Safety evaluation of root extract of Pueraria lobata and Scutellaria baicalensis in rats.

BACKGROUND: The roots of Pueraria lobata and Scutellaria baicalensis, herbal medicines with a long history of widespread use, have been traditionally prescribed in combination to treat stroke, diabetes, and acute infectious diarrhea in East Asia. Nevertheless, toxicological data on these herbs and their combination are limited. This study investigated the acute and 13-week subchronic toxicity of root extract of P. lobata and S. baicalensis (HT047) for stroke treatment in male and female Sprague-Dawley rats. METHODS: In the acute toxicity study, HT047 was administered orally at a single dose of 5000 mg/kg. In the subchronic toxicity study, HT047 was administered orally at repeated daily doses of 800, 2000, and 5000 mg/kg/day for 13 weeks, followed by a 4-week recovery period. RESULTS: In the acute toxicity study, there were no deaths or toxicologically significant changes in clinical signs, body weight, and necropsy findings. In the subchronic toxicity study, HT047 at all doses caused no death and no treatment-related adverse effects on food consumption; organ weight; ophthalmologic, urinalysis, and hematological parameters; and necropsy findings of both rat sexes. There were some treatment-related alterations in clinical signs, body weight, and serum biochemistry and histopathological parameters; however, these changes were not considered toxicologically significant because they were resolved during the recovery period or resulted from the pharmacological effects of P. lobata and S. baicalensis. CONCLUSIONS: The oral approximate lethal dose (the lowest dose that causes mortality) of HT047 was greater than 5000 mg/kg in male and female rats. The oral no-observed-adverse-effect level of HT047 was greater than 5000 mg/kg/day in rats of both sexes, and no target organs were identified. The present findings support the safety of an herbal extract of P. lobata and S. baicalensis as a therapeutic agent for stroke and further confirm the safety of the combined use of P. lobata and S. baicalensis in clinical practice.

Assessment of fertility and reproductive toxicity in adult female mice after long-term exposure to Pueraria mirifica herb.

The present study investigated the effects of long-term administration of Pueraria mirifica (PM) at non-toxic doses on the ovarian function and fertility of adult female mice based on evaluation of hematological and biochemical parameters. Female mice were divided into 4 groups (36 mice/group). Groups 1-3 were orally treated with a dose of 0 (PM-0), 10 (PM-10) or 100 mg/kg BW/day PM (PM-100), and group 4 was subcutaneously injected with 200 mug/kg BW/day of synthetic estrogen diethylstilbestrol (DES). The treatment schedule was separated into treatment and post-treatment periods. The duration of each period was 8 weeks. The PM-10 mice exhibited regular estrous cycles, while the PM-100 and DES treatments induced prolonged estrous cycles. Although no changes were observed in the uterus and ovary weights of the mice after the PM-100 and DES treatments, hyperplasia of the uterine endothelium and a decrease in the number of growing ovarian follicles were detected. The changes in the ovarian histologies of the PM-100 and DES mice were related to reductions in the levels of LH and FSH, which subsequently caused a decrease in mating efficiency. Once the PM mice were able to copulate, they were capable of successfully becoming pregnant and mothering offspring. No abnormalities were observed in the external morphologies and reproductive organ weights of the 50-day-old offspring. In conclusion, our results suggest that long-term exposure to 100 mg/kg BW of PM has adverse effects on the mating efficiency and reproduction of adult female mice and that administration of 10 mg/kg BW of PM does not induce any changes in the hypothalamic-pituitary-ovarian-uterine axis.

Three indigenous Thai medicinal plants for control of Aedes aegypti and Culex quinquefasciatus.

The potential larvicidal activity and insect growth regulator (IGR) properties of three selected indigenous medicinal Thai plants were tested against two species of mosquito with special reference to the late 3rd and early 4th instar larvae (L3 and L4, respectively). In case of larvicidal activity, Thevetia peruviana was the most potent, followed by Pueraria mirifica, and Butea superba was the least effective. In all cases, the late 3rd instar was more susceptible than the early 4th instar larvae, and the 48-hours exposure yielded more potent larvicidal activity than 24-hours exposure. However, at sublethal dosages, both P. mirifica and B. superba showed some dispersed effects interfering with ecdysis. A variety of toxic effects were observed and recorded in eight categories according to the stage of metamorphosis when death occurred. P. mirifica rendered the main deleterious effects in the pupa-adult period in both instar of Ae. aegypti and Cx. quinquefasciatus, whereas B. superba showed highest effect in black-pupa period of the late 3rd instar larval stage. The results were reversed for the early 4th instar larvae of both species of mosquito as the main effect appeared in the pupa-adult category. The overall results indicated that T. peruviana did not show any IGR properties; whereas, P. mirifica and B. superba seemed to exhibit the juvenile hormone type activity which resulted in abnormal death at various stages of development. B. superba was more promising than P. mirifica, and Ae. aegypti was about 2 times more susceptible than Cx. quinquefasciatus. In addition, L3 was always more susceptible than L4 with both mosquito species.

Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and antimutagenicity of Thunbergia laurifolia Linn.

Thunbergia laurifolia Linn has been reputed to have antitoxic effects for all toxic substances. In this present study, we evaluated its effect against the mutagenicity induced by aqueous extracts from Pueraria mirifica Airy Shaw & Suvatabundhu in male rats. The formation of micronuclei in polychromatic erythrocytes was induced by oral administration of an aqueous extract of P. mirifica at the doses of 400, 600, and 800 mg/kg to the rats for 30 days. The results were that the extracts of P. mirifica at doses of 600 and 800 mg/kg acted as a mutagenic agent by inducing higher frequencies of micronuclei as compared to the controls. For the antimutagenic test, P. mirifica extract at a dose of 600 mg/kg (minimal effective dose) was mixed with fresh and dried extracts of T. laurifolia in proportions of 7:3 and 1:1, respectively. The results of 4-week-treatment indicated that aqueous extracts of T. laurifolia, prepared by both fresh and dry methods, could significantly inhibit the induction of micronuclei as induced by P. mirifica. It could be concluded from the results that, under certain circumstances, T. laurifolia exhibits a significant antimutagenic activity. The use of P. mirifica and T. laurifolia as fusion herbal medicines is suggested.