Budesonide-liposomes inclusion complex in thermosensitive gel alleviates DSS-induced ulcerative colitis in mice.

PURPOSE: A novel formulation for Ulcerative Colitis (UC) treatment by rectal administration with budesonide liposomes (Bud Lip) and thermosensitive gel (Gel) was developed for future clinical use. To evaluate the anti-inflammatory activity and colon mucosal protection of this novel formulation compared with the other three in mice. METHODS: Bud Lip was prepared by reverse evaporation method and then dispersed in solutions with PL407 and PL188 by a cold method. Male mice were induced to UC by dextran sulfate sodium (DSS) and were treated for 14 days by rectal administration, as follows: Bud enema (a conventional suspension formulation); Bud Lip; Bud Gel; Bud Lip-Gel; saline. And a negative control without colitis was also used. Disease activity index (DAI), and macroscopic and microscopic damage scores in colon tissues were used to evaluate the effect of therapy. The levels of IL-6 and IL-10 in serum and the concentrations of TNF-α and IL-10 and myeloperoxidase (MPO) activity in colon tissue were also introduced. RESULTS: In UC mice model, Bud Lip-Gel showed inflammation was alleviated significantly, and the treatment was highly associated with lower DAI, less macroscopic and microscopic colonic damage and downregulation of pro-inflammatory cytokines TNF-α, IL-6 and MPO. Bud Lip-Gel had advantages over Bud, Bud Lip, Bud Gel in the treatment of active UC. CONCLUSION: Novel Bud liposomes complex in thermosensitive Gel effectively mitigated symptoms, alleviated macroscopic and microscopic colon damage, and reduced inflammatory reaction in UC mice, which might be a potential strategy for UC treatment.

The phytochemical constituents and protective effect of Fritillaria hupehensis on acute lung injury.

Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.

Yanghe Decoction Effectively Alleviates Lung Injury and Immune Disorder in Asthmatic Mice Induced by Ovalbumin.

Objective: To probe into the ameliorative effect of Yanghe Decoction on pulmonary injury and immunologic derangement in asthmatic mice. Methods: C57BL/6 mice were randomized into control (Con), Model, and Yanghe Decoction (YHF) groups, with 12 in each. The asthma model of adult female mice was induced by ovalbumin in the Model group, and the YHF group was treated by Yanghe Decoction on the basis of asthma modeling. The Con group received the same amount of normal saline. Inspiratory resistance (Ri), expiratory resistance (Re), lung compliance (CL), and maximal voluntary ventilation (MVV) were measured after modeling. Lung tissue was collected for the measurement of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, and tumor necrosis factor-α (TNF-α) by ELISA kits. Combined with HE staining and PAS staining, the pathological alterations of the lung in each group were observed, and CD4+, Th2, and Th1 contents were determined by flow cytometry (FCM). Results: The pulmonary function (PF) test revealed notably reduced Ri and Re as well as enhanced CL and MVV in asthmatic mice after the application of Yanghe Decoction. Yanghe Decoction dramatically ameliorated the pathological changes of lung tissue in asthmatic mice, as demonstrated by the staining results. ELISA results showed that Yanghe Decoction validly reduces lung tissue IL-4, IL-5, IL-6, IL-13, TNF-α and upregulates IL-10 in asthmatic mice. FCM indicated that Yanghe Decoction obviously reduced the number of Th1 and Th2 cells in asthmatic mice, although it caused the decrease of CD4+ cells, but the difference was not statistically significant. Conclusions: Yanghe Decoction can effectively ameliorate the inflammatory reaction, immune cell disorder, and PF injury in ovalbumin-induced asthmatic mice.

Avaliação do controle da expressão gênica de citocinas pró inflamatórias mediado pela IL-10. Participação da IL-10 na modulação da resposta inflamatória exercida pela glutamina e na restrição alimentar / Proinflammatory cytokines gene expression control mediated by IL-10. Participation of IL-10 on inflammatory response exerted by glutamine and dietary restriction

O desenvolvimento de uma resposta imune adequada é um processo extremamente importante para a manutenção da homeostase do organismo. Uma série de processos são desencadeados a partir do primeiro contato com micro-organismos patógenos até a efetivação da resposta imune de memória. Todos esses processos envolvem a participação e a complexa atuação de mediadores como as citocinas inflamatórias e também citocinas regulatórias, que exercerão efeitos controlando o processo inflamatório. Diversos mecanismos moleculares, subjacentes à resposta inflamatória, ainda não estão totalmente compreendidos, como por exemplo o controle da expressão de genes inflamatórios exercido pela IL-10. Os processos envolvidos na resposta inflamatória são mantidos às custas do consumo de nutrientes, dentre eles podemos destacar o aminoácido glutamina, que atua em nível molecular, fornecendo nitrogênio para a formação do material genético e fonte energética para determinadas células do sistema imunológico como os macrófagos. Portanto, neste trabalho, investigamos os efeitos da IL-10 na modificação de nucleossomos, evidenciando o papel dessa citocina em regular a expressão de genes inflamatórios em macrófagos. Avaliamos também a função da glutamina, modulando a expressão de RNAm de citocinas inflamatórias e regulatórias dessas células. E por último, desenvolvemos um modelo de restrição alimentar em camundongos, nos quais avaliamos os efeitos desse modelo considerando-se alguns aspectos hematológicos e estudamos as alterações na resposta inflamatória em células esplênicas e do peritônio, bem como avaliamos a suplementação de glutamina in vitro na produção das citocinas (IL-12, TNF-alfa, IL-10) e a expressão do fator de transcrição NFkB. Os resultados compilados mostraram que a IL-10 leva a uma rápida redução da acetilação de nucleossomos, modulando a arquitetura da cromatina de genes inflamatórios como a IL-12. A glutamina modula a expressão de citocinas inflamatórias, regulando positivamente a expressão de IL-10 e Interferon beta. E a restrição alimentar induz a redução de citocinas proinflamatórias (IL-12 e TNF-α), influenciadas pelo aumento da produção de IL-10 e finalmente a suplementação com glutamina não interfere nesses parâmetros nas células peritoneiais e esplênicas do grupo submetido à restrição alimentar. Conclusão: a IL-10 modula a expressão gênica através da modificação de nucleossomos em macrófagos derivados da medula; a glutamina modula a expressão de IL-10 inibindo a resposta inflamatória, e a restrição alimentar modula alguns aspectos hematológicos e possui propriedades anti-inflamatórias

The development of an appropriate immune response is an important process to the organism's homeostatic maintenance. A series of processes are triggered upon the very first contact with pathogens, up to the immunological memory establishment. These processes implicate in the participation of complex mediators, such as inflammatory and regulatory cytokines that will control the inflammatory process. Some mechanisms underlying the inflammatory response are not totally understood, the control of inflammatory genes exerted by IL-10 is an example. The processes involved in the inflammatory response are kept with nutrients expense, among these nutrients we can highlight the amino acid glutamine. It acts in a molecular level, supplying nitrogen to genetic material formation and as an energy supply for immune cells such as macrophages. Thus, we investigated the IL-10 effects on nucleosome modifications evidencing this cytokine role regulating inflammatory genes expression in macrophages. We also evaluated glutamine functions modulating inflammatory and regulatory cytokines mRNA expression on these cells. Ultimately, we developed a dietary restriction animal model where we evaluated it's effects on selected haematological aspects, analyzing the alteration in the inflammatory response of splenic and peritoneal cells. We also evaluated in vitro glutamine supplementation assessing cytokines production (IL-12, TNF-α, and IL-10) and the expression of NFkB transcription factor. The compiled results a expressive reduction in nucleosome acetylation modifying the chromatin architecture of inflammatory genes such as IL-12 and IL-6. Glutamine modulates inflammatory cytokines gene expression upregulating the expression of IL-10 and interferon beta. The dietary restriction reduces proinflammatory cytokines production (IL-12 and TNF-α), these results are influenced by the upregulated IL-10 production, glutamine supplementation have no effect on these parameters in the dietary restriction group. In conclusion, we can infer that IL-10 modulates gene expression trough nucleosome modification in bone marrow derived macrophages, glutamine has a potential effect on IL-10 expression, inhibiting the inflammatory response and dietary restriction modifies hematological parameters, presenting anti-inflammatory properties