demethylzeylasteral and celastrol

Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese medicine, is widely used in the treatment of rheumatoid arthritis. Due to multiorgan toxicity, particularly hepatotoxicity, the application of TwHF is restricted. To clarify the hepatotoxic substances, zebrafish, hepatocytes and macrophages were used for screening based on hepatotoxic injury patterns. This study provides a basis for further elucidation of the hepatotoxic mechanism of TwHF.. First, 12 compounds were selected according to the chemical categories of TwHF. The fluorescence area and fluorescence intensity of zebrafish livers were observed and calculated. The viability of two hepatocyte lines was detected by CCK. Parthenolide, triptolide, triptonide, triptobenzene H, celastrol, demethylzeylasteral, wilforlide A, triptotriterpenic acid A and regelidine significantly reduced the fluorescence area and fluorescence intensity of zebrafish livers. The viability of L-02 or AML-12 cells was significantly inhibited by parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, and triptotriterpenic acid A. Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral and triptobenzene H significantly increased TNF-α and IL-1β mRNA levels in macrophages, while triptophenolide, hypodiolide and wilforine significantly reduced TNF-α and IL-1β mRNA levels. Triptotriterpenic acid A, celastrol and triptobenzene H at a dose of 10 mg/kg significantly increased the levels of mouse serum alanine aminotransferase and aspartate aminotransferase and aggravated liver inflammation.. Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury.

Topics: Animals; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Mice; RNA, Messenger; Tripterygium; Tumor Necrosis Factor-alpha; Zebrafish

Tripterygium wilfordii Radix, a well-known traditional medicine in china which is used for treatment of inflammation, pain, tumor and immune regulation for centuries in china, accompany with the serious toxic side effects. This study was carried out for simultaneously analyzing the four main components (triptolide, triptophenolide, demethylzeylasteral and celastrol) in Tripterygium wilfordii Radix under different drying processes, which was important for reducing the toxicity and quality control of Tripterygium wilfordii Radix in future.. The terpenes were extracted by using ultrasonic method with ethyl acetate from root or cortex of Tripterygium wilfordii Radix, and the sensitive and rapid HPLC-PDA method was developed for simultaneous quantification of triptolide, triptophenolide, demethylzeylasteral and celastrol in root and cortex of Tripterygium wilfordii Radix for evaluation of the impacts by different drying processes.. The method established is high sensitivity, accuracy, reliability and suitable for the simultaneous analysis of terpenoids in Tripterygium wilfordii Radix. The data provide a scientific basis and reference for the quality control of herb and preparations related to Tripterygium wilfordii Radix.

Topics: China; Desiccation; Diterpenes; Epoxy Compounds; Molecular Structure; Pentacyclic Triterpenes; Phenanthrenes; Plant Roots; Terpenes; Tripterygium; Triterpenes

The male antifertility effect of a water-chloroform extract of Tripterygium wilfordii Hook. f. (GTW) and several monomers isolated from GTW has attracted worldwide interest. In the present study, the effects of two isolated monomers from GTW, demethylzeylasteral and celastrol, on the Ca(2+) channels in mouse spermatogenic cells and on the sperm acrosome reaction were investigated by whole-cell patch-clamp recording and chlortetracycline staining methods, respectively. The results showed that demethylzeylasteral concentration-dependently and in a partially reversible manner inhibited the Ca(2+) current in spermatogenic cells with an IC(50) of 8.8 microg/ml. Celastrol decreased the Ca(2+) current in the cells time-dependently and irreversibly. The changes in the activation and inactivation time constants of Ca(2+) currents after application of these two compounds were also examined. Demethylzeylasteral increased both activation and inactivation time constants of Ca(2+) currents, and celastrol had no significant effect on them. The two compounds also inhibited significantly the sperm acrosome reaction initiated by progesterone. These data suggest that inhibition of Ca(2+) currents could be responsible for the antifertility activity of these compounds.

Topics: Acrosome Reaction; Amiloride; Animals; Calcium Channels; Catechin; Contraceptive Agents, Male; Dose-Response Relationship, Drug; Gossypol; Male; Membrane Potentials; Mice; Mice, Inbred ICR; Pentacyclic Triterpenes; Progesterone; Spermatozoa; Time Factors; Triterpenes