Characterization of inthomycin biosynthetic gene cluster revealing new insights into carboxamide formation.

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B (1) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the 15N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.

Sesquiterpenes and diterpenes with cytotoxic activities from the aerial parts of Carpesium humile.

Carpesium humile Winkl is an endemic Chinese species and no previous phytochemical studies have been reported for this species. Two new germacranolides (1 and 2) and a new phytane diterpene (5), together with five known compounds (two sesquiterpenoids and three diterpenoids), were isolated from the aerial parts of C. humile. Their structures were elucidated on the basis of extensive spectroscopic analysis. The conformations and absolute configurations of 1 and 2 were established by combinative analysis of NMR, CD exciton chirality, and X-ray crystallography data. Four germacranolides (1-4) showed strong cytotoxic activities, with broad spectrum activities against six human cancer (HepG2, HeLa, HL60, SGC7901, Lewis, and MDA231) cell lines in vitro using MTT assay, with IC50 values from 3.09 to 7.71 µg/mL. Diterpenes (5, 6, and 8) also displayed good cytotoxic activities for selected cancer cell lines, with IC50 values in the range 5.46-8.08 µg/mL.

Immunomodulatory effect of a formula developed from American ginseng and Chinese jujube extracts in mice.

BACKGROUND: American ginseng (Panax quinquefolius L.) and Chinese jujube (Zizyphus jujuba Mill.) are commonly used in traditional Chinese medicine to enhance immune function. OBJECTIVE: The present study aimed to develop one Chinese prescription, Shenzao Cha (SZC), consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice. METHODS: Normal ICR mice received intragastric administration of SZC (1.3, 2.6, and 5.2 g raw material/kg body weight) once daily for four weeks, while a control group received the same amount of sterile water. RESULTS: SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4-fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased. CONCLUSIONS: SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement.

New nor-ursane type triterpenoids from Gelsemium elegans.

Five new nor-ursane type triterpenoids, gelse-norursane A-E, together with twenty known compounds, were isolated from the whole plant of Gelsemium elegans. The structures of new compounds were established as (2R,3R,7R,17S,19R)-2,3,7,19-tetrahydroxy-6-oxo-24-norurs-4(23),12-dien-28-oic acid (1), (2R,3R,7R,17S)-2,3,7-trihydroxy-6-oxo-24-norurs-4(23), 12-dien-28-oic acid (2), (2R,3R,7R,17S)-2,3,4-trihydroxy-23-norurs-20(30),12-dien-28-oic acid (3), (2R,3R,30R)-2,3-dihydroxy-24-norurs-4(23),12-dien-30-oic acid (4), and (2R,3R,30R)-2, 3-dihydroxy-24-norurs-4,12-dien-30-oic acid (5), using spectroscopic analysis, including HRESIMS, 1D and 2D NMR. The absolute configurations of 1 and 4 were established through comparison of experimental and calculated ECD spectra. The gelse-norursane A-E are isolated as the 24-nor-ursane type triterpenoids from the family Loganiaceae for the first time. The cytotoxicities of the selected compounds against a panel of four human cancer HL60, Hela, Hep-G2, and Smmc 7221 cell lines were evaluated using the MTT assay in vitro.