Withaperuvin O, a new withanolide from Physalis peruviana L.

Physalis peruviana L. (Solanaceae) has been used in tropical and subtropical countries of the world as medicinal and fruit trees. In this study, a new withanolide named withaperuvin O (1) and seven known ones, including physalolactone B-3-O-ß-D-glucopyranoside (2), withanolide J (3), physapruin A (4), physaperuvin G (5), withaperuvin (6), withaperuvin C (7) and 28-hydroxywithaperuvin C (8), were isolated from the whole plants of P. peruviana. Their structures were elucidated based on extensive spectroscopic analyses including NMR and HR-ESI-MS. The bioactivities of these compounds against lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells and cytotoxicity against HepG2 were tested. Compound 3 showed strong anti-inflammatory activities with IC50 3.55 ± 0.12 µM (compared to positive control L-NMMA 7.72 ± 0.46 µM). Compounds 3 and 4 inhibited HepG2 cell line with the IC50 values of 2.01 ± 0.12 µM, 0.96 ± 0.05 µM, respectively (Ellipticine, 0.32 ± 0.02 µM). Our study indicated that compounds 3 and 4 could be new potential natural products for the development of anti-inflammatory and anti-cancer agents.

Stigmastane-type steroid saponins from the leaves of Vernonia amygdalina and their α-glucosidase and xanthine oxidase inhibitory activities.

Two new vernonioside K (1) and vernonioside L (2) and four known Δ7,9(11) stigmastane-type steroidal saponins-vernonioside B2 (3), vernoniacum B (4), vernonioside B1 (5), and vernoamyoside A (6)-were isolated from the leaves of Vernonia amygdalina. Their structures were determined by comprehensive spectroscopic analysis with one-dimensional nuclear magnetic resonance, two-dimensional nuclear magnetic resonance, and high-resolution mass spectrometry. All isolated compounds (1-6) were evaluated to determine their inhibitory effects on α-glucosidase and xanthine oxidase. Among them, two new compounds 1 and 2 showed significant inhibition of α-glucosidase with IC50 values of 78.56 ± 7.28 and 14.74 ± 1.57 (µM), respectively, comparable with acarbose as a positive control (127.53 ± 1.73 µM); none of these compounds inhibited xanthine oxidase activity. Compounds 1 and 2 are promising candidates for the development of antidiabetic agents from natural sources.

Acetylcholinesterase inhibition studies of alkaloid components from Crinum asiaticum var. sinicum: in vitro assessments by molecular docking and molecular dynamics simulations.

Alkaloids are among the most important and best-known secondary metabolites as sources of new drugs from medicinal plants and marine organisms. A phytochemical investigation of the whole plant of Crinum asiaticum var. sinicum resulted in the isolation of seven alkaloids (1-7), including one new dimeric compound, bis-(-)-8-demethylmaritidine (1). Their structures were elucidated using NMR and HR-ESI-MS. The absolute configuration of new compound 1 was established by circular dichroism spectroscopy. All isolated compounds were evaluated for their inhibitory effects on acetylcholinesterase (AChE) activity in vitro. Among them, compound 1 exhibited the most potent AChE inhibition. Moreover, molecular docking and molecular dynamics simulations were carried out for the most active compound to investigate their binding interactions and dynamics behavior of the AChE protein-ligand complex. Therefore, compound 1 may be a potential candidate for effectively treating Alzheimer's disease.

The Relationship Between Dry Eye in Adults with Indications for Kidney Transplantation and Influence Factors.

PURPOSE: Patients with end-stage renal failure are susceptible to dry eye disease. This study explores the relationship between dry eye disease and influence factors. PATIENTS AND METHODS: The control group consisted of 57 healthy subjects who were kidney donors. They were of the same age and sex as the kidney transplant recipients. The outcome variable was the dry eye condition of the participants. The Schirmer test confirmed dry eye disease, TBUT (breakup time test), and the Eye Surface Disease Index (OSDI) questionnaire, using linear regression to evaluate the association. RESULTS: The total number of subjects was 146 (89 kidney recipients and 57 kidney donors). When univariate analysis found the level of visual acuity, the age group involved was statistically significant, while the other factors were not statistically significant. In multivariable logistic regression analysis, age (odds ratio: 2.8, p<0.05), smoking history (odd ratio: 0.1, p<0.05), corneal conjunctival calcification (odd ratio: 0.2, p<0.05); central corneal thickness (odd ratio: 1.02, p<0.05) is considered to be an influence factor for disease progression. CONCLUSION: Age group, smoking history, corneal central thickness, and conjunctival calcification are factors for dry eye disease in patients preparing to receive a kidney. These results reinforce the evidence for multifactorial dry eye disease in patients with renal impairment.

Bioactive compounds from Physalis angulata and their anti-inflammatory and cytotoxic activities.

A new compound, physalucoside A (1), together with seven withanolides (2-8) and three flavonoids (9-11), were isolated from Physalis angulata L. (Solanaceae), a medicinal plant native to Vietnam. The chemical structures of these compounds were elucidated by one- and two-dimensional NMR spectra, high-resolution electrospray ionization mass spectrometry analyses, and chemical reactivity. The anti-inflammatory and cytotoxic activities of isolated compounds were also evaluated. These data suggest that the anti-inflammatory activity of P. angulata is due primarily to its withanolide content. This study demonstrates the potential of withanolides as promising candidates for the development of new anti-inflammatory drugs.

Cytotoxic and anti-inflammatory activities of secondary metabolites from Ophiorrhiza baviensis growing in Thua Thien Hue, Vietnam.

A new ursane-type triterpene, 3ß,23,24-trihydroxyurs-12-en-28-oic acid (1), together with eight known compounds (2-9) were isolated from the aerial parts of Ophiorrhiza baviensis. Among them, compounds 2-5 were found for the first time from the genus Ophiorrhiza, while compounds 6-9 were reported from O. baviensis for the first time. Their structures were elucidated by analysis of HR-ESI-MS and NMR (1H-NMR, 13C-NMR, HSQC, and HMBC) spectra, as well as comparison with those reported in the literature. Moreover, all isolated compounds were evaluated for their cytotoxic activities against MCF-7, Hela, KB, A549, and SK-LU-1 cancer cell lines and their effects on LPS-induced NO production in RAW264.7 cells. This is the first report of chemical constituents and biological activities of O. baviensis.

Bioactive compounds from the aerial parts of Hypericum sampsonii.

Hypericum sampsonii is an important medicinal plant used in Vietnam to treat many diseases such as backache, burns, diarrhea, and swelling. In order to study the chemical constituents in the aerial parts of H. sampsonii, five compounds, including two xanthones (1-2), and three benzophenones (3-5) were isolated from the aerial parts of the H. sampsonii with various chromatographic separations. Their chemical structures were established on the basis of spectroscopic data such as 1D- and 2D-NMR, HR-ESI-MS. Their anti-inflammatory activities were investigated by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Moreover, the DPPH radical scavenging was evaluated. As the obtained results, compound 5 showed the strongest inhibitory activity against LPS-stimulated NO production in RAW264.7 cells with IC50 value ranging from 2.00 ± 0.34 µM.

Identification Of Potential Cytotoxic Inhibitors From Physalis Minima.

A phytochemical investigation of Physalis minima led to the isolation of six withanolides, including withanolide E (1), withaperuvin C (2), 4ß-hydroxywithanolide E (3), 28-hydroxywithaperuvin C (4), physaperuvin G (5), and 4-deoxywithaperuvin (6). Their chemical structures were elucidated by 1 D-NMR and 2 D-NMR data, as well as comparison with the data reported in the literature. All isolated compounds were evaluated for their cytotoxic activity against HepG2, SK-LU-1, and MCF7 cancer cell lines. As the obtained results, compounds 1 and 3 displayed the strongest cytotoxicity against HepG2, SK-LU-1, and MCF7 cell lines with IC50 value ranging from 0.051 ± 0.004 to 0.86 ± 0.09 µg/mL.

Cytotoxic activity of steroidal glycosides from the aerial parts of Solanum torvum collected in Thua Thien Hue, Vietnam.

A phytochemical investigation of Solanum torvum led to the isolation of eleven steroidal glycosides, including neochlorogenin 6-O-ß-D-quinovopyranoside (1), (22 R,23S,25R)-3ß-6α,23-trihydroxy-5α-spirostane 6-O-ß-D-xylopyranosyl-(1→3)-ß-D-quinovopyranoside (2), neochlorogenin 6-O-α-L-rhamnopyranosyl-(1→3)-ß-D-quinovopyranoside (3), solagenin 6-O-α-L-rhamnopyranosyl-(1→3)-ß-D-quinovopyranoside (4), paniculonin A (5), paniculonin B (6), 6α-O-[ß-D-xylopyranosyl-(1→3)ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (7), torvoside J (8), torvoside K (9), torvoside L (10) and solagenin 6-O-ß-D-quinovopyranoside (11). Their chemical structures were elucidated by 1D-NMR and 2D-NMR data as well as comparison with the data reported in the literature. Moreover, all isolated compounds were evaluated for their cytotoxic activities against SK-LU-1, HepG2, MCF-7 and T24 cancer cell lines. Among them, compounds 1, 3, 7 and 11 exhibited cytotoxicity against all four tested cell lines with IC50 values ranging from 7.89 ± 0.87 to 46.76 ± 3.88 µM.

Molecular Screening of Nasopharyngeal Carcinoma: Detection of LMP-1, LMP-2 Gene Expression in Vietnamese Nasopharyngeal Swab Samples.

Objective: This study aimed to characterize the expression of LMP-1, LMP-2 in clinical swab samples in order to find out the potential molecular based biomarker for NPC diagnosis and screening, which could offer a chance in development of rapid method for NPC diagnosis in Vietnamese population. Materials and Methods: A total of 93 nasopharyngeal carcinoma swab samples and 100 healthy nasopharyngeal swab samples were collected to evaluate LMP-1, LMP-2 expression by Real-time reversed PCR. Results: we figured out the significant association between the expression of LMP-1 (counting for 48.39%), LMP-2 (counting for 39.78%) and NPC. No LMP-1 expression was observed, and only 1 of 100 specimens was detected with LMP-2 positive in healthy samples. In the combination of LMP-1 (+) and/or LMP-2 (+), the frequency of positive was 53.76%, greater than each gene expression. Additionally, sensitivity, specificity, positive predictive value, negative predictive value of assay were 99.00%, 98.04%, 69.72%, and 77.02%, respectively. Additionally, the LMP-2 expression level was 5.50 times higher in NPC samples than non-cancerous samples. Conclusion: Our results indicated the molecular invasive method based on the expression of LMP-1, LMP-2 in swab samples would be a promising supplement in NPC diagnosis, screening in the near future in Vietnam.

Degalactotigonin, a Steroidal Glycoside from Solanum nigrum, Induces Apoptosis and Cell Cycle Arrest via Inhibiting the EGFR Signaling Pathways in Pancreatic Cancer Cells.

Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.

Anti-inflammatory coumarins from Paramignya trimera.

CONTEXT: Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated. OBJECTIVE: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds. MATERIALS AND METHODS: Cytotoxicity of isolated compounds (5-40 µM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 µM) on nitrite and PGE2 concentrations were determined using Griess reaction and PGE2 ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 µM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS). RESULTS: Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6',7'-dihydroxy-3',7'-dimethylocta-2'-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1-4 and 7 inhibited NO and PGE2 production in LPS-stimulated BV2 cells, with IC50 values ranging from 9.8 to 46.8 and from 9.4 to 52.8 µM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression. DISCUSSION AND CONCLUSION: The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.

Prenylated isoflavones from Cudrania tricuspidata inhibit NO production in RAW 264.7 macrophages and suppress HL-60 cells proliferation.

Inhibitory effects of NO production in RAW 264.7 macrophages guided the isolation of nine prenylated isoflavones, including a new cudraisoflavone L (1) and eight known metabolites furowanin B (2), erysubin A (3), wighteone (4), lupalbigenin (5), laburnetin (6), isolupalbigenin (7), 6,8-diprenylorobol (8), millewanin H (9) from the leaves of Cudrania tricuspidata. At the concentration of 10 µM, compounds 1, 2, and 4 significantly inhibited NO production with the inhibitory values of 72.5 ± 2.4, 66.9 ± 1.8, and 55.4 ± 2.7%, respectively. In addition, all of isolated compounds 1-9 showed promising cytotoxic effects toward HL-60 cells (IC50 4.3 ± 0.7 to 18.0 ± 1.7 µM).

Chemical constituents of the Annona glabra fruit and their cytotoxic activity.

CONTEXT: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. Annona glabra Linn (Annonaceae) is used in traditional medicine as an anticancer drug. Phytochemical investigation of this plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids. In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria. OBJECTIVE: Isolation, structure determination, and cytotoxic activity evaluation of compounds from the methanol extract from A. glabra fruits. MATERIALS AND METHODS: Using chromatographic methods to isolate compounds from the A. glabra methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds which showed significant cytotoxic activity were chosen for further study apoptosis characteristics. RESULTS: One new, (2E,4E,1'R,3'S,5'R,6'S)-dihydrophaseic acid 1,3'-di-O-ß-d-glucopyranoside, and eight known compounds, (2E,4E,1'R,3'S,5'R,6'S)-dihydrophaseic acid 3'-O-ß-d-glucopyranoside (2), icariside D2 (3), icariside D2 6'-O-ß-d-xylopyranoside (4), 3,4-dimethoxyphenyl O-ß-d-glucopyranoside (5), 3,4-dihydroxybenzoic acid (6), blumenol A (7), cucumegastigmane I (8), and icariside B1 (9), were isolated from the fruits of A. glabra. Icariside D2 (3) was found to show significant cytotoxic activity on the HL-60 cell line with the IC50 value of 9.0 ± 1.0 µM and did not show cytotoxic activity on the Hel-299 normal cell line. The further test indicated that compound 3 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells. DISCUSSION AND CONCLUSION: The results suggested that the constituents from A. glabra may contain effective compounds which can be used as anticancer agents.

Chemical constituents of Trichosanthes kirilowii and their cytotoxic activities.

One new lignan, trichobenzolignan (1), and seven known compounds, ligballinol (2), (-)-pinoresinol (3), ehletianol C (4), luteolin 7-O-ß-D-glucopyranoside (5), chrysoeriol-7- O-ß-D-glucopyranoside (6), 10α-cucurbita-5,24-dien-3ß-ol (7), and arvenin I (8). Their structures were established on the basis of spectral and chemical evidence, which were in agreement with those reported in literature. The cytotoxic activities of these compounds were evaluated on four cancer cell lines such as A-549 (human lung cancer), HT-29 (human colon adenocarcinoma), OVCAR (human ovarian carcinoma), and MCF-7 (human breast cancer). As the results, compound 7 showed significant activity on HT-29 and OVCAR cancer cell lines with IC50 of 4.1 and 6.5 µM, respectively. Compounds 1, 5, 6, and 8 exhibited moderate activities in all cancer cell lines with IC50 ranging from 11.3 to 42.8 µM.

Muurolane-type sesquiterpenes from marine sponge Dysidea cinerea.

Seven new muurolane-type sesquiterpenes, (4R,5R)-muurol-1(6),10(14)-diene-4,5-diol (1), (4R,5R)-muurol-1(6)-ene-4,5-diol (2), (4R,5R,10R)-10-methoxymuurol-1(6)-ene-4,5-diol (3), (4S)-4-hydroxy-1,10-seco-muurol-5-ene-1,10-dione (4), (4R)-4-hydroxy-1,10-seco-muurol-5-ene-1,10-dione (5), (6S,10S)-6,10-dihydroxy-7,8-seco-2,8-cyclo-muurol-4(5),7(11)-diene-12-oic acid (6), and (6R,10S)-6,10-dihydroxy-7,8-seco-2,8-cyclo-muurol-4(5),7(11)-diene-12-oic acid (7) were isolated from the marine sponge Dysidea cinerea. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D-NMR, 2D-NMR, and CD spectra as well as by comparing the NMR data with those reported in the literature.