptive and anti-inflammatory activities of Azadirachta indica fruit skin extract and its isolated constituent azadiradione,” Natural Product Research, vol. 27, no. 16, pp. 1463–1467, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. N. S. Baligar, R. H. Aladakatti, M. Ahmed, and M. B. Hiremath, “Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats,” Canadian Journal of Physiology and Pharmacology, vol. 92, no. 4, pp. 267–277, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. N. S. Baligar, R. H. Aladakatti, M. Ahmed, and M. B. Hiremath, “Evaluation of acute toxicity of neem active constituent, nimbolide and its hepatoprotective activity against acute dose of carbon tetrachloride treated albino rats,” International Journal of Pharmaceutical Sciences and Research, vol. 5, no. 8, pp. 3455–3466, 2014. View at Google Scholar
  65. S. Bhanwra, “Effect of Azadirachta indica (neem) leaf aqueous extract on paracetamol induced liver damage in rats,” Indian Journal of Physiology and Pharmacology, vol. 44, no. 1, pp. 64–68, 2000. View at Google Scholar
  66. B. P. Kale, M. A. Kothekar, H. P. Tayade, J. B. Jaju, and M. Mateenuddin, “Effect of aqueous extract of Azadirachta indica leaves on hepatotoxicity induced by antitubercular drugs in rats,” Indian Journal of Pharmacology, vol. 35, pp. 177–180, 2003. View at Google Scholar
  67. T. Kalaivani, E. Meiganam, N. Premkumpatoprotectivear, and R. Siva, “Studies on hepatoprotective properties of leaf extracts of Azadirachta indica A. Juss (Meliaceae),” Ethnobotanical Leaflets, vol. 13, no. 2, pp. 165–170, 2009. View at Google Scholar
  68. V. P. Devmurari and N. P. Jivani, “Hepatoprotective activity of methanolic and aqueous extracts of Azadirchata indica leaves,” International Journal of PharmTech Research, vol. 2, no. 2, pp. 1037–1040, 2010. View at Google Scholar · View at Scopus
  69. D. A. Ofusori, B. A. Falana, A. E. Ofusori, T. A. Abayomi, S. A. Ajayi, and G. B. Ojo, “Gastroprotective effect of aqueous extract of neem Azadirachta indica on induced gastric lesion in rats,” International Journal of Biological and Medical Research, vol. 1, pp. 219–222, 2010. View at Google Scholar
  70. C. C. Barua, A. Talukdar, A. G. Barua, A. Chakraborty, R. K. Sarma, and R. S. Bora, “Evaluation of the wound healing activity of methanolic extract of Azadirachta Indica (Neem) and Tinospora cordifolia (Guduchi) in rats,” Pharmacologyonline, vol. 1, pp. 70–77, 2010. View at Google Scholar · View at Scopus
  71. A. Osunwoke Emeka, J. Olotu Emamoke, A. Allison Theodore, and C. Onyekwere Julius, “The wound healing effects of aqueous leave extracts of azadirachta indica on wistar rats,” Journal of Natural Science and Research, vol. 3, no. 6, 2013. View at Google Scholar
  72. P. R. Patil, S. P. Patil, A. Mane, and S. Verma, “Antidiabetic activity of alcoholic extract of Neem (Azadirachta indica) root bark,” National Journal of Physiology, Pharmacy and Pharmacology, vol. 3, no. 2, pp. 142–146, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. S. K. Dholi, R. Raparla, S. K. Mankala, and K. Nagappan, “Invivo antidiabetic evaluation of Neem leaf extract in alloxan induced rats,” Journal of Applied Pharmaceutical Science, vol. 1, no. 4, pp. 100–105, 2011. View at Google Scholar · View at Scopus
  74. B. N. Joshi, M. Bhat, S. K. Kothiwale, A. R. Tirmale, and S. Y. Bhargava, “Antidiabetic properties of Azardiracta indica and Bougainvillea spectabilis: In vivo studies in murine diabetes model,” Evidence-Based Complementary and Alternative Medicine, vol. 2011, Article ID 561625, 9 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. R. Akter, M. Mahabub-Uz-Zaman, M. S. Rahman et al., “Comparative studies on antidiabetic effect with phytochemical screening of Azadirachta indicia and Andrographis paniculata,” IOSR Journal of Pharmacy and Biological Sciences, vol. 5, no. 2, pp. 122–128, 2013. View at Publisher · View at Google Scholar
  76. W. N. Ghonmode, O. D. Balsaraf, V. H. Tambe, K. P. Saujanya, A. K. Patil, and D. D. Kakde, “Comparison of the antibacterial efficiency of neem leaf extracts, grape seed extracts and 3% sodium hypochlorite against E. feacalis—an in vitro study,” Journal of International Oral Health, vol. 5, no. 6, pp. 61–66, 2013. View at Google Scholar
  77. M. D. Mahfuzul Hoque, M. L. Bari, Y. Inatsu, V. K. Juneja, and S. Kawamoto, “Antibacterial activity of guava (Psidium guajava L.) and neem (Azadirachta indica A. Juss.) extracts against foodborne pathogens and spoilage bacteria,” Foodborne Pathogens and Disease, vol. 4, no. 4, pp. 481–488, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. M. B. Yerima, S. M. Jodi, K. Oyinbo, H. M. Maishanu, A. A. Farouq, and A. U. Junaidu, “Effect of neem extracts (Azadirachta indica) on bacteria isolated from adult mouth,” Journal of Basic and Applied Sciences, vol. 20, pp. 64–67, 2012. View at Google Scholar
  79. V. Tiwari, N. A. Darmani, B. Y. J. T. Yue, and D. Shukla, “In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type-1 infection,” Phytotherapy Research, vol. 24, no. 8, pp. 1132–1140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Badam, S. P. Joshi, and S. S. Bedekar, “'In vitro' antiviral activity of neem (Azadirachta indica. A. Juss) leaf extract against group B coxsackieviruses,” Journal of Communicable Diseases, vol. 31, no. 2, pp. 79–90, 1999. View at Google Scholar · View at Scopus
  81. N. K. Mondali, A. Mojumdar, S. K. Chatterje, A. Banerjee, J. K. Datta, and S. Gupta, “Antifungal activities and chemical characterization of Neem leaf extracts on the growth of some selected fungal species in vitro culture medium,” Journal of Applied Sciences and Environmental Management, vol. 13, no. 1, pp. 49–53, 2009. View at Google Scholar
  82. K. Anjali, K. Ritesh, M. Sudarshan, S. C. Jaipal, and S. Kumar, “Antifungal efficacy of aqueous extracts of neem cake, karanj cake and vermicompost against some phytopathogenic fungi,” The Bioscan, vol. 8, pp. 671–674, 2013. View at Google Scholar
  83. D. K. Shrivastava and K. Swarnkar, “Antifungal activity of leaf extract of neem (Azadirachta indica Linn),” International Journal of Current Microbiology and Applied Sciences, vol. 3, no. 5, pp. 305–308, 2014. View at Google Scholar
  84. V. Natarajan, P. V. Venugopal, and T. Menon, “Effect of Azadirachta indica (Neem) on the growth pattern of dermatophytes,” Indian Journal of Medical Microbiology, vol. 21, no. 2, pp. 98–101, 2003. View at Google Scholar · View at Scopus
  85. C. A. C. Lloyd, T. Menon, and K. Umamaheshwari, “Anticandidal activity of Azadirachta indica,” Indian Journal of Pharmacology, vol. 37, no. 6, pp. 386–389, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. A. C. Amadioha and V. I. Obi, “Fungitoxic activity of extracts from Azadirachta indica and Xylopia aethiopica on Colletotrichum lindemuthianum in cowpea,” Journal of Herbs, Spices and Medicinal Plants, vol. 6, no. 2, pp. 33–40, 1998. View at Publisher · View at Google Scholar · View at Scopus
  87. K. Jabeen, S. Hanif, S. Naz, and S. Iqbal, “Antifungal activity of Azadirachta indica against Alternaria solani,” Journal of Life Sciences and Technologies, vol. 1, no. 1, pp. 89–93, 2013. View at Publisher · View at Google Scholar
  88. B. C. Akin-Osanaiya, A. J. Nok, S. Ibrahim et al., “Antimalarial effect of Neem leaf and Neem stem bark extracts on plasmodium berghei infected in the pathology and treatment of malaria,” International Journal of Research in Biochemistry and Biophysics, vol. 3, no. 1, pp. 7–14, 2013. View at Google Scholar
  89. M. S. Mulla and T. Su, “Activity and biological effects of neem products against arthropods of medical and veterinary importance,” Journal of the American Mosquito Control Association, vol. 15, no. 2, pp. 133–152, 1999. View at Google Scholar · View at Scopus
  90. R. Dhar, H. Dawar, S. Garg, S. F. Basir, and G. P. Talwar, “Effect of volatiles from neem and other natural products on gonotrophic cycle and oviposition of Anopheles stephensi and An. culicifacies (Diptera: Culicidae),” Journal of Medical Entomology, vol. 33, no. 2, pp. 195–201, 1996. View at Publisher · View at Google Scholar · View at Scopus
  91. S. S. Nathan, K. Kalaivani, and K. Murugan, “Effects of neem limonoids on the malaria vector Anopheles stephensi Liston (Diptera: Culicidae),” Acta Tropica, vol. 96, no. 1, pp. 47–55, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. J. I. Udeinya, E. N. Shu, I. Quakyi, and F. O. Ajayi, “An antimalarial neem leaf extract has both schizonticidal and gametocytocidal activities,” American Journal of Therapeutics, vol. 15, no. 2, pp. 108–110, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Chatterjee, M. Saluja, N. Singh, and A. Kandwal, “To evaluate the antigingivitis and antipalque effect of an Azadirachta indica (neem) mouthrinse on plaque induced gingivitis: a double-blind, randomized, controlled trial,” Journal of Indian Society of Periodontology, vol. 15, no. 4, pp. 398–401, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. N. C. J. P. Lekshmi, N. Sowmia, S. Viveka, Jr. Brindha, and S. Jeeva, “The inhibiting effect of Azadirachta indica against dental pathogens,” Asian Journal of Plant Science and Research, vol. 2, no. 1, pp. 6–10, 2012. View at Google Scholar
  95. V. R. Chava, S. M. Manjunath, A. V. Rajanikanth, and N. Sridevi, “The efficacy of neem extract on four microorganisms responsible for causing dental caries viz Streptococcus mutans, Streptococcus salivarius, Streptococcus mitis and Streptococcus sanguis: an in vitro study,” Journal of Contemporary Dental Practice, vol. 13, no. 6, pp. 769–772, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. A. E. Abdel Moneim, M. S. Othman, and A. M. Aref, “Azadirachta indica attenuates cisplatin-induced nephrotoxicity and oxidative stress,” BioMed Research International, vol. 2014, Article ID 647131, 11 pages, 2014. View at Publisher · View at Google Scholar
  97. A. E. Abdel Moneim, “Azadirachta indica attenuates cisplatin-induced neurotoxicity in rats,” Indian Journal of Pharmacology, vol. 46, no. 3, pp. 316–321, 2014. View at Publisher · View at Google Scholar · View at Scopus
  98. F. R. Durrani, N. Chand, M. Jan, A. Sultan, Z. Durrani, and S. Akhtar, “Immunomodulatory and growth promoting effects of neem leaves infusion in broiler chicks,” Sarhad Journal of Agriculture, vol. 24, pp. 655–659, 2008. View at Google Scholar
  99. R. D. Sadekar, A. Y. Kolte, B. S. Barmase, and V. F. Desai, “Immunopotentiating effects of Azadirachta indica (Neem) dry leaves powder in broilers, naturally infected with IBD virus,” Indian Journal of Experimental Biology, vol. 36, no. 11, pp. 1151–1153, 1998. View at Google Scholar · View at Scopus
  100. D. Sinniah and G. Baskaran, “Margosa oil poisoning as a cause of Reye's syndrome,” The Lancet, vol. 317, no. 8218, pp. 487–489, 1981. View at Publisher · View at Google Scholar · View at Scopus
  101. S. M. Lai, K. W. Lim, and H. K. Cheng, “Margosa oil poisoning as a cause of toxic encephalopathy,” Singapore Medical Journal, vol. 31, no. 5, pp. 463–465, 1990. View at Google Scholar · View at Scopus
  102. N. Sundaravalli, B. Bhaskar Raju, and K. A. Krishnamoorthy, “Neem oil poisoning,” The Indian Journal of Pediatrics, vol. 49, no. 3, pp. 357–359, 1982. View at Publisher · View at Google Scholar · View at Scopus
  103. A. K. Jaiswal, S. K. Bhattacharya, and S. B. Acharya, “Anxiolytic activity of Azadirachta indica leaf extract in rats,” Indian Journal of Experimental Biology, vol. 32, no. 7, pp. 489–491, 1994. View at Google Scholar · View at Scopus
  104. R. B. Raizada, M. K. Srivastava, R. A. Kaushal, and R. P. Singh, “Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats,” Food and Chemical Toxicology, vol. 39, no. 5, pp. 477–483, 2001. View at Publisher · View at Google Scholar · View at Scopus
  105. K. O. Boadu, S. K. Tulashie, M. A. Anang, and J. D. Kpan, “Toxicological analysis of the effect of neem tree extract in an organism,” European Journal of Experimental Biology, vol. 1, pp. 160–171, 2011. View at Google Scholar
  106. Y.-X. Deng, M. Cao, D.-X. Shi et al., “Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity,” Environmental Toxicology and Pharmacology, vol. 35, no. 2, pp. 240–246, 2013. View at Publisher · View at Google Scholar · View at Scopus
  107. A. A. Biu, S. D. Yusufu, and J. S. Rabo, “Acute toxicity study on neem (Azadirachta indica, Juss) leaf aqueous extract in chicken (Gallus gallus domesticus),” African Scientist, vol. 11, no. 4, pp. 241–244, 2010. View at Google Scholar
  108. B. C. Akin-Osanaiya, A. J. Nok, S. Ibrahim et al., “Antimalarial effect of neem leaf and neem stem bark extracts on Plasmodium berghei infected in the pathology and treatment of malaria,” International Journal of Research in Biochemistry and Biophysics, vol. 3, no. 1, pp. 7–14, 2013. View at Google Scholar
  109. S. A. Bakr, “Evaluation of acute toxicity of water extract of Azadirachta indica leaves and seeds in rats,” Pakistan Journal of Biological Sciences, vol. 16, no. 14, pp. 697–700, 2013. View at Publisher · View at Google Scholar · View at Scopus
  110. M. F. Khan and S. M. Ahmed, “Toxicity of crude Neem leaf extract against housefly Musca domestica L. Adults as compared With DDVP, Dichlorvos,” Turkish Journal of Zoology, vol. 4, pp. 219–223, 2000. View at Google Scholar
  111. S. N. Okpanyi and G. C. Ezeukwu, “Anti-inflamatory and antipyretic activities of Azadirachta indica,” Planta Medica, vol. 41, no. 1, pp. 34–39, 1996. View at Google Scholar
  112. S. S. Pandey, A. K. Jha, and V. Kaur, “Aqueous extract of neem leaves in treatment of Psoriasis vulgaris,” Indian Journal of Dermatology, Venereology and Leprology, vol. 60, no. 2, pp. 63–67, 1994. View at Google Scholar · View at Scopus
  113. M. R. Pai, L. D. Acharya, and N. Udupa, “Evaluation of antiplaque activity of Azadirachta indica leaf extract gel—a 6-week clinical study,” Journal of Ethnopharmacology, vol. 90, no. 1, pp. 99–103, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. N. R. Pillai and G. Santhakumari, “Effects of nimbidin on acute and chronic gastro-duodenal ulcer models in experimental animals,” Planta Medica, vol. 50, no. 2, pp. 143–146, 1984. View at Publisher · View at Google Scholar · View at Scopus