Fan Cheng

The anti-ulcer activities of bisabolangelone from Angelica polymorpha

AIM OF THE STUDY Evaluate the anti-ulcer effects of bisabolangelone from Angelica polymorpha Maxim and provide the basic data to further study for the Angelica polymorpha and bisabolangelone. MATERIALS AND METHODS Bisabolangelone was isolated from Angelica polymorpha Maxim collected from Shennongjia Forest District of China. The structure of bisabolangelone was elucidated by NMR and MS spectrums. The anti-ulcer effects were evaluated with length of lesion (mm) and activity of H(+)/K(+)-ATPase in two models induced by ethanol and Pylorus ligation. Experimental groups were administered with different doses of bisabolangelone (3.8, 7.6 and 15.3 mg/kg). The positive control group was administered omeprazole with a dose of 3.3 mg/kg. RESULTS Bisabolangelone significantly reduced the length of lesion (3.8, 7.6 and 15.3 mg/kg, P<0.01), inhibited the activity of H(+)/K(+)-ATPase (3.8, 7.6 and 15.3 mg/kg, P<0.01), decreased the volume of gastric juice (7.6 and 15.3 mg/kg, P<0.05), and increased the pH value of gastric juice (7.6 and 15.3 mg/kg, P<0.01, 3.8 mg/kg, P<0.05). CONCLUSIONS Bisabolangelone is the main anti-ulcer active compound of Angelica polymorpha, and remarkably preventive and therapeutic action on gastric ulcer. It is possible that bisabolangelone inhibited the activity of the H(+)/K(+)-ATPase, then reducing the secretion of H(+), and the anti-ulcer mechanism of bisabolangelone was deserved to be further studied.

Five new furostanol saponins from the rhizomes of Tupistra chinensis

Five new furostanol saponins (1-5), together with three known compounds (6-8) were obtained from the n-butanol soluble fraction of ethanol extract from Tupistra chinensis. Their structures were determined on the basis of chemical methods and spectral data. The isolated compounds were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, compounds 6, 7, and 8 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 6.6, 6.7 and 29.1 μM, respectively.

Three new steroidal glycosides from roots of Reineckia carnea.

Two new spirostanols and a new furostanol, reinocarnoside A (1), B (2) and C (3), were isolated from the roots of Reineckia carnea, together with two known compounds, (25S)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside (4), kitigenin-5β-O-β-D-glucopyranoside (5). The structures of three new compounds were elucidated by spectroscopic methods including 1-D NMR, 2-D NMR and MS spectrums, and their anticancer activities were evaluated by MTT method.

Estrogenic and anti-estrogenic activities of hispolon from Phellinus lonicerinus (Bond.) Bond. et sing.

Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17β-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (-) MDA-MB-231 cells at the concentration of 5.00×10(-5) M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERβ at a concentration of 1.00×10(-6) M. The ERβ-binding ability of hispolon was larger than ERα in the concentration range of 1.00×10(-9) M and 1.00×10(-7) M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10×10(-6) mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERβ docked complexes were -7.93 kcal/mol and -7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.

Cytotoxic 1,3-Thiazole and 1,2,4-Thiadiazole Alkaloids from Penicillium oxalicum: Structural Elucidation and Total Synthesis

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target.

Anti-PRRSV effect and mechanism of tetrahydroaltersolanol C in vitro

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important arterivirus that causes substantial economic losses to the swine industry. Current control strategies against PRRSV are still inadequate and there is an urgent need for new antiviral therapies. Tetrahydroaltersolanol C (TD-C) is a new anthraquinone derivative isolated from the marine-derived fungi. In the present study, we first demonstrated its anti-PRRSV activity in vitro through assessing the inhibition of TD-C on cytopathic effect, viral ORF7 gene and N protein expressions, progeny virions production by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, relative-quantitative RT-PCR, Western blotting, and indirect immunofluorescence assay. Our experimental results showed that TD-C could significantly inhibit PRRSV replication in a dose-dependent manner. The 50% effective concentration, 50% cytotoxic concentration and the selectivity index were 12.11, 395.31 μM, and 32.64, respectively. Furthermore, the possible anti-PRRSV mechanism was explored by virucidal assay, virus adsorption inhibition assay, and the time-of-addition assay. The results showed that TD-C might inhibit the internalization and replication of PRRSV, but did not directly inactivate the virus or block its adsorption to cell surface. In conclusion, our findings indicated that TD-C possessed a significant anti-PRRSV activity, and provided a strong basis for further exploration of this compound as an antiviral agent against PRRSV.

Alkaloids from Penicillium oxalicum, a Fungus Residing in Acrida cinerea

Five alkaloids, (Z)-N-(4-hydroxystyryl) formamide (1), (E)-N-(4-hydroxystyryl) formamide (2), 2-(4-hydroxybenzyl) quinazolin-4(3H)-one (3), penipanoid A (4), asperazine (5), were isolated from cultures of Penicillium oxalicum, a fungus residing in Acrida cinerea. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. Compounds 1-5 were evaluated for their cytotoxic activity against the HepG2 and CaSki cell lines.

Caroguaianolide A–E, five new cytotoxic sesquiterpene lactones from Carpesium abrotanoides L.

Five new guaiane-type sesquiterpene lactones, caroguaianolide A-E (1-5), along with nine known sesquiterpene lactones (6-14) were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic date, HRESIMS analysis, and comparison of experimental and calculated ECD data. All isolated compounds (1-14) were tested in vitro for their cytotoxic activities against the MDA-MB-231, HGC-27 cancer cell lines, of which compounds 1-3, 6, 7, 11 and 12 showed significant cytotoxic activities with IC50 values ranging from 2.67 to 12.34 μM.

A Steroidal Saponin RCE-4 Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses via Blocking PI3K/Akt-Mediated Nf-κB Activation in RAW264.7 Cells

Steroidal saponin: (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside] (RCE-4) is the most abundant and bioactive members in Reineckia carnea, has been reported to possess antiinflammatory activity, but the underlying mechanisms remain largely unknown. The present aim was to study expression of inflammatory cytokines, on the basis of this investigation, the possible mechanism of RCE-4 was elucidated. In the present study, we found that the concentrations of TNF-α, IL-1β and IL-6 released from LPS-stimulated RAW264.7cells significantly increased compared to control (P<0.01, respectively). After pretreatment with RCE-4, the TNF-α, IL-1β and IL-6 levels significantly decreased compared with the LPS group (P<0.05, P<0.01, respectively). Further studies indicated that RCE-4 significantly suppressed Akt phosphorylation and NF-қB activation, and with the dose of RCE-4 increasing; their improvement became more and more strong. Our results showed that RCE-4 inhibited LPS-stimiulated TNF-α, IL-1β, IL-6 productions through the blockage of PI3K/Akt-mediated NF-κB activation. Our findings might provide a molecular basis for the ability of RCE-4 serving as a promising candidate for treating various inflammatory diseases.

A New Wutaifuranol Derivative From Solanum cathayanum

The plant Solanum cathayanum is widely distributed in China, and the whole plant has been clinically available in Chinese folk medicine as anti-cancer, anti-inflammatory, and anti-bacterial agents. Our previous phytochemical investigations of the plant revealed the existence of phenylpropanoids, coumarins, lignans, and alkaloids [1]. Recently, further exploitation of the chemical constitutions of Solanum cathayanum led to the discovery of 3-hydroxymethyl-7-methoxywutaifuranol (1), a new wutaifuranol analogue. Wutaifuranol and its derivatives are characteristic members of the benzofuran family and are widespread in nature. They exhibit a broad range of biological activities such as anticancer [2], anti-inflammatory [3], antifungal [4], and antitubercular [5]. Herein, we report the detailed isolation and structural elucidation of 1. The dried Solanum cathayanum (20 kg) was extracted with 95% ethanol under reflux for three times. After removal of solvent under reduced pressure, the extract was suspended in water and degreased with ligarine. The water layer was acidified with 4% HCl and filtered. The alkalized filtrate, pH adjusted to 7.0 with Na2CO3, was extracted with chloroform for three times. The combined organic layers were concentrated to give a residue (400 g). The crude residue (20 g) was chromatographed on a reverse-phase column eluting with 5–70% CH3CN–H2O to give 153 fractions. Fractions 26–28 were combined and further separated by semipreparative reverse-phase HPLC on a Diamonsil C18 column (5 m, 250 4.6 mm) eluting with 17.5% CH3CN–H2O (v/v) to afford compound 1 (5 mg). Compound 1 was isolated as a yellow amorphous powder, and its molecular formula was established as C13H14O4 by HR-ESI-MS (m/z [M + H]+ 235.0960, calcd 235.0970) and NMR spectrum. The 1H NMR spectrum revealed two meta-coupled protons characteristic of a benzene ring at 7.25 (1H, d, J = 1.2 Hz, H-4) and 7.02 (1H, d, J = 1.2 Hz, H-6), a trans-3-hydroxy-1-propenyl group [ 6.60 (1H, d, J = 15.8 Hz, H-8), 6.37 (1H, dt, J = 15.8 and 5.2 Hz, H-9) and 4.14 (2H, m, H-10)], an alkene proton at 7.79 (1H, s, H-2), an oxygenated methylene proton at 4.59 (2H, d, J = 3.5 Hz, H-11) in the downfield region, a methoxy proton at 3.95 (3H, s, 7-OCH3), and two exchangeable proton at 4.82 (1H, br.s, 10-OH) and 5.11 (1H, br.s, 11-OH). The 13C NMR and DEPT spectra displayed five olefinic methine carbons at 142.7, 110.5, 104.8, 129.7, and 129.0, two oxygenated methylene carbons at C 61.5 and 53.8, a methoxy carbon at 55.8, and five sp2 quaternary carbon at 144.9, 143.5, 132.8, 128.7, and 121.9. The 1H and 13C NMR spectra of compound 1 (Table 1) were similar to those of 7-methoxywutaifuranol [5], having a benzofuran framework, except that a proton of furan ring was observed at 7.79 (1H, s, H-2). Inspection of the HMBC spectrum revealed that a hydroxymethyl group signal at H 4.59 (2H, d, J = 3.5 Hz, H-11) and 5.11 (1H, br.s, 11-OH) in 1 replaced the ortho-coupled protons in the furan ring of the benzofuran unit in 7-methoxywutaifuranol. The location of the hydroxymethyl group at C-3 in the furan ring was determined by the HMBC correlations (Fig. 1) from H-11 ( 4.59) to C-3 ( 121.9), C-3a ( 128.7), and C-2 ( 142.7). On the basis of the above evidence, the structure of compound 1 was elucidated as the hitherto unreported 3-hydroxymethyl-7-methoxywutaifuranol.