Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin.

INTRODUCTION: Forsythin is the main ingredient of Forsythia suspensa and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use. METHODS: Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of Salmonella typhimurium were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin. RESULTS: Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture (p > 0.05). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture (p > 0.05). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method. CONCLUSION: Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.

Reproductive Systemic Toxicity and Mechanism of Glucosides of Tripterygium wilfordii Hook. F. (GTW).

BACKGROUND: To study the mechanism of reproductive systemic toxicity of Tripterygium wilfordii on SD rats. METHODS: The SD rats were randomly divided into groups and allocated three different treatments: control, 37.8 mg/kg Tripterygium glycosides, and 94.5 mg/kg Tripterygium glycosides, with each treatment applied for different lengths of time to 20 animals. Each group received treatment by intragastric administration once per day for 90 days. The estrus cycle was continuously observed throughout treatment. Animals were killed at each time point and analyses of sex hormones, sexual organ weights and coefficients, semen, pathology, and immunohistochemistry were conducted. RESULTS: The metestrus phase of the rats administered the low-dose and high-dose treatments was significantly decreased. The uterus organ-body coefficients of female rats were significantly increased, whereas the testis and epididymis organ-body and organ-brain coefficients in male rats were significantly decreased by the high-dose and low-dose treatments at different time points. An increase in immature sperm and sperm abnormality rate was observed at different times in the low-dose and high-dose groups. Pathological changes were clear in the testis, epididymis, ovary, and uterus. The levels of multiple hormones were significantly decreased. The hypothalamus estrogen receptor alpha (ER-α) receptor expression in female rats was also significantly decreased. The androgen receptor (AR) expression in the hypothalamus and the testis and epididymis was significantly decreased at different times by the high-dose treatment. CONCLUSION: Tripterygium glycosides affected the estrus cycle in female rats and caused damage to the uterus; in male rats, the testicles and sperm were damaged. The mechanism of reproductive toxicity occurred through the secretion of multiple hormones.

Evaluating the safety of forsythin from Forsythia suspensa leaves by acute and sub-chronic oral administration in rodent models.

OBJECTIVE: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety. METHODS: Acute toxicity was determined by oral administration of a single dose of 18100 mg/kg forsythin in NIH mice. Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0, 540, 1620, and 6480 mg/kg in SD rats. RESULTS: In the acute toxicity study, mortality was not observed after 14 days. In addition, clinically relevant adverse effects, or variations in body weight or food consumption were not observed. Similarly, after 30 days in the sub-chronic toxicity study, no mortality or significant toxicological effects such as decreased food consumption, body weight, biochemical parameters and vital organs etc. were noticed. CONCLUSION: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration, and therefore is suitable for further development and applications.