Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations ≥ 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential

Bioactive compounds fractionated from endophyte Streptomyces SUK 08 with promising ex-vivo antimalarial activity

Objective:To determine ex vivo antimalarial activity and cytotoxicity of endophytic Streptomyces SUK 08 as well as the main core structure fractionated from its crude extract.Methods:The activities of SUK 08 crude extract were evaluated by using the Plasmodium lactate dehydrogenase assay and synchronization test against rodent malaria parasite Plasmodium berghei,instead of human malarial parasite Plasmodium falciparum.The cytotoxicity of the crude extract was determined by MTT assay.The crude extract was analyzed by thin-layer chromatography and gas chromatography-mass spectrophotometry.Results:The ethyl acetate crude extract showed very promising antimalarial activity with IC50 of 1.25 mg/mL.The synchronization tests showed that ethyl acetate extraction could inhibit all stages of the Plasmodium life cycle,but it was most effective at the Plasmodium ring stage.On the basis of a MTT assay on Chang Liver cells,ethyl acetate and ethanol demonstrated IC50 values of ＞ 1.0 mg/mL.The IC50 of parasitemia at 5％ and 30％ for this extract was lower than chloroquine.Thin-layer chromatography,with 1∶9ratio of ethyl acetate:hexane,was used to isolate several distinct compounds.Based on gas chromatography-mass spectrophotometry analysis,three core structures were identiffed as cyclohexane,butyl propyl ester,and 2,3-heptanedione.Structurally,these compounds were similar to currently available antimalarial drugs.Conclusions:The results suggest that compounds isolated from Streptomyces SUK 08 are viable antimalarial drug candidates that require further investigations.

Comparative study of three Marantodes pumilum varieties by microscopy, spectroscopy and chromatography

Abstract Marantodes pumilum (Blume) Kuntze (synonym: Labisia pumila (Blume) Fern.-Vill), Primulaceae, is well known for its traditional use as a post-partum medication among women in Malaysia. Three varieties of M. pumilum, var. alata Scheff., var. pumila and var. lanceolata (Scheff.) Mez. are commonly used. Nowadays, M. pumilum powder or extracts are commercially available as herbal supplements and beverages. Authentication of the variety is an important component of product quality control. Thus, the present work was aimed to compare the three varieties using microscopic, spectroscopic and chromatographic techniques. Microscopic anatomical examination and powder microscopy were performed on fresh and dried plant materials, respectively. Fingerprint profiles of the varieties were obtained using attenuated total reflectance-Fourier transform infrared spectrophotometer, high performance thin layer chromatography and high performance liquid chromatography. The microscopic examination showed presence of anisocytic stomata, scale and capitate glandular trichome in all varieties. The type of stomata and trichomes, outline structure of stem and leaf margin, petiole and midrib, organization of vascular system, areolar venation, pattern of anticlinal walls, the distribution of secretory canals and cell inclusion as well as the measurement of selected structures could be used to distinguish and identify each variety of M. pumilum. In addition, spectroscopic and chromatographic fingerprint analyses of the three varieties exhibited distinguishable profiles based on the intensity of certain peaks or bands. The findings from this study will provide systematic identification for these varieties.