Synthesis and biological evaluation of ambradiolic acid as an inhibitor of glycogen phosphorylase.

Ambradiolic acid (3) with oleanane skeleton is a natural pentacyclictriterpene. The first synthesis of 3 starting from 23-hydroxybetulinic acid (2) has been accomplished in 12-steps with a total yield of 18.1% in our study. Compound 3 was further biologically evaluated and found to exhibit significant inhibitory activity against rabbit muscle glycogen phosphorylase (GP) with an IC50 value of 12.4 µM, suggesting it could be a potential lead compound for the development of hypoglycemic drugs.

Alleviating effects of si-ni-san, a traditional Chinese prescription, on experimental liver injury and its mechanisms.

The present study aims at examining the effects of Si-Ni-San, a prescription usually used for treating hepatitis in Traditional Chinese Medicine (TCM), on various experimental liver injury models and its mechanisms. The prescription showed significant hepatoprotection against CCl(4)-induced hepatic damage, both in vivo and in vitro. To the liver injury induced by Bacillus Calmette-Guerin (BCG) with lipopolysaccharide (LPS), Si-Ni-San also provided significant alleviation through enhancing nitric oxide (NO) release by macrophages. Against the liver injury induced by a delayed-type hypersensitivity reaction to picryl chloride (PCl-DTH), Si-Ni-San alleviated it remarkably when administered during either the induction or effector phase. A significant reduction of in-vitro hepatotoxicity, as measured by the inhibition of serum transaminase evaluation, was observed in nonparenchymal cells from liver-injured mice treated with Si-Ni-San. Si-Ni-San facilitated apoptosis in nonparenchymal cells from liver-injured mice, as well as in spleen cells activated by PCl in vivo or by Con A in vitro. These results suggest that Si-Ni-San provides alleviating effects against liver injury through multiple mechanisms, including protection of the hepatocyte membrane, enhancement of NO release, and dysfunction of liver-infiltrating cells mainly through causing their apoptosis.

Immunomodulatory activity of the aqueous extract from rhizome of Smilax glabra in the later phase of adjuvant-induced arthritis in rats.

Our previous paper has reported that the aqueous extract from Rhizoma Smilacis Glabrae (RSG) remarkably inhibited the primary inflammation of adjuvant arthritis (AA) in rats. In the present study, we further examined the activity of RSG and its mechanism on the secondary inflammation of AA. The administration of RSG (400 and 800 mg/kg) during the later phase significantly inhibited the swelling of the adjuvant-non-injected footpad of AA rats. The lipopolysaccharide-induced production of IL-1, TNF and NO by peritoneal macrophages was significantly reduced. In contrast, the extract significantly recovered the decrease in weight gain of the AA rats and Concanavalin A-induced T lymphocyte proliferation and IL-2 production by their splenocytes, while prednisolone (10mg/kg) showed a significant aggravation. Furthermore, RSG significantly recovered the picryl chloride-induced delayed-type hypersensitivity to almost normal levels from the higher or lower levels induced by different treatments of cyclophosphamide with a normalization of CD4/CD8 ratio. These results suggest that RSG exhibit an improvement on AA through down-regulating over-activated macrophages and up-regulating the dysfunctional T lymphocytes during the later phase of arthritis. Such characteristics of RSG on AA may be advantageous to the long-term treatment of clinical rheumatoid arthritis.