Xiao-Sheng Yang

Effects of spiramine T on antioxidant enzymatic activities and nitric oxide production in cerebral ischemia-reperfusion gerbils.

Spiramine T, an atisine-type diterpene alkaloid isolated from the Chinese herbal medicine Spiraea japonica var. acuta (Rosaceae), was shown to have neuroprotective effects on cerebral ischemia-reperfusion injury. In this study, the effects of spiramine T on antioxidant enzymes and nitric oxide production were evaluated in gerbils subjected to global forebrain ischemia (10 min) and reperfusion (5 days). Spiramine T (1.0 and 2.0 mg kg(-1) i.p.) markedly reduced the content of lipid peroxide (LPO), increased the glutathione peroxidase (GSH-PX) activity, and inhibited the increase of nitric oxidase (NOS) activity and nitric oxide production in the cortex during ischemia-reperfusion in gerbils. These results suggested that the neuroprotective effects of spiramine T were related to modulation of endogenous antioxidant enzymatic activities and reduction of the formation of nitric oxide.

Antiplatelet aggregation activity of diterpene alkaloids from Spiraea japonica

Six diterpene alkaloids with an atisine-type C(20)-skeleton isolated from the Chinese herbal medicines Spiraea japonica var. acuta and S. japonica var. ovalifolia, as well as eight derivatives of spiramine C and spiradine F were evaluated for the ability to inhibit aggregation of rabbit platelets induced by arachidonic acid, ADP, and platelet-activating factor (PAF) in vitro. The results showed that 12 of the 14 atisine-type diterpene alkaloids significantly inhibited PAF-induced platelet aggregation in a concentration-dependent manner, but had no effect on ADP- or arachidonic acid-induced aggregation, exhibiting a selective inhibition. It is the first report that C(20)-diterpene alkaloids inhibit PAF-induced platelet aggregation. However, spiramine C1 concentration-dependently inhibited platelet aggregation induced by PAF, ADP and arachidonic acid with IC(50) values of 30.5+/-2.7, 56.8+/-8.4 and 29.9+/-9.9 microM, respectively, suggesting a non-selective antiplatelet aggregation action. The inhibitory effect of spiramine C1 on arachidonic acid was as potent as that of aspirin. Primary studies of the structure-activity relationships for inhibition of PAF-induced aggregation showed that the oxygen substitution at the C-15 position and the presence of an oxazolidine ring in spiramine alkaloids were essential to their antiplatelet aggregation effects. These results suggest that the atisine-type alkaloids isolated from S. japonica are a class of novel antiplatelet aggregation agents.

Alkaloids from Daphniphyllum oldhami

Four new Daphniphyllum alkaloids, daphnioldhanines H-K ( 1- 4), along with 34 known alkaloids, were isolated from Daphniphyllum oldhami. The known alkaloid dehydrodaphnigraciline ( 5) is now reported as a natural product. Their structures were elucidated by spectroscopic methods, especially 2D NMR techniques. The effects against platelet aggregation of compounds 1, 3, and 5 were evaluated, and 3 showed stronger activity against platelet aggregation induced by PAF. This is the first report of quinolizidine alkaloids from the genus Daphniphyllum.

Six New O-Terpenoidal Coumarins, Excavacoumarins B-G from Clausena excavata

Six new O-terpenoidal coumarins named excavacoumarins B-G (1-6) were isolated from the aerial part of Clausena excavata collected in Xishuangbanna, Yunnan.

Three new diterpene alkaloids from Spiraea japonica

Chemical investigation of the basic fraction from the roots of Spiraea japonica var, acuta has resulted in the isolation of three new diterpene alkaloids, spiramines X (1), Y (2) and Z (3), along with five known compounds, spiradine F (4), and spiramines A, B, P (5), and U (6). The structures of 1-3 were determined by spectral and chemical methods. Antiplatelet aggregation activities of compounds (1-6) were tested.

Two new coumarin glycosides from Chimonanthus nitens

Two new coumarin glycosides, namely nitensosides A–B (1–2), together with six known compounds, scopolin (3), 5,6,7-trimethoxycoumarin (4), d-calycanthine (5), calycanthoside (6), xeroboside (7), and scopoletin (8), were isolated from Chimonanthus nitens. The structures of the new compounds were elucidated by comprehensive analysis of IR, MS, and NMR spectroscopic data. Compounds 3, 4, 7, and 8 showed moderate inhibitory activity against Micrococcus luteus.

A new triterpene from Luculia pinciana Hook.

A new triterpene named luculiaoic acid A (1), showing inhibitory activity of a leukaemia cell line, along with eleven known compounds, has been isolated from the ethyl acetate extract of the stems of Luculia pinciana Hook. All the structures were elucidated on the basis of NMR, MS, and IR methods. The activity to inhibit Staphylococcus aureus and Candida albicans of all compounds showed that ursolic acid inhibits the growth of Staphylococcus aureus with an MIC of 0.5 mg ml−1 and an MBC of 10 mg ml−1, and scopletin inhibits Candida albicans with an MIC of 1 mg ml−1 and an MBC of 5 mg ml−1.

18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents

The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

1α,2α-Epoxy-3β-hydroxy oleanolic acid derivatives regulation of the metabolism, haemolysis and β-lactamase gene expression in vitro and their structure–microbicidal activity relationship

Oleanolic acid (OA), one of the major pentacyclic triterpenes abundantly present in nature, is a promising compound with various biological activities, including anti-inflammatory, anti-ulcer, hepatoprotective, antidiabetic, fungicidal and antiparasitic properties. Therefore, a series of derivatives of 1α,2α-epoxy-3β-hydroxyl oleanolic acid derivatives were designed and synthesized, and their antibacterial activities were investigated in vitro. Based on these results, the compounds with antibacterial activity were screened by RT-PCR to determine whether they can regulate the expression of genes related to metabolism, haemolysis, and β-lactamase in vitro, and the structure-microbicidal activity relationship of each compound was analyzed. Our study shows that some of the modifications in the synthetic compounds, such as the introduction of an ortho-cyano-substituted benzyl group and a short chain alkyl ester at the 28-carboxyl, as well as the introduction of an acetyl group at the 3-hydroxyl group of ring A, could enhance antibacterial activity. This provides basic evidence for the optimization of 1α,2α-epoxy-3β-hydroxyl oleanolic acid derivatives. The antibacterial mechanism of the active OA derivatives appears to involve the regulation of expression of metabolism-associated genes in Escherichia coli, haemolysis-associated genes in Bacillus subtilis, metabolism-related genes in Klebsiella pneumonia and β-lactamase-associated genes in Acinetobacter baumannii. Some OA derivatives were bactericidal to three of the strains and appeared to regulate gene expression associated with metabolism, haemolysis, and β-lactamase in vitro. These newly designed OA derivatives possess unique antibacterial activities and may be potentially useful for prophylactic or therapeutic intervention of bacterial infections.