ARE Activation Of Scutellarin And Baicalin Derivatives

Cerebral Stroke and Infarction is one of the most important mortal factors foraged people. With the improvement of people’s living standard, more and more youngpeople suffer from cerebral stroke and infarction. Cerebral Stroke and infarction areinduced by the decrease of the blood flow of cerebral artery because of obstruction bythrombosis. Cerebral stroke and infarction can bring about serious sequela, whichobviously reduce the living quality of the patients.The researches about cerebral stroke and infarction focus on the pathology of thedevelopment of the disease and its treatment. There are many explanations about thepathogenesis, including ischemia induced oxidative stress, abnormality of calciumchannel, cell membrane depolarization accompanied with series of abnormal ionicchannels and signal pathways, inflammation and necrosis. In the process of discoveryand development of treatment medicine, it has been found that Nrf2/ARE has playedan important role in relieving the oxidative stress and eliminating ROS. It has beenproved that ARE is the promoter of hundreds of antioxidant factors, such as SODs,HOs, NQOs and so on, which are named phase Ⅱdetoxification enzymes because oftheir obvious antioxidant and protective effects. Expression of ARE can promote theactivity of these enzymes and protect the cells from oxidative stress. Manycompounds can upregulate ARE and have protective utility, of which the effects offlavonoids are extraordinarily good and have attracted much attention. Flavonoids caneliminate the free radicals and reduce the ROS. Recently researches have discoveredthat flavonoids can promote the expression of Nrf2/ARE signal pathway and play animportant role in neuroprotection.This thesis focuses on the chief constituent scutellarin of traditional medicinetreating for cerebral ischemia-fleabane injection and the recently discovered baicalin,which has effective protective effects on central neuro system. We’ve verified theirNrf2/ARE upregulation effects and proposed that their protective functions might berelated with their influences on this signal pathway, which provides a new way tolook at their pharmacological actions. Based on the structures of scutellarin and baicalin, we’ve modified the8-position of A ring of these two compounds throughhalogenations, nitration, amination and mannich reactions. In addition, we’vedeglucuronated scutellarin and baicalin to obtain scutellarein and baicalein, and theabove modifications were also carried out on these two deglucuronated products.With these analogues, we’ve tested their ARE promotion activity throughDual-Luciferase Reporter Gene Assay, which showed that baicalin, baicalein and adiaza cyclopenta analogue of scutellarin were more active than scutellarin. Westernblotting and green or red fluorescent protein analysis were then executed to furtheranalyze the effects of these three compounds on Nrf2/ARE pathway. Resultspresented that these three analogues had good upregulation effects on ARE. It can bededuced that they would be effective on relieving oxidative stress, and furtherneuroprotective tests were required.