Subchronic oral toxicity of herbal formula PM012 in Beagle dogs Hwan-Suck Chung Han Kyum Kim Dong Wook Kim Sun Kwang Kim Insop Shim Hyunsu Bae Email author Original Paper First Online: 23 October 2014 Received: 30 April 2014 Accepted: 20 June 2014 DOI :
10.1007/s13273-014-0037-4
Cite this article as: Chung, HS., Kim, H.K., Kim, D.W. et al. Mol. Cell. Toxicol. (2014) 10: 329. doi:10.1007/s13273-014-0037-4 Abstract PM012 is a modified oriental medicinal prescription based on Yukmijihwang-tang.We previously reported that PM012 has a neuro-protective effect and has no toxicity with chronic administration in rats. As a process of the development of herbal new drug, we assessed the oral toxicity of PM012 in Beagle dogs. PM012 was administered orally for 28 days at doses of 0, 250, 500, 1000 and 1500 mg/kg/day. When we analyzed the body weight gain, food consumption, clinical observations, blood biochemical, hematology, organ weight ratios and histopathological findings, there were no significant differences between the control and treated groups. It was concluded that orally administered PM012 was safe in dogs, and no treatment-related toxicity was detected, even at the highest doses investigated in repeated dose oral toxicity studies.
Keywords PM012 Beagle dogs Sub-chronic toxicity Oriental medicinal prescription
References 1.
Shin, I. S., Lee, M. Y., Ha, H. K., Seo, C. S., & Shin, H. K. Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats.
BMC Complement Altern Med
12 :48 (2012).
PubMed CrossRef PubMedCentral Google Scholar 2.
Kang, D. G.
et al. Yukmijihwang-tang ameliorates ischemia/reperfusion-induced renal injury in rats.
J Ethnopharmacol
104 :47–53 (2006).
PubMed CrossRef Google Scholar 3.
Shim, K. S., Ma, C. J., Kim, D. S., & Ma, J. Y. Yukmijihwang-tang inhibits receptor activator for nuclear Factor-kappaB ligand-induced osteoclast differentiation.
J Med Food
14 :1439–1447 (2011).
PubMed CrossRef Google Scholar 4.
Kang, M.
et al. Effects of Yukmijihwang-tang derivatives (YMJd) on ibotenic acid-induced amnesia in the rat.
Biol Pharm Bull
29 :1431–1435 (2006).
PubMed CrossRef Google Scholar 5.
Park, E.
et al. Yukmijihwang-tang derivatives enhance cognitive processing in normal young adults: a double-blinded, placebo-controlled trial.
Am J Chin Med
33 :107–115 (2005).
PubMed CrossRef Google Scholar 6.
Ha, H.
et al. Safety evaluation of Yukmijihwang-tang: assessment of acute and subchronic toxicity in rats.
Evid Based Complement Alternat Med 2011, 672136 (2011).
PubMed CrossRef PubMedCentral Google Scholar 7.
Ha, H.
et al. Evaluation of genotoxicity of Yukmijihwang-tang, a herbal formula.
Regul Toxicol Pharmacol
59 :391–396 (2011).
PubMed CrossRef Google Scholar 8.
Park, J., Kim, H. Y., & Lee, S. M. Protective effects of Moutan Cortex Radicis against acute hepatotoxicity.
Afr J Tradit Complement Altern Med
8 :220–225 (2011).
PubMed PubMedCentral Google Scholar 9.
Shon, Y. H., & Nam, K. S. Protective effect of Moutan Cortex extract on acetaminophen-induced hepatotoxicity in mice.
J Ethnopharmacol
90 :415–419 (2004).
PubMed CrossRef Google Scholar 10.
Fu, P. K., Wu, C. L., Tsai, T. H., & Hsieh, C. L. Anti-inflammatory and anticoagulative effects of paeonol on LPS-induced acute lung injury in rats.
Evid Based Complement Alternat Med 2012, 837513 (2012).
PubMed PubMedCentral Google Scholar 11.
Lee, H., Lee, G., Kim, H., & Bae, H. Paeonol, a major compound of moutan cortex, attenuates Cisplatin-induced nephrotoxicity in mice.
Evid Based Complement Alternat Med 2013, 310989 (2013).
PubMed PubMedCentral Google Scholar 12.
Liu, J.
et al. Neuroprotective effect of paeonol on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat.
Neurosci Lett
549 :63–68 (2013).
PubMed CrossRef Google Scholar 13.
Kim, K. H.
et al. Therapeutic effect of the tuber of alisma orientale on lipopolysaccharide-induced acute lung injury.
Evid Based Complement Alternat Med 2013, 863892 (2013).
PubMed PubMedCentral Google Scholar 14.
Jin, H. G.
et al. A new triterpenoid from Alisma orientale and their antibacterial effect.
Arch Pharm Res
35 :1919–1926 (2012).
PubMed CrossRef Google Scholar 15.
Lee, J. H.
et al. The rhizomes of Alisma orientale and alisol derivatives inhibit allergic response and experimental atopic dermatitis.
Biol Pharm Bull
35 :1581–1587 (2012).
PubMed Google Scholar 16.
Sohn, S. H., Kim, S. J., Kim, Y., Shim, I., & Bae, H. Safety and efficacy assessment of standardized herbal formula PM012.
BMC Complement Altern Med
12 :24 (2012).
PubMed CrossRef PubMedCentral Google Scholar 17.
Elwood, C.
et al. Emesis in dogs: a review.
J Small Anim Pract
51 :4–22 (2010).
PubMed CrossRef Google Scholar 18.
Liu, Z., Li, C., Li, M., Li, D., & Liu, K. The subchronic toxicity of hydroxysafflor yellow A of 90 days repeatedly intraperitoneal injections in rats.
Toxicology
203 :139–143 (2004).
PubMed CrossRef Google Scholar © The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2014
Authors and Affiliations Hwan-Suck Chung Han Kyum Kim Dong Wook Kim Sun Kwang Kim Insop Shim Hyunsu Bae Email author 1. Department of Physiology, College of Korean Medicine Kyung Hee University Seoul Republic of Korea 2. The Graduate School of Basic Science of Korean Medicine, College of Korean Medicine Kyung Hee University Seoul Republic of Korea