Investigation of the mechanism of hepatotxicity induced by Fructus Psoraleae combined with UPLC-QTOF-MS and network toxicology technology / 国际药学研究杂志

Objective: To analyze and identify the chemical constituents from Fructus Psraleae(FP)in the rat liver after intragastric FP administration, and explore the potential mechanism of FP- induced hepatotoxicity via the network toxicology study. Methods: UPLC-QTOF-MS and UNIFI data screening platform were used to quickly identify the chemical constituents from FP in the rat liver afte intragastric FP administration, and multiple databases were used to search for information about chemical component targets, hepatotoxic targets, component hepatotoxic common targets and indirect targets. The construction of protein protein interaction (PPI)network and the enrichment analysis of gene ontology(GO)biological function and Kyoto Encycolpenia of Genes and Genomes (KEGG)pathway were carried out on the searched targets by using the String database and Cytoscape 3.6.1 software to explore the key targets and potential mechanism of hepatotoxicity induced by constituents from FP. Results: Eleven prototypic components of FP were identified in the rat liver. The network toxicology studies showed that there were a total of 52 potential targets and 23 pathways for the FP hepatotoxicity, among which ALB, HOMX1, GSR, GSTM3 and CYP2C9 targets, as well as the thyroid synthesis pathway and the glutathione metabolism pathway had a strong correlation with the FP hepatotoxicity. Conclusion: By UPLC-QTOF-MS combined with the UNIFI platform, the 11 chemical constituents from FP could be quickly identified in the liver of rats that were intragastrically administered FP, and the network toxicology study has predicted potential molecular mechanism of the hepatotoxicity induced by FP. The present results provide a reference for further study the hepatotoxicity of FP.

Effect of Tripterygium Glycosides Tablets on reproductive toxicity in male rats with Ⅱ type collagen induced arthritis / 中国中药杂志

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.

Effect of Tripterygium Glycosides Tablets on reproductive toxicity in female rats with Ⅱ type collagen induced arthritis / 中国中药杂志

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.

Research Progress of Epidemiology and Mechanism of PM2.5 on the Damage of Respiratory System / 沈阳医学院学报

Body exposure to fine particulate matter air pollution (PM2.5) can cause a variety of health damage. PM2.5 can act directly on the respiratory system and through the blood barrier, which is closely related to the body's various diseases. This paper elaborated possible mechanism of PM2.5 on the respiratory system as well as varying degrees of damage,pointed out the mechanism of toxicity, and a more in-depth toxicity mechanism from epidemiological studies. Meanwhile, this paper provides a scientific basis about PM2.5 and other cutting-edge issues.

Biological Toxicology of Lunar Dust / 沈阳医学院学报

Lunar dust is widely distributed on the lunar surface. Due to long?term various physical and chemical factors, lunar dust have complex shapes, high surface reactivity and complex component. Lunar dust can adhere to spacecraft and be inhaled by astro?nauts easily, and then damage the spacecraft and threaten the health of astronauts, which can cause respiratory effects, skin effects and potential ocular effects. So it is important to understand the current research of lunar biology toxicity.