Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries.To date,microbiota-directed foods selectively promote the targeted human gut microbes,providing a strategy for A.muciniphila enhancement.Multiple studies have indicated the potential regulation of the polyphenol on A.muciniphila.Therefore,a polyphenol screening based on A.muciniphila upregulation was performed in mice.Chlorogenic acid(CGA)exhibited a greater response to A.muciniphila upregulation.Furthermore,we found that CGA did not directly promote A.muciniphila growth or mucin secretion.Microbiome and metabolomics revealed that the increased abundance of A.muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid,β-hydroxybutyrate,and N-acetyl-lactosamine.Finally,to confirm the regulation of CGA on A.muciniphila under disease conditions,high-fat diet-fed mice were established.The results showed CGA promoted A.muciniphila growth,and we expectedly found that CGA suppressed the augment in body weight of mice,significantly attenuated adipose tissue abnormality,provided liver protection and improved gut barrier integrity.These results suggest that CGA inhibits the development of obesity.Overall,our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice

Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Exploring the anti-aging effects of chlorogenic acid and the underlying mechanisms based on a Caenorhabditis elegans model

Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.

Chlorogenic acid complex(CGA7),standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells

Coffee is commonly consumed beverage in the world and it has been suggested to have beneficial effect.Chlorogenic acids(CGAs)are main ingredient of coffee beans which has been extensively used in nutraceuticals and medicine.Recently,various therapeutic effects of chlorogenic acids have been investigated.However,there are limited studies to investigate its anticancer properties.In the present study,we have used chlorogenic acid complex(CGA7)a decaffeinated water soluble green coffee bean extract to evaluate its cytotoxic effect on human and mouse cancer cell lines by using different approaches.From our results we found CGA7 treatment induces cell death in a dose and time dependent manner in different cancer cell lines.Further,CGA7 induced apoptosis was characterized by DNA fragmentation,PARP-1 cleavage,caspase-9 activation,and down regulation of Bcl-2,an anti-apoptotic protein and up regulation of pro-apoptotic protein BAX.Overall findings indicated that CGA7 complex a potent anticancer molecule found in green coffee beans could be a safe bioactive ingredient for prevention of cancer.

Identification and expression analysis of chlorogenic acid biosynthesis key gene PpHCT in peach

Shikimic acid/quinic acid hydroxy cinnamyl transferase(HCT)is one of the key enzymes in the phenylpropanoid pathway.However,the role of the HCT gene in chlorogenic acid(CGA)biosynthesis in peach fruit remains unclear.For this,we identified the accumulation pattern of CGA in four peach cultivars,cloned and characterized 11 PpHCT gene members,and further analyzed the expression patterns of these PpHCT genes during fruit development.The contents of CGAs in the four peach cultivars all exhibited a trend of increasing and then decreasing during the fruit growth and development.Moreover,the contents of CGAs in the peel and flesh were tissue-specific.Gene structure analysis indicated that the PpHCT genes were highly conserved,containing two exons and one intron.The protein structure analysis demonstrated that the PpHCT proteins contained two conserved motifs(HXXXD,DFGWG)and a transferase domain(PF02458),which belonged to the BAHD acyltransferase family.The cis-acting element analysis suggested that the promoters of PpHCT genes contained many light-related,hormone-related,stress-related,tissue-specific,and circadian-related elements,and they could participate in a variety of biological processes.Phylogenetic analysis showed that the HCT proteins of peach were closely related to the HCT proteins of plum and had a close evolutionary relationship.The qRT-PCR analysis indicated that the expression levels of PpHCT1 and PpHCT2 showed an opposite trend to the accumulation of CGA,whereas the expression levels of PpHCT4,PpHCT5,PpHCT7,PpHCT8,and PpHCT11 demonstrated the same trend as CGA accumulation.It was worth noting that only PpHCT4 and PpHCT5 were highly expressed in the two high-CGA cultivars but showed low levels of expression in the two low-CGA cultivars.Therefore,it was hypothesized that these two genes might be key genes to the synthesis of CGA in peach fruit.Those findings provide a theoretical basis for further study on the biological functions of the HCT gene and help to reveal the molecular mechanism of CGA.

松萝酸调节cGAS-STING信号通路对大鼠心肌缺血再灌注损伤的保护作用研究

目的 探究松萝酸调节环磷酸鸟苷-磷酸腺苷合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对大鼠心肌缺血再灌注损伤的保护作用。方法 选取50只SD健康大鼠,分为假手术组、模型组、松萝酸低剂量组(25 mg/kg)、松萝酸高剂量组(100 mg/kg)和RU.521组(cGAS抑制剂,5 mg/kg),每组10只通过结扎冠状动脉左前降支再灌注方法建立大鼠心肌缺血再灌注模型。HE染色观察大鼠心肌组织病理学变化;TUNEL染色检测心肌细胞凋亡情况;NBT染色检测心肌梗死面积百分比;商品化试剂盒检测心肌组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)水平;ELISA法检测大鼠血清肌酸激酶同工酶(CKMB)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平;RT-PCR法检测心肌组织cGAS mRNA、STING mRNA表达;Western blot检测大鼠心肌组织中Bax、Bcl-2、Caspase-3、cGAS、STING蛋白表达。结果 假手术组大鼠心肌组织结构形态正常,凋亡率较低;与假手术组比较,模型组大鼠心肌细胞受损严重、凋亡率、心肌梗死面积百分比、血清CKMB、TNF-α、IL-6水平、MDA水平、cGAS mRNA、STING mRNA表达水平、Bax、Caspase-3、cGAS、STING蛋白表达水平显著升高,SOD、CAT、Bcl-2蛋白表达水平显著降低(P<0.05);与模型组相比,松萝酸低、高剂量组和RU.521组大鼠心肌细胞形态结构明显改善,炎性细胞浸润显著减少、细胞凋亡率、心肌梗死面积百分比、血清CKMB、TNF-α、IL-6水平、MDA、cGAS mRNA、STING mRNA表达水平、Bax、Caspase-3、cGAS、STING蛋白表达水平显著降低,大鼠心肌组织SOD、CAT、Bcl-2蛋白表达水平显著升高(P<0.05);RU.521组各项指标与松萝酸高剂量组几乎相当。结论 松萝酸对心肌缺血再灌注大鼠具有保护作用,可能是通过抑制cGAS-STING信号通路实现的。

UPLC-DAD法同时测定刺五加叶中Chlorogenic acid,Rutin,Hyperoside及Isoquercitrin四种成分的含量

目的：建立UPLC同时定量刺五加叶药材中Chlorogenic acid,Rutin,Hyperoside及Isoquercitrin等4种有效成分的方法。方法：色谱柱：HSS T3（100 mm×2.1 mm,1.8μm,Waters）;柱温：40℃;流速：0.4m L/min;进样量：5μL;流动相A：0.1%甲酸水溶液,流动相B：乙腈;梯度洗脱,洗脱条件：0-8 min,88%-75%A;8-9 min,75%-88%A;9-10 min,88%-88%A;紫外检测波长：360 nm。结果：对9批产地的刺五加叶药材进行测定,绿原酸最高的是虎林（1.287 mg/g）;芦丁含量最高的是鸡东（0.122mg/g）;金丝桃苷含量最高的是宾县（0.528 mg/g）;异槲皮苷含量最高的是五常（0.337 mg/g）。结论：该方法可用于刺五加叶中四种成分的含量测定,本研究所建立的方法稳定性、精密度、重复性良好,适用于刺五加叶的含量测定;不同来源的药材成分含量差异显著,对刺五加实施多指标的含量控制是保证其临床药用安全可控的必要途径。

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

Chlorogenic Acid Maintains Glucose Homeostasis through Modulating the Expression of SGLT-1,GLUT-2,and PLG in Different Intestinal Segments of Sprague-Dawley Rats Fed a High-Fat Diet

Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.

Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUCo-t, AUCo-∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosting of 50.0 mg/kz.

Determination of chlorogenic acid by flow injection irreversible biamperometry

A flow injection irreversible biamperometric method for the determination of chlorogenic acid is described. The proposed method is based on the electrochemical oxidation of chlorogenic acid at pretreated platinum electrode and the reduction of permanganate at another electrode to form an irreversible biamperometric detection system. Under the external potential difference （z^v） of 0 V, in the 0.05 mol/L sulfuric acid, chlorogenic acid can be determined over the range 0.8-120 mg/L with a sample measurement frequency of 80 samples/h. The detection limit is 0.18 mg/L. The proposed method exhibits the satisfactory reproducibility with a relative standard derivation （R.S.D.） of 2.21% for 19 successive determinations of 40 mg/L.

Chlorogenic acid loaded chitosan nanoparticles with sustained release property,retained antioxidant activity and enhanced bioavailability

In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively.A regular,spherical shaped distribution of nanoparticles was observed through scanning electron microscopy(SEM)and the success of entrapment was confirmed by FTIR analysis.The encapsulation efficiency of CGA was at about 59%with the loading efficiency of 5.2%.In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further,the release kinetics study revealed the burst release of 69%CGA from nanoparticles at the end of 100th hours.Pharmacokinetic analysis in rats showed a lower level of Cmax,longer Tmax,longer MRT,larger AUC0et and AUC0e∞for the CGA nanoparticles compared to free CGA.Collectively,these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

Anti-encystment and amoebicidal activity of Lonicera japonica Thunb. and its major constituent Chlorogenic acid in vitro

Objective:To examine the acanthamoebicidal effects of ethyl acetate,aqueous and butanol fractions of dried flower buds of Lonicera japonica(L.japonica) Thunb.(Flos Lonicerae) in vitro.Methods:Acanthamoeba triangularis isolates were obtained from environmental water samples and identified by PCR.They were exposed to ethyl acetate,water and butanol fractions of L.japonica Thunb.at concentrations ranging from 0.5 mg/m L to 1.5 mg/m L.The extracts were evaluated for growth inhibition at 24,48 and 72 h,respectively.Chlorogenic acid at a concentration of 1 mg/mL was examined for inhibition of encystment.Results:Ethyl acetate fraction at a concentration of 1.5 mg/mL evoked a significant reduction of trophozoite viability by 48.9% after 24 h,49.2% after 48 h and 33.7% after 72 h Chlorogenic acid,the major active constituent of L.japonica Thunb.at the concentration of 1 mg/mL reduced the cysts/trophozoite ratio by 100% after 24 h,84.0% after 48 h and 72.3% after 72 h.This phenolic compound at concentration of 1 mg/mL concurrent with 0.6% hydrogen peroxide inhibited hydrogen peroxide-induced encystment by 92.8% at 72 h.Conclusions:Results obtained from this study show that ethyl acetate fraction at 1.5 mg/m L is the most potent fraction of L.japonica Thunb.and its major constituent chlorogenic acid showed the remarkable inhibition of encystment at a concentration of 1 mg/mL.

Extraction process of chlorogenic acid in flos lonicerae by enzymatic treatment

A new method of extracting chlorogenic acid from flos lonicerae, and treating the materials with enzyme before being extracted by ethanol is developed, and the optimum conditions are also investigated in detail. Three important factors, enzyme dosage, treatment time and treatment temperature are adapted to optimize the extraction process. The experimental results show that the extract yield of flos lonicerae and chlorogenic acid can be obviously increased by the cellulase treatment, 61.5 mg chlorogenic acid is obtained from 1.00 g flos lonicerae at most. The optimal temperature of enzymatic treatment is 40 50 ℃. Compared with the use of single cellulase, the combined treatment of cellulase and pectinase increase the extract yield obviously but fail to improve that of chlorogenic acid.

Overexpression of IbPAL1 promotes chlorogenic acid biosynthesis in sweetpotato

Sweetpotato[Ipomoea batatas(L.)Lam.],a food crop with both nutritional and medicinal uses,plays essential roles in food security and health-promoting.Chlorogenic acid(CGA),a polyphenol displaying several bioactivities,is distributed in all edible parts of sweetpotato.However,little is known about the specific metabolism of CGA in sweetpotato.In this study,IbPAL1,which encodes an endoplasmic reticulum-localized phenylalanine ammonia lyase(PAL),was isolated and characterized in sweetpotato.CGA accumulation was positively associated with the expression pattern of IbPAL1 in a tissue-specific manner,as further demonstrated by overexpression of IbPAL1.Overexpression of IbPAL1 promoted CGA accumulation and biosynthetic pathway genes expression in leaves,stimulated secondary xylem cell expansion in stems,and inhibited storage root formation.Our results support a potential role for IbPAL1 in sweetpotato CGA biosynthesis and establish a theoretical foundation for detailed mechanism research and nutrient improvement in sweetpotato breeding programs.

Simultaneous determination of geniposidic acid. chlorogenic acid and geniposide in eucommia by HPLC

A high performance liquid chromatography (HPLC) method was established for simultaneous determina-tion of geniposidic acid, chlorogenic acid and geniposide in eucommia. Detection at 240 nm with a reversed-phasecolumn, CH3OH volume fraction, acidic additive and pH value of mobile phase were studied for their effects on theseparability of the compounds. The most suitable separation was obtained with isocratic gradient elution systemusing CH3OH-H2O-H3 PO4 (12.00: 87.96: 0.04, volume ratio) at a flow-rate of 1.0 mL/min. Under the experi-mental conditions, the capacity factors of three compounds are in 3-13. The sample is separated rightly. Theanalysis time is 30 min and the retention time of genfposidic acid, chlorogenic acid and geniposide are 6. 7 min,10.5 min and 21 min, respectively.

Effect of chlorogenic acid on antioxidant activity of Flos Lonicerae extracts

Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and ethanolic extracts prepared from Flos Lonicerae to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduce Fe3+ to Fe2+ is examined. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with high performance liquid chromatography (HPLC) and its antioxidant capacity is characterized. The total phenolic compounds and chlorogenic acid con-tents in Flos Lonicerae are determined. The present results demonstrate that the Flos Lonicerae extracts exhibit antioxidant ac-tivity and chlorogenic acid is a major contributor to this activity.

Differences Between the Concentrations in Rabbit Body Fluid of Berberine Hydrochloride, Chlorogenic Acid, Baicalin, and Their Minimal Inhibitory Concentrations

To explore the relationship between the heat-clearing and detoxicating functions and the bacteriostatic actions of berberine hydrochloride （Ber. H）, chlorogenic acid （Chlo. A）, and baicalin （Bai）, their concentrations in rabbit body fluid were compared with their minimal inhibitory concentrations （MICs）. Their concentrations in rabbit blood and tissue fluid were determined by reversed-phase high performance liquid chromatography, and their MICs to Escherichia coli were determined by tube dilution method. The results showed that the peak concentrations of Ber. H, Chlo. A, and Bai in rabbit blood were 3.2, 5.03, and 7.63 μg mL^-1, and in rabbit tissue fluid were 0.12, 0.11, and 0.12 μg mL^-1, respectively. Their MICs to E. coli were, respectively, 1.0×10^3, 3.75 × 10^3, and 6.75 ×10^3μg mL^-1, which were far higher than the concentrations in rabbit body fluids. This study indicates that Ber. H, Chlo. A, and Bai have weak bacteriostatic actions and do not reach their effective inhibitory concentrations in rabbit body fluids, and their heat-clearing and detoxicating functions are independent on the bacteriostatic actions.

Ionic Liquid and HP-β-CD Modified Capillary Zone Electrophoresis to Separate Hyperoside, Luteolin and Chlorogenic Acid

Ionic liquid （1-ethyl-3-methylimidazolium tetrafluoroborate, 1E-3MI-TFB） and HP-β- CD as modifier was added to the buffer to separate hyperoside, luteolin and chlorogenic acid. Experiments explored the effect of concentration of 1E-3MI-TFB and HP-β-CD on separation. The results indicated that 1.0 mmol/L HP-β-CD and 1%0 （v/v） 1E-3MI-TFB added to the buffer simultaneously could achieve a good compromise of resolution and analysis time. Capillary experiments and UV spectra indicated that there was interaction between 1E-3MI-TFB and analytes.

Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons

Chlorogenic acid（5-caffeoylquinic acid, CGA） is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer＇s disease and neuropathic pain disorders. However, its mechanism of action is unclear.Voltage-gated potassium channel（Kv） is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,Aand IK,Vchannels. Trigeminal ganglion（TRG）neurons were acutely disassociated from the rat TRG, and two different doses of CGA（0.2 and 1 mmol·L21） were applied to the cells.Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,Aand IK,Vchannels. The results demonstrated that 0.2 mmol·L21CGA decreased the peak current density of IK,A. Both 0.2 mmol·L21and1 mmol·L21CGA also caused a significant reduction in the activation and inactivation thresholds of IK,Aand IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,Aand IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects.