ABSTRACT
Ferroptosis is a newly discovered non-apoptotic regulatory form of cell death characterized by accumulation of iron-dependent lipid peroxides and reactive oxygen species （ROS）. p53 is a tumor suppressor gene that can induce cell cycle arrest， apoptosis， autophagy， and senescence to maintain genomic stability by mediating transcriptional regulation of a variety of key cellular genes. Recent studies have found that p53 can also regulate ferroptosis bidirectionally by multiple cellular responses including iron metabolism， polyunsaturated fatty acid （PUFAs） metabolism， amino acid metabolism and nicotinamide adenine dinucleotide phosphate （NADPH）-mediated metabolisms， and participate in the pathological progression of diseases such as tumors， nervous system diseases， cardiovascular diseases， liver disease， and kidney disease. This paper provided a systematic review of the mechanism of p53-mediated ferroptosis in the outcome of related diseases and its influencing factors. And the research advance in the mechanisms of targeted regulation of p53-mediated ferroptosis in the prevention and treatment of cancer， stroke， acute ischemic cardiomyopathy， chronic heart failure， atherosclerosis， ulcerative colitis， and adjuvant arthritis by traditional Chinese medicine was also elaborated. This paper was expected to provide new ideas for the prevention and treatment against related diseases.
ABSTRACT
Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.
ABSTRACT
This systematic review was aimed to evaluation the effectiveness and safety of supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. Dtabases both at home and abroad were electronically searched for randomized controlled trials (RCTs) on supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. And meta-analyses were performed using RevMan 5.0 software. The results showed that 27 studies were included, which contained 2 908 cases. There were 1 490 cases in the treatment group, and 1 418 cases in the control group. The results of meta-analyses indicated that supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had significant differences in the effective rate for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (OR = 5.39, 95%CI (4.03, 7.22),P < 0.000 01). The treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on neurological function defects for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (WMD = -2.99, 95%CI (-3.26, -2.72),P < 0.000 01). In addition, the treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on improving the activity of daily living (WMD = 9.65, 95%CI (8.36, 10.93),P < 0.000 01). Adverse reaction and event was mild in 2 included research reports. It was concluded that the treatment of supplementingqi and activating blood circulation prescription or it combined with routine treatment in modern medicine was quite effective in the treatment of cerebral ischemic stroke by the existed limited evidences. It can also improve the nerve dysfunction and the ability of daily living. Due to the limited quantity of the included studies and the evidence with limited strength, further high-quality RCTs were needed to verify the forementioned conclusion.
ABSTRACT
Through comparative study on Naotaifang containing serum and plasma proteomics (peptide), this article revealed differential proteins (peptides) in the Naotaifang. The characteristics of differential proteins were identified with mass spectrometry. It provides scientific evidences for the pharmacodynamic material basis and Chinese herbal medicine plasma pharmacological method development in the exploration of Naotaifang. A total of 20 healthy adult SD rats were randomly divided into the control group, Naotaifang treatment group according to their weights. Ten rats in each group. Intragastric administration of medication was given for seven consecutive days. Before surgery, rats were fed with water but without food. One hour after the last drug administration, 10% chloral hydrate was injected for intraperitoneal anesthesia. Blood was taken through the common carotid artery. Serum and plasma samples were made after blood was taken from each rat. Serum and plasma samples of five rats were randomly selected from each group. And the two-dimensional electrophoresis (2-DE) technique was used in the comparative study of serum pro-teomics (peptide). The 300 DPI scanning and PDQuest 7.3.0 were used in the analysis. The ESI-MS/MS was used to identify important differences in proteins and screen characteristic serum and plasma protein. The results showed that 20 differential proteins of 5 plasma samples were identified. There were 15 types of proteins expressing up-regulation and 5 types expressing down-regulation. Comparative analysis on the 2-DE gel pictures of Naotaifang containing serum, 19 differential proteins of 5 plasma samples were identified, among which 15 types of proteins express up-regulation and 4 down-regulation. Comparative analysis on the 2-DE gel pictures of Naotaifang containing serum and Naotaifang containing plasma showed that 24 differential proteins of 5 plasma samples were identified, among which 9 types of proteins express up-regulation and 15 down-regulation. The highly expressed proteins were selected to MALDI-TOF-MS between Naotaifang containing serum and Naotaifang containing plasma. There were six successful-ly identified proteins, which were inter-alpha trypsin inhibitor, heavy chain 3, group-specific component, comple-ment factor B, Receptor Complexed with A Heterodimeric Fc, isoform CRA-d, Transferrin. It was concluded that protein with obvious changes in the Naotaifang containing serum and plasma may be related with fibrinolysis and an-ticoagulant. These proteins are involved in angiogenesis, inflammation and other pathological regulations of physiolog-ical processes. They are of great significance in the study of effective target and its signal transduction pathway of Naotaifang.
ABSTRACT
Objective:To approach the effect of Naotangfang extracts on expression of vascular endothelial growth factor(VEGF) after focal cerebral infarct in rats. Methods:30 Sprague-Dawley(SD) rats were randomly divided into 6 groups:sham operation group,model group,Naotaifang extract groups(low,middle,and high dosage) ,and Naofukang group. Some indexes were detected such as neurological scores,VEGF mRNA expression by RT-PCR,and the number of VEGF positive cells by immunohistochemical methods. Results:The symptoms in nervous function were improved in the Admin. groups,especially in the Naotaifang middle dosage group. The number of VEGF positive cells and VEGF PCR production in Naotaifng middle dosage group was higher than that in the model group. Conclusion:Naotaifang has neuroprotective effect against focal cerebral ischemic injury by improving the expression of VEGF.