Effect of pseudolaric acid B on gastric cancer cells: Inhibition of proliferation and induction of apoptosis

AIM: To examine the effect of pseudolaric acid B on the growth of human gastric cancer cell line, AGS, and its possible mechanism of action.METHODS: Growth inhibition by pseudolaric acid B was analyzed using MTT assay. Apoptotic cells were detected using Hoechst 33258 staining, and confirmed by DNA fragmentation analysis. Western blot was used to detect the expression of apoptosis-regulated gene Bcl-2, caspase 3, and cleavage of poly (ADP-ribose)polymerase-1 (PARP-1).RESULTS: Pseudolaric acid B inhibited the growth of AGS cells in a time- and dose-dependent manner by arresting the cells at G2/M phase, which was accompanied with a decrease in the levels of cdc2.AGS cells treated with pseudolaric acid B showed typical characteristics of apoptosis including chromatin condensation and DNA fragmentation. Moreover,treatment of AGS cells with pseudolaric acid B was also associated with decreased levels of the anti-apoptotic protein Bcl-2, activation of caspase-3, and proteolytic cleavage of PARP-1.CONCLUSION: Pseudolaric acid B can dramatically suppress the AGS cell growth by inducing apoptosis after G2/M phase arrest. These findings are consistent with the possibility that G2/M phase arrest is mediated by the down-regulation of cdc2 levels. The data also suggest that pseudolaric acid B can trigger apoptosis by decreasing Bcl-2 levels and activating caspase-3 protease.

Pseudolaric acid B extracted from the Chinese medicinal herb Cortex Pseudolaricis ameliorates DNFB-induced atopic dermatitis-like skin lesions in BALB/c mice

Objective:Pseudolaric acid B(PB)is a newly identified diterpenoid isolated from Tujinpi(Cortex Pseudolaricis).In the present study,we aimed to explore the anti-inflammatory effects of PB on atopic dermatitis(AD),as well as the molecular mechanisms underlying its effects.Methods:BALB/c mice treated with 2,4-dinitrofluorobenzene were orally administered with PB(10 mg?kg-1?d-1).After evaluating the AD score,serum levels of IgE and the mRNA expression of NLRP3 inflammasome and IL-1βwere measured by ELISA and qRT-PCR respectively.Results:The results showed that PB treatment significantly ameliorated the development of AD-like clinical symptoms and effectively suppressed the infiltration of inflammatory cells.Furthermore,PB inhibited the expression of NLRP3 inflammasome and IL-1βin skin lesions,and downregulated serum IgE levels.Conclusion:The anti-inflammatory properties of PB were demonstrated using the 2,4-dinitrofluorobenzene-induced mouse model of AD-like skin lesions.Our study highlighted the potential use of PB as a novel therapeutic agent for the treatment of inflammation-associated skin diseases.

Synthetic studies on pseudolaric acid B:Enantioselective synthesis of C4,C10-di-epi-trans-fused[5-7]-bicyclic skeleton

Studies on the synthesis of antifungal and anticancer natural product,pseudolaric acid B,have led to the enantioselective synthesis of di-epi-trans-fused[5-7]-bicyclic co re skeleton.The synthesis was achieved in 10 linear steps,which features the Sharpless asymmetric epoxidation,cyanide-opening reaction of epoxide,and intramolecular[5+2]cycloaddition reaction as the key transformations.The stereochemistry was determined by the X-ray crystallographic analysis.