Xiao-Ping Song

Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

BackgroundHighly active anti-retroviral therapy (HAART) is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication.MethodsCrude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to identify potential anti-HIV mechanisms of these extracts.ResultsTwo extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE) and one from Dipterocarpaceae, Vatica astrotricha (VAD) inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus.ConclusionThese results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.

Bioactive Anthraquinone Derivatives from the Mangrove-Derived Fungus Stemphylium sp. 33231

Four new anthraquinone derivatives (1-4) and four new alterporriol-type anthranoid dimers (14-17), along with 17 analogues, were isolated from the solid rice fermentation of the fungus Stemphylium sp. 33231 obtained from the mangrove Bruguiera sexangula var. rhynchopetala collected from the South China Sea. Their structures were elucidated using comprehensive spectroscopic methods. The absolute configurations of 1, 3, and 4 were determined by single-crystal X-ray diffraction of their derivatives (1a, 3b, and 4a). The absolute configurations of the chiral 17-19 were determined by comparing their CD spectra with 21. The inhibitory activities of most of the compounds against seven terrestrial pathogenic bacteria and two cancer cell lines were evaluated.

Antibacterial α-pyrone derivatives from a mangrove-derived fungus Stemphylium sp. 33231 from the South China Sea

Two new α-pyrone derivatives, infectopyrones A (1) and B (2), were obtained from the EtOAc extract of the endophytic fungus Stemphylium sp. 33231 isolated from the mangrove Brguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Compounds 1 and 2 were evaluated for their antibacterial activities, and they had a broad spectrum of antibacterial activity against five terrestrial pathogenic bacteria.

Bioactive Phenanthrene and Bibenzyl Derivatives from the Stems of Dendrobium nobile

A new enantiomeric pair of spirodiketones, (+)- and (-)-denobilone A (1 and 2), three new phenanthrene derivatives (3-5), and three new biphenanthrenes (22-24), along with 11 known phenanthrene derivatives (6-16), five known bibenzyl derivatives (17-21), and four known biphenanthrenes (25-28), were isolated from Dendrobium nobile. The structures of 1-5 and 22-24 were elucidated using comprehensive spectroscopic methods. (+)-Denobilone and (-)-denobilone A (1 and 2) were isolated as a pair of enantiomers by chiral HPLC. The absolute configurations of (+)- and (-)-denobilone A (1 and 2) were determined by comparing their experimental and calculated electronic circular dichroism spectra. The absolute configuration of denobilone B (3) was determined by X-ray crystallographic analysis. The inhibitory activities of all compounds against nine phytopathogenic fungi and three cancer cell lines were evaluated.

Trigoxyphins H and I: two new daphnane diterpenoids from Trigonostemon xyphophylloides.

Two new daphnane diterpenoids (1 and 2), together with four known analogues (3-6) were isolated from Trigonostemon xyphophylloides. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2 were evaluated for in vitro cytotoxic activities against the SPCA-1 (human lung cancer) and BEL-7402 (human hepatocellular carcinoma) cancer cell lines. Trigoxyphin I (2) showed modest cytotoxicity against two tumor cell lines.

A new naphthoquinone and other antibacterial constituents from the roots of Xanthium sibiricum

Reinvestigating the chemical constituents of the roots of Xanthium sibiricum led to the isolation of a new naphthoquinone (1), together with 13 known compounds (2–14). Their structures were elucidated by using spectroscopic analyses, including HR-ESI-MS, 1D and 2D NMR, and by comparing their NMR data with those of related compounds. Compound 1 showed moderate antibacterial activity against Escherichia coli, Bacillus subtilis, Micrococcus tetragenus and Staphylococcus aureus, while 6 and 12 showed stronger antibacterial activity than the positive control ciprofloxacin against E. coli, with minimum inhibitory concentration values of 0.17 and 0.35 μg/mL, respectively.

New clerodane diterpenoids from the roots of Polyalthia laui.

Five new clerodane diterpenoids, polylauiester A (1), (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-14-oic acid (2) and polylauiamides B-D (3-5), together with 11 known clerodane diterpenoids (6-16), were isolated from the roots of Polyalthia laui. Among them, polylauiester A (1) represents the first example of a novel norclerodane diterpenoid only containing 17 carbon atoms on the carbon skeleton, and polylauiamide B (3) is an unusual diterpenoid with a p-substituted benzene ring as a substituent. Their structures were elucidated by extensive spectroscopic methods, and the relative configuration of polylauiamide B (3) was further confirmed by the single crystal X-ray diffraction method. Biological evaluation of new compounds against human Hela, MCF-7 and A549 human cancer cell lines showed that all compounds displayed weak cytotoxicities against various human cancer cell lines in the range of IC50 at 25.01-39.31μM.

Two new stemphol sulfates from the mangrove endophytic fungus Stemphylium sp. 33231

Two new stemphol sulfates, stemphol A (1) and stemphol B (2), along with known compound stemphol (3) were isolated from the EtOAc extract of the fermentation of an endophytic Stemphylium sp. 33231. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The isolated compounds exhibited potent antibacterial activities against six terrestrial pathogenic bacteria with MIC values of 0.6–10 μg ml−1. The inhibitory activities of all compounds against five cancer cell lines were evaluated.

Chemical constituents and in vitro anticancer cytotoxic activities of Polyalthia plagioneura

Polyalthia plagioneura (Annonaceae) is a typical medium-sized tree in P. R. China occurring mainly in Hainan, Guangdong, Guangxi, and Yunnan Provinces [1]. In a previous study, only four compounds, howiicin A and plagionicin A [2], marcanine A [3], and isoevodionol [4], were isolated from P. plagioneura. In our previous cytotoxic activities study of P. plagioneura it was found that the ethyl acetate fraction of the stems show remarkable anti-proliferative effects on SPCA-1 cells. To determine the cytotoxically active constituent, we study the active ingredient of P. plagioneura. We used the methods of extraction, separation, purification, characterization, etc. Ten compounds, namely, cinnamic anhydride (1), telisatin A (2), telisatin B (3), liriodenine (4), O-methylmoschatoline (5), stigmast-4-en-3-one (6), ursolic acid (7), friedelin (8), citric acid (9), and (E)-1,2,3-trimethoxy-5-(prop-1-enyl)benzene (10), were isolated from the stems of P. plagioneura, and their structures were identified using modern spectrum technology (ESI-MS, 1D, 2D NMR) that combines physicochemical methods and literature comparison. All the compounds, except compounds 4 and 5, are reported for the first time from Polyalthia genus. Compounds 2 and 3 are telisatin-type aporphine alkaloids that form a very small subgroup of the aporphine alkaloids in which N-6 and C-7 are fused to an oxalyl function. To date, only five members of compounds 2 and 3 that of type of aporphine alkaloids have been found to occur in nature. Compound 1 was isolated as a natural product for the first time. The cytotoxic activity on three human cancer cell lines (GSC-7901, K562, and SPCA-1) of compounds 2–6 were studied. Compounds 2–4 showed cytotoxic activity against three human cancer cell lines with IC50 in the range from 3.87 to 135.16 M. Stems of P. plagioneura were collected in Bawangling Country, Hainan Province, P. R. China, in June 2008 and identified by Prof. Qiong-xin Zhong (College of Life Science, Hainan Normal University). A voucher specimen was deposited in the Key Laboratory of Tropical Medicinal Plant Chemistry of the Ministry of Education. Air-dried stems of P. plagioneura (20 kg) were cut into small pieces and extracted with ethanol (75%), then fractionated with various solvents to yield a chloroform extract (350 g). The ethyl acetate extract was subjected to silica gel (200–300 mesh) CC using a chloroform–methanol gradient (100:0 to 0:100) and finally washed with methanol to give 18 subfractions from which compounds 1–10 were isolated. Identification of the isolated compounds was achieved by comparison with reported literature data.

Lactones from Ficus auriculata and their effects on the proliferation function of primary mouse osteoblasts in vitro

Bioassay-guided fractionation of the petroleum ether, chloroform and EtOAc extracts of the stems of Ficus auriculata led to the isolation of five new 12-membered lactones (3R,4R)-4-hydroxy-de-O-methyllasiodiplodin (1), 6-oxolasiodiplodin (2) and ficusines A-C (3-5), together with three known related analogues (6-8). The structures of the new compounds were elucidated by comprehensive spectroscopic data. The absolute configurations of 3 and 8 were established by single crystal X-ray diffraction analysis. Compounds 3-5 represent the first 12-membered lactones with a quinone ring unit. Compounds 6 and 7 exhibited significant proliferation function of primary osteoblasts (OBs) in vitro. Especially, the promotion rate of 6 reached 151.55±1.34% (P<0.001) at the concentration of 100 μM.