Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

The Toxicity and Anti-cancer Activity of the Hexane Layer of Melia azedarach L. var. japonica Makino's Bark Extract

  • Received : 2011.11.22
  • Accepted : 2012.03.29
  • Published : 2012.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

Keywords

References

  1. Baguley, B.C. and Nash, R. (1981). Antitumour activity of substituted 9-anilinoacridines-comparison of in vivo and in vitro testing systems. Eur. J. Cancer, 17, 671-679. https://doi.org/10.1016/0014-2964(81)90271-1
  2. Boyd, M.R. (1989). Status of the NCI preclinical antitumor drug discovery screen. Principles and Practice of Oncology, 3, 1-12.
  3. Cespedes, C.L., Alarcón, J., Aranda, E., Becerra, J. and Silva, M. (2001). Insect growth regulator and insecticidal activity of beta-dihydroagarofurans from Maytenus spp. (Celastraceae). Z. Naturforsch C., 56, 603-613.
  4. Cha, S.M. (1977). Potential anticancer medicinal plants. A statistical evaluation of their frequencies of appearance in oriental medicine formularies. Kor. J. Pharmacogn., 8, 1-15.
  5. Ford, R.A., Letizia, C. and Api, A.M., (1988). Monographs on fragrance raw materials. Food Chem. Toxicol., 26, 273-415. https://doi.org/10.1016/0278-6915(88)90137-8
  6. Geran, R.I., Greenberg, N.H., Macdonald, M.M. and Abbott, B.J. (1977). Modified protocol for the testing of new synthetics in the L1210 lymphoid leukemia murine model in the DR&D program, DCT, NCI. Natl. Cancer Inst. Monogr., 45, 151-153.
  7. Gonzalez, V.M., Fuertes, M.A., Alonso, C. and Perez, J.M. (2001). Is cisplatin-induced cell death always produced by apoptosis? Mol. Pharmacol., 59, 657-663.
  8. Hong, M.H. (1972). Statistical studies on the formularies of oriental medicine (1) prescription frequency and their origin distribution of herb drugs. Kor. J. Pharmacogn., 3, 57-64.
  9. Hwang, W.I., Lee, S.D. and Oh, S.K. (1982). A study on the pharmacological activities of Korean medicinal herbs mainly on the antitumor activities (in Korean). Kor. Biochem. J., 15, 205-219.
  10. Hwang, W.I. and Oh, S.K. (1984). Effects of petroleum ether extract of ginseng root on same enzyme activity in human colon cancer cells. Kor. J. Ginseng Sci., 8, 153-166.
  11. Itokawa, H., Qiao, Z.S., Hirobe, C. and Takeya, K. (1995). Cytotoxic limonoids and tetranortriterpenoids from Melia azedarach. Chem. Pharm. Bull., 43, 1171-1175. https://doi.org/10.1248/cpb.43.1171
  12. Keshri, G., Lakshmi, V. and Singh, M.M. (2003). Pregnancy interceptive activity of Melia azedarach Linn. in adult female Sprague- Dawley rats. Contraception, 68, 303-306. https://doi.org/10.1016/S0010-7824(03)00143-4
  13. Khan, M.R., Kihara, M. and Omoloso, A.D. (2001). Antimicrobial activity of Horsfieldia helwigii and Melia azedarach. Fitoterapia, 72, 423-427. https://doi.org/10.1016/S0367-326X(00)00334-8
  14. Kim, H.W. and Kang, S.C (2009). Anti-cancer activities of extract from the bark of Melia azedarach L. var. japonica Makino. Kor. J. Plant Resources, 22, 312-316.
  15. Kwon, H.C., Lee, B.G., Kim, S.H., Jung, C.M., Hong, S.Y., Han, J.W., Lee, H.W., Zee, O.P. and Lee, K.R. (1999). Inducible nitric oxide synthase inhibitors from Melia azedarach var. japonica. Arch. Pharm. Res., 22, 410-413. https://doi.org/10.1007/BF02979067
  16. Lee, B.G., Kim, S.H., Zee, O.P., Lee, K.R., Lee, H.Y., Han, J.W. and Lee, H.W. (2000). Suppression of inducible nitric oxide synthase expression in RAW 264. 7 macrophages by two betacarboline alkaloids extracted from Melia azedarach. Eur. J. Pharmacol., 406, 301-309. https://doi.org/10.1016/S0014-2999(00)00680-4
  17. Losa, J.H., Parada Cobo, C., Viniegra, J.G., Sanchez-Arevalo Lobo, V.J., Ramon y Cajal, S. and Sanchez-Prieto, R. (2003). Role of the p38 MAPK pathway in cisplatin-based therapy. Oncogene, 22, 3998-4006. https://doi.org/10.1038/sj.onc.1206608
  18. Miyazaki, T. and Nishijima, M. (1981). Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem. Pharm. Bull., 29, 3611-3616. https://doi.org/10.1248/cpb.29.3611
  19. Son, H.S. and Hwang, W.I. (1990). A study on the cytotoxic activity of garlic (Allium sativum) extract against cancer cells (in Korean). Kor. J. Nutrition, 23, 135-147.
  20. Takeya, K., Quio, Z.S., Hirobe, C. and Itokawa, H. (1996a). Cytotoxic trichilin-type limonoids from Melia azedarach. Bioorg. Med. Chem., 4, 1355-1359. https://doi.org/10.1016/0968-0896(96)00128-9
  21. Takeya, K., Qiao, Z.S., Hirobe, C. and Itokawa, H. (1996b). Cytotoxic azadirachtin-type limonoids from Melia azedarach. Phytochemistry, 42, 709-712. https://doi.org/10.1016/0031-9422(96)00044-1
  22. Thayer, P.S., Himmelfarb, P. and Watts, G.L. (1971). Cytotoxicity assays with L1210 cells in vitro: comparison with L1210 in vivo and KB cells in vitro. Cancer Chemother. Rep. 2, 2, 1-25.

Cited by

  1. var. japonica in Korea vol.163, pp.11-12, 2014, https://doi.org/10.1111/jph.12356
  2. The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents vol.6, pp.10, 2016, https://doi.org/10.1016/j.apjtb.2016.08.007
  3. A review: Melia azedarach L. as a potent anticancer drug vol.12, pp.23, 2018, https://doi.org/10.4103/phrev.phrev_41_17