A series of (2RS,3S)-3-amino-2-hydroxy-4-phenyl-butanoic acids (AHPA) derivatives (MA0-MA7) were synthesized. The in vitro aminopeptidase N (APN) enzyme and cell proliferation assay of target compounds were investigated. The results showed that most compounds displayed potent inhibitory activities against APN, compound MA0 showed even better inhibitory effects than bestatin on both enzyme activity and HL60 cell proliferation. The FlexX docking result showed the mode of binding between MA0 and APN.
We developed a method to predict bacterial pathogenicity against mammals by measuring bacterial virulence in silkworms at 37°C, human body temperature. One hundred and twenty-two strains of bacteria were isolated from the intestines of fish and shellfish and tested for their virulence against silkworms. Overnight cultures of 50 strains killed at least 50% of the silkworms when injected into the hemolymph. Of 10 strains that showed the most potent pathogenicity against silkworms, 8 also killed mice within 4 days after injection, including Staphylococcus simiae and Staphylococcus pasteuri, neither of which was previously reported to be pathogenic against mammals. These findings suggest that bacterial pathogenicity against mammals can be predicted based on measurements of silkworm-killing activity.
Physical dependence on morphine is evidenced by the withdrawal syndromes, including body weight loss, which are induced by the discontinuation of morphine exposure or by the treatment with naloxone, an opioid receptor antagonist. The present study was designed to examine whether the elevation of serum corticosterone (SCS) level induced by naloxone-precipitated morphine withdrawal was a useful index to quantify the physical dependence on morphine in mice, which was compared with body weight loss induced by naloxone-precipitated morphine withdrawal. The SCS level was dependent on the dosage and the number of dosing of morphine and challenging dosage of naloxone. Intraplantar injection of formalin, potentially producing inflammatory pain, inhibited both body weight loss and SCS increase induced by naloxone challenge in mice receiving repeated exposure of morphine, indicating that formalin-induced pain attenuated the development of physical dependence on morphine. The magnitude of body weight loss in morphine withdrawal was significantly correlated with the magnitude of naloxone challenge-induced SCS increase. These results suggest that the naloxone-induced increase in SCS level is a quantitative index of the magnitude of physical dependence on morphine in mice.
YGY-E is an active ingredient in traditional Chinese medical herbs which have anti-ischemic activity. The present work was designed to study its therapeutic time window in cerebral ischemic injury as well as its effect on neuronal apoptosis. Animals received an intravenous injection of YGY-E at 1, 3, and 6 h, respectively, after permanent focal cerebral ischemia induced by electrocoagulation of the middle cerebral artery. Infarct ratio and neurological function were employed to assess the effects of YGY-E on the therapeutic time window in this animal model. Furthermore, we evaluated effects of this compound on neuronal apoptosis and synthesis of Bcl-2 and Bax in ischemic brain tissue with in situ DNA end labeling (TUNEL), immunohistochemistry assay, and Western blot analysis. YGY-E (2-8 mg/kg) delivered at all the three time points dose-dependently decreased infarct ratio, neurological deficits, percentage of TUNEL-positive cells (p < 0.01) and Bax-positive cells (p < 0.01 or p < 0.05). In contrast, it increased the percentage of Bcl-2 positive cells (p < 0.01 or p < 0.05). These data demonstrated that YGY-E had protective effects against cerebral ischemia injuries in rats. But more importantly, they indicate that YGY-E has an unusually long (up to 6 h)therapeutic time window relative to classical drugs in treating cerebral ischemia. In addition, our results suggest that the anti-apoptotic effects of YGY-E are due to its regulation of the balance between Bcl-2 and Bax protein levels.
The use of natural antimicrobial agents is garnering attention due to consumer and producer awareness of health problems. This study found that the essential oil of A. galanga had strong bactericidal activity against both Gram-negative and Gram-positive bacteria. The bactericidal action of A. galanga oil was extremely rapid. Results of scanning electron microscopy observations suggested that A. galanga oil had antibacterial action probably as a result of its modification of the bacterial cell membrane, disrupting the membrane's permeability. This study suggested that the essential oil of A. galanga shows promise as a natural antimicrobial agent for use as a food preservative.
The objectives of the present study are to evaluate guar gum in combination with hydroxy propyl methylcellulose (HPMC) as compression coat for colonic delivery of prednisolone as well as improving the mechanical properties of the compressed coated tablets. The core tablets containing 5 mg prednisolone were compression coated with 125 mg of coating materials consisted of guar gum alone or mixtures of guar gum in combination with different ratios of HPMC. The compressed coated tablets were evaluated for their mechanical properties, in vitro drug release and in vivo performance in human volunteers. The compressed coated tablets with coats containing HPMC exhibited acceptable mechanical properties. In vitro drug release studies in pH 7.4 phosphate-buffered saline medium containing 2% (w/v) rat caecal content have shown that increase in concentration of HPMC in the prepared coats from 10% to 20% resulted in an increase in the release rate. However, further increase in HPMC concentration to constitute 30% caused a reduction in the release rate. Based on the drug release results, tablets coated with coat consisted of 80% guar gum and 20% HPMC were selected for in vivo evaluation. In vivo gamma scintigraphic study on human volunteers using technetium-99m-diethylenetriamine pentaacetic acid as a tracer was performed. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. In conclusion, guar gum in combination with HPMC would be successfully used as a carrier for drug delivery to the colon.
A hexane extract of the flower-heads of Euryops pectinatus L. (Cass.) was formulated into local anti-inflammatory implantation patches with controlled release. Cross-linked sodium hyaluronate patches (F1-F3) and chitosan patches (F4-F6) were prepared by a casting/solvent evaporation technique. Morphological and mechanical characterizations including the components ratio, surfactant and the loaded amount of the hexane extract (50, 100, and 200 mg/kg b.wt.) were investigated. Release studies were performed during 24 h using a diffusion cell. Films with optimum in vitro release rate have been investigated for testing the anti-inflammatory activity and the sustaining effect of the formulations. The sustained anti-inflammatory effect of the hexane extract of E. pectinatus flower-heads from the selected films was studied by inducing paw edema in rats with 1% (w/v) carrageenan solution. The results indicated the compatibility of hexane extract with both sodium hyaluronate and chitosan patches forming yellowish transparent films. Based on variations in drug release profiles throughout the 24-h among the formulations (F1-F6) studies, F3 and F6 were selected for further investigation. When the films were applied 1 h before the subplantar injection of carrageenan in the hind paw of male Albino rats, formulation (F3) provided its maximum inhibition of paw edema in rats (91.3%) 4 h after edema induction whereas, formulation (F6) showed less inhibition after 4 h (70.6%). The previous two formulations (F3 and F6) produced potent results (95.3 and 89.5%, respectively) after 24 h when compared with a local market preparation containing 25% β-sitosterol used as positive control. Histophathological investigation was conducted for 1, 4, and 12 weeks to study the tissue response for the two formulations (F3 and F6)at the implantation site. Chemical investigation of the hexane extract was achieved for both unsaponifiable matter (USM) and fatty acid methyl esters (FAME) using gas liquid chromatography (GLC). The USM was dominated by n-pentacosane (14.40%), phytosterols (Cholesterol, Campesterol, Stigmasterol, β-sitosterol, α-amyrin) reached 33.44% and the FAME was dominated by Linoleinic (49.97%). Quality control of the local implantation was evaluated by GLC using cholesterol as an analytical marker and phytosterols as an active marker compared to the plain extract.