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,...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.展开更多
The mortality rate of neurological disorders is increasing globally,and natural antioxidant geniposidic acid(GPA)holds great potential in the treatment of neuronal oxidative damage.Nevertheless,its inherent instabilit...The mortality rate of neurological disorders is increasing globally,and natural antioxidant geniposidic acid(GPA)holds great potential in the treatment of neuronal oxidative damage.Nevertheless,its inherent instability constrains its pragmatic utilization.Herein,we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation.Among the various methods for preparing drug-loaded microspheres,the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity.Nevertheless,this method results in microspheres with heterogeneous particle sizes.To address this limitation,we developed a two-step emulsification method involving stirring and homogenization.Using the biocompatible,synthetic,biodegradable polymer polycaprolactone(PCL)as the drug delivery carrier,we prepared GPA-loaded PCL microspheres via the two-step emulsification method.The results demonstrated that the microspheres possessed uniform particle size(polydispersity index=0.12),excellent drug loading capacity(∼4.86%),sustained drug release profiles(∼68.55%in 264 h),and biocompatibility(cell viability>85%).The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species(ROS)induced by oxidative stress,thereby protecting neuronal cells from oxidative damage.This work presents a promising new approach for the treatment of neuronal oxidative damage.展开更多
Depression is a prevalent mental disorder with limited effective treatments,posing a significant global issue.This study explored L-theanine and geniposide,key components in“food-medicine homology”materials,to deter...Depression is a prevalent mental disorder with limited effective treatments,posing a significant global issue.This study explored L-theanine and geniposide,key components in“food-medicine homology”materials,to determine if their combination(TG)could alleviate depression-like behaviors and hippocampal neuronal damage in a chronic unpredictable mild stress(CUMS)mouse model.Male C57BL/6J mice were divided into control,CUMS model,and CUMS+TG groups with varying doses.The CUMS group displayed depressionlike behaviors,including reduced activity and sucrose preference.TG treatment partially reversed these changes,significantly increasing antioxidant enzyme activities,decreasing pro-inflammatory cytokine levels,and improving neuromodulator levels.RNA-seq analysis identified the transthyretin(TTR)gene,upregulated in the model group but downregulated after TG treatment.TG treatment modulated intestinal microbiota composition compared to the CUMS group,including increased Firmicutes,reduced Bacteroidetes and Prevotella,and variable changes in Bifidobacterium abundance.In conclusion,our study indicates that CUMS exposure upregulates stress hormones and TTR expression,associated with neuroinflammation,oxidative stress,monoamine depletion,depression-like behaviors,and intestinal microbiota dysbiosis.TG treatment alleviates these effects and modulates intestinal microbiota,suggesting L-theanine and geniposide's potential as a novel depression therapy.展开更多
Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,...Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,it is of great significance to search for effective hepatoprotective drugs from natural products.Geniposide(GS)is a cyclic ether terpenoid compound and a key component in the traditional Chinese medicine Gardenia jasminoides.It has a significant inhibitory effect on LD.However,there is currently no literature systematically analyzing its mechanism of action.To adapt to the environment of new drug research and the need for precision medication,this article summarizes the pathways and possible mechanisms of action discovered by GS in the treatment of LD,based on recent research literature:regulating bile stasis,antioxidant and anti-apoptosis,improving amino acid metabolism,improving energy metabolism,regulating lipid metabolism,anti-inflammatory and analgesic effects,etc.It also summarizes the pharmacokinetics of GS in vivo and discusses the liver toxicity of GS that is positively correlated with dosage.In addition,the existing problems in current research and possible future development directions were also discussed,to lay the foundation for the clinical development of natural product GS.展开更多
Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease in...Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Geniposide,the principal active iridoid glucoside ingredient in Fructus gardeniae used in numerous traditional Chinese clinical prescriptions,has been shown to cause herbal hepatotoxicity because of its glycone metabo...Geniposide,the principal active iridoid glucoside ingredient in Fructus gardeniae used in numerous traditional Chinese clinical prescriptions,has been shown to cause herbal hepatotoxicity because of its glycone metabolite genipin.This study explored the role of gut microbiota in alleviating geniposide hepatotoxicity with isoflavones in soy products.Metabolic profiling using ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q/TOF-MS)revealed two metabolic pathways and six main forms of geniposides in vivo.Enzyme inhibitor experiments have shown that isoflavones alter geniposide metabolism by mediating specific enzymes,includingβ-glucosidase(β-GC)and sulfotransferase(SULT),in an established pseudo-sterile rat model.Isoflavones pretreatment by gavage for three weeks optimized the structure of the gut microbiota was linked to the regulation of key metabolic enzymes.Furthermore,experiments involving fecal microbiota transplantation(FMT)established the direct contribution of the gut microbiota to the regulation of enzyme activities and geniposide metabolism.This study demonstrated that isoflavones in soy products regulated the metabolic enzymes of geniposode dependent on gut microbiota,especially Lactobacillus spp.,which was further verified in our clinical trials analyzed using 16S ribosomal RNA(rRNA)and metagenomic sequencing,thus regulating geniposide metabolism.Furthermore,as dominant beneficial bacterium,Lactobacillus spp.were discovered to be promising microbial targets for the better management of geniposide hepatotoxicity.These findings provide valuable insights for the prevention and intervention of drug-induced liver injury.展开更多
Geniposide is a major bioactive constituent isolated from Gardeniajasminoides Ellis. To evaluate the pharmacokinetics of geniposide in pre-clinical studies, a rapid and specific liquid chromatography-tandem mass spect...Geniposide is a major bioactive constituent isolated from Gardeniajasminoides Ellis. To evaluate the pharmacokinetics of geniposide in pre-clinical studies, a rapid and specific liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was developed and validated. After simple protein precipitation, geniposide was analyzed on a DiamonsilR C18 column with a mobile phase of 10 mM ammonium acetate and methanol （20：80, v/v） at a flow rate of 0.6 mL/min. Detection was performed in ＂Truncated＂ multiple-reaction monitoring （MRM） mode with positive electrospray ionization （ESI） at m/z 411→411 for geniposide, and MRM mode with negative ESI ionization at m/z 415→295 for puerarin （internal standard, IS）. Linearity was established in the concentration range from 10.0 to 5000 ng/mL. The extraction recoveries ranged from 84.8% to 90.5% at concentrations of 10.0, 500 and 4.5x 103 ng/mL. The lower limit of quantification （LLOQ） was 10.0 ng/mL with 50 ~tL plasma. The validated method was successfully applied to the pharmacokinetic study of geniposide in rats at a dose of 200 mg/kg by oral administration.展开更多
Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin...Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.展开更多
Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. ...Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.展开更多
Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta prot...Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease(AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng(GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.展开更多
BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare disease,and its etiology and risk factors remain uncertain.AIM To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP...BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare disease,and its etiology and risk factors remain uncertain.AIM To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP.METHODS The detailed formula of herbal liquid prescriptions of all patients was studied,and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor.Abdominal computed tomography(CT)and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis.The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images.The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor.Subsequently,Spearman’s correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score.RESULTS The mean age of the 8 enrolled patients was 75.7 years and male predominance was found(all 8 patients were men).The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics(e.g.,threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images).Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients(75%)and involved the left-side mesenteric vein of 2 cases(25%)and the calcifications extended to the mesorectum in 1 of them.The thickening of colon wall mainly occurred in the right colon and the transverse colon.The median disease CT score was 4.88(n=7)and the median drinking index was 5680(n=7).After Spearman’s correlation analysis,the median CT score of the disease showed a significant positive correlation with the median drinking index(r=0.842,P<0.05).CONCLUSION Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.展开更多
In vitro cultured human neuroblastoma SH-SY5Y cells were pretreated with 50 or 5 ug/mL geniposide for 12 hours and exposed to 400 umol/L corticosterone. Corticosterone exposure in cultures not pretreated with geniposi...In vitro cultured human neuroblastoma SH-SY5Y cells were pretreated with 50 or 5 ug/mL geniposide for 12 hours and exposed to 400 umol/L corticosterone. Corticosterone exposure in cultures not pretreated with geniposide resulted in inhibited cell growth, reduced cell survival, and increased P53 and P21 protein expression. However, in geniposide pretreated SH-SY5Y cells, cell viability and the number of cells in the G2 phase of the cell cycle were significantly increased, P21 and P53 protein expression was reduced, and cell apoptosis was inhibited following corticosterone exposure. These results indicate that geniposide can protect SH-SY5Y cells against high-dose corticosterone-induced injury.展开更多
OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and cons...OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.展开更多
Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action re...Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.展开更多
The effects of pulse ultrasound with different pulse parameters on the breakthrough curves of Geniposide on Resin 1300 were studied. The mass transfer model describing the adsorption process was constructed. Adsorptio...The effects of pulse ultrasound with different pulse parameters on the breakthrough curves of Geniposide on Resin 1300 were studied. The mass transfer model describing the adsorption process was constructed. Adsorption capability and the overall mass-transfer coefficient were obtained by fitting the constructed mass-transfer model and the experimental data. The effects of pulse ultrasound on adsorption of Geniposide on Resin1300 in a fixed bed were studied and compared. Amount of Geniposide adsorbed on Resin 1300 in the presence of ultrasound is lower than that in the absence of ultrasound, but the mass-transfer rate with ultrasonic irradiation is higher than that without ultrasound. Furthermore, mass transfer rate is enhanced by pulse modulation. In the conditions studied, the adsorption equilibrium constant decreases with increasing ultrasonic power, while the overall mass-transfer co-efficient increases. With increasing pulse duty ratio, adsorption equilibrium constant decreases initially, reaches a minimum when pulse duty ratio is 0.5, and then increases. On the contrary, the overall mass-transfer coefficient in-creases initially and reaches a maximum when pulse ratio is 0.5, and then decreases. Effects of pulse period on ad-sorption equilibrium and mass transfer rate reached the peak at pulse period of 28.6 ms.展开更多
Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sou...Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.展开更多
Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風...Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.展开更多
Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- ...Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- bral ischemia reperfusion injury （CIRI） rats. Method： 100 rats were divided into 5 groups： sham, CIRI model group, baicalin and geniposide （7 ： 3） （30 mg · kg^-1 ,60 mg · kg^-1） group, allyl chloride （0. 0021 ml· kg^-1）group. The model of CIRI made by improved suture method, Neural function defect, morphology and number of neurons in cerebral cortex was observed by Nissl staining; tested the contental change of P-gp and Na＋ , K＋-ATP enzymes of brain tissue, the contental change of S100β, Glucose, pyruvic acid and lactic acid of plasma by ELISA; the dry wet weight and Evans Blue （EB） tracing method served BBB permeabilitical changes; immunohis- tochemistry staining and semi-quantitation analysis were performed to detect the AQP-4 and GFAP in cerebra ische- mia; the expression of AQP-4 in cerebra hippocampus was determined by RT-qPCR and Western blot; pathological change was observed in brain issueby HE staining; observed the changes of brain tissue ultrastructure usingtrans- mission electron microscope with Lanthanum nitrate tracer ; monitored the size and location of the ischemia injury in brain regions with magnetic resonance imaging （MRI）. Results Compared with CIRI group, baicalin and genipo- side group can restore nerve function defect; increase the number of Nissl positive cells in cerebral cortex; weaken Na＋ ,K＋-ATP enzyme dynamic, reduce the content of S10013 Glucose and P-gp, reduce the content of water and volume EB in brain, elevated the7content of pyruvic acid and pyruvic acid; remarkable attenuation of AQP-4 and GFAP over-expression in the brain; remarkable attenuation of AQP-4 mRNA expression in hippocampus; The mor- phology is became clear, eased lumen of blood vessel compression deformation, loose organization, lessened cell volume and edema; Reduction of lanthanum particles into the blood vessels and the cells, reduce the vascular endo- thelial cell edema. Conclusion Baicalin and geniposide （7 ： 3 ） can reduce the permeability of blood brain barri- er, and has a protective effect on the brain edema induced by CIRI.展开更多
基金Project (02JZY3029) supported by the Department of Science and Technology of Hunan Province Pro-ject (2002-772) supported by the Development Planning Commission of Hunan Province
文摘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.
基金supported by the Fundamental Research Funds for the Central Universities(grant No.PTYX202449).
文摘The mortality rate of neurological disorders is increasing globally,and natural antioxidant geniposidic acid(GPA)holds great potential in the treatment of neuronal oxidative damage.Nevertheless,its inherent instability constrains its pragmatic utilization.Herein,we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation.Among the various methods for preparing drug-loaded microspheres,the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity.Nevertheless,this method results in microspheres with heterogeneous particle sizes.To address this limitation,we developed a two-step emulsification method involving stirring and homogenization.Using the biocompatible,synthetic,biodegradable polymer polycaprolactone(PCL)as the drug delivery carrier,we prepared GPA-loaded PCL microspheres via the two-step emulsification method.The results demonstrated that the microspheres possessed uniform particle size(polydispersity index=0.12),excellent drug loading capacity(∼4.86%),sustained drug release profiles(∼68.55%in 264 h),and biocompatibility(cell viability>85%).The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species(ROS)induced by oxidative stress,thereby protecting neuronal cells from oxidative damage.This work presents a promising new approach for the treatment of neuronal oxidative damage.
基金funded by Innovation Project for Chinese Academy of Agricultural Sciences(CAAS-ASTIP-TRI)China Agriculture Research System of MOF and MARA(CARS-19)。
文摘Depression is a prevalent mental disorder with limited effective treatments,posing a significant global issue.This study explored L-theanine and geniposide,key components in“food-medicine homology”materials,to determine if their combination(TG)could alleviate depression-like behaviors and hippocampal neuronal damage in a chronic unpredictable mild stress(CUMS)mouse model.Male C57BL/6J mice were divided into control,CUMS model,and CUMS+TG groups with varying doses.The CUMS group displayed depressionlike behaviors,including reduced activity and sucrose preference.TG treatment partially reversed these changes,significantly increasing antioxidant enzyme activities,decreasing pro-inflammatory cytokine levels,and improving neuromodulator levels.RNA-seq analysis identified the transthyretin(TTR)gene,upregulated in the model group but downregulated after TG treatment.TG treatment modulated intestinal microbiota composition compared to the CUMS group,including increased Firmicutes,reduced Bacteroidetes and Prevotella,and variable changes in Bifidobacterium abundance.In conclusion,our study indicates that CUMS exposure upregulates stress hormones and TTR expression,associated with neuroinflammation,oxidative stress,monoamine depletion,depression-like behaviors,and intestinal microbiota dysbiosis.TG treatment alleviates these effects and modulates intestinal microbiota,suggesting L-theanine and geniposide's potential as a novel depression therapy.
基金supported by the National Natural Science Foundation of China Key Project(81830110)。
文摘Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,it is of great significance to search for effective hepatoprotective drugs from natural products.Geniposide(GS)is a cyclic ether terpenoid compound and a key component in the traditional Chinese medicine Gardenia jasminoides.It has a significant inhibitory effect on LD.However,there is currently no literature systematically analyzing its mechanism of action.To adapt to the environment of new drug research and the need for precision medication,this article summarizes the pathways and possible mechanisms of action discovered by GS in the treatment of LD,based on recent research literature:regulating bile stasis,antioxidant and anti-apoptosis,improving amino acid metabolism,improving energy metabolism,regulating lipid metabolism,anti-inflammatory and analgesic effects,etc.It also summarizes the pharmacokinetics of GS in vivo and discusses the liver toxicity of GS that is positively correlated with dosage.In addition,the existing problems in current research and possible future development directions were also discussed,to lay the foundation for the clinical development of natural product GS.
基金supported by grants from the National Natural Science Foundation of China(U21A20400,81973789,82004327).
文摘Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
基金supported by the National Natural Science Foundation of China(82461160264,82474056,and 82104124)the grant from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0502605)+2 种基金the Science and Technology Development Fund,Macao SAR(FDCT 0025/2021/A1)the Shanghai Municipal Health Commission(2022XD037)the Shanghai Magnolia Talent Plan Pujiang Project(23PJD113)。
文摘Geniposide,the principal active iridoid glucoside ingredient in Fructus gardeniae used in numerous traditional Chinese clinical prescriptions,has been shown to cause herbal hepatotoxicity because of its glycone metabolite genipin.This study explored the role of gut microbiota in alleviating geniposide hepatotoxicity with isoflavones in soy products.Metabolic profiling using ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q/TOF-MS)revealed two metabolic pathways and six main forms of geniposides in vivo.Enzyme inhibitor experiments have shown that isoflavones alter geniposide metabolism by mediating specific enzymes,includingβ-glucosidase(β-GC)and sulfotransferase(SULT),in an established pseudo-sterile rat model.Isoflavones pretreatment by gavage for three weeks optimized the structure of the gut microbiota was linked to the regulation of key metabolic enzymes.Furthermore,experiments involving fecal microbiota transplantation(FMT)established the direct contribution of the gut microbiota to the regulation of enzyme activities and geniposide metabolism.This study demonstrated that isoflavones in soy products regulated the metabolic enzymes of geniposode dependent on gut microbiota,especially Lactobacillus spp.,which was further verified in our clinical trials analyzed using 16S ribosomal RNA(rRNA)and metagenomic sequencing,thus regulating geniposide metabolism.Furthermore,as dominant beneficial bacterium,Lactobacillus spp.were discovered to be promising microbial targets for the better management of geniposide hepatotoxicity.These findings provide valuable insights for the prevention and intervention of drug-induced liver injury.
基金Laboratory for Rare Disease of Shandong Province
文摘Geniposide is a major bioactive constituent isolated from Gardeniajasminoides Ellis. To evaluate the pharmacokinetics of geniposide in pre-clinical studies, a rapid and specific liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was developed and validated. After simple protein precipitation, geniposide was analyzed on a DiamonsilR C18 column with a mobile phase of 10 mM ammonium acetate and methanol （20：80, v/v） at a flow rate of 0.6 mL/min. Detection was performed in ＂Truncated＂ multiple-reaction monitoring （MRM） mode with positive electrospray ionization （ESI） at m/z 411→411 for geniposide, and MRM mode with negative ESI ionization at m/z 415→295 for puerarin （internal standard, IS）. Linearity was established in the concentration range from 10.0 to 5000 ng/mL. The extraction recoveries ranged from 84.8% to 90.5% at concentrations of 10.0, 500 and 4.5x 103 ng/mL. The lower limit of quantification （LLOQ） was 10.0 ng/mL with 50 ~tL plasma. The validated method was successfully applied to the pharmacokinetic study of geniposide in rats at a dose of 200 mg/kg by oral administration.
基金This study was funded by grants from the Natural Science Foundation of Hubei Province in China （2012FFB02508）.
文摘Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.
基金supported by the National Natural Science Foundation of China (No. 81073057)the Key New Drug Creation and Development Programme of China (Nos. 2009ZX09502-008 and 2009ZX09308-003)the Doctoral Fund of the Ministry of Education of China(No. 20090013110007)
文摘Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.
基金supported by programs of Thousand Talents Program Research Park(Jiangsu,China)Provincial Innovation and Entrepreneurial Talent,Jiangsu,China(to I.F.P,)Development of Society and Technology(Kunshan City,Jiangsu,China)
文摘Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease(AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng(GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.
基金Supported by the Fund of Medical and Health Research Projects of Health Commission of Zhejiang Province,No.2018KY247 and No.2019KY035.
文摘BACKGROUND Idiopathic mesenteric phlebosclerosis(IMP)is a rare disease,and its etiology and risk factors remain uncertain.AIM To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP.METHODS The detailed formula of herbal liquid prescriptions of all patients was studied,and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor.Abdominal computed tomography(CT)and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis.The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images.The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor.Subsequently,Spearman’s correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score.RESULTS The mean age of the 8 enrolled patients was 75.7 years and male predominance was found(all 8 patients were men).The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics(e.g.,threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images).Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients(75%)and involved the left-side mesenteric vein of 2 cases(25%)and the calcifications extended to the mesorectum in 1 of them.The thickening of colon wall mainly occurred in the right colon and the transverse colon.The median disease CT score was 4.88(n=7)and the median drinking index was 5680(n=7).After Spearman’s correlation analysis,the median CT score of the disease showed a significant positive correlation with the median drinking index(r=0.842,P<0.05).CONCLUSION Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.
基金the Capital Specific Clinical Medical Subject of Beijing Science and Technology Commission,No.Z090507017709030
文摘In vitro cultured human neuroblastoma SH-SY5Y cells were pretreated with 50 or 5 ug/mL geniposide for 12 hours and exposed to 400 umol/L corticosterone. Corticosterone exposure in cultures not pretreated with geniposide resulted in inhibited cell growth, reduced cell survival, and increased P53 and P21 protein expression. However, in geniposide pretreated SH-SY5Y cells, cell viability and the number of cells in the G2 phase of the cell cycle were significantly increased, P21 and P53 protein expression was reduced, and cell apoptosis was inhibited following corticosterone exposure. These results indicate that geniposide can protect SH-SY5Y cells against high-dose corticosterone-induced injury.
基金Supported by the Ministry of Education,Science and Technology (MEST)Korea Institute for Advancement of Technology (KIAT) through the Human Resource Training Project for Regional Innovation
文摘OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.
基金supported by the National Natural Science Foundation of China No.81072901the New Teacher Fund for Doctor Station,Ministry of Education,No.20120013110013+1 种基金grants from the Nautical Traditional Chinese Medicine Discipline,No.522/0100604054grants from the Nautical Traditional Chinese Medicine Collaborative Innovation Center,No.522/0100604299
文摘Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.
基金Supported by the National lqatural Science Foundation of China （20346003）.
文摘The effects of pulse ultrasound with different pulse parameters on the breakthrough curves of Geniposide on Resin 1300 were studied. The mass transfer model describing the adsorption process was constructed. Adsorption capability and the overall mass-transfer coefficient were obtained by fitting the constructed mass-transfer model and the experimental data. The effects of pulse ultrasound on adsorption of Geniposide on Resin1300 in a fixed bed were studied and compared. Amount of Geniposide adsorbed on Resin 1300 in the presence of ultrasound is lower than that in the absence of ultrasound, but the mass-transfer rate with ultrasonic irradiation is higher than that without ultrasound. Furthermore, mass transfer rate is enhanced by pulse modulation. In the conditions studied, the adsorption equilibrium constant decreases with increasing ultrasonic power, while the overall mass-transfer co-efficient increases. With increasing pulse duty ratio, adsorption equilibrium constant decreases initially, reaches a minimum when pulse duty ratio is 0.5, and then increases. On the contrary, the overall mass-transfer coefficient in-creases initially and reaches a maximum when pulse ratio is 0.5, and then decreases. Effects of pulse period on ad-sorption equilibrium and mass transfer rate reached the peak at pulse period of 28.6 ms.
基金supported by grants from the Shanxi Science and Technology Department in China,No.2011081060Shanxi Scholarship Council of China,No.2011-44
文摘Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.
文摘Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.
文摘Aim To investigate the protection effect of the compatibility of baicalin and geniposide （7 ： 3 ） on blood-brain barrier （BBB） damage and the mechanism of down-regulating the expression of AQP-4 protein in cere- bral ischemia reperfusion injury （CIRI） rats. Method： 100 rats were divided into 5 groups： sham, CIRI model group, baicalin and geniposide （7 ： 3） （30 mg · kg^-1 ,60 mg · kg^-1） group, allyl chloride （0. 0021 ml· kg^-1）group. The model of CIRI made by improved suture method, Neural function defect, morphology and number of neurons in cerebral cortex was observed by Nissl staining; tested the contental change of P-gp and Na＋ , K＋-ATP enzymes of brain tissue, the contental change of S100β, Glucose, pyruvic acid and lactic acid of plasma by ELISA; the dry wet weight and Evans Blue （EB） tracing method served BBB permeabilitical changes; immunohis- tochemistry staining and semi-quantitation analysis were performed to detect the AQP-4 and GFAP in cerebra ische- mia; the expression of AQP-4 in cerebra hippocampus was determined by RT-qPCR and Western blot; pathological change was observed in brain issueby HE staining; observed the changes of brain tissue ultrastructure usingtrans- mission electron microscope with Lanthanum nitrate tracer ; monitored the size and location of the ischemia injury in brain regions with magnetic resonance imaging （MRI）. Results Compared with CIRI group, baicalin and genipo- side group can restore nerve function defect; increase the number of Nissl positive cells in cerebral cortex; weaken Na＋ ,K＋-ATP enzyme dynamic, reduce the content of S10013 Glucose and P-gp, reduce the content of water and volume EB in brain, elevated the7content of pyruvic acid and pyruvic acid; remarkable attenuation of AQP-4 and GFAP over-expression in the brain; remarkable attenuation of AQP-4 mRNA expression in hippocampus; The mor- phology is became clear, eased lumen of blood vessel compression deformation, loose organization, lessened cell volume and edema; Reduction of lanthanum particles into the blood vessels and the cells, reduce the vascular endo- thelial cell edema. Conclusion Baicalin and geniposide （7 ： 3 ） can reduce the permeability of blood brain barri- er, and has a protective effect on the brain edema induced by CIRI.
