Comparison on anti-inflammatory activity of Gynostemma pentaphyllum processed with different methods / 中国中药杂志

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1β, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1β and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

Nitro-fatty acids: novel anti-inflammatory lipid mediators

Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases.

Mecanismos de ação dos corticosteróides na polipose rinossinusal: [revisão] / Mechanism of action of glucocorticoids in nasal polyposis: [review]

Os glicocorticóides (GC) são drogas de escolha no tratamento clínico da polipose nasossinusal conforme recomendação da literatura. Entretanto, seus mecanismos de ação nas regressões dos sintomas clínicos e dos pólipos não são totalmente compreendidos. Sabe-se que a administração tópica e ou sistêmica dos glicocorticóides leva a variações na expressão de citocinas, quimiocinas e linfocinas, além das alterações celulares. Assim, os GC suprimem a expressão de citocinas pró-inflamatórias, de quimiocinas, de moléculas de adesão, além de estimular a transcrição de citocinas antiinflamatórias. Citocinas pró-fibróticas como a IL-11, fator básico de crescimento do fibroblasto (b-FGF) e fator de crescimento endotelial vascular (VEGF), relacionados com o crescimento do pólipo, também são suprimidos pela ação do GC. Tal ação depende fundamentalmente da interação com os seus receptores (GR), pois alguns indivíduos apresentam algum grau de resistência celular ao seu efeito, que parece estar relacionada com a presença da isoforma b do GR. Genes envolvidos nas fases de produção de imunoglobulinas, apresentação e processamento do antígeno também sofrem ação dos GC de forma variada. OBJETIVOS: Fazer uma revisão da literatura sobre os mecanismos de ação do GC na PNS. CONCLUSÃO: A compreensão desses mecanismos implicará no desenvolvimento de drogas mais eficazes na sua terapêutica.

Glucocorticoids (GC) are the drugs of choice for the clinical treatment of nasal polyposis, according to the medical literature. Its mechanism of action in the regression of clinical symptoms and polyps, however, is not fully understood. The topical and/or systemic use of glucocorticoids lead to variable expression of cytokines, chemokines and lymphokines, as well as changes in cells. It is known that GC suppresses the expression of pro-inflammatory cytokines, chemokines and adhesion molecules such as ICAM-1 and E-selectin; GC also stimulate the transcription of anti-inflammatory cytokines such as TGF-b. GC suppress pro-fibrotic cytokines related to polyp growth, such as IL-11, the basic fibroblast growth factor (b-FGF), and the vascular endotelial growth factor (VEGF). The action of GC depends fundamentally on their interaction with receptors (GR); certain subjects have a degree of resistance to its effect, which appears to be related with the presence of a b isoform of GR. GC also act variably on the genes involved in immunoglobulin production, presentation, and antigen processing. AIM: We present a review of the literature on the mechanisms of GC action in nasal polyosis. CONCLUSION: Understanding the mechanism of action of GC in nasal polyposis will aid in the development of new, more efficient, drugs.

Biological properties of 8-methoxypyrimido[4(1),5(1):4,5]thieno(2,3-b)quinoline-4(3H)-one, a new class of DNA intercalating drugs.

BACKGROUND & OBJECTIVES: The compounds containing novel tetracyclic condensed quinoline ring system is of interest because of its close relationship with anticancer drug ellipticine. 8-Methoxypyrimido[4(1),5(1):4,5]thieno(2,3-b)quinoline-4(3H)-one (MPTQ) was investigated to study its effect on in vitro growth inhibition and clonogenic cell survival assay on three tumour cell lines, human promyelocytic leukemia HL-60, melanoma B16F10 and neuro 2a. A systematic study was carried out to evaluate its antitumour efficacy against B16 murine melanoma. Antiinflammatory and analgesic activities of MPTQ were also studied. METHODS: The cytotoxicity of MPTQ on HL-60, B16F10 and neuro 2a cells was estimated by trypan blue exclusion test. The antitumour activity was evaluated using single dose, multiple/daily injections (days 3-6) or intermittent treatments over two weeks against s.c. implanted B16melanoma, both in terms of increased life span and tumour growth inhibition. Antiinflammatory activity was seen on carrageenan induced hind paw oedema. Counting the number of abdominal constrictions after the injection of acetic acid assessed the analgesic response. RESULTS: MPTQ is cytotoxic to all the cell lines tested and ID50 being in the range of 0.08-1.0 microM. MPTQ was studied for anticancer activity in the clonogenic assay. Drug was applied over a wide dose range by 24 h exposure, yielding clear dose-response effects. In vivo antitumour efficacy against B16 melanoma showed evidence of major antitumour activity for MPTQ. Single and multiple i.p. doses of drug proved high level activity against the s.c. grafted B16melanoma, significantly increasing survival (P<0.001) and inhibiting tumour growth (T/C of 3.0%). A reduction (76.48%) in paw volume was noted in 40 mg/kg dose of which was comparable to antiinflammatory activity of 150 mg/kg i.p. of phenylbutazone. Analgesic activity was found to be of peripheral type as there was reduction of 74 per cent in writhing response by MPTQ in dose of 40 mg/kg in mice. INTERPRETATION & CONCLUSION: The results suggested that the compounds containing pyrimidothienoquinoline system particularly 8-methoxy derivative might be potentially useful antitumour agent. We conclude that the correlation of physicochemical properties of the new series of pyrimidothienoquinolines with their pharmacological properties, might help in trying to understand the mechanism of pyrimidothienoquinolines series.

Orientaciones terapéuticas en los síndromes reumatológicos inflamatorios / Therapeutic guidelines in the inflamatory reumathologic syndromes

El autor hace una revisión conceptual sobre el tratamiento de los reumatismos inflamatorios. Fija esquemas de los mecanismos de producción y de las consecuencias de la enfermedad inflamatória, sobre los que ubica todos los medios terapéuticos que se disponen en la actualidad. Sugiere un agrupamiento de los fármacos antiinflamatorios así como determinadas normas para su uso y finaliza con algunas consideraciones sobre el empleo de la medicina física, la ortopedia y la cirujía