Jin-Shan Tang

Characterization and Online Detection of Surfactin Isomers Based on HPLC-MS n Analyses and Their Inhibitory Effects on the Overproduction of Nitric Oxide and the Release of TNF-α and IL-6 in LPS-Induced Macrophages

A rapid method for characterization and online detection of surfactin isomers was developed based on HPLC-MSn (n = 1, 2, 3) analyses, and many surfactin isomers were detected and characterized from the bioactive fraction of the mangrove bacterium Bacillus sp. Inhibitory activities of surfactin isomers on the overproduction of nitric oxide and the release of TNF-α and IL-6 in LPS-induced macrophages were systematically investigated. It was revealed that the surfactin isomers showed strong inhibitory properties on the overproduction of nitric oxide and the release of IL-6 on LPS-induced murine macrophage cell RAW264.7 with IC50 values ranging from 1.0 to 7.0 μM. Structure-activity relationship (SAR) studies revealed that the existence of the free carboxyl group in the structure of surfactin isomers was crucial. These findings will be very helpful for the development of this novel kind of natural product as new anti-inflammatory agents.

Cardiac Glycosides from the Seeds of Thevetia peruviana.

Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2-16) and 18 known (1 and 17-33) cardiac glycosides. Eight 19-nor-cardenolides (1-8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of cardiac glycosides 1-33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure-activity relationship is discussed. In addition, cardiac glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02-0.53 μM.

Stauntoside B inhibits macrophage activation by inhibiting NF-κB and ERK MAPK signalling

Inflammation is a defensive reaction of body to resist foreign invasion. However, it has been demonstrated that excessive and continuous inflammatory responses contribute to various inflammatory diseases, including rheumatoid arthritis. Nuclear factor-κB (NF-κB) regulates the expression of an array of inflammatory mediators, cytokines and chemokine genes in activated macrophages. Therefore, NF-κB has become an attractive drug target for controlling inflammation. In this study, stauntoside B, a C21 steroidal glycosides compound isolated from a Chinese medicine Cynanchi Stauntonii, was for the first time found to suppress macrophage activation induced by lipopolysaccharide (LPS) in RAW264.7 cells and rat primary peritoneal macrophages and could be a potent NF-κB inhibitor. The results showed that stauntoside B significantly reduced the release of inflammatory mediators in activated RAW264.7 cells and rat peritoneal macrophages, including nitric oxide (NO) and prostaglandin E2 (PGE2). The mRNA expressions of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), microsomal prostaglandin synthetase-1 (mPGES-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) as well as the production of TNF-α and IL-6 were also inhibited by stauntoside B. Mechanistic investigation implies that the anti-inflammatory activity of stauntoside B could result from the suppression of LPS-induced IKKα/β activation, IκBα phosphorylation, p65 (ser536) NF-κB phosphorylation, and ERK MAPK activation by stauntoside B treatment in activated macrophages. Meanwhile, stauntoside B could induce apoptosis in LPS-activated macrophages. The current study suggests stauntoside B being a valuable candidate drug for the treatment of inflammatory diseases, especially for NF-κB activation associated inflammatory diseases.

Antioxidative Phenylpropanoid-Substituted Epicatechin Glycosides from Parabarium huaitingii

Three new phenylpropanoid-substituted epicatechin glycosides, namely parabarosides A - C ( 1- 3), together with three known compounds, 5-caffeoylquinic acid (4), 5-caffeoylshikimic acid (5), and 3,4-dicaffeoylquinic acid (6), were obtained from the plant Parabarium huaitingii. Their structures were determined and full assignments of (1)H- and (13)C-NMR spectroscopic data were achieved by analyses of 1D- and 2D-NMR, mass, and CD spectra. The oxygen radical absorbance capacity (ORAC) assay was applied to evaluate their antioxidative capacity in vitro, which revealed that 1- 6 showed strong antioxidative properties.

New oxidized sterols from Aspergillus awamori and the endo-boat conformation adopted by the cyclohexene oxide system.

Two new oxidized sterols 1 and 2 were obtained from the active fraction of a mangrove fungus Aspergillus awamori isolated from the soils around the mangrove plant Acrostichum speciosum. Their structures were elucidated using spectroscopic methods as 22E‐7α‐methoxy‐5α,6α‐epoxyergosta‐8(14),22‐dien‐3β‐ol (1) and 22E‐3β‐hydroxy‐5α,6α,8α,14α‐diepoxyergosta‐22‐en‐7‐one (2). The NMR data and complete assignments for both DMSO‐d6 and CDCl3 were given. Their cytotoxic activity against A549 cell line was evaluated. Furthermore, the detailed conformation analysis for ring B (cyclohexene oxide system) of sterol 1 was given on the basis of NOEs. The endo‐boat conformation was considered as the preferred conformation for ring B rather than half‐chair conformation. Copyright

Cyclohexanone derivatives with cytotoxicity from the fungus Penicillium commune

Four new cyclohexanone derivatives (2-5) and one known analog, (-)-Palitantin (1) were isolated from the EtOAc extract of Penicillium commune, a fungal strain of low-temperature habitats. The structures of 2-5 were determined on the basis of extensive spectroscopic analysis. Furthermore, the absolute configuration of 2 was assigned by electronic circular dichroism (ECD) calculations, whereas that 3-5 were deduced via the CD data. Cytotoxicities of 2-5 against five human carcinoma cell lines (Hela, A549, MCF7, HCT116, T24) were evaluated.

A new staurosporine analog from Actinomycetes Streptomyces sp. (172614)

A new staurosporine analog, 10′-{5″-[(methoxycarbonyl)amino]-2″-methyl}-phenylaminocarbonylstaurosporine (1), together with staurosporine (2), was obtained from the culture broth of Actinomycetes Streptomyces sp. (172614). Their structures were elucidated by comprehensive spectroscopic analysis including UV, MS, NMR, and CD spectra. Pharmacological experiments revealed that 1 and 2 showed significant cytotoxicity against human colon tumor cell HCT-116.

New isocoumarins from a cold-adapted fungal strain mucor sp. and their developmental toxicity to zebrafish embryos.

Three new isocoumarin derivatives, mucorisocoumarins A–C (1–3, resp.), together with seven known compounds, 4–10, were isolated from the cold‐adapted fungal strain Mucor sp. (No. XJ07027‐5). The structures of the new compounds were identified by detailed IR, MS, and 1D‐ and 2D‐NMR analyses. It was noteworthy that compounds 1, 2, 4, and 5 were successfully resolved by chiral HPLC, indicating that 1–7 should exist as enantiomers. In an embryonic developmental toxicity assay using a zebrafish model, compound 3 produced developmental abnormalities in the zebrafish embryos. This is the first report of isocoumarins with developmental toxicity to zebrafish embryos.

Three new bis-styryllactones from Goniothalamus cheliensis.

Three new bis-styryllactone analogues, goniolactones G-I (1-3), have been isolated from the root barks of Goniothalamus cheliensis. Their structures were established on the basis of extensive spectroscopic investigation including HR-ESI-MS and 2D NMR (HSQC, HMBC, (1)H-(1)H COSY, ROESY).

¹H and ¹³C NMR spectral assignments of 2-pyrone derivatives from an endophytic fungus of sarcosomataceae.

Endophytic fungi is one kind of organism which spends the whole or part of its life cycle colonizing interand/or intra-cellularly inside the healthy tissues of the host plant, typically causing no apparent symptoms of disease. Because of the first discovery of endophytic fungus in darnel in 1904, many kinds of bioactive secondary metabolites have been found in the cultures of endophytic fungi. Among them, 2-pyrone derivative is one kind of most important components, which showed broad pharmacological activities including anticancer, antimicrobial, and anti-leukemic effects, et al. In our search for bioactive components from microorganisms, eight new 2-pyrone derivatives (1–7 and 17), together with nine known ones (8–16), were obtained from the solid cultures of Sarcosomataceae No. 49-14-2-1, an endophytic fungus isolated from Everniastrum nepalense (Taylor) Hale ex Sipman. Herein, we described the isolation and structure elucidation of new 2-pyrone derivatives. In addition, full assignments of the H and C NMRdata of 2-pyrone derivatives were achieved by MS, 1Dand 2D-NMR spectral analyses.