Enterobacter cloacae is a highly pathogenic Gram-negative proteobacterium which is responsible for a wide array of infections. In the present study, the fermentation culture of E. cloacae has yielded one new oxolane compound, Rimboxo (1) in addition to three known compounds, i.e. Maculosine (2), phenylacetic acid (3) and methyl myristate (4). These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.
Burkholderia cenocepacia and Serratia marcescens are Gram-negative proteobacteria commonly found in the natural
environment and are also opportunistic pathogens that caused a number of human diseases. The fermentation culture of
Burkholderia cenocepacia yielded three compounds, 4-(2-hydroxyethoxy)-phenol (1), Maculosin (2) and methyl myristate
(3). Compound 2 was also isolated together with cyclo(L-Leu-L-Pro) (4) from Serratia marcescens. Compound 1 was
isolated from a natural source for the first time and the first isolation of compounds 2-4 was also reported from both
Burkholderia cenocepacia and Serratia marcescens.
The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches.
Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.
The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.