Evaluation of safety of modified-Danggui Buxue Tang in rodents:immunological, toxicity and hormonal aspects.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali (RA), Radix Angelicae Sinensis (RAS) and Folium Epimedii (FE) are three of the extensively applied herbs among traditional Chinese medicines for gynecological disorders and osteoporosis. A derivative herbal formula-RRF, consisting of the three medicines with a weight ratio of 5:1:5, is derived from a famous Chinese herbal formula-Danggui Buxue Tang (DBT). RRF has shown noteworthy perimenopause ameliorating effect in both ovariectomized rats and natural aging female rats, which might represent a promising candidate for the treatment of perimenopausal disorders. The aim of this study was to evaluate its immunological potential, chronic toxicity and reproductive effects by 26-week repeated daily administration in female rats, in order to optimize its safe use. MATERIALS AND METHODS: The effect of RRF on immunological function was studied by macrophage phagocytosis, immune organ index, serum immunoglobulin level as well as delayed type hypersensitivity (DTH) in mice. For toxicity assessment, acute toxicity study was performed according to fixed dose procedure with a single oral administration of RRF to mice. In the oral chronic toxicity, 120 female rats were administrated RRF orally in 0, 1100, 4400, or 8800mg/kg/day doses for 26 weeks. Clinical signs, mortality, body weights, feed consumption, haemato-biochemical parameters, organ weights, histopathology and reproductive hormone profiles were examined at the end of the 13- and 26-week dosing period, as well as after the 4-week recovery period. RESULTS: Oral administration of RRF at three doses (282, 564 and 1128mg/kg) significantly increased the indices of phagocytosis K, as compared with prednisone acetate (PR) group (p<0.05 or 0.01). Exposure of RRF dose-dependently boosted circulating serum IgM level (all p<0.01) in response to CRBC in PR-induced mice. Furthermore, RRF treatment elicited a significant increment (all p<0.01) in DNFB-induced DTH response and the immune organ indices in a dose-dependent manner in mice, in parellel to DNFB-induced group. In the single dose acute toxicity and repeated dose 90-day chronic toxicity investigations, no toxic signs/mortality were observed. RRF treatment did not cause any toxicologically significant changes in clinical signs, food consumption, body weight, relative organ weight, hematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. No treatment related gross/histopathological lesions were observed and no target organ was identified. Long-term repeated administration of RRF exerted a significant promotion on serum level of steroid hormone estradiol, progesterone and testosterone release, along with decrease of circulating pituitary follicle stimulating hormone, luteinizing hormone, and prolactin levels in female rats. The No Observed Adverse Effect Level (NOAEL) of RRF was determined to be over 8800mg/kg/day for elderly female rats, a dose that was equivalent to 50 times of human dose. CONCLUSION: The present investigation demonstrated that RRF possessed appreciable immunopotentiating activity and had a relatively wide margin of safety. Long-term treatment of RRF exhibited estrogenic properties, and retarded certain age-associated degenerations. RRF might have the potential for further development as a safe and effective alternative/complementary to conventional medication in relieving perimenopausal symptoms.

The roles of methanogens and acetogens in dechlorination of trichloroethene using different electron donors.

We evaluated the effects of methanogens and acetogens on the function and structure of microbial communities doing reductive dechlorination of trichloroethene (TCE) by adding four distinct electron donors: lactate, a fermentable organic; acetate, a non-fermentable organic; methanol, a fermentable 1-C (carbon) organic; and hydrogen gas (H2), the direct electron donor for reductive dechlorination by Dehalococcoides. The fermentable electron donors had faster dechlorination rates, more complete dechlorination, and higher bacterial abundances than the non-fermentable electron donors during short-term tests. Phylotypes of Dehalococcoides were relatively abundant (≥9%) for the cultures fed with fermentable electron donors but accounted for only ~1-2% of the reads for the cultures fed by the non-fermentable electron donors. Routing electrons to methanogenesis and a low ratio of Dehalococcoides/methanogenesis (Dhc/mcrA) were associated with slow and incomplete reductive dechlorination with methanol and H2. When fermentable substrates were applied as electron donors, a Dhc/mcrA ratio ≥6.4 was essential to achieve fast and complete dechlorination of TCE to ethene. When methanogenesis was suppressed using 2-bromoethanesulfonate (BES), achieving complete dechlorination of TCE to ethane required a minimum abundance of the mcrA gene. Methanobacterium appeared to be important for maintaining a high dechlorination rate, probably by providing Dehalococcoides with cofactors other than vitamin B12. Furthermore, the presence of homoacetogens also was important to maintain a high dechlorination rate, because they provided acetate as Dehalococcoides's obligatory carbon source and possibly cofactors.