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

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

Effect of Alpinia katsumadai Hayata on House Dust Mite-Induced Atopic Dermatitis in NC/Nga Mice

We evaluated the effects of Alpinia katsumadai Hayata (AKH, Zingiberaceae) extract on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells, thymus- and-activation-regulated chemokine (TARC/CCL17) in HaCaT cells, and histamine level in HMC-1 cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for 4 weeks, and the protective effects of AKH was investigated by measuring the severity of the skin reaction on the back and ears, and plasma levels of immunoglobulin E (IgE) and histamine. AKH extract suppressed the production of NO and PGE2 in RAW 264.7 cells, TARC in HaCaT cells, and histamine in HMC-1 cells in a dose-dependent manner. In in vivo experiments, the severity of dermatitis, including erythema/hemorrhage, edema, erosion and scaling, and plasma levels of IgE, and histamine were lower in NC/Nga mice with atopic dermatitis, treated with AKH extract than in untreated mice. AKH extract reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration on the skin of the back and ear. These results suggest that AKH inhibits the development of house dust mite-induced atopic dermatitis in NC/Nga mice

Antiatopic Dermatitis Effect of Artemisia iwayomogi in Dust Mice Extract-Sensitized Nc/Nga Mice

Aims. Artemisia iwayomogi (AI) has been used for fever reduction, diuresis, and hepatoprotection in Korea. The present study was performed to evaluate the anti-inflammatory and antiatopic dermatitis effects of AI using both in vitro and in vivo systems. Methods. The compositions in AI were analyzed by HPLC. To determine the anti-inflammatory effects of AI, the production of nitric oxide (NO) was measured in lipopolysaccharide treated RAW264.7 cells. Histamine levels were assayed to evaluate the antiallergic effects on MC/9 cells stimulated with phorbol-12 myristate 13-acetate and A23187. Finally, AI (10 mg/mouse/day) was topically applied onto the backs and ears of Dermatophagoides farinae-sensitized Nc/Nga mice for four weeks. Results. Isochlorogenic acid A (20.63 ± 0.26 mg/g), chlorogenic acid (9.04 ± 0.08 mg/g), and scopoletin (8.23 ± 0.01 mg/g) were among the major components of AI. AI inhibited the NO and histamine productions in RAW264.7 and MC/9 cells, respectively. In the mice, the topical application of AI reduced the dermatitis scores in the dorsal skin and ears and reduced the plasma levels of IgE. Conclusions. These results suggest that AI might be explored as a potential therapeutic agent to treat AD, and that the analytic method using HPLC will facilitate the development of quality control for AI