Triterpenoids from fruits of Sorbus pohuashanensis inhibit acetaminophen-induced acute liver injury in mice.

Drug-related hepatotoxicity has become a serious social issue nowadays. Acetaminophen (APAP) was widely used in clinical treatment, although commonly acknowledged that it is a general material that caused drug-related hepatotoxicity. In this study, triterpenoids (Trds) which are mainly composed of ursolic acid and oleanolic acid, were isolated and prepared from fruits of Sorbus pohuashanensis. Further, the effect of Trds against APAP-induced liver injury and the pharmacological mechanism were investigated. The results showed that Trds treatment significantly restrained the increase of serum aspartate transaminase (AST), alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) levels, as well as evidently reversed the decrease of hepatic superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) levels induced by APAP. There are further evidences provided by liver histopathology which demonstrated Trds treatment observably inhibited hepatic tissues necrosis, hemorrhage and infiltration of inflammatory cell induced by APAP. According to the results of western-blot and RT-PCR, the over-expressions of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2) were inhibited by Trds. Moreover, Trds also effectively restrained APAP-induced phosphorylation of mitogen-activated protein kinase (MAPK) family signals such as p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). These results demonstrated the liver-protection effects that Trds exhibited were related to its property of anti-oxidantion and anti-inflammation.

Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice.

Beta-sitosterol (Sit) widely exists in natural plants, is classed as phytosterol and known as the "key of life". Most pharmacological studies and clinical applications are limited because of the fact that Sit is difficult to be solved. Therefore, it is viable to enhance pharmacologic activities of Sit by using its derivatives which can be obtained through the modification of Sit. In this study, 4 kinds of new Sit derivatives were obtained by the esterification reaction. Further, the hepatoprotective effects of Sit and its derivatives were investigated against acute liver injury induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and its mechanism was illustrated by western blot analysis and real-time PCR. The results demonstrated that among its derivatives, 2-naphthoyl Sit ester (Sit-N) (50 mg/kg) showed the strongest activities against acute liver injury. Final experimental results showed that Sit-N significantly decreased the serum activity of aspartate transaminase (AST) and alanine aminotransferase (ALT); Sit-N also markedly reduced tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels. Meanwhile, Sit-N drastically improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and suppressed the expression of malondialdehyde (MDA). Results also displayed that over-expression of Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) induced by LPS/Gal N were inhibited by Sit-N. Meanwhile, the expression of nuclear respiratory factor2 (Nrf2) and heme oxygenase-1 (HO-1) were enhanced. The results all above verified the effectiveness of Sit-N against acute liver injury induced by LPS/GalN mediated by TLR4 and Nrf2 pathways.

The effect of beta-sitosterol and its derivatives on depression by the modification of 5-HT, DA and GABA-ergic systems in mice.

Beta-sitosterol belongs to the group of phytosterols, which are active trace components existing in natural plants, known as the "key of life", and have a steroid nucleus structure similar to cholesterol. Due to the insolubility issue of beta-sitosterol, most pharmacological studies and clinical applications are limited. Therefore, the modification of beta-sitosterol into its derivatives to enhance its pharmacologic activity is viable. In this study, 4 kinds of new beta-sitosterol derivative were obtained by an esterification reaction with beta-sitosterol, organic acids, EDCI and DMAP in dichloromethane. The chemical structures were defined by IR and NMR. Beta-sitosterol and its derivatives were used to carry out antidepressant research in the tail suspension test (TST) and the forced swimming test (FST) in mice. Additionally, the roles of different parts of the central nervous system (CNS) in the antidepressant-like effect of Sit-S, which is one of the beta-sitosterol derivatives, were also investigated. The results showed that the derivatives exhibited a stronger antidepressant activity than beta-sitosterol. Among the derivatives, administration of Sit-S (4 mg kg-1) gave the lowest immobility time in the TST, demonstrating that Sit-S exhibited the strongest antidepressant-like activity. The study into the roles of different parts of the CNS in the antidepressant-like effect of Sit-S showed that agomelatine (40 mg kg-1), haloperidol (0.2 mg kg-1) and bicuculline (4 mg kg-1) reversed the antidepressant effect of Sit-S (4 mg kg-1). This study confirmed the conclusions that beta-sitosterol derivatives broaden the pharmacological effects of beta-sitosterol, Sit-S (4 mg kg-1) exhibits antidepressant-like effects, and this antidepressant-like effect on male adult mice is mediated by the 5-HT, DA and GABA-ergic systems.