8-Epidiosbulbin E acetate (EEA), a furanoid, was unexpectedly found to be the most abundant diterpenoid lactone in certain varieties of Dioscorea bulbifera L. (DB), a traditional herbal medicine widely used in Asian nations. This herb has been reported to cause liver injury in humans and experimental animals. The occurrence of EEA in DB was dependent on its commercial source. The present study shows that EEA exhibits time- and dose-dependent liver injury in mice. Pretreatment with ketoconazole prevented the animals from developing EEA-induced liver injury, caused 7- and 13-fold increases in the plasma Cmax and AUC of EEA, and decreased urinary excretion of glutathione conjugates derived from EEA. Pretreatment with buthionine sulfoximine exacerbated EEA-induced hepatotoxicity. In order to define the role of EEA’s furan moiety in EEA-induced hepatotoxicity, we synthesized tetrahydro-EEA by catalytic hydrogenation of the furan moiety. No liver injury was observed in the animals given the same doses of tetrahydro-EEA as those used with EAA. The results indicate that EEA itself does not appear to be hepatotoxic but that the electrophilic intermediate generated by the metabolic activation of the furan ring mediated by cytochromes P450 is responsible for EEA-induced liver injury.

•Cassane furanoditerpenes, six previously unreported were isolated from seeds of Caesalpinia minax Hance.•Neocaesalminin A, a furanoditerpene, has an unusual A-seco-rearranged cassane skeleton.•Inhibitory effects on NO production for all compounds were evaluated in vitro.•Cassane furanoditerpenes were responsible for the Caesalpinia minax Hance anti-inflammation activity.Cassane skeletons are rare in nature, but often possess valuable medicinal properties. A furanoditerpenoid with an unusual A-seco-rearranged cassane skeleton, neocaesalminin A, and five furanoditerpenoids were isolated from seeds of Caesalpinia minax Hance, along with six known cassane derivatives, 7-O-acetyl-bonducellpin C, caesalmin F, caesalmin C, ζ-caesalmin, caesalmin E1 and caesalpinin K. Compound structures were determined by spectroscopy (HR-ESI-MS, UV, IR, 1D NMR, 2D NMR), X-ray crystallography and quantum chemical computation of electronic circular dichroism). Three of the previously known compounds exhibited significant inhibition of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).Graphical abstractTwelve furanocassane derivatives, including six previously unreported were isolated from the seeds of Caesalpinia minax Hance. Neocaesalminin A (1) was found with an unusual A-seco-rearranged cassane skeleton. The inhibitory effect on NO production for all compounds was evaluated in vitro. Furanoditerpenes were responsible for this herb’s anti-inflammation activity.

The high edible oil content of Xanthoceras sorbifolia Bunge seeds contributes to its economic value. In this study, we analysed the barrigenol-like triterpenoids derived from X. sorbifolia husks. We also identified anti-tumour agents that could enhance the health benefits and medicinal value of X. sorbifolia. We isolated 10 barrigenol triterpenoids, including six new compounds (1–6) and four known compounds (7–10). New compounds 3 and 5 showed significant inhibitory activity against the proliferation of three human tumour cell lines, namely, HepG2, HCT-116 and U87-MG. We determined the relationship between the structures and inhibitory activity of 25 barrigenol triterpenoids and 15 penta-cyclic triterpenoids through analysis of three-dimensional quantitative structure activity relationships (3D-QSAR). The isolation of novel barrigenol derivatives with anti-tumour activity from X. sorbifolia implied that husks of this plant may be a good source of anti-tumour agents.Download high-res image (195KB)Download full-size image

Ethnopharmacological relevanceSaussurea involucrate (Kar. et Kir.) Sch. -Bip is an endangered species of the Compositae family, and this species has long been used for the treatment of rheumatoid arthritis, dysmenorrhea, stomachache, and altitude sickness in Uighur folk and Chinese medicine.Aim of the studyThis study aimed to investigate the different therapeutic efficacy of alcohol infusion (SEI) and water decoction (SWD) of S. involucrata in treating rheumatoid arthritis using complete Freund's adjuvant (CFA)-induced arthritis (AA) in a rat model.Materials and methodsMale Wistar rats (160–180 g) were immunized by intradermal injection of 0.1 mL of CFA into the left hind metatarsal footpad. Aspirin was chosen as the positive drug. Alcohol infusion (SEI, 400 and 800 mg/kg) and water decoction (SWD, 443 and 886 mg/kg) of S. involucrata aerial parts were orally administered from day 1 and continued for 21 days. Arthritis severity was evaluated by arthritic score, body weight loss, and paw swelling. The levels of TNF-α, IL-β, and IL-6 in the serum of AA rats were detected by enzyme linked immunosorbent assay (ELISA). Histological changes in the ankle joint were also analyzed in the AA rats.ResultsBoth SEI and SWD significantly ameliorated AA severity, as suggested by the modulatory effects on body weight loss, paw swelling, and arthritic score. Histopathological improvement in the joint architecture was also observed in the SEI- and SWD-treated AA rats. The overproduction of TNF-α, IL-1β, and IL-6 was remarkably attenuated in the serum of all treated rats. Furthermore, the therapeutic effect of SWD was more potent than that of SEI in treating rheumatoid arthritis using AA in a rat model, which was reported for the first time.ConclusionsThese results suggested that the extract of S. involucrata significantly attenuated adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β, and IL-6 in the serum. S. involucrata has the potential to be regarded as a candidate for the treatment of human arthritis. Moreover, the therapeutic effect of SWD was much better than alcohol infusion, indicting that active constituents are mainly in the water extract, which is helpful for the clinical treatments to choose the appropriate process.Download high-res image (192KB)Download full-size image