Nrf2,a key transcriptional factor in regulating endog-enous antioxidant signaling pathway,maintains the redox bal-ance by controlling the expression of a battery of antioxidant en-zymes,phase-Ⅱ detoxification enzymes and phase-Ⅲ transport-ers.Furthermore,Nrf2 regulates inflammation.Recent resear-ches have confirmed that Nrf2 provides a vital physiological role in kidney diseases,activation of Nrf2 enhances the antioxidant and anti-inflammatory ability in cellular and tissue levels,thusalleviates renal injury.Here,this article aims to summarize the protective effect of Nrf2 on various models of kidney impairment and explore the potential of Nrf2 as a therapeutic target to pre-vent kidney diseases.

Aim Tostudytheantidepressanteffectand mechanism of Gross saponins of Tribulus terrestris. Methods Themodelofdepressionwasestablishedby unpredictable chronic mild stress(UCMS),then open filed test (OFT)and tail suspension test (TST)were used to evaluate the behavioral changes.LC-MS/MS method was employed to measure blood neurotransmit-ters.mRNA expressions of IDO,IL-10 and IL-1βwere detected by quantitative PCR method.Hippocampus protein expression was detected by Western blot.Re-sults Comparedwithcontrolgroup,modelgroup's total distance,number of standing and tail suspension fixed time increased significantly (P <0. 05 ),Neuro-transmitter level of 5-HT in the blood was significantly decreased(P<0. 05 ).mRNA expression of IDO and IL-1βwas increased in hippocampus.Protein expres-sion of IDO was significantly increased in hippocampus (P <0. 05 ).Compared with model group,the treat-ment group was significantly decreased in total distance,number of standing and tail suspension fixedtime(P<0. 05).Neurotransmitter level of 5-HT in the blood and mRNA expression of IL-10 in hippocampus were significantly increased after treatment (P <0. 05 ).mRNA and protein expression of IDO were ob-viously down-regulated in hippocampus (P <0. 05 ). Conclusions GrosssaponinsofTribulusterrestriscan obviously improve rat behavior and show antidepressanteffect,which can increase neurotransmitter level of 5-HT in the blood,down-regulate mRNA expression of IDO and IL-1β,and obviously increase protein expres-sion levels of IDO in hippocampus(P<0. 05 ).

HM(hibernating myocardium)is an adaptive phenome-non of myocardium against sustained ischemia,which maintains its tissue vitality through balancing energy supply and demand.It widely exists in patients suffering from coronary heart disease. HMhas its own metabolic pattern,instead of regular FAO(fatty acid β-oxidation)-based metabolism,glycolysis became main pro-cedure.Reduction of FAO,TCA (tricarboxylic cacidcycle),ETC (electron transport chain)enzyme has been observed,ROS(reac-tive oxygen species)and UCP2(uncoupling protein 2)have been up-regulated.UCP2,which promotes proton leak across innermembrane of mitochondrial and leads to ATP reduction,has e-merged as an important regulator of the energy production.It is regulated by up-stream proteins such as AMPK,PPARs,PGC-1α,and other factors like FFA(free fat acid),ROS and purine nucleotide.HM has potential function of ischemic myocardium, which can improve cardiac function through reasonable interven-tion.Modulation of UCP2 can optimize energy production,and is essential to HM metabolism.

Aim Toinvestigatetheeffectofhigh,me-dium and low doses of Mahuang decoction on the re-lease amount of rat hippocampal neural transmitter (Glu,Gly,Asp,GABA),then compare Mahuang de-contion with ephedra alkaloids and ephedra.Methods Ratswererandomlydividedinto6groupsandgiven orally with Mahuang decoction of high dose (calculated by ephedra 4 g·kg-1 ),medium dose (calculated by ephedra 2 g·kg-1 ),low dose (calculated by ephedra 1 g · kg-1 ),ephedra (calculated by ephedra 2 g · kg-1 ),ephedra alkaloids (ephedrine 7 mg · kg-1 , pseudoephedrine 2. 4 mg · kg-1 , methylephedrine 1. 12 mg · kg-1 )and blank control group.Samples were obtained from the hippocampus of conscious rat by microdialysis sampling technique.The content of ami-no acid neurotransmitters in dialysates was detected u-sing the established HPLC-ECD with OPA pre-column derivationmethod.Results Fouraminoacidneuro-transmitters could be well separated in 28 min.High, medium and low doses of Mahuang decoction,ephedra and ephedra alkaloids significantly increased the con-tent of these four amino acid neurotransmitters,com-pared with blank control group (P<0. 05 ).Ephedra alkaloids significantly reduced the levels of inhibitoryamino acid neurotransmitters GABA and Gly in 90 min,compared with the medium dose of Mahuang de-coction.Excitatory neurotransmitters of ASP and Glu in hippocampus showed the trend of increase first and then decrease after oral administration of Mahuang de-coction and ephedra. The levels of Glu and Asp reached peaks from 90 min to 120 min after treatment with Mahuang decoction,and also increased along with dose increase of Mahuang decoction.In comparison with the medium dose of Mahuang decoction group,the level of Glu reached peak at 90 min and 150 min in ephedra alkaloids group and ephedra group respective-ly,and the content of Glu significantly increased at peaktime.Conclusions Increasedcontentofexcita-tory amino acid neurotransmitters (Asp and Glu ) shows positive correlation with the dose of Mahuang de-coction.Other components in Mahuang decoction in-hibits the up-regulation effect of ephedra and ephedra alkaloids on Glu,and promotes the up-regulation effect of ephedra alkaloids on GABA and Gly.

Aim Toobservetheeffectofconcisepre-scriptions of Chinese medicine Huannao Yicong Decoc-tion(HYD)on regulatory pathway of secretase in APP/PS1 double transgenic cell line(HEK293),and to in-vestgateitsmechanism.Methods Theproliferationof AD cell model and the toxicity of each investigational drugs were ebserved by CCK-8;the changes in micro-scopic structure of each group were observed by(Trans-mission electron microscope,TEM);the activities of gamma-secretes was observed by Dual Luciferase Re-porter Gene Assay Kit ,and then the expression of pre-senilin 1(PS1),carboxyl terminus of Hsc70-interacting protein(CHIP),GTP binding protein (CDC42 ),ante-rior pharynx defective-1α(APH-1α),Hypoxia induc-ible factor-1α(HIF-1α) were detected by Western blot.Results 15%HYDserumincreasedthecellac-tivity compared to blank serum (P <0. 01 ).Under TEM,human APP/PS1 Double Transgenic cell line's mitochondria showed swelling and degenerat,and lipo-fuscin was deposited;after 48 h of medication,theswelling of mitochondria was reduced and crista was clear,and the number of lipofuscin was reduced.For the activity ofγsecretase,after 24 h medication,com-pared to control group,HYD directly group and DAPT group obviously inhibited the activity ofγsecretase (P<0. 05 or P<0. 01 ),compared to DAPT group,only 15% serum containing HYD group had significant difference (P <0. 05 );after 48 h medication,com-pared to control group,the other group all showed sig-nificant difference(P<0. 05 or P<0. 01 ).For the in-fluence of PS pathway,after 48 h medication,com-pared to control group,the other group all inhibited the PS1protein expression(P<0. 05 or P<0. 01),HYD directly group could activate the CDC42 protein expres-sion(P<0. 05 );compared to 0 h midicaiton,DAPT group inhibited the CHIP protein expression at the point of 48 h(P<0. 05 )and activated the CDC42 pro-tein expression at the point of 24 h.For the influence of Aph-1 pathway,there was no significant difference for Aph-1α(P>0. 05 );compared to control group,HYD directly group inhibited the HIF-1αprotein ex-pression after 48h medication(P<0. 05);compared to 0h midicaiton,DAPT group inhibited the HIF-1αpro-tein expression at the point of 24 h (P<0. 05 ).Con-clusions HYDcantreatADthroughprotectingthe mitochondrial function,reducing the formation of lipo-fuscin,inhibiting the activity of γsecretase by down-regulating the activity of HIF-1α,decreasing the stabil-ity and activity of PS1 by promoting the expression of CDC42.This shows that HYD has good research and development prospect as an effective drug for preven-tion and treatment of AD.

Aim TodevelopandvalidateaLC-MS/MS assay to quantify halometasone in rabbit plasma and study pharmacokinetics of halometasone after dermal topical administration of Halometasone Cream.Meth-ods Theplasmasamplewassubmittedtoliquid-liquid extraction using methyl tertiary butyl ether,with dexa-methasone as the internal standard (IS ).Chromato-graphic separations were performed on a Diamonsil C18 column(100 mm ×4. 6 mm,5 μm)with a linear gra-dient of methanol and 2 mmol · L-1 ammonium ace-tate.Halometasone and dexamethasone(IS)were ion-ized with an ESI source operated in negative ion mode, and the detected ions were m/z 503. 1→413. 0 (halo-metasone),m/z 391. 0→361. 0 (dexamethasone ). The test article could be monitored in rabbit plasma when following single dermal topical administration of Halometasone Cream at 1 g/100 cm2 to rabbits by u-singavalidatedLC-MS/MSassay.Results Calibra-tion curve was linear over the concentration range of0. 02~20 μg·L-1 in rabbit plasma.For low,medi-um,high concentration of QC solutions,the intra-and inter-day precision was in the range of 3. 72% ~7. 87%, and the accuracy was within 99. 1% to 103%. The pharmacokinetic parameters in rabbits were as follows:Tmax,Cmax,AUC0-t,T1/2 was (7. 38 ± 1. 06)h,(1. 16 ±0. 527)μg·L-1,(18. 8 ±7. 23)h·μg·L-1 ,(13. 8 ±3. 70)h,respectively.Conclusions ThisLC-MS/MSanalysismethodhashighsensitivi-ty,and sample processing method is simple,which has been rigorously validated.The method could be suc-cessfully applied to the pharmacokinetic study of halo-metasone after skin administration of Halometasone Cream to rabbits.

Aim Tostudytheanalgesiceffectofoxyso-phoridine (OSR)on GABA transporter-1 (GAT-1 )mR-NA expression and its influence on GAT-1 expression inmice.Methods Formalintestwasusedtodetectthe analgesic effect of OSR(iv).Immunohistochemis-try was taken to inspect the expression of GAT-1 in cerebral cortex and thalamus in mouse brain. The quantitative real-time PCR method was used to inspect the influence of OSR on GAT-1 mRNA expression of braininmice.Results OSR(500,250,125mg· kg-1 ,iv ) could significantly increase the foot-licking latency.OSR(500 mg·kg-1,ip)could significantly decrease the number of GAT-1 immuopositive cells incerebral cortex and thalamus in mouse brain,and re-duce GAT-1 mRNA expression in brain(P<0. 01,P<0.05)intheformalintest.Conclusion OSRhasa significant analgesic effect,and its analgesic mecha-nism is related to the GAT-1 expression in mouse brain.

Aim Toexplorewhether1-methylhydan-toin(MH)could inhibit the basal secretion of growth hormone (GH ) and suppress the promoting effect of growth hormone-releasing hormone (GHRH ) in rab-bits.Methods Thirty-sixrabbitswererandomlydi-vided into six experimental groups according to the kind of dosing drugs,namely normal saline group(A), MH group (B ),octreotide group (C ),GHRH group (D),GHRH +MH group(E),GHRH +octreotide group(F),with 6 rabbits in each group.Blood was sampled (1. 0 mL each time)from each rabbit before injecting drugs and 5,15,30,45,60 min after drug administration.Clotting spontaneously,rabbits blood samples were centrifugated for 20 minutes at approxi-mately 1000 ×g and the supernatant was collected. Serum GH concentrations were determined by enzyme linked immunosorbent assay kit(ELISA Kit).Mean-while,the behavior of rabbits in each group after injec-tingdrugswascloselyobserved.Results TheGH level of rabbits in group A at each time point had no significant differences(P>0. 05 ).Group B and group C rabbit GH levels were significantly lower than those of group A (P<0. 05 ),while GH levels in group D were obviously higher than those of group A (P <0. 05 ).Compared with group D,rabbit GH levels in group E and group F decreased markedly(P<0. 05 ). No obvious toxic and side effects had been observed within one week after the experimental rabbits were ad-ministered corresponding drugs by intravenous injec-tion.Conclusions 1-methylhydantoincouldinhibit the basal secretion of GH in rabbits.1-methylhydan-toin could suppress the promoting effect of GHRH in rabbits.

Aim Toinvestigatetheeffectofrecombi-nant snake venom metalloproteinase inhibitor (rSVM-PI ) on neovascularization and its molecular mecha-nism.Methods Chickenchorioallantoicmembrane (CAM)assay was used to examine the antiangiogenic effect of rSVMPI.Alamar blue analysis was used to de-tect cell proliferation.Annexin V-FITC double labeling flow cytometry was used to assay cell apoptosis. Scratch marker was used to assay cell migration.Boy-den chamber analysis method was used to detect cells chemotaxis in vitro.Tube like structure(TLS)of HU-VECs was used to detect the ability of neovasculariza-tion in vitro.Real-time PCR and Western blot were used to assay the expressions of KDR and FGFR-1 inHUVECs. Results Thevasculardensityindex (VDI)of CAM was drastically decreased after rSVMPI treatment, chemotaxis of HUVECs in response of VEGF was inhibited in the presence of rSVMPI,TLS of HUVECs was less than control group.The expres-sions of KDR and FGFR-1 were down-regulated by re-al-timePCRandWesternblotassay.Conclusion rS-VMPI may inhibit neovascularization by blocking the VEGF-KDR or bFGF-FGFR signal transduction path-way.

Aim Modelorganismzebrafishwasusedto study metabolites and metabolite profile of the gallic acid and protocatechuic acid of effective fractions of Polygonum capitatum,and discuss the feasibility and rationality of the model organism zebrafish in the study ofdrugmetabolism.Methods Thetwocomponents were exposed to model organism zebrafish after 24 h of solution treatment by using ultra-high performance liq-uid chromatography-quadrupole-time-of-flight tandem mass spectrometry technology (UHPLC-Q-TOF MS ) method with mass defect filter (MDF ),and the data was treated with data mining software(Metabolite Tool-sTM).Results Afterzebrafishmetabolism,themain reactions of gallic acid and protocatechuic were methyl-ation sulfated. In addition to the two parent com-pounds,six phase II metabolites were identified,in-cluding four methyl sulfate products and two sulfation products.Conclusions Themetabolismofthegallic acid and protocatechuic acid of effective fractions of Polygonum capitatum by zebrafish presents phase Ⅱmetabolites,which is highly consistent with the meta-bolic mechanism of rats.Thus it indicates the rationali-ty of the methods.At the same time,it also provides the experimental basis for clarifying the substance basis of the drug.