Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

Abstract

Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day.

Acute and subacute toxicity of an ethanolic extract of Melandrii Herba in Crl:CD sprague dawley rats and cytotoxicity of the extract in vitro

“…Gross postmortem examinations were performed after an overdose of anesthetic as described previously [ 11 ]. Absolute organ weights were measured and relative organ weights (organ-to-body weight ratios) were calculated for the following: brain, pituitary gland, adrenal gland, liver, spleen, kidneys, heart, thymus, lung, salivary gland, thyroids, testes, ovaries, epididymides, seminal vesicle, prostate, and uterus.…”

Subacute Oral Toxicity of Yukmijiwhang‐Tang in Crl:CD Sprague‐Dawley Rats and Its Cytotoxicity

“…In the pharmacokinetic aspect, the metabolism rate in small animals including mouse and rat is faster than in humans [ 25 ]. As we previously reported [ 13 ], the equivalent dose of YMJ in rats converted from its single dose in humans was 1,329 mg according to van Miert [ 26 ], which is a value less than the NOAEL (2000 mg/kg in rats). The single administration dose of YMJ in human is 46.875 g dried herb [ 1 ], which is equivalent to 12.656 g of the extract (yield = 27.0% of the raw material).…”

“…Previously, we reported on the acute and subchronic toxicity as well as genotoxicity of YMJ in an animal model. We found that YMJ had no acute and subchronic toxicity or genotoxicity and its no-observed-adverse-effect-level (NOAEL) is 2000 mg/kg/day [ 13 , 14 ]. However, there has been no report on the subacute toxicity of YMJ.…”

Rokumi-jio-gan-Containing Prescriptions Attenuate Oxidative Stress, Inflammation, and Apoptosis in the Remnant Kidney

“…Traditional medicines, including Chinese prescriptions, have attracted much attention due to their extensive and unique biological activities without toxicity and/or side effects [4]. Hachimi-jio-gan has been long and widely used to treat several chronic diseases, including nephritis, infertility diabetes, and vegetative ataxia [5], although scientific evidence supporting the pharmacological basis for its therapeutic effects has not yet been well established.…”