[Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill prepared from Polygoni Multiflori Radix preparata in dogs].

To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.

Effect of maternal folic acid supplementation on prostatitis risk in the rat offspring.

PURPOSE: Folic acid (FA) intake has increased to high levels in many countries for the prevention of neural tube defects. However, the impact of excess FA intake, particularly before and during pregnancy, requires further investigation. Our aim was to investigate the effect of maternal folic acid supplementation on prostatitis risk in the rat offspring. METHODS: Female SD rats were administrated with different doses of FA by oral gavage from 2 weeks prior to mating to GD14: 0 mg/kg (distilled water), 0.2 mg/kg FA and 2.0 mg/kg FA respectively. The male rat offspring from each maternal FA group were castrated on PND56 and injected different doses of 17ß-estradiol (E2) subcutaneously for 30 days to induce prostatitis: 0 mg/kg (corn oil) and 1.25 mg/kg E2 respectively. At necropsy, the prostates were collected for histopathological analysis. Fasting blood was collected for the determination of serum E2, T, DHT, and folic acid levels. The expression of TNF-α, COX-2, and ER-α was determined by immunohistochemistry. RESULTS: High-dose (2.0 mg/kg) maternal folic acid supplementation significantly increased the proportion of prostatitis in FA(2.0) + E2(1.25) group (87.5%) compared with FA(0) + E2(1.25) group (25%). The inflammation was focal and severe, and large amounts of inflammatory cells appeared in different regions of the prostate in FA(2.0) + E2(1.25) group. The serum T, DHT, and FA levels in FA(2.0) + E2(1.25) group were significantly higher than those in FA(0) + E2(1.25) group. The expression of TNF-α, COX-2, and ER-α in three 1.25 mg/kg E2 groups presented positive, and the number and distribution of positive cells increased as FA dosage increased. CONCLUSIONS: Our findings suggest that high-dose (2.0 mg/kg) maternal folic acid supplementation significantly increases the proportion of prostatitis and the prostatic inflammation is more obvious and severe in the rat offspring.

[Research progress in mechanism of traditional Chinese medicine treatment of polycystic ovary syndrome].

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder, which is characterized by hyperandrogenism, insulin resistance and chronic anovulation, and has become a serious threat to the health of adolescents and women of childbearing age.At present,lowering androgen, improving insulin resistance and inducing ovulation are the main methods adopted by doctors to treat the disease, but the adverse reactions of the western medicine and the long-term treatment are hard to be accepted by the patients. PCOS treated by traditional Chinese medicine has achieved a certain effect in recent years.Traditional Chinese medicine is relatively safe and has more effect in many links and targets in improving the symptom of endocrine and metabolic disorder in patients with PCOS. This paper expounds the traditional Chinese medicine pathogenesis of PCOS through clinical and experimental aspects of the literature research：correcting endocrine hormone disorder,the effects of the expression of gene and regulatory factors,improving insulin resistance,correcting lipid metabolic disorder,improving the pregnancy outcome and improving ovarian morphology to summarize the treatment of traditional Chinese medicine in PCOS research results in recent years.

[Establishment of an in vitro screening model for steroid 5 alpha-reductase inhibitors with the microplate reader].

OBJECTIVE: To establish an in vitro screening model for steroid 5 alpha-reductase inhibitors using the microplate reader. METHODS: Steroid 5 alpha-reductase was obtained from the liver of female rats, an in vitro screening model for steroid 5 alpha-reductase inhibitors established using the 96-well plate and microplate reader after determination of the enzymatic activity, and the reliability of the model verified with the known 5 alpha-reductase inhibitors epristeride and finasteride. Added to the 96-well plate were the final concentrations of testosterone (0-40 micromol/L), NADPH (22 micromol/L), epristeride (0-60 nmol/L) or finasteride (0-60 nmol/ L) and steroid 5 alpha-reductase (20 microl), the total volume of each well adjusted to 200 microl with Tris-Hcl buffer. The 96-well plate was placed in the microplate reader, mixed and incubated at 37 degrees C, followed by detection of the A340nm value at 0 and 10 min and analysis of the data. RESULTS: The Km value of steroid 5 alpha-reductase was 3.794 micromol/L, with a Vmax of 0.271 micromol/(L. min). The Ki of epristeride was 148.2 nmol/L, with an IC50 of 31.5 nmol/L, and the enzymatic reaction kinetic curve suggested that epristeride was an uncompetitive enzyme inhibitor. The Ki of finasteride was 158. 8 nmol/L, with an IC50 of 13.6 nmol/L. The enzymatic reaction kinetic curve showed that both epristeride and finasteride were competitive enzyme inhibitors, similar to those reported in the published literature. CONCLUSION: A screening model was successfully established, which could rapidly and effectively screen steroid 5 alpha-reductase inhibitors in vitro.