Share This Article:

Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing Rhus verniciflua and Some Other Herbs

Abstract Full-Text HTML XML Download Download as PDF (Size:469KB) PP. 39-49
DOI: 10.4236/oji.2015.51005    3,398 Downloads   4,081 Views   Citations

ABSTRACT

A novel antitumor agent was developed from six kinds of herbs containing Rhus verniciflua (Rv-PEM01). The components were traditionally established for each formula for traditional medicine. The formula was designed to affect antitumor effect as well as maintain host immune functions. First, we investigated the antiproliferative activities of Rv-PEM01 on human and canine tumor cell lines in vitro, and on antitumor effects using BALB/cAJcl-nu/nu mice in vivo. Acute oral toxicity of Rv-PEM01 was also investigated in vivo in ddY mice. Rv-PEM01 exhibited antiproliferative activities against PC-3 (IC50: 0.328 ± 0.081 mg/ml), A549 (IC50: 0.520 ± 0.070 mg/ml), D-17 (IC50: 0.124 ± 0.037 mg/ml) and MRC-5 (IC50: 0.505 ± 0.058 mg/ml) cells. Luteolin 7-β-D-glucopyranoside and apigenin 7-β-D-glucopyranoside were identified as the main active compounds in Rv-PEM01 by HPLC analysis. The single dose toxicity study of Rv-PEM01 did not result in any deaths or abnor-malities in daily behavior, body weight gain, or anatomical observations at necropsy. Thus, so we could not calculate the 50% lethal dose (LD50) in mice, but it would be higher than 5.0 g/kg. Treat- ment with Rv-PEM01 at a dose of 2.5 g/kg tended to show antitumor activities on mice bearing Colon26 tumors compared with the control group. It was concluded that the formula was a safe antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Hiruma, W. , Suruga, K. , Kadokura, K. , Tomita, T. , Miyata, A. , Sekino, Y. , Kimura, M. , Yamaguchi, N. , Komatsu, Y. , Buffington, C. and Ono, N. (2015) Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing Rhus verniciflua and Some Other Herbs. Open Journal of Immunology, 5, 39-49. doi: 10.4236/oji.2015.51005.

References

[1] Cherng, J.M., Shieh, D.E., Chiang, W., Chang, M.Y. and Chiang, L.C. (2007) Chemopreventive Effects of Minor Dietary Constituents in Common Foods on Human Cancer Cells. Bioscience, Biotechnology, and Biochemistry, 71, 1500- 1504.
http://dx.doi.org/10.1271/bbb.70008
[2] Sharma, N., Samarakoon, K.W., Gyawali, R., Park, Y.H., Lee, S.J., Oh, S.J., Lee, T.H. and Jeong, D.K. (2014) Evaluation of the Antioxidant, Anti-Inflammatory, and Anticancer Activities of Euphorbia hirta Ethanolic Extract. Molecules, 19, 14567-14581.
http://dx.doi.org/10.3390/molecules190914567
[3] Yu, T., Moh, S.H., Kim, S.B., Yang, Y., Kim, E., Lee, Y.W., Cho, C.K., Kim, K.H., Yoo, B.C., Cho, J.Y. and Yoo, H.S. (2013) HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-kB and JNK/ATF-2 Pathways. Journal of Medicinal Food, 16, 56-65.
http://dx.doi.org/10.1089/jmf.2012.2374
[4] Eo, H.J., Park, J.H., Park, G.H., Lee, M.H., Lee, J.R., Koo, J.S. and Jeong, J.B. (2014) Anti-Inflammatory and Anti-Cancer Activity of Mulberry (Morus alba L.) Root Bark. BMC Complementary and Alternative Medicine, 14, 200.
http://dx.doi.org/10.1186/1472-6882-14-200
[5] Ohno, T., Inoue, M. and Ogihara, Y. (2002) Suppressive Effect of Shichimotsu-Koka-To (Kampo Medicine) on Pulmonary Metastasis of B16 Melanoma Cells. Biological and Pharmaceutical Bulletin, 25, 880-884.
http://dx.doi.org/10.1248/bpb.25.880
[6] Sun, A., Chia, J.S., Wang, W.B. and Chiang, C.P. (2004) Immunomodulating Effects of “Tien-Hsien Liquid” on Peripheral Blood Mononuclear Cells and T Lymphocytes from Patients with Recurrent Aphthous Ulcerations. American Journal of Chinese Medicine, 32, 221-234.
http://dx.doi.org/10.1142/S0192415X04001886
[7] Sun, A., Chia, J.S., Chiang, C.P., Hsuen, S.P., Du, J.L., Wu, C.W. and Wang, W.B. (2005) The Chinese Herbal Medicine Tien-Hsien Liquid Inhibits Cell Growth and Induces Apoptosis in a Wide Variety of Human Cancer Cells. Journal of Alternative and Complementary Medicine, 11, 245-256.
http://dx.doi.org/10.1089/acm.2005.11.245
[8] Kim, J.S. and Kim, M.J. (2011) Anti-Oxidant Activity of Rhus verniciflua Stokes by Extract Conditions. Journal of Medicinal Plants Research, 5, 2617-2623.
[9] Rayne, S. and Mazza, G. (2007) Biological Activities of Extracts from Sumac (Rhus spp.): A Review. Plant Foods for Human Nutrition, 62, 165-175.
http://dx.doi.org/10.1007/s11130-007-0058-4
[10] Kadokura, K., Suruga, K., Tomita, T., Hiruma, W., Yamada, M., Kobayashi, A., Takatsuki, A., Nishio, T., Oku, T. and Sekino, Y. (2015) Novel Urushiols with Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitory Activity from the Leaves of Rhus verniciflua. Journal of Natural Medicines, 69, 148-153.
http://dx.doi.org/10.1007/s11418-014-0871-7
[11] Hiruma, W., Suruga, K., Kadokura, K., Tomita, T., Sekino, Y., Komatsu, Y., Kimura, M. and Ono, N. (2013) The Antitumor Effects of a Plant Extract Mixture. Yakugaku Zasshi, 133, 487-491.
http://dx.doi.org/10.1248/yakushi.12-00278-1
[12] Cory, A.H., Owen, T.C., Barltrop, J.A. and Cory, J.G. (1991) Use of an Aqueous Soluble Tetrazolium/Formazan Assay for Cell Growth Assays in Culture. Cancer Communications, 3, 207-212.
[13] Du, Y. and Oshima, R. (1984) Reversed-Phase Liquid Chromatographic Separation and Identification of Constituents of Urushiol in the Sap of the Lac Tree Rhus vernicifera. Journal of Chromatography A, 284, 463-473.
http://dx.doi.org/10.1016/S0021-9673(01)87848-1
[14] Sano, Y., Satoh, H., Chiba, M., Okamoto, M., Serizawa, K., Nakashima, H. and Omae, K. (2005) Oral Toxicity of Bismuth in Rat: Single and 28-Day Repeated Administration Studies. Journal of Occupational Health, 47, 293-298.
http://dx.doi.org/10.1539/joh.47.293
[15] Kiyama, S. (1995) Effect of Growth Hormone on Cancerous Cachexia in Mice Bearing Colon 26 Tumor. Journal of Tokyo Women’s Medical University, 65, 873-882.
[16] Poindessous, V., Koeppel, F., Raymond, E., Comisso, M., Waters, S.J. and Larsen, A.K. (2003) Marked Activity of Irofulven toward Human Carcinoma Cells: Comparison with Cisplatin and Ecteinascidin. Clinical Cancer Research, 9, 2817-2825.
[17] Lee, J.C., Kim, J., Lim, K.T., Yang, M.S. and Jang, Y.S. (2001) Ethanol Eluted Extract of Rhus verniciflua Stokes Showed both Antioxidant and Cytotoxic Effects on Mouse Thymocytes Depending on the Dose and Time of the Treatment. Journal of Biochemistry and Molecular Biology, 34, 250-258.
[18] Lee, J.C., Lim, J. and Jang, Y.S. (2002) Identification of Rhus verniciflua Stokes Compounds That Exhibit Free Radical Scavenging and Anti-Apoptotic Properties. Biochimica et Biophysica Acta, 1570, 181-191.
http://dx.doi.org/10.1016/S0304-4165(02)00196-4
[19] Lee, J.C., Lee, K.Y., Kim, J., Na, C.S., Jung, N.C., Chung, G.H. and Jang, Y.S. (2004) Extract from Rhus verniciflua Stokes Is Capable of Inhibiting the Growth of Human Lymphoma Cells. Food and Chemical Toxicology, 42, 1383- 1388.
http://dx.doi.org/10.1016/j.fct.2004.03.012
[20] Kitts, D.D. and Lim, K.T. (2001) Antitumorigenic and Cytotoxic Properties of an Ethanol Extract Derived from Rhus verniciflua Stokes (RVS). Journal of Toxicology and Environmental Health, Part A, 64, 357-371.
[21] Watson, E.S., Murphy, J.C., Wirth, P.W., Waller, C.W. and Elsohly, M.A. (1981) Immunologic Studies of Poisonous Anacardiaceae: I. Production of Tolerance and Desensitization to Poison Ivy and Oak Urushiols Using Esterified Urushiol Derivatives in Guinea Pigs. Journal of Investigative Dermatology, 76, 164-170.
http://dx.doi.org/10.1111/1523-1747.ep12525589
[22] Hong, D.H., Han, S.B., Lee, C.W., Park, S.H., Jeon, Y.J., Kim, M.J., Kwak, S.S. and Kim, H.M. (1999) Cytotoxicity of Urushiols Isolated from Sap of Korean Lacquer Tree (Rhus vernicifera Stokes). Archives of Pharmacal Research, 22, 638-641.
http://dx.doi.org/10.1007/BF02975339
[23] Kim, M.J., Choi, Y.H., Kim, W.G. and Kwak, S.S. (1997) Antioxidative Activity of Urushiol Derivatives from the Sap of Lacquer Tree (Rhus vernicifera Stokes). Korean Journal of Plant Resources, 10, 227-230.
[24] Johnson, R.A., Baer, H., Kirkpatrick, C.H., Dawson, C.R. and Khurana, R.G. (1972) Comparison of the Contact Allergenicity of the Four Pentadecylcatechols Derived from Poison Ivy Urushiol in Human Subjects. Journal of Allergy and Clinical Immunology, 49, 27-35.
http://dx.doi.org/10.1016/0091-6749(72)90120-0
[25] London, C.A., Bernabe, L.F., Barnard, S., Kisseberth, W.C., Borgatti, A., Henson, M., Wilson, H., Jensen, K., Ito, D., Modiano, J.F., Bear, M.D., Pennell, M.L., Saint-Nartin, J.R., Mccauley, D., Kauffman, M. and Shacham, S. (2014) Preclinical Evaluation of the Novel, Orally Bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Spontaneous Canine Cancer: Results of a Phase I Study. PLoS ONE, 9, e87585.
http://dx.doi.org/10.1371/journal.pone.0087585
[26] Rashed, K.N., Ciric, A., Glamoclija, J., Calhelha, R.C., Ferreira, I.C.F.R. and Sokovic, M. (2013) Antimicrobial Activity, Growth Inhibition of Human Tumour Cell Lines, and Phytochemical Characterization of the Hydromethanolic Extract Obtained from Sapindus saponaria L. Aerial Parts. BioMed Research International, 2013, Article ID: 659183.
http://dx.doi.org/10.1155/2013/659183
[27] Nakazaki, E., Tsolmon, S., Han, J. and Isoda, H. (2013) Proteomic Study of Granulocytic Differentiation Induced by Apigenin 7-Glucoside in Human Promyelocytic Leukemia HL-60 Cells. European Journal of Nutrition, 52, 25-35.
http://dx.doi.org/10.1007/s00394-011-0282-4
[28] Kim, S., Park, S.E., Sapkota, K., Kim, M.K. and Kim, S.J. (2011) Leaf Extract of Rhus verniciflua Stokes Protects Dopaminergic Neuronal Cells in a Rotenone Model of Parkinson’s Disease. Journal of Pharmacy and Pharmacology, 63, 1358-1367.
http://dx.doi.org/10.1111/j.2042-7158.2011.01342.x
[29] Wang, D., Xia, M.Y., Cui, Z., Tashiro, S., Onodera, S. and Ikejima, T. (2004) Cytotoxic Effects of Mansonone E and F Isolated from Ulmus pumila. Biological and Pharmaceutical Bulletin, 27, 1025-1030.
http://dx.doi.org/10.1248/bpb.27.1025
[30] Ahn, M.J., Kim, C.Y., Yoon, K.D., Ryu, M.Y., Cheong, J.H., Chin, Y.W. and Kim, J. (2006) Steroidal Saponins from the Rhizomes of Polygonatum sibiricum. Journal of Natural Products, 69, 360-364.
http://dx.doi.org/10.1021/np050394d

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.