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

Wataru Hiruma^1,2, Kohei Suruga^1*, Kazunari Kadokura¹, Tsuyoshi Tomita¹, Ayaka Miyata¹, Yoshihiro Sekino¹, Masahiko Kimura², Nobuo Yamaguchi^3,4, Yasuhiro Komatsu^5,6, C. A. Tony Buffington⁷, Nobufumi Ono²

¹International Operation Department (FM Center for R & D), Kibun Foods Inc., Tokyo, Japan.
²Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
³Ishikawa Natural Medicinal Products Research Center, Ishikawa, Japan.
⁴Department of Fundamental Research for CAM, Kanazawa Medical University, Ishikawa, Japan.
⁵Kitasato Institution for Life Science, Kitasato University, Tokyo, Japan.
⁶Sun R & D Institute for Natural Medicines Co. Inc., Tokyo, Japan.
⁷Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, USA.

DOI: 10.4236/oji.2015.51005                

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.

Keywords

Rhus verniciflua, Antitumor, Antiproliferation, Acute Toxicity

Conflicts of Interest

The authors declare no conflicts of interest.

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