1.Network pharmacological analysis and experimentalverification of the mechanism of Yindan Xinnaotong in protecting myocardial ischemia⁃reperfusion inj ury
Qili Xu ; Changchao Zou ; Lili Mo ; Haiyan Zhou ; Xingde Liu
Acta Universitatis Medicinalis Anhui 2022;57(1):131-138
Objective :
To explore the material basis and mechanism of Yindan Xinnaotong soft capsule( YD) in treating myocardial ischemia⁃reperfusion injury (MIRI) based on network pharmacology , so as to provide theoreti⁃ cal reference for the treatment of MIRI.
Methods :
The main active components and action targets of YD were searched by TCMSP , SwissTargetPrediction and China knowledge Network . The disease targets of MIRI were screened by GeneCards database. The“ drug⁃component⁃disease⁃target ”network relationship was constructed by fication was carried out between the top three main active components and the top six targets in PPI network. Human myocardial AC⁃16 cells were constructed hypoxia/reoxygenation (H/R) model to initially verify the core target. Using CCK⁃8 assay was usedto detect cell viability and explore the optimal drugconcentration. The influence of YD on cell morphology was observed by using optical microscope. LDH content was detected to assess the integrity of cell membrane ; Western blot was used to detect the expression of STAT3 , p ⁃STAT3 , PI3K , AKT1 and p ⁃AKT1 .
Results :
A total of 105 active components , 382 drug targets , 1223 MIRI disease targets and 160 drug⁃disease common targets of YD were obtained. The key targets involved AKT1 , STAT3 , VEGFA , TNF , MAPK8 , PIK3CA and so on. GO analysis mainly involved apoptosis , lipolysis , muscle cell proliferation , cytokine⁃mediated inflammation , oxidative stress and so on. The results of molecular docking showed that VEGFA , APP and PIK3CA could bind to quercetin , luteolin and kaempferol. Our results showed that 200 mg/L YD could significantly promote the proliferation of AC⁃16 cells and reduce LDH leakage. Western blot results showed that YD could activate STAT3 and PI3K⁃AKT1 signaling pathways and protect myocardium.
Conclusion
YD can protect MIRI through multi⁃components , multi⁃targets and multi⁃pathways.
2.Research progress of receptor ,pathway and pharmacological effect of 3-iodothyronine
Lili MO ; Changchao ZOU ; Qili XU ; Bo WEI ; Wei LI ; Anning ZENG ; Zhangrong CHEN ; Xingde LIU ; Haiyan ZHOU
China Pharmacy 2022;33(2):244-250
3-iodothyronamine(T1AM)is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ,slowing heart rate ,promoting lipolysis , reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine,but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger , T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM,in order to provide new therapeutic drugs of cardiovascular ,metabolic diseases and nervous system diseases.