Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics / 中国中药杂志

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Study on the Viability Inhibitory Effects and Mechanism of Dictamnine on Mice Spleen Lymphocyte in vitro / 中国药房

OBJECTIVE： To study the inhibitory effect of dictamnine on the viability of mice spleen lymphocyte in vitro and explore its potential mechanism. METHODS： The primary spleen lymphocytes of mice were isolated and cultured. The cells were treated with 0 （blank control）， 50， 100， 150 μmol/L dictamnine for 24 h. MTT assay was used to determine the cell viability； Lactic dehydrogenase （LDH） assay was used to determine release rate of LDH. Early apoptosis rate was detected by flow cytometry. Necrosis rate was detected by Hoechst 33342 and PI double staining； Western blot assay was used to detect the protein expressions of Caspase 3 and Cleaved-Caspase 3 in cells. Comet assay was used to detect DNA damage in cells （reflected in the proportion of DNA tail area）. RESULTS： Compared with blank control， 100， 150 μmol/L dictamnine could significantly inhibit the viability of lymphocytes （P＜0.01）. 150 μmol/L dictamnine could significantly increase the release of LDH （P＜0.05）， and release rate reached 79.37％. 50， 100， 150 μmol/L dictamnine could improve the early apoptotic rate of lymphocyte， but there was no statistical significance （P＞0.05）. 150 μmol/L dictamnine could significantly increase the necrosis rate （P＜0.05）， and necrosis rate reached 78.64％. 50， 100， 150 μmol/L dictamnine could increase the protein expression of Caspase 3， but there was no statistical significance （P＞0.05）， while 50， 100 μmol/L dictamnine could improve the protein expression of Cleaved-Caspase 3 significantly （P＜0.05）. DNA damage was induced in a dose-dependent manner by dictamnine， in which 100 and 150 μmol/L dictamnine could significantly increase DNA tail area （P＜0.01）. CONCLUSIONS： Dictamnine can inhibit spleen lymphocyte viability， and the mechanism may be related to inducing spleen lymphocyte necrosis and DNA damage.

Chemical Constituents in Methanol Parts of Toddalia Asiatica(Linn) Lam / 中国药师

Objective:To study the chemical constituents in methanol parts of Toddalia asiatica ( Linn) Lam. Methods: The compounds were isolated by silica gel, Sephadex LH-20 column chromatograph and TLC. The structures were elucidated by physico-chemical properties and spectral analysis. Results:Nine compounds were obtained and elucidated as dictamnine(1), hesperetin(2), 4-hydroxy-N-methylproline(3), 8-hydroxy-dihydrochelerythrine(4), hesperetin7-O-β-D-glucopyranoside(5), daucosterol(6), hes-peridin(7), diosmin(8) and neohesperidin(9). Conclusion:Compound 5, 6, 8 and 9 are isolated from the plant for the first time.