Anti-hypoxia Effects And Mechanism Of Phenylethanoid Glycosides Constituents From Phlomis Younghusbandii Mukerjee

Objective:To screen the anti-hypoxia activity components of Phlomis younghusbandii Mukerjee, and study the anti-hypoxia pharmacological effect and explore its mechanism. Method:1、The anti-hypoxia activity components of Phlomis younghusbandii Mukerjee were screened by the simulated acute high altitude hypoxia rats model, and study the anti-hypoxia pharmacological effect.2、The anti-hypoxia effect and mechanism were investigated by the simulated acute high altitude hypoxia model with Wistar rats. Rats were divided into six groups, i.e. normoxia group, hypoxia group, drug-treated groups(3), and positive control group. All drugs were adminstered by intragastric administrations(i.g.). The anti-hypoxia effect and mechanism were systematically evaluated by immune system, oxidative stress system, and inflammatory rection. The followed indicators were tested: general living state of hypoxia rats, the peripheral hemogram index, the brain and lung water content, the SOD、GSH activity and the MDA、IL-1β、TNF-α、VEGF content in barin and lung tissues, the IL-1β、TNF-α、VEGF content in serum, the IL-1β、TNF-α、VEGF、IL-6 and HIF-1α mRNA relative expression in brain and lung tissues, and the IL-1β、TNF-α、VEGF and NF-κB protein relative expression in brain tissues, pathological sections of cerebra and lung. Results:1、Phlomis younghusbandii Mukerjee exhibited significantly anti-hypoxia effect, and the phenylethanoid glycosides was active fraction, which was abundant with acteosides.2、The PhGCs(400 mg·kg-1, i.g.) of Phlomis younghusbandii Mukerjee can improve general living state of hypoxia rats, such as, the increase of water and food intaking, independent activities strengthen, and mental state improved, the decreased of respiratory frequency. PhGCs could significantly improve blood components of hypoxia rats, increase blood oxygen carrying capacity, decrease white blood cells, red blood cells, hemoglobin, lymphocyte, neutrophil, PhGCs could effectively improve the immune system function of rats exposed to hypoxia.3 、 PhGCs(400 mg·kg-1, i.g.) of Phlomis younghusbandii Mukerjee significantly decreased MDA content, increased SOD and GSH activity in brain and lung tissues; Meanwhile, PhGCs(400 mg·kg-1, i.g.) could also improve water and salt metabolism, reduce the barin water content and lung water content, redcue the cerebral edema and lung edema formation; The pathological study proved the exhibition of damages in brain and lung tissues in hypoxia rats, which could be protected by treatment of PhGCs(400 mg·kg-1, i.g.).4 、 PhGCs(400 mg·kg-1, i.g.) of Phlomis younghusbandii Mukerjee significantly decreased the content of IL-1β、TNF-α and VEGF in serum and IL-1β、TNF-α and VEGF in brain and lung tissues.5 、 PhGCs(400 mg·kg-1, i.g.) of Phlomis younghusbandii Mukerjee significantly down-regulated the IL-1β、TNF-α、VEGF、IL-6、HIF-1α mRNA expression in brain and lung tissues; Meanwhile, PhGCs(400 mg·kg-1, i.g.) also significantly down-regulated the IL-1β、TNF-α、VEGF and NF-κB protein expression in brain tissues, and NF-κB protein expression in lung tissues. Conclusion:1、The phenylethanoid glycosides(PhGCs) of Phlomis younghusbandii Mukerjee, which is rich of acteoside, showed significant anti-hypoxia effect.2、The phenylethanoid glycosides(PhGCs) of Phlomis younghusbandii Mukerjee can significantly alleviate the brain and lung function injury induced by simulated acute high altitude hypoxia, and the mechanism might be through scavenging free radicals, improving water and salt metabolism, resisting to oxidative stress.3、The phenylethanoid glycosides(PhGCs) of Phlomis younghusbandii Mukerjee can significantly alleviate the brain and lung function injury induced by simulated acute high altitude hypoxia, the mechanism might also related with the inhibition of NF-κB mediated inflammatory signaling pathway, down-regulation the IL-1β、TNF-α、VEGF、IL-6、HIF-1α mRNA expression in brain and lung tissues, and IL-1β、TNF-α、VEGF、NF-κB protein expression in brain tissues.