1.Hydrogen can alleviate post-cardiac arrest brain injury in rabbits
Jingao WANG ; Jiyan LIN ; Dequan KONG ; Zili ZHANG ; Xiangmei YU ; Jiaquan LIU ; Dongmei CAI
Chinese Journal of Emergency Medicine 2012;21(10):1111-1115
Objective To investigate the effects of hydrogen on post - cardiac arrest brain injury in rabbits.Method Sixty New Zealand rabbits were randomly divided into two groups,namely experiment group ( group A,n =30 ) and control group ( group B,n =30 ).Inhalation of 2% hydrogen gas was conferred to rabbits immediately at the end of cardiac arrest modeling for 72 hours in the group A. Air instead was given to rabbits in the group B.Blood samples were collected before cardiac arrest (CA),and 4,12,24 and 72 hours after restoration of spontaneous circulation (ROSC) in all rabbits for determining the levels of hydrogen,tumor necrosis factor - α ( TNF - α),neuron - specific enolase (NSE) and protein S100β.At the same time,rectal temperature,mean arterial pressure,heart rate and respiration rate were recorded,and the neurologic deficit scoring (NDS) was carried out.The rate of systemic inflammatory response syndrome ( SIRS ) and the rate of survival of rabbits were analyzed. Results There was no significant difference in level of TNF - α activation between group A and group B within12 h of cardiopulmonary resuscitation (CPR).In group A,TNF - α level and the rate of SIRS peaked at 24 hours after CPR,which were higher than those in group B,and then decreased gradually,and the rate of survival was higher than that in group B in 72 hours after ROSC,the NSE was lower than that in group B at 24 hours after ROSC.In group B,S100β level began to increase significantly 4 hours after CPR,which was higher than that in group A,the level of NDS in group B was higher than that in group A 72 hours after ROSC.Conclusions Inhalation of hydrogen gas lessened inflammation and alleviated the brain injury after CPR.
2.Nuciferine,an aromatic ring-containing alkaloid,delivers sedative-hypnotic effects through serotoner-gic system
Luoxuan WANG ; Yumeng LIU ; Jingao LI ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2023;37(7):489-489
OBJECTIVE Insomnia is the most fre-quent sleep disorder worldwide and the clinical applica-tion of therapeutic drugs has various adverse effects.In recent years,drugs developed from natural herbs have become potential alternative therapies for insomnia.Nuciferine,one of the main bioactive components obtained from the lotus leaves,has been reported to possess extensive pharmacological activities.However,its hypnotic and sleep regulatory effects have rarely been reported.Hence,this study was intended to investigate the pharma-cological effects of nuciferine and its mechanisms of action in insomnia.METHODS The hypnotic and seda-tive effects of nuciferine were investigated using the eval-uation of locomotor activity test and pentobarbital-induced sleep test in normal and serotonin(5-HT)depletion-induced insomniac mice.Furthermore,the sleep regulatory effects,including sleep time,sleep architecture,and δ-wave power spectral density,were explored using elec-troencephalography/electromyogram(EEG/EMG)-based sleep profiling in normal rats.Finally,the mechanisms of the hypnotic and sedative effects of nuciferine were explored usingin vivoand in silico experiments.RESULTS Nuciferine reduced locomotor activity and prolonged pen-tobarbital-induced sleep time in a dose-dependent man-ner in normal and insomniac model mice.Nuciferine sig-nificantly increased the total sleep time and non-rapid eye movement(NREM)sleep time,inhibited NREM sleep fragmentation,and improved delta power between 0.5 Hz and 1 Hz in normal rats.The results of molecular experiments showed that nuciferine could increase the 5-HT content and 5-HT1A receptor level in the hypothala-mus of insomnia model mice.CONCLUSION This study combined network pharmacological prediction and experi-mental pharmacological techniques to discover the seda-tive-hypnotic effect of nuciferine for the first time Nucif-erine can ameliorate sleep disorder in mice with insom-nia,possibly via serotonergic system.Nuciferine may rep-resent a novel treatment that alleviate the insomnia-like symptoms by modulating 5-HT system.
3.Hydrogen can alleviate post-cardiac arrest myocardium injury in rabbits
Jingao WANG ; Jiyan LIN ; Minwei ZHANG ; Yujing HE ; Xiaowen PAN ; Chengbin YANG ; Dongmei CAI
Chinese Critical Care Medicine 2017;29(10):911-915
Objective To investigate the effects of hydrogen (H2) on myocardium injury post-cardiac arrest (CA) in rabbits.Methods Sixty New Zealand rabbits were randomly divided into H2 treatment group (n = 30) and control group (n = 30) by random number table. The rabbit CA model was established by means of electrical stimulation of external membrane, both groups were mechanically ventilated. Cardiopulmonary resuscitation (CPR) was performed after 6 minutes of nonintervention, and stopped after restoration of spontaneous circulation (ROSC). Inhalation of 2% H2 gas was conferred to rabbits immediately at the end of CA modeling for 72 hours in H2 treatment group. Air was given to rabbits in control group instead. The survival rate of rabbits was analyzed. Heart rate, ventricular premature beat frequency, and the levels of blood samples cardiac troponin I (cTnI), left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), and blood lactic acid (Lac) were collected before CA and after ROSC in all rabbits. Rabbits were sacrificed and microstructure injury was observed by electric microscope after ROSC 72 hours.Results There were 28 animals ROSC in both groups; the survival number in H2 treatment group was higher than that in control group at 72 hours after ROSC (number: 15 vs. 7,χ2 = 4.791,P = 0.029). In the early stage of ROSC, the heart rate of two groups slowed down, the number of premature ventricular increased, and then gradually recovered; the heart rate in H2 treatment group was returning to normal more quickly than that in control group at 48 hours after ROSC (bpm: 319±63 vs. 362±40,P < 0.05); the ventricular premature beat frequency was lower than that in control group at 72 hours after ROSC (times per minutes: 9.1±4.3 vs. 15.0±8.0,P < 0.05). The animals of two groups had different degrees of myocardial damage and cardiac insufficiency after ROSC, and restored with the extension of time. Compared with control group, the level of BNP in H2 treatment group was significant decreased at 24 hours after ROSC (ng/L: 385±98 vs. 488±174,P < 0.05), the levels of cTnI and Lac were significant decreased at 48 hours after ROSC [cTnI (μg/L:1.83±0.68 vs. 2.83±0.98, Lac (mmol/L): 5.5±1.6 vs. 7.9±2.6, bothP < 0.01], the LVEF was slightly higher than that at 72 hours after ROSC (0.690±0.040 vs. 0.650±0.041,P = 0.051). Compared with control group, less damage to myocardial ultra structure was found in H2 treatment group at 72 hours after ROSC.Conclusion Inhalation of H2 alleviates cardiac dysfunction and myocardial injury after CPR.
4.Mechanism prediction of Zhikepipa Mixture in the treatment of COVID-19
Rui ZHOU ; Yanru LIU ; Hongbo XU ; Jingao YU ; Zheng WANG ; Junwei ZHANG ; Zhongxing SONG ; Feng HUANG ; Zhishu TANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(2):190-196,218
【Objective】 To explore the effect of Zhikepipa Mixture on the treatment of COVID-19 through network pharmacology analysis and molecular docking technology. 【Methods】 First, we performed the network pharmacology method to screen active compounds and targets so as to explore the mixture’s potential mechanisms in the treatment of COVID-19. In line with ADME screening index, like oral bioavailability (OB) ≥30% or drug likeness index (DL) ≥0.18, the active compounds against COVID-19 related targets were selected to construct the 'herb-compound-target’ network. Mechanism prediction of Zhikepipa mixture in the treatment of COVID-19 was analyzed by the interaction of the target sites, the bioinformatic annotation, and the metabolic pathway. Then, we used a molecular docking model to evaluate the binding ability between active compounds and 2019-nCoV (SARS-CoV-2) 3-chymotrypsin-like cysteine protease (3CLpro) receptor-binding domain (PBD ID 6LU7), which was involved in mediating viral replication and transcription functions. 【Results】 The'herb-compound-target’ network showed 34 key compounds and 30 disease targets after overlapping with disease targets. The network topology analysis showed that those selected compounds with higher degree would produce marked anti-inflammatory effects by regulating 30 targets like PTGS1, IL1B, IL6, IL10, CXCL8 and JUN. AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway were involved in regulating hepatitis B and diabetic complications. In addition, Folium eriobotryae and Radix stemonae played important roles in the network. The molecular docking results showed that nine compounds were identified with higher docking score rank against 2019-nCoV 3CLpro protease, and most of them were attributed to flavonoids. 【Conclusion】 Zhikepipa Mixture could exhibit both anti-inflammatory and anti-virus actions through multi-component, multi-target, and multi-pathway.