Chenopodin as an anti-inflammatory compound.

Chenopodin is an 11S-type globulin purified from Chenopodium quinoa seeds, which can bind carbohydrates and hemagglutinating human erythrocytes. The present study aimed to evaluate the N-terminal structure of the heterodimeric Chenopodin and its effects in models of inflammation. Chenopodin presented two subunits on its structure and has N-terminal homology with other Chenopodin in 92%. Chenopodin decreased paw edema and neutrophil recruitment induced by carrageenan in mice. Concluding, we demonstrated that Chenopodin exhibits in vivo anti-inflammatory activity.

Electrochemical evidence of nitrate release from the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid and its antinociceptive and anti-inflammatory activities in mice.

Considering the many biological activities of nitric oxide (NO), some lines of research focused on the modulation of these activities through the provision of this mediator by designing and synthesizing compounds coupled with an NO donor group. Thus, the objectives of the present study were to carry out an electrochemical investigation of the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid (1) and evaluate its activities and putative mechanisms in experimental models of pain and inflammation. Voltammetric studies performed in aprotic medium (mimetic of membranes) showed important electrochemical reduction mechanisms: nitroaromatic reduction, self-protonation, and finally reductive elimination, which leads to nitrate release. Systemic administration of the nitrooxy compound (1) inhibited the nociceptive response induced by heat and the tactile hypersensitivity and paw edema induced by carrageenan in mice. The activities in the models of inflammatory pain and edema were associated with reduced neutrophil recruitment and production of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and CXCL-1, and increased production of IL-10. Concluding, electrochemical analysis revealed unequivocally that electron transfer at the nitro group of the nitrooxy compound (1) results in the cleavage of the organic nitrate, potentially resulting in the generation of NO. This electrochemical mechanism may be compared to a biochemical electron-transfer mediated nitrate release that, by appropriate in vivo bioreduction (enzymatic or not) would lead to NO production. Compound (1) exhibits activities in models of inflammatory pain and edema that may be due to reduced recruitment of neutrophils and production of inflammatory cytokines and increased production of IL-10. These results reinforce the interest in the investigation of NO donor compounds as candidates for analgesic and anti-inflammatory drugs.

Encapsulating paclitaxel in polymeric nanomicelles increases antitumor activity and prevents peripheral neuropathy.

Paclitaxel (PTX) has a great clinical significance as an antitumor drug, although several side effects are strongly dose-limiting. In this way, we prepared a PTX-loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] polymeric micelles (PM/PTX) in an attempt to improve safety and effectiveness of conventional PTX formulation (CrEL/EtOH/PTX). In this study, we evaluated from both formulations: stability after dilution, hemocompatibility, cellular uptake, acute toxicity in healthy mice, antitumor activity, and toxicity after multiple-dose treatment. PM/PTX appeared to be more stable than CrEL/EtOH/PTX after dilution. PM/PTX did not exhibit hemolytic activity (values <1%), even at high concentrations. In vitro cellular uptake study indicated that polymeric micelles were able to deliver more PTX (5.8 %) than CrEL/EtOH (2.7 %) to 4T1 cells. In the acute toxicity evaluation in healthy mice, CrEL/EtOH/PTX (single dose of 20 mg/kg) induced peripheral neuropathy, which was not observed in PM/PTX group. Similar results were observed after tumor-bearing mice received a multiple-dose regimen (seven doses of 10 mg/kg). Worth mentioning, we also evaluated vehicles, and CrEL/EtOH alone was not capable of inducing neuropathic pain. Besides, PM/PTX exhibited a higher antitumor activity with an inhibition ratio approximately 1.5-fold higher than CrEL/EtOH/PTX group. This study suggested that PM/PTX is safer than CrEL/EtOH/PTX, and was able to improve the antitumor effectiveness in a 4T1 breast cancer model.

A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer.

The aim of this study was to verify whether the use of bethanechol during radiotherapy (RT) for head and neck cancer (HNC) prevents radiation-induced xerostomia and salivary flow reduction. Patients that would begin RT were randomly allocated into bethanechol (group 1) or artificial saliva (group 2). Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected from all the patients at the following four stages: baseline, during, immediately after, and at least two months after the end of RT. Xerostomia was assessed by a subjective visual analogue scale (VAS), and by asking patients whether they felt dry mouth. Forty-three patients were randomized into this trial. The use of bethanechol during RT for HNC cancer was associated with significantly higher WRS immediately after RT (p=0.03) in comparison to a similar cohort of patients who had not received bethanechol.

Simultaneous quantitation of nicorandil and its denitrated metabolite in plasma by LC-MS/MS: application for a pharmacokinetic study.

A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous quantitation of nicorandil and its denitrated metabolite, N-(2-hydroxyethyl)-nicotinamide, in rat plasma. After a liquid-liquid extraction step, chromatographic separation was performed on a ShinPack C(18) column with an isocratic mobile phase composed of methanol and 2 mM aqueous ammonium acetate containing 0.03% (v/v) formic acid (33:67 v/v). Procainamide was used as an internal standard (IS). Selected reaction monitoring was performed using the transitions m/z 212 → m/z 135, m/z 166 → m/z 106 and m/z 236 → m/z 163 to quantify nicorandil, its denitrated metabolite and IS, respectively. Calibration curves were constructed over the range of 5-15,000 ng.ml(-1) for both nicorandil and its metabolite. The mean relative standard deviation (RSD%) values for the intra-run precision were 5.4% and 7.3% and for the inter-run precision were 8.5% and 7.3% for nicorandil and its metabolite, respectively. The mean accuracy values were 100% and 95% for nicorandil and its metabolite, respectively. No matrix effect was detected in the samples. The validated method was successfully applied to a pharmacokinetic study after per os administration of nicorandil in rats.

Antiedematogenic activity and phytochemical composition of preparations from Echinodorus grandiflorus leaves.

The leaves of Echinodorus grandiflorus (Alismataceae) are traditionally used in Brazil to treat inflammatory conditions. The aim of the present study was to evaluate the antidematogenic activity of crude aqueous, dichloromethane and hydroethanolic extracts from E. grandiflorus leaves using the carrageenan-induced paw edema model in mice, along with of fractions enriched in diterpenes, flavonoids and hydroxycinnamoyltartaric acids (HCTA). Significant inhibitions of paw edema were elicited by the 50% and 70% EtOH extracts (1000 mg/kg, p.o.), as well as by the fractions enriched in diterpenes (70-420 mg/kg, p.o.) and flavonoids (7.2-36 mg/kg, p.o.). Isovitexin, isoorientin, trans-aconitic and chicoric acids were identified in all extracts by HPLC analysis. Trans-aconitic acid itself exhibited significant antiedematogenic effect (270 mg/kg, p.o.). The biological activity correlated positively with the contents of flavonoids and diterpenes, but negatively with HCTA concentrations, demonstrating the participation of the two classes of compounds in the antiedematogenic activity of E. grandiflorus.

Avaliaçäo farmacológica preliminar do extrato liofilizado de angico (Piptadenia colubrina Bth) / Preliminary pharmacologic evaluation of freeze-dried extract of angico (Piptadenia colubrina Bth)

Cascas de angico (Piptadenia colubrina Bth) foram coletadas na regiäo do Alto Paranaiba/Minas Gerais e submetidas a processos de extraçäo e liofilizaçäo. O extrato foi empregado em testes farmacológicos com camundongos e ratos machos albinos. Observou-se que doses variáveis do extrato provocaram sinais de depressäo do sistema nervoso central e insuficiência respiratória. Observou-se também que o extrato acarretou um efeito sinérgico quando associado a doses sub-hipnóticas de pentobarbital sódico e a doses sedativas de clorpromazina e diazepam. Embora a informaçäo popular se refira a propriedades antiepilépticas do "chá de angico", os resultados näo demonstraram açäo anticonvulsivante em relaçäo ao pentetrazol. Além do mais, observou-se que o extrato näo possui açäo analgésica e nem altera a açäo analgésica do cloridrato de morfina. Os resultados obtidos sugerem propriedades psicotrópicas do tipo psicoléptico (depressoras do sistema nervoso central) para o material estudado.