Experimental Research On The Effect Of The Effect Of Anti-airway Inflammation By Hesperidin

Diseases mainly based on and featured by airway inflammation take the most proportion in respiratory system disease. Therefore, the chose of medicine on effective anti-inflammation action appear more important. Natural products are becoming increasingly important as sources of pharmacotherapeutics, either as herbal drugs for treatment of chronic diseases or as raw materials form which compounds with particular biological activities are isolated.Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant,anti-inflammatory,antihypercholesterolemic and anticarcinogenic actions. There is no sufficient demonstration of Hesperidin in anti-airway inflammation effect . In order to study the anti-airway inflammation effect of Hesperidin, we use LPS stimulate the mice cell of RAW264.7, and investigate the effects of Hesperidin on the inflammation induced by LPS in vitro. In addition, we use animal model of acute lung injury and asthma to investigate the anti-airway inflammation effect in vivo, and preliminary investigate the mechanism of anti-inflammation by Hesperidin.Firstly, we use LPS to stimulate the cell of RAW264.7 and produced inflammatory response in vitro, detect the influence of Hesperidin to inflammatory cytokines TNF-α,IL-1βand IL-6. The results showed that the level of TNF-α,IL-1βand IL-6 can be significantly inhibited by Hesperidin. Consequently, Hesperidin may exert the role of antimicrobial agents by suppress the secrete of inflammatory cytokines.To investigate the anti-airway inflammation effect of Hesperidin in vivo, we induce acute lung injury animal model use LPS intranasally administered into mice. Lipopolysaccharide (LPS) or endotoxin, the major constituent of the outer membrane of Gram negative bacteria. The inhalation of LPS results in acute, neutrophilic inflammation of the distal airspaces of the lungs. The molecular mechanisms underlying the inflammatory response to LPS involve the detection of LPS by pattern recognition receptors, followed by the coordinated expression of proinflammatory cytokines. We detect the influence of Hesperidin to the secretion of inflammatory cytokines TNF-α,IL-1β,IL-6 and inflammatory cells aggretation of BALF in ALI mice; We observe effect of Hesperidin on the W/D ratio and histopathological change of lung; Western-blot method was also used to observe the expression of IκB in Nucleus transcription factorκB transduction pathway. Nucleus transcription factorκB (NF-κB) is a classical signal transduction pathway induced by LPS. IκB is a inhibitory protein of NF-κB.Under normal condition, IκB binding with NF-κB and restraint it in cytoplasm. When stimulate by external substances, LPS,double-stranded RNA and virus, IκB degradate, and nuclear localization signal of NF-κB exposured, combined withκB site of specific gene, then target gene begin to transcript. The results showed that: Hesperidin suppress level of inflammatory cytokines and inflammatory cells aggretation,attenuate degree of pneumonedema,increase expression of IκB compared with modle. It declare that Hesperidin can inhibit the nuclear import of NF-κB by suppress the degradate of IκB possibly. Acute airway inflammation was decreased.To study on the ability of Hesperidin confront chronic airway inflammation, we establish a asthma model of mice use OVA to detect the influence of Hesperidin in common symptoms of asthma. Allergic asthma is a chronic airway disorder characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). High level IgE in serum and Th2 cytokines in BALF contribute to asthma. In this study, We observe the influence of Hesperidin to the secretion of Th2 cytokines cytokines IL-4,IL-5,IL-13 and inflammatory cells aggretation in BALF of asthma mice; We observe effect of Hesperidin on the AHR and histopathological change of lung in asthma mice. The results showed that: the administration of hesperidin significantly decreased the number of infiltrating inflammatory cells,IgE level in serum and Th2 cytokines IL-4,IL-5,IL-13 in bronchoalveolar lavage (BAL) fluid compared with the OVA-induced group of mice. Based on lung histopathological studies, hesperidin inhibited inflammatory cell infiltration,goblet cell hyperplasia and mucus hypersecretion compared with the OVA-induced group of mice. Airway responsiveness was assessed as the percent alteration of RI and Cdyn in response to increasing doses of methacholine. OVA-challenged mice developed AHR, typically reflected by high RI and low Cdyn. Hesperidin treatment dramatically reduced RI and restored Cdyn in OVA-challenged mice in response to methacholine.The innovation of the study demonstrate the anti-airway inflammation effect of Hesperidin. Hesperidin showed confronting effect to LPS-induced acute airway inflammatory reaction by attenuating NF-?B activation suppress the degradate of I?B; Moreover, Hesperidin is also an inhibitor to chronic airway inflammation of asthma mice, probably due to the downregulation of allergen sentization and Th2 polarizing pathways. It will provide new thread and evidence for the use of Hesperidin in anti-airway inflammation.