Investigation of HIV-1 Viral Protein R Inhibitory Activities of Twelve Thai Medicinal Plants and Their Commercially Available Major Constituents.

Viral protein R (Vpr) is an accessory protein in Human immunodeficiency virus-1 (HIV-1) and has been suggested as an attractive target for HIV disease treatment. Investigations of the ethanolic extracts of twelve Thai herbs revealed that the extracts of the Punica granatum fruits, the Centella asiatica aerials, the Citrus hystrix fruit peels, the Caesalpinia sappan heartwoods, the Piper betel leaves, the Alpinia galangal rhizomes, the Senna tora seeds, the Zingiber cassumunar rhizomes, the Rhinacanthus nasutus leaves, and the Plumbago indica roots exhibited the anti-Vpr activity in HeLa cells harboring the TREx plasmid encoding full-length Vpr (TREx-HeLa-Vpr cells). Moreover, the investigation of the selected main constituents in Punica granatum, Centella asiatica, A. galangal, and Caesalpinia sappan indicated that punicalagin, asiaticoside, ellagic acid, madecassic acid, madecassoside, zingerone, brazilin, and asiatic acid possessed anti-Vpr activities at the 10 µM concentration. Among the tested extracts and compounds, the extracts from Centella asiatica and Citrus hystrix and the compounds, punicalagin and asiaticoside, showed the most potent anti-Vpr activities without any cytotoxicity, respectively.

Molecular epidemiology of vancomycin-resistant Enterococcus faecium clinical isolates in a tertiary care hospital in southern Thailand: a retrospective study.

OBJECTIVE: Vancomycin-resistant enterococci are nosocomial pathogens that are responsible for commonly causing healthcare-associated infections, and they exhibit increased resistance to many antimicrobials, particularly to vancomycin. The epidemiological data available on vancomycin-resistant enterococci (VRE) in Thailand are inadequate. METHODS: Using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), this study investigated genes that encode antimicrobial resistance and genetic relatedness to further understand VRE prevalence. Ninety VRE isolates were collected between 2011 and 2019 from a tertiary care hospital in southern Thailand. Antimicrobial susceptibility was determined using the disk diffusion method and E-test methods. Multiplex PCR was performed to detect the van gene and virulence genes. RESULTS: The study showed a high prevalence of diverse multidrug-resistant VRE strains. The prevalence of VRE infection was the highest in 2014 (28 isolates, 39.4%). VRE were mostly found in the urogenital tract (26 isolates, 28.9%), followed by the digestive tract (20%), body fluid, i.e., pancreatic cyst fluid, peritoneal dialysis fluid, Jackson-Pratt (JP) drain (20%), and blood specimens (10%). Patients in medical and surgical wards had 71.1% multi-drug-resistant and 28.9% extensively drug-resistant (XDR) VRE strains, respectively. The most prevalent antibiotic resistance was to ampicillin (74.4%). Susceptibility to gentamicin and meropenem were similar (7% and 10%, respectively). Four isolates (4.4%) were resistant to colistin. Only vanA was detected among the strains. The virulence gene test showed that the detection rates of enterococcal surface protein (esp) and hyaluronidase (hyl) genes were 91.1% and 5.6%, respectively. According to ERIC-PCR analysis, 51 of 90 strains had clonality, with a similarity rate of 95%. CONCLUSIONS: We conclude that there is a need to implement infection control practices and active surveillance. Molecular techniques can effectively detect antibiotic-resistant genes, which would allow monitoring to control VRE infection in hospitals.

(-)-Kusunokinin inhibits breast cancer in N-nitrosomethylurea-induced mammary tumor rats.

Natural and synthetic (-)-kusunokinin inhibited breast cancer, colon cancer and cholangiocarcinoma cells at the G2/M phase and induced apoptosis. However, there is no report on the action and adverse effects of (-)-kusunokinin in animal models. In this study, we investigated the cytotoxic effect of (-)-kusunokinin from Piper nigrum on cancer cells. NMU-induced rat mammary tumors, an ER positive breast cancer model, were treated with (-)-kusunokinin. Proteins of interest related to cell cycle, angiogenesis, migration and signaling proteins were detected in tumor tissues. Results showed that (-)-kusunokinin exhibited strong cytotoxicity against breast, colon and lung cancer cells and caused low toxicity against normal fibroblast cells. For in vivo study, 7.0 mg/kg and 14.0 mg/kg of (-)-kusunokinin reduced tumor growth without side effects on body weight, internal organs and bone marrow. Combination of (-)-kusunokinin with a low effective dose of doxorubicin significantly inhibited tumor growth and provoked cell death in cancer tissues. Mechanistically, 14.0 mg/kg of (-)-kusunokinin decreased cell proliferation (c-Src, PI3K, Akt, p-Erk1/2 and c-Myc), cell cycle (E2f-1, cyclin B1 and CDK1), and metastasis (E-cadherin, MMP-2 and MMP-9) proteins in tumor tissues, which supports its anticancer effect. We further confirmed the antimigration effect of (-)-kusunokinin; the results show that this compound inhibited breast cancer cell (MCF-7) migration in a dose-dependent manner. In conclusion, the results suggest that 14 mg/kg of (-)-kusunokinin inhibited tumors through the reduction of signaling proteins and their downstream molecules. Therefore, (-)-kusunokinin becomes an intriguing candidate for cancer treatment as it provides a strong potency in cancer inhibition.

(-)-Kusunokinin and piperloguminine from Piper nigrum: An alternative option to treat breast cancer.

Several studies have reported that active compounds isolated from Piper nigrum possess anticancer properties. However, there are no data on anticancer activity of (-)-kusunokinin and piperlonguminine. The purposes of this study were to isolate active compounds from P. nigrum and identify the molecular mechanisms underlying growth and apoptosis pathway in breast cancer cells. Two bioactive compounds, (-)-kusunokinin and piperlonguminine, were isolated from P. nigrum. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Western blot analysis. We found that the active compounds, which effect cancer cell lines were (-)-kusunokinin and piperlonguminine. These compounds have potent cytotoxic effects on breast cancer cells (MCF-7 and MDA-MB-468) and colorectal cells (SW-620). (-)-Kusunokinin demonstrated a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.18 and 1.62µg/mL, respectively. Piperlonguminine had a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.63 and 2.19µg/mL, respectively. Both compounds demonstrated lower cytotoxicity against normal breast cell lines with IC50 values higher than 11µg/mL. Cell cycle and apoptotic analysis using flow cytometry, showed that the (-)-kusunokinin and piperlonguminine induced cell undergoing apoptosis and drove cells towards the G2/M phase. Moreover, both compounds decreased topoisomerase II and bcl-2. The increasing of p53 levels further increased p21, bax, cytochrome c, caspase-8, -7 and -3 activities, except caspase-9. These results suggest that the (-)-kusunokinin and piperlonguminine have been shown to have potent anticancer activities through extrinsic pathway and G2/M phase arrest.

Potential applicability of MALDI-MS for low-molecular-weight pesticide determination.

The application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for pesticide analysis was demonstrated. Fifteen pesticides were chosen as the model pesticides and twenty-six MALDI matrices were screened for the most suitable matrix. Under the optimized conditions, the obtained limits of detections were lower than the maximum residue limit values stated with 12 pesticides out of 15 tested. The proposed methodology showed a good analytical performance in terms of rapid, good sensitivity and high throughput of the method as an alternative method for pesticide residues evaluation.

Menisporopsin B, a new polyester from the seed fungus Menisporopsis theobromae BCC 4162.

A new linear polyester, menisporopsin B, along with the known macrocyclic polyester, menisporopsin A, was isolated from the seed fungus Menisporopsis theobromae BCC 4162. The structure of menisposopsin B was addressed primarily by spectroscopic analyses, and the stereochemistry was established by chemical correlation. Menisporopsin B exhibited antimalarial activity with an IC(50) value of 1.0 microg/ml.

Depsidones from the endophytic fungus BCC 8616.

Three new depsidones (1-3) have been isolated from the endophytic fungus BCC 8616 and their structures analyzed on the basis of spectroscopic data interpretation. Compound 1 exhibited weak cytotoxic activity against breast and epidermoid carcinoma cell lines.

Antiviral and antiplasmodial spirodihydrobenzofuran terpenes from the fungus Stachybotrys nephrospora.

Two known spirodihydrobenzofuran terpenes (1 and 2) were isolated from a mycelium extract of the fungus Stachybotrys nephrospora BCC 3900. Compound 1 (Mer-NF5003F or stachybotrydial) exhibited potent antiviral activity (the IC50 value of 4.32 microg/mL) comparable to the standard drug, acyclovir, while compound 2 was inactive against the HSV-1 virus. Both 1 and 2 possessed antiplasmodial activity (IC50 values of 0.85 and 0.15 microg/mL for 1 and 2, respectively), and were not toxic towards the Vero cell line. A regiospecific conversion of the dialdehyde 1 to the lactone 2 proceeded simply under acidic conditions.