Catalpol,an iridoid glucoside isolated from Rehmannia glutinosa,has gained attention due to its potential use in treating cardio-cerebrovascular diseases(CVDs).This extensive review delves into recent studies on catal...Catalpol,an iridoid glucoside isolated from Rehmannia glutinosa,has gained attention due to its potential use in treating cardio-cerebrovascular diseases(CVDs).This extensive review delves into recent studies on catalpol's protective properties in relation to various CVDs,such as atherosclerosis,myocardial ischemia,infarction,cardiac hypertrophy,and heart failure.The review also explores the compound's anti-oxidant,anti-inflammatory,and anti-apoptotic characteristics,emphasizing the role of vital signaling pathways,including PGC-1a/TERT,PI3K/Akt,AMPK,Nrf2/HO-1,estrogen receptor(ER),Nox4/NF-kB,and GRP78/PERK.The article discusses emerging findings on catalpol's ability to alleviate diabetic cardiovascular complications,thrombosis,and other cardiovascular-related conditions.Although clinical studies specifically addressing catalpol's impact on CVDs are scarce,the compound's established safety and well-tolerated nature suggest that it could be a valuable treatment alternative for CVD patients.Further investigation into catalpol and related iridoid derivatives may unveil new opportunities for devising natural and efficacious CVD therapies.展开更多
Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathog...Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expression of galectin-3,VEGFR1,.VEGFR2,and HIF-1αin renal cortices was analyzed by Western blotting.The expression of galectin-3,F4/80(a macrophage biomarker),and CD34(an endothelium biomarker)in renal cortices was detected by IF staining,and collagen accumulation by Masson staining.Results:The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50μg/mL AGEs for 48 h than those in untreated cells.Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages.Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells.Catalpol could significantly decrease the levels of Ang-1,Ang-2 and Tie-2 released by AGEs-treated mGECs,which could be reversed by over-expression of galectin-3.Catalpol could significantly inhibit AGEs-induced expression of galectin-3,HIF-1α,VEGFR1,and VEGFR2 in mGECs.The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478.Moreover,catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages,which was weakened by PX-478.Additionally,catalpol significantly inhibited the expression of galectin-3,macrophage infiltration,collagen accumulation,and angiogenesis in the kidney of diabetic rats.Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol.Conclusion:Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3.It could prevent the progression of diabetes-induced renal damage.展开更多
Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To anal...Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To analyze the pathological status and impact of catalpol on the rats, 3 weeks after intragastric gavage, the animals were verified for myocardial infarcts with electrocardiogram and measured for enzyme activity of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) and superoxide dismutase (SOD) in myocardium, and further analyzed using HE and TTC staining, as well as visual examination of infarct area. Flow cytometry study of endothelial progenitor cells (EPCs) indicated that the EPCs were mobilized during infarction. The roles of Notch1 signaling pathway in angiogenesis of the infracted animals were studied using immunohistochemistry analysis of RBPjκ and Western blot analysis of Notch1 and Jagged1. Our results obtained from the rats treated with catalpol, positive drug and control showed that catalpol could protect rats from infarction probably by mobilization of EPCs and activation of Notch1 signaling pathway.展开更多
A rapid and sensitive liquid chromatography-tandem mass chromatography (LC-MS/MS) method has been developed and validated for simultaneous determination of catalpol and harpagide in rat plasma. The samples were extrac...A rapid and sensitive liquid chromatography-tandem mass chromatography (LC-MS/MS) method has been developed and validated for simultaneous determination of catalpol and harpagide in rat plasma. The samples were extracted by one-step protein precipitation and separated on a SunFireTM C18 column (100 mm × 2.1 mm, 3.5 μm;Waters) using acetonitrile-10 mM ammonium formate as mobile phase at a flow rate 0.3 mL/min in gradient mode. The analytes were detected without interference in Multiple Reaction Monitoring (MRM) mode with negative electrospray ionization. Linear responses were obtained for catalpol ranging from 20 to 5000 ng/mL and harpagide ranging from 10 to 2500 ng/mL. Coefficients of correlation (r) for the calibration curves were more than 0.99 for both analytes. Intra- and inter-day accuracy and precision were within the acceptable limits of less than 15.0% at all concentrations. The quantitation method was successfully applied for simultaneous estimation of catalpol and harpagide after oral administration of Zeng Ye Decoction.展开更多
Rehmannia glutinosa is a traditional Chinese medical herb and has a long history in cognitive deficits therapy. Its ther-apeutic efficacy has been confirmed by clinical studies. In this study, we attempted to investig...Rehmannia glutinosa is a traditional Chinese medical herb and has a long history in cognitive deficits therapy. Its ther-apeutic efficacy has been confirmed by clinical studies. In this study, we attempted to investigate the effects of catalpol, an iridoid from Rehmannia glutinosa, on cognitive and behavioral function of aged rats with memory loss. 22 - 24 month Sprague-Dawley spontaneous rats of memory loss with aging were selected by step-down type passive avoidance test and randomly allocated to two groups: the aged rats with memory loss (control group) and the catal- pol-treated (5 mg/kg) group. We performed open-field and Y-maze test to evaluate special performance and behavior response before and after catalpol treatment for 5 and 10 days. Growth-associated protein (GAP-43) in hippocampus and frontal cortex was measured using immunohistochemistry and quantitative Western Blotting. The results showed that catalpol could significantly improve not only spatial learning and memory but also locomotor activity and ex-plora- tory behavior of aged rats with memory loss. GAP-43 protein in hippocampal CA3 region and dentate granule of catal- pol-treated rats was significantly enhanced than that of control group. Western blot analysis demonstrated a catal- pol-associated increase of GAP-43 in hippocampus of catalpol-treated rats and correlated with spatial memory, loco- motor activity and exploratory behavior. However, there was no difference in GAP-43 protein in frontal cortex between two groups. These results indicated that catalpol could enhance spatial performance and behavioral responses in aged rats with memory loss, and the mechanism may involve up-regulation of GAP-43 level of hippocampus in the brain. It also suggested that catalpol may be a useful natural drug for Alzheimer’s disease (AD) treatment by modulating hippo- campal neuroplasticity.展开更多
The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using...The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using electrocoagulation. The rats were intraperitoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week. Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.展开更多
Objective: Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol(CAT) and stachyose(STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on d...Objective: Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol(CAT) and stachyose(STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes.Methods: Streptozotocin(STZ) with the feeding of high-sugar-high-fat diet(HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medicaltreated groups: metformin(MET), STA, CAT, and three combinations of CAT:STA(1:1, 1:2, 2:1). Blood, liver,and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues.Results: It turned out that CAT, STA and their three combinations(1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c,TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine(Ucr). However, there were no such consistent observations on serum creatinine(Scr) and creatinine clearance rate(Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications,compared to the sole CAT or STA treatment.Conclusion: Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.展开更多
Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mi...Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice.The db/db mice were randomly divided into six groups(10/group) according to their blood glucose levels:db/db control,metformin(positive control),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal control.All the groups were administered orally for 8 weeks.The levels of fasting blood glucose(FBG),random blood glucose(RBG),glucose tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were analyzed.Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner.Catalpol treatment also remarkably reduce fasting blood glucose(FBG) and random blood glucose(RBG) in a dose-dependent manner.The RBG-lowering effect of catalpol was better than that of metformin.Furthermore,catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity.Catalpol treatment significantly decreased GSP level.The comparisons of gene expression in liver tissues among normal control mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to stress.Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(glucose-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In conclusion,catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.展开更多
OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 ...OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 mice were randomly divided into four groups(n=30):(a)normal salinecontrol,(b)EAE control,(c)EAE+prednisone acetate(PA,6 mg/kg),and(d)EAE+catalpol(40 mg/kg)and rhein(5 mg/kg).EAE was induced by injection of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally administered daily for 40 d.Disease progression and neurological function were assessed using a semi-quantitative scale of tail and limb paralysis.Brains and spinal cords were collected on Days 6,20,and 40 and assessed for histopathological changes by hematoxylin and eosin staining.Production of interleukin(IL)-2,IL-4,IL-10,and IL-17 A protein was measured by enzyme-linked immunosorbent assay.Expression of the T helper(Th)1-,Th2-,Th17-,and regulatory T cell(Treg)-specific transcription factors T-bet,GATA3,ROR-γt,and Foxp3,respectively,were analyzed by quantitative reverse-transcription polymerase chain reaction and western blot analysis.RESULTS:Combination treatment with catalpol and rhein significantly alleviated the clinical disability and neurological dysfunction of mice with EAE.Catalpol and rhein treatment also reduced the infiltration of pro-inflammatory T cells into pathological lesions;significantly increased the expression of the anti-inflammatory factors GATA3,Foxp3,IL-4,and IL-10;and significantly decreased the expression of the pro-inflammatory factors T-bet,ROR-γt,IL-2,and IL-17 A.CONCLUSION:Catalpol and rhein reduced the neurological disabilities of mice with EAE,at least in part by rebalancing the pro-and anti-inflammatory environment in the brains and spinal cords.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos:.82070356 and 81770337)the Key Project of Hunan Provincial Science and Technology Innovation,China(Grant No.:2020SK1013)the Hunan Provincial Natural Science Foundation of China(Grant No.:2021JJ30033).
文摘Catalpol,an iridoid glucoside isolated from Rehmannia glutinosa,has gained attention due to its potential use in treating cardio-cerebrovascular diseases(CVDs).This extensive review delves into recent studies on catalpol's protective properties in relation to various CVDs,such as atherosclerosis,myocardial ischemia,infarction,cardiac hypertrophy,and heart failure.The review also explores the compound's anti-oxidant,anti-inflammatory,and anti-apoptotic characteristics,emphasizing the role of vital signaling pathways,including PGC-1a/TERT,PI3K/Akt,AMPK,Nrf2/HO-1,estrogen receptor(ER),Nox4/NF-kB,and GRP78/PERK.The article discusses emerging findings on catalpol's ability to alleviate diabetic cardiovascular complications,thrombosis,and other cardiovascular-related conditions.Although clinical studies specifically addressing catalpol's impact on CVDs are scarce,the compound's established safety and well-tolerated nature suggest that it could be a valuable treatment alternative for CVD patients.Further investigation into catalpol and related iridoid derivatives may unveil new opportunities for devising natural and efficacious CVD therapies.
基金supported by grants from the National Natural Science Foundation of China(No.81374029,No.81073111,No.81874359)Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.18KJD360002)+1 种基金a Project Funded by Jiangsu Agri-animal Husbandry Vocational College(No.NSF2021CB04)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(No.JKLPSE201604).
文摘Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expression of galectin-3,VEGFR1,.VEGFR2,and HIF-1αin renal cortices was analyzed by Western blotting.The expression of galectin-3,F4/80(a macrophage biomarker),and CD34(an endothelium biomarker)in renal cortices was detected by IF staining,and collagen accumulation by Masson staining.Results:The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50μg/mL AGEs for 48 h than those in untreated cells.Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages.Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells.Catalpol could significantly decrease the levels of Ang-1,Ang-2 and Tie-2 released by AGEs-treated mGECs,which could be reversed by over-expression of galectin-3.Catalpol could significantly inhibit AGEs-induced expression of galectin-3,HIF-1α,VEGFR1,and VEGFR2 in mGECs.The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478.Moreover,catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages,which was weakened by PX-478.Additionally,catalpol significantly inhibited the expression of galectin-3,macrophage infiltration,collagen accumulation,and angiogenesis in the kidney of diabetic rats.Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol.Conclusion:Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3.It could prevent the progression of diabetes-induced renal damage.
文摘Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To analyze the pathological status and impact of catalpol on the rats, 3 weeks after intragastric gavage, the animals were verified for myocardial infarcts with electrocardiogram and measured for enzyme activity of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) and superoxide dismutase (SOD) in myocardium, and further analyzed using HE and TTC staining, as well as visual examination of infarct area. Flow cytometry study of endothelial progenitor cells (EPCs) indicated that the EPCs were mobilized during infarction. The roles of Notch1 signaling pathway in angiogenesis of the infracted animals were studied using immunohistochemistry analysis of RBPjκ and Western blot analysis of Notch1 and Jagged1. Our results obtained from the rats treated with catalpol, positive drug and control showed that catalpol could protect rats from infarction probably by mobilization of EPCs and activation of Notch1 signaling pathway.
文摘A rapid and sensitive liquid chromatography-tandem mass chromatography (LC-MS/MS) method has been developed and validated for simultaneous determination of catalpol and harpagide in rat plasma. The samples were extracted by one-step protein precipitation and separated on a SunFireTM C18 column (100 mm × 2.1 mm, 3.5 μm;Waters) using acetonitrile-10 mM ammonium formate as mobile phase at a flow rate 0.3 mL/min in gradient mode. The analytes were detected without interference in Multiple Reaction Monitoring (MRM) mode with negative electrospray ionization. Linear responses were obtained for catalpol ranging from 20 to 5000 ng/mL and harpagide ranging from 10 to 2500 ng/mL. Coefficients of correlation (r) for the calibration curves were more than 0.99 for both analytes. Intra- and inter-day accuracy and precision were within the acceptable limits of less than 15.0% at all concentrations. The quantitation method was successfully applied for simultaneous estimation of catalpol and harpagide after oral administration of Zeng Ye Decoction.
文摘Rehmannia glutinosa is a traditional Chinese medical herb and has a long history in cognitive deficits therapy. Its ther-apeutic efficacy has been confirmed by clinical studies. In this study, we attempted to investigate the effects of catalpol, an iridoid from Rehmannia glutinosa, on cognitive and behavioral function of aged rats with memory loss. 22 - 24 month Sprague-Dawley spontaneous rats of memory loss with aging were selected by step-down type passive avoidance test and randomly allocated to two groups: the aged rats with memory loss (control group) and the catal- pol-treated (5 mg/kg) group. We performed open-field and Y-maze test to evaluate special performance and behavior response before and after catalpol treatment for 5 and 10 days. Growth-associated protein (GAP-43) in hippocampus and frontal cortex was measured using immunohistochemistry and quantitative Western Blotting. The results showed that catalpol could significantly improve not only spatial learning and memory but also locomotor activity and ex-plora- tory behavior of aged rats with memory loss. GAP-43 protein in hippocampal CA3 region and dentate granule of catal- pol-treated rats was significantly enhanced than that of control group. Western blot analysis demonstrated a catal- pol-associated increase of GAP-43 in hippocampus of catalpol-treated rats and correlated with spatial memory, loco- motor activity and exploratory behavior. However, there was no difference in GAP-43 protein in frontal cortex between two groups. These results indicated that catalpol could enhance spatial performance and behavioral responses in aged rats with memory loss, and the mechanism may involve up-regulation of GAP-43 level of hippocampus in the brain. It also suggested that catalpol may be a useful natural drug for Alzheimer’s disease (AD) treatment by modulating hippo- campal neuroplasticity.
基金the National Natural Science Foundation of China, No. 81073084the Fundamental Research Funds for the Central Universities, No.XDJK2009C081+1 种基金the Natural Science Foundation Project of CQ CSTC, No.2010BB5127Science and Technology Innovative Capacity Construction Program of Chongqing(CSTC) No.2009CB1010
文摘The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using electrocoagulation. The rats were intraperitoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week. Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.
基金financially supported by the National Standardization of Ttraditional Chinese Medicine Project(ZYBZH-C-JL-24-03)
文摘Objective: Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol(CAT) and stachyose(STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes.Methods: Streptozotocin(STZ) with the feeding of high-sugar-high-fat diet(HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medicaltreated groups: metformin(MET), STA, CAT, and three combinations of CAT:STA(1:1, 1:2, 2:1). Blood, liver,and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues.Results: It turned out that CAT, STA and their three combinations(1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c,TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine(Ucr). However, there were no such consistent observations on serum creatinine(Scr) and creatinine clearance rate(Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications,compared to the sole CAT or STA treatment.Conclusion: Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.
文摘Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice.The db/db mice were randomly divided into six groups(10/group) according to their blood glucose levels:db/db control,metformin(positive control),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal control.All the groups were administered orally for 8 weeks.The levels of fasting blood glucose(FBG),random blood glucose(RBG),glucose tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were analyzed.Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner.Catalpol treatment also remarkably reduce fasting blood glucose(FBG) and random blood glucose(RBG) in a dose-dependent manner.The RBG-lowering effect of catalpol was better than that of metformin.Furthermore,catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity.Catalpol treatment significantly decreased GSP level.The comparisons of gene expression in liver tissues among normal control mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to stress.Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(glucose-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In conclusion,catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
基金Supported by the National Natural Science Foundation(No.81973599)Beijing Natural Science Foundation-Key Project of Science and Technology Plan of Beijing Education Commission(KZ/KM/SZ/SM201910025035)The Fund for Beijing Science&Technology Development of Traditional Chinese Medicine(No.QN2018-30)
文摘OBJECTIVE:To examine the effects of catalpol and rhein on pro-and anti-inflammatory responses in C57 BL/6 mice with experimental autoimmune encephalomyelitis(EAE),a model of multiple sclerosis.METHODS:Female C57 BL/6 mice were randomly divided into four groups(n=30):(a)normal salinecontrol,(b)EAE control,(c)EAE+prednisone acetate(PA,6 mg/kg),and(d)EAE+catalpol(40 mg/kg)and rhein(5 mg/kg).EAE was induced by injection of myelin oligodendrocyte glycoprotein 35-55 plus pertussis toxin.Treatments were orally administered daily for 40 d.Disease progression and neurological function were assessed using a semi-quantitative scale of tail and limb paralysis.Brains and spinal cords were collected on Days 6,20,and 40 and assessed for histopathological changes by hematoxylin and eosin staining.Production of interleukin(IL)-2,IL-4,IL-10,and IL-17 A protein was measured by enzyme-linked immunosorbent assay.Expression of the T helper(Th)1-,Th2-,Th17-,and regulatory T cell(Treg)-specific transcription factors T-bet,GATA3,ROR-γt,and Foxp3,respectively,were analyzed by quantitative reverse-transcription polymerase chain reaction and western blot analysis.RESULTS:Combination treatment with catalpol and rhein significantly alleviated the clinical disability and neurological dysfunction of mice with EAE.Catalpol and rhein treatment also reduced the infiltration of pro-inflammatory T cells into pathological lesions;significantly increased the expression of the anti-inflammatory factors GATA3,Foxp3,IL-4,and IL-10;and significantly decreased the expression of the pro-inflammatory factors T-bet,ROR-γt,IL-2,and IL-17 A.CONCLUSION:Catalpol and rhein reduced the neurological disabilities of mice with EAE,at least in part by rebalancing the pro-and anti-inflammatory environment in the brains and spinal cords.
