Diuretic and hypotensive effect of morelloflavone from Garcinia dulcis in two-kidneys-one-clip (2K1C) hypertensive rat

Morelloflavone, a biflavonoid from Southeast Asian folk medical plant Garcinia dulcis, possesses powerful antioxidant activity both in vivo and in vitro. We aimed to evaluate the hypotensive and diuretic effect of morelloflavone in two-kidneys-one-clip (2K1C) renovascular hypertensive rats together with its vasorelaxant mechanism. Male Wistar rats (175±4 g) were undergone 2K1C and sham operation (SO) (n=6, each group). Four weeks after the rats were anesthetized and clearance markers (0.5% para-aminohippuric acid and 1% inulin) were given via a jugular vein (1.6 mL/h/100 g BW) to estimate renal blood flow (RBF) and glomerular filtration rate. The arterial blood pressure (AP) was monitored via a carotid artery and urine samples were collected. After equilibration, either morelloflavone or vehicle (DMSO) was given (0.1 mg/kg BW+5 μg/min/kg BW). Baroreflex sensitivity (BRS) (ΔHR/ΔMAP) was performed by an intravenous injection of 1, 2, 4, 8, 16 and 32 μg/kg BW phenylephrine (PE) or sodium nitroprusside. The PE-preconstricted isolated thoracic aortic rings (intact and denuded) relaxation were experimented using organ bath technique by cumulative additions of morelloflavaone (10-13-10-5 M) in the presence of specific vasorelaxant inhibitors and expressed as %relaxation from pre-contraction tension. In 2K1C rats, morelloflavone significantly lowered mean AP, increased RBF and increased urine flow rate when compared to vehicle control (138±6 vs. 152±1 mmHg, 3.44±0.49 vs. 2.29±0.25 mL/min/g KW and 42.0±9.4 vs. 18.2±3.9 μL/min/g KW, p<0.05), respectively and also restored the blunt BRS. Nitric oxide signaling pathway triggered by morelloflavone might be responsible for its diuretic and hypotensive effect

Bioassay-guided fractionation of Emilia sonchifolia extract on the induction of ovarian maturation in Fenneropenaeus merguiensis

This study was carried out to identify the active compounds of Emilia sonchifolia on induction of ovarian maturation in Fenneropenaeus merguiensis. The crude extracts from dichloromethane and acetone were investigated in vitro. The crude extract from acetone induced up-regulation of shrimp ovarian peritrophin (SOP) and translationally controlled tumor protein (TCTP) genes, which were highly expressed during early phase of ovarian development higher than dichloromethane extract. Furthermore, fraction 14 (F14) from acetone extract up-regulated both of the SOP and the TCTP genes to the greatest extent. Leading to in vivo study, the effect of ribosomal protein L10a (RPL10a), which acts as shrimp ovarian stimulator plus with F14 on shrimp ovarian maturation was investigated by injection. The best result was observed in the group that received RPL10a plus with F14 at 0.8 μg/g body weight of shrimp. The RPL10a plus F14 enhanced the shrimp ovaries from undeveloped stage to 57% of early developing stage within 15 days. Meanwhile, the control group remained 100% of the undeveloped stage. Hence, F14 seems to play a positive role in the induction of shrimp ovarian maturation. The component of F14 was identified using mass spectroscopy and presented as 1,2-benzenedicarboxylic acid; 2,4-di-tert-butyl phenol; 2,4,5-trimethoybenzylidene;palmitic acid; 1-heneicosyl formate; 1-heptadecanol; ethyl-4-ethoxybenzoate and stearic acid

2′-Chloro-4-meth­oxy-3-nitro­benzil

In the title compound, C15H10ClNO5, the dihedral angle between the aromatic rings is 87.99 (5)°. The O—C—C—O torsion angle between the two carbonyl units is −119.03 (16)°. The crystal structure is stabilized by a weak intermolecular C—H⋯O hydrogen bond

Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries.

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors from the NCI repository. One is the potent but non-selective michellamine B, a natural product, anti-viral agent. The other four compounds were selective inhibitors against 12-hLO, with three being synthetic compounds and one being alpha-mangostin, a natural product, caspase-3 pathway inhibitor. In addition, a selective inhibitor was isolated from the UCSC-MEL (neodysidenin), which has a unique chemical scaffold for a hLO inhibitor. Due to the unique structure of neodysidenin, steady-state inhibition kinetics were performed and its mode of inhibition against 12-hLO was determined to be competitive (K(i)=17microM) and selective over reticulocyte 15-hLO-1 (K(i) 15-hLO-1/12-hLO\u3e30)

Anti-Acanthamoeba activity of a semi-synthetic mangostin derivative and its ability in removal of Acanthamoeba triangularis WU19001 on contact lens

Garcinia mangostana L., also known as the mangosteen tree, is a native medicinal plant in Southeast Asia having a wide variety of pharmacologically active compounds, including xanthonoid mangostin. In this study, we examined the pharmacological activities of the selected semi-synthetic mangostin derivative, namely, amoebicidal activity, encystation inhibition, excystation activity, and removal capacity of adhesive Acanthamoeba from the surface of contact lens (CL). Among the three derivatives, C1 exhibited promising anti-Acanthamoeba activity against Acanthamoeba triangularis WU19001 trophozoites and cysts. SEM images displayed morphological changes in Acanthamoeba trophozoites, including the loss of acanthopodia, pore formation in the cell membrane, and membrane damage. In addition, the treated cyst was shrunken and adopted an irregular flat cyst shape. Under a fluorescence microscope, acridine orange and propidium iodide (AO/PI) staining revealed C1 induced condensation of cytoplasm and chromatin with the loss of cell volume in the treated trophozoites, while calcofluor white staining demonstrated the leakage of cell wall in treated cysts, leading to cell death. Interestingly, at the concentration ranges in which C1 showed the anti-Acanthamoeba effects (IC50 values ranging from 0.035–0.056 mg/mL), they were not toxic to Vero cells. C1 displayed the highest inhibitory effect on A. triangularis encystation at 1/16×MIC value (0.004 mg/mL). While C1 demonstrated the excystation activity at 1/128×MIC value with a high rate of 89.47%. Furthermore, C1 exhibited the removal capacity of adhesive Acanthamoeba from the surface of CL comparable with commercial multipurpose solutions (MPSs). Based on the results obtained, C1 may be a promising lead agent to develop a therapeutic for the treatment of Acanthamoeba infections and disinfectant solutions for CL