Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy....Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.展开更多
Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studie...Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studies suggest that GPs have beneficial effects on T2DM,but the underlying mechanisms remain unclear.This study aims to investigate whether GPs exert therapeutic effects by influencing RNA N^(6)-methyladenosine(m6A)methylation modification,thereby regulating the downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:Expression levels and methylation changes of METTL3,METTL14,and FTO in T2DM were analyzed using public databases,and related pathways were explored via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The main active components of GPs were screened from pharmacological databases,followed by compound-target network construction,enrichment analyses,and prediction of potential targets and pathways.A T2DM model was induced in Sprague-Dawley rats using a high-fat/high-sugar diet combined with low-dose streptozotocin.Rats were randomly divided into 4 groups:GPs-treated group(GPG,400 mg/kg),positive control group(PCG,metformin 100 mg/kg),normal saline control group(CONTROL),and T2DM model group(MODEL).Fasting blood glucose(FBG),oral glucose tolerance test(OGTT)-area under the glucose curve from 0 to 120 min(AUC0-120),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),serum inflammatory factors,and tissue pathology of pancreas and liver hematoxylin and eosin(HE)staining were assessed.Real-time fluorescence quantitative PCR and Western blotting were used to detect RNA and protein expression levels of METTL3,METTL14,FTO,PI3K,and AKT in pancreatic tissues.Molecular docking was applied to evaluate interactions between GPs’main components and METTL3,METTL14,and FTO to infer potential binding modes.Results:Bioinformatic analyses showed downregulation of METTL3/14 and upregulation of FTO in T2DM samples(all P<0.05),with enrichment in pathways related to insulin signaling,PI3K/AKT activation,oxidative stress response,and hormone secretion.Network pharmacology indicated that GPs components may act on targets involved in RNA modification and insulin-related pathways.In diabetic rats,GPs significantly reduced FBG,improved glucose tolerance,decreased HOMA-IR,and decreased the serum tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 levels compared with MODEL(all P<0.05).Pancreatic pathology showed alleviated islet injury and improved cell morphology.GPs treatment upregulated METTL3/14 mRNA and protein levels,and down-regulated FTO mRNA/protein levels in pancreatic tissue(all P<0.05).PI3K and AKT expression levels increased(both P<0.05),consistent with activation of downstream signals related to glucose uptake and improved insulin sensitivity.Metformin also improved metabolic indices but exhibited a different regulatory pattern on m6A-related enzymes compared with GPs.Molecular docking revealed stable interactions between core GPs saponin structures and methyltransferase-like 3(METTL3),methyltransferase-like 14(METTL14),or obesityassociated protein(FTO),suggesting that GPs may directly or indirectly modulate m6A regulatory proteins.Conclusion:GPs can effectively improve glucose-metabolism disorders,reduce inflammation,and protect pancreatic tissue in T2DM rats.The mechanisms may be associated with METTL3/14 up-regulation and FTO down-regulation,leading to enhanced m6A methylation and subsequent activation of the PI3K/AKT signaling pathway.These findings provide strong evidence for GPs regulation of epigenetic m6A RNA modification and insulin-related downstream pathways,and suggest that natural compounds targeting m6A regulation may be explored in the future for metabolic disease interventions.展开更多
AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated...AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.展开更多
Neural stem cell has a potential to differentiate into neurons, astrocytes and oligodendrocytes. It provides an in vitro model to screen herbal medicines on the cellular differentiation and development level. In this ...Neural stem cell has a potential to differentiate into neurons, astrocytes and oligodendrocytes. It provides an in vitro model to screen herbal medicines on the cellular differentiation and development level. In this work, active component from gypenosides and soyasaponins was prepared to investigate their effects on the differentiation of neural stem cells.. Both gypenosides and soyasaponins promote the differentiation of neural stem cells. This method provides speed and practicality for screening effective herbal medicine. It is well suited for studying the mechanism of cell differentiation and development.展开更多
AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density ...AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density gypenosides monotherapy,methylprednisolone monotherapy,combination of gypenosides and methylprednisolone group.The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein（MOG） 35-55 peptide to induce EAON.Mice in the gypenosides groups were administered injections daily with three concentrations（15 mg/kg,30 mg/kg,45 mg/kg） of gypenosides respectively.Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone（20 mg/kg） or methylprednisolone（20 mg/kg） ＋ gypenosides（30 mg/kg）,respectively.After MOG immunization,visual evoked potential（VEP）,optical coherence tomography（OCT）,and histopathologic examination were performed at 14,20,30,and 40 d post-inoculation（p.i.）.All results were expressed as mean±SEM.The data were evaluated by oneway ANOVA followed by Tukey or Games-Howell test.RESULTS：Compared with the control group,p2 latency was prolonged in the model group（P=0.041）.Combination treatment can alleviated the change in VEP at 20 d p.i.（P=0.012）.Average peripapillary retinal nerve fiber layer（RNFL） thickness was reduced in the model group（P= 0.000,30d;P=0.000,40d） and gypenosides treatment remarkably diminished the degree of RNFL degenerationat 30 d and 40 d p.i（P=0.000,30d;P=0.000,40d）.The pathomorphological results showed a decrease in demyelination（P=0.020） and inflammatory reactions in the combination group compared with the model group（20d p.i.）.Gypenosides treatment also alleviated the degree of axonal loss（40d p.i.）（P=0.003）.CONCLUSION：Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.When combined with gypenosides,methylprednisolone reduces demyelination in the acute stage of EAON.展开更多
Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported w...Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported with hypoglycemic activity.However,the underlying mechanisms are unclear.The effects of two Gps(Gp-Ⅰand Gp-Ⅱ)on type 2 diabetic mellitus(T2DM)mice,induced by high-fat and high-sugar diet and streptozotocin,were evaluated to explore the mechanism of their hypoglycemic actions.Gps reduced fasting blood glucose and serum lipids,as well as significantly improved T2DM mice glucose tolerance and insulin resistance(IR).After Gps treatment,the severity of liver injury was reduced and liver glycogen content increased.In addition,Gps promoted the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK),and downregulated the key proteins phosphoenolpyruvate carboxy kinase and glucose-6 phosphatase,in the AMPK signaling pathway.Thus,our study suggests that Gps mediate hepatic gluconeogenesis and improve IR via activating AMPK signaling pathway in T2DM mice.展开更多
The significant inhibition action of Gypenosides (GP) to many kinds or tumor strain wesreported before. The erfects of GP on the ultrastructures, without any findiys in present litrature,of S-180 sarcoma in mouse were...The significant inhibition action of Gypenosides (GP) to many kinds or tumor strain wesreported before. The erfects of GP on the ultrastructures, without any findiys in present litrature,of S-180 sarcoma in mouse were studied through electron microscope in this article. The results indicated that the ultrastructures of.S-180 sarcoma cells were destructed obviously by the administratiouof GP to the tumor-bearing mouse with a Pattern or dose-depeudant, especially to the cellular nuclear. We saw both apoptosis and necrosis in morphologic alterations in tumor cells, suck as a reductionin cellular volume. an increase in cytoplasm, uucleoplasm electron density and condensation of nuclear chromatiu either to periphery or the nuclear membrane or inclumps within the cell, lots of inthe cytoplasm and apoptotic body in some turner cells or some cytoplast breaking into small frag- ments etc.展开更多
Objective： To study the effects of gypenoside （Gyp） on the activity of microsomalNa^＋, K^＋-ATPase in rat＇s heart and brain in vitro. Methods： The microsomal Na^＋, K^＋-ATPase was prepared from rat＇s heart a...Objective： To study the effects of gypenoside （Gyp） on the activity of microsomalNa^＋, K^＋-ATPase in rat＇s heart and brain in vitro. Methods： The microsomal Na^＋, K^＋-ATPase was prepared from rat＇s heart and brain by differential centrifugation. The activity of microsomal Na^＋, K^＋-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na^＋, K^＋-ATPase of rats. Results： Gyp reversibly inhibited the brain and heart＇s microsomal Na^＋, K^＋-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC50 of Gyp for the heart and brain were 58.79± 8.05 mg/L and 52.07± 6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na^＋, or K^＋-concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na^＋, the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K^＋. Cenclusien： Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain＇s microsomal Na^＋, K^＋-ATPase activities in rats.展开更多
Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are...Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are the key enzymes for gypenoside biosynthesis, The objective of this study was to elucidate the rela- tionship between light quality and biosynthesis key enzyme involving the regulation of gypenoside accu- mulation. Methods： The content of total gypenosides was measured by colorimetric method and the expression of SS and SE gene was determined by quantitative Real-time PCR in the seedlings of G. pentaphyllum which were grown with different light quality. Results： Light quality showed remarkable impacts on the accumulation of total gypenosides. The highest content of total gypenosides in the plant under red light condition was determined, followed by blue light and white light, while the lowest content was recorded under dark condition, qRT-PCR analysis proved that the expression levels of SS and SE genes were also affected by light quality. The high-level gene expressions of SS and SE were found in the plant under red light condition, followed by blue light, with the least content in darkness. The statistical analysis revealed that the total gypenosides were significantly different in different light treatment and the content of total gypenosides was positively related to the expression of SS and SE genes. Conclusions： Light quality regulates gypenoside accumulation via altering the expression of SS and SE in G. pentaphyllum.展开更多
Background:Diabetic nephropathy(DN),as a complication of diabetes,is featured with hypertension,hyper-glycemia,proteinuria and edema.Gypenoside(GP),the main active compound of Gynostemma pentaphyllum,is proved to be e...Background:Diabetic nephropathy(DN),as a complication of diabetes,is featured with hypertension,hyper-glycemia,proteinuria and edema.Gypenoside(GP),the main active compound of Gynostemma pentaphyllum,is proved to be effective for DN.In our previous research,we found that GP could protect the glomerulus and re-duce proteinuria by up-regulating the expression of nestin and down-regulating TGFB1.However,the panoramic mechanism of GP against DN is still unclear.Objective:This research is designed to reveal the mechanism of GP on DN through network pharmacology and in vivo and in vitro experimental verification.Methods:In this study,active compounds and targets of Gynostemma pentaphyllum were collected from TCMSP.DisGeNET was used for obtaining the targets of DN.The protein-protein interaction network was acquired from the STRING database and analyzed by the MCODE plugin.GO and KEGG enrichment analysis were constructed to explore further information.In vivo and in vitro experiments were also carried out to evaluate the reliability of this study.Western blotting and RT-PCR were used to detect mTOR,4E-BP1,p70s6k protein expression and Mtor mRNA expression in DN rats,respectively.AKT1,TP53,ESR1 and PTEN protein expression in MPC-5 cells were detected by Western blotting.Results:Twenty-four compounds and 217 targets were selected from Gynostemma pentaphyllum,of which 36 targets overlapped with DN were taken for the potential targets.The results showed that Quercetin,Rhamnazin,Isofucosterol and 3′-methyleriodictyol corresponded to more targets,AKT1,TP53,MYC,ESR1,PTEN were more active.36 potential targets were mainly involved in autoimmunity,inflammatory response,metabolism and autophagy.In vivo and in vitro experiments showed that GP might protect the podocytes of DN rats by decreasing the protein expression of mTOR,4EBP1,p70s6k,as well as the mRNA expression of Mtor,and it had the function in regulating the potential targets through decreasing the protein expression of AKT1,TP53 and ESR1 and increasing the expression of PTEN.Conclusion:This research demonstrates that various compounds of Gynostemma pentaphyllum may intervenes in DN through targets of multiple signaling pathways,which involves a large number of biological processes.It can provide novel insights for further research of the mechanism of GP in the treatment of DN.展开更多
<正> Seven polystyrene-type adsorbents (Ⅰ—Ⅶ) were synthesized by the modification of styrene-divinylbenzene copolymer respectively with hydroxymethyl, aminomethyl, methoxymethyl, phenoxymethyl, (4-hydroxy phe...<正> Seven polystyrene-type adsorbents (Ⅰ—Ⅶ) were synthesized by the modification of styrene-divinylbenzene copolymer respectively with hydroxymethyl, aminomethyl, methoxymethyl, phenoxymethyl, (4-hydroxy phenoxy)methyl, (4-acetylphenoxy)methyl, and acetyl groups. Their structures were characterized with chemical methods and physical techniques. The adsorption capacities of the adsorbents to stevioside and gypenosides were determined via batch test in which the HPLC method was used for the analysis of Saponin concentration of solution. The results showed that all the adsorbents could adsorb these saponins to a certain extent, but Ⅵ and Ⅶ had large capacities owing to their moderate polarities.展开更多
Opioid abuse can suppress the lymphatic system function,and produce severe immunosuppression that poses a significant risk of opportunistic infections such as methicillinresistant Staphylococcus aureus(MRSA)pneumonia....Opioid abuse can suppress the lymphatic system function,and produce severe immunosuppression that poses a significant risk of opportunistic infections such as methicillinresistant Staphylococcus aureus(MRSA)pneumonia.^(1,2)Gypenosides(Gps)are the most important immunomodulator components in the Chinese herbal medicine Gynostemma pentaphyllum.展开更多
Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal...Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease(PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53 T α-synuclein transgenic mouse models of PD(A53 T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53 T mice for 20 weeks.α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53 T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase(ERK1/2), Bcl-2-associated death promoter(Bad) at Ser112, and c-Jun N-terminal kinase(JNK1/2) due to α-synuclein overexpression. In the A53 T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53 T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University(approval No. CBNUA-956-16-01) on September 21, 2016.展开更多
Gypenosides,structurally analogous to ginsenosides and derived from a sustainable source,are recognized as the principal active compounds found in Gynostemma pentaphyllum,a Chinese medicinal plant used in the treatmen...Gypenosides,structurally analogous to ginsenosides and derived from a sustainable source,are recognized as the principal active compounds found in Gynostemma pentaphyllum,a Chinese medicinal plant used in the treatment of the metabolic syndrome.By bioactive tracking isolation of the plants collected from different regions across China,we obtained four new gypenosides(1−4),together with nine known gypenosides(5−13),from the methanol extract of the plant.The structures of new gypenosides were elucidated by one-dimensional(1D)and two-dimensional(2D)nuclear magnetic resonance(NMR)spectra,complemented by chemical degradation experiments.Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cαactivity assays,we established a definitive structure-activity relationship for these dammarane-type triterpenoids,affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix(ECM)deposition within hepatic stellate cells.Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration.These results underscore the potential of dammarane-type triterpenoids as prospective antifibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.展开更多
基金supported by grants from the Health Commission of Zigong High-Level Talent Development Project(WJW-GCCRC007).
文摘Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.
基金supported by College Students’Innovative Entrepreneurial Training Plan Program of Guizhou Province,China(S202210660105,S202310660055)。
文摘Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studies suggest that GPs have beneficial effects on T2DM,but the underlying mechanisms remain unclear.This study aims to investigate whether GPs exert therapeutic effects by influencing RNA N^(6)-methyladenosine(m6A)methylation modification,thereby regulating the downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:Expression levels and methylation changes of METTL3,METTL14,and FTO in T2DM were analyzed using public databases,and related pathways were explored via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The main active components of GPs were screened from pharmacological databases,followed by compound-target network construction,enrichment analyses,and prediction of potential targets and pathways.A T2DM model was induced in Sprague-Dawley rats using a high-fat/high-sugar diet combined with low-dose streptozotocin.Rats were randomly divided into 4 groups:GPs-treated group(GPG,400 mg/kg),positive control group(PCG,metformin 100 mg/kg),normal saline control group(CONTROL),and T2DM model group(MODEL).Fasting blood glucose(FBG),oral glucose tolerance test(OGTT)-area under the glucose curve from 0 to 120 min(AUC0-120),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),serum inflammatory factors,and tissue pathology of pancreas and liver hematoxylin and eosin(HE)staining were assessed.Real-time fluorescence quantitative PCR and Western blotting were used to detect RNA and protein expression levels of METTL3,METTL14,FTO,PI3K,and AKT in pancreatic tissues.Molecular docking was applied to evaluate interactions between GPs’main components and METTL3,METTL14,and FTO to infer potential binding modes.Results:Bioinformatic analyses showed downregulation of METTL3/14 and upregulation of FTO in T2DM samples(all P<0.05),with enrichment in pathways related to insulin signaling,PI3K/AKT activation,oxidative stress response,and hormone secretion.Network pharmacology indicated that GPs components may act on targets involved in RNA modification and insulin-related pathways.In diabetic rats,GPs significantly reduced FBG,improved glucose tolerance,decreased HOMA-IR,and decreased the serum tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 levels compared with MODEL(all P<0.05).Pancreatic pathology showed alleviated islet injury and improved cell morphology.GPs treatment upregulated METTL3/14 mRNA and protein levels,and down-regulated FTO mRNA/protein levels in pancreatic tissue(all P<0.05).PI3K and AKT expression levels increased(both P<0.05),consistent with activation of downstream signals related to glucose uptake and improved insulin sensitivity.Metformin also improved metabolic indices but exhibited a different regulatory pattern on m6A-related enzymes compared with GPs.Molecular docking revealed stable interactions between core GPs saponin structures and methyltransferase-like 3(METTL3),methyltransferase-like 14(METTL14),or obesityassociated protein(FTO),suggesting that GPs may directly or indirectly modulate m6A regulatory proteins.Conclusion:GPs can effectively improve glucose-metabolism disorders,reduce inflammation,and protect pancreatic tissue in T2DM rats.The mechanisms may be associated with METTL3/14 up-regulation and FTO down-regulation,leading to enhanced m6A methylation and subsequent activation of the PI3K/AKT signaling pathway.These findings provide strong evidence for GPs regulation of epigenetic m6A RNA modification and insulin-related downstream pathways,and suggest that natural compounds targeting m6A regulation may be explored in the future for metabolic disease interventions.
基金Supported by Bureau of Public Health of Hubei Province
文摘AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.
基金Project supported by the National Basic Research Program of China （Grant No.2006CB500702）, the National Natural Science Foundation of China （Grant No.30570590）, and the Science Foundation of Shanghai Municipal Commission of Science and Technology （Grant No.03JC14030）
文摘Neural stem cell has a potential to differentiate into neurons, astrocytes and oligodendrocytes. It provides an in vitro model to screen herbal medicines on the cellular differentiation and development level. In this work, active component from gypenosides and soyasaponins was prepared to investigate their effects on the differentiation of neural stem cells.. Both gypenosides and soyasaponins promote the differentiation of neural stem cells. This method provides speed and practicality for screening effective herbal medicine. It is well suited for studying the mechanism of cell differentiation and development.
基金Supported by the National Natural Science Foundation of China(No.81260149No.81360152No.81560162)
文摘AIM：To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis（EAON）.METHODS：Mice were randomly divided into seven groups：control group,model group,three different density gypenosides monotherapy,methylprednisolone monotherapy,combination of gypenosides and methylprednisolone group.The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein（MOG） 35-55 peptide to induce EAON.Mice in the gypenosides groups were administered injections daily with three concentrations（15 mg/kg,30 mg/kg,45 mg/kg） of gypenosides respectively.Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone（20 mg/kg） or methylprednisolone（20 mg/kg） ＋ gypenosides（30 mg/kg）,respectively.After MOG immunization,visual evoked potential（VEP）,optical coherence tomography（OCT）,and histopathologic examination were performed at 14,20,30,and 40 d post-inoculation（p.i.）.All results were expressed as mean±SEM.The data were evaluated by oneway ANOVA followed by Tukey or Games-Howell test.RESULTS：Compared with the control group,p2 latency was prolonged in the model group（P=0.041）.Combination treatment can alleviated the change in VEP at 20 d p.i.（P=0.012）.Average peripapillary retinal nerve fiber layer（RNFL） thickness was reduced in the model group（P= 0.000,30d;P=0.000,40d） and gypenosides treatment remarkably diminished the degree of RNFL degenerationat 30 d and 40 d p.i（P=0.000,30d;P=0.000,40d）.The pathomorphological results showed a decrease in demyelination（P=0.020） and inflammatory reactions in the combination group compared with the model group（20d p.i.）.Gypenosides treatment also alleviated the degree of axonal loss（40d p.i.）（P=0.003）.CONCLUSION：Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON.When combined with gypenosides,methylprednisolone reduces demyelination in the acute stage of EAON.
基金supported by the National Natural Science Foundation of China(81602983)。
文摘Gynostemma pentaphyllum,also called"Southern Ginseng"in China,is a traditional Asian folk medicinal plant.Gypenosides(Gps)are the biologically active constituents of G.pentaphyllum,which have been reported with hypoglycemic activity.However,the underlying mechanisms are unclear.The effects of two Gps(Gp-Ⅰand Gp-Ⅱ)on type 2 diabetic mellitus(T2DM)mice,induced by high-fat and high-sugar diet and streptozotocin,were evaluated to explore the mechanism of their hypoglycemic actions.Gps reduced fasting blood glucose and serum lipids,as well as significantly improved T2DM mice glucose tolerance and insulin resistance(IR).After Gps treatment,the severity of liver injury was reduced and liver glycogen content increased.In addition,Gps promoted the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK),and downregulated the key proteins phosphoenolpyruvate carboxy kinase and glucose-6 phosphatase,in the AMPK signaling pathway.Thus,our study suggests that Gps mediate hepatic gluconeogenesis and improve IR via activating AMPK signaling pathway in T2DM mice.
文摘The significant inhibition action of Gypenosides (GP) to many kinds or tumor strain wesreported before. The erfects of GP on the ultrastructures, without any findiys in present litrature,of S-180 sarcoma in mouse were studied through electron microscope in this article. The results indicated that the ultrastructures of.S-180 sarcoma cells were destructed obviously by the administratiouof GP to the tumor-bearing mouse with a Pattern or dose-depeudant, especially to the cellular nuclear. We saw both apoptosis and necrosis in morphologic alterations in tumor cells, suck as a reductionin cellular volume. an increase in cytoplasm, uucleoplasm electron density and condensation of nuclear chromatiu either to periphery or the nuclear membrane or inclumps within the cell, lots of inthe cytoplasm and apoptotic body in some turner cells or some cytoplast breaking into small frag- ments etc.
基金Supported by Guangdong Provincial Natural Science Foundation (No010742)
文摘Objective： To study the effects of gypenoside （Gyp） on the activity of microsomalNa^＋, K^＋-ATPase in rat＇s heart and brain in vitro. Methods： The microsomal Na^＋, K^＋-ATPase was prepared from rat＇s heart and brain by differential centrifugation. The activity of microsomal Na^＋, K^＋-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na^＋, K^＋-ATPase of rats. Results： Gyp reversibly inhibited the brain and heart＇s microsomal Na^＋, K^＋-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC50 of Gyp for the heart and brain were 58.79± 8.05 mg/L and 52.07± 6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na^＋, or K^＋-concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na^＋, the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K^＋. Cenclusien： Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain＇s microsomal Na^＋, K^＋-ATPase activities in rats.
基金financially supported by the National Natural Science Foundation of China (31760044,31260039)Key Course of Hunan Province (Ecology),Jishou University (2015005)
文摘Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are the key enzymes for gypenoside biosynthesis, The objective of this study was to elucidate the rela- tionship between light quality and biosynthesis key enzyme involving the regulation of gypenoside accu- mulation. Methods： The content of total gypenosides was measured by colorimetric method and the expression of SS and SE gene was determined by quantitative Real-time PCR in the seedlings of G. pentaphyllum which were grown with different light quality. Results： Light quality showed remarkable impacts on the accumulation of total gypenosides. The highest content of total gypenosides in the plant under red light condition was determined, followed by blue light and white light, while the lowest content was recorded under dark condition, qRT-PCR analysis proved that the expression levels of SS and SE genes were also affected by light quality. The high-level gene expressions of SS and SE were found in the plant under red light condition, followed by blue light, with the least content in darkness. The statistical analysis revealed that the total gypenosides were significantly different in different light treatment and the content of total gypenosides was positively related to the expression of SS and SE genes. Conclusions： Light quality regulates gypenoside accumulation via altering the expression of SS and SE in G. pentaphyllum.
文摘Background:Diabetic nephropathy(DN),as a complication of diabetes,is featured with hypertension,hyper-glycemia,proteinuria and edema.Gypenoside(GP),the main active compound of Gynostemma pentaphyllum,is proved to be effective for DN.In our previous research,we found that GP could protect the glomerulus and re-duce proteinuria by up-regulating the expression of nestin and down-regulating TGFB1.However,the panoramic mechanism of GP against DN is still unclear.Objective:This research is designed to reveal the mechanism of GP on DN through network pharmacology and in vivo and in vitro experimental verification.Methods:In this study,active compounds and targets of Gynostemma pentaphyllum were collected from TCMSP.DisGeNET was used for obtaining the targets of DN.The protein-protein interaction network was acquired from the STRING database and analyzed by the MCODE plugin.GO and KEGG enrichment analysis were constructed to explore further information.In vivo and in vitro experiments were also carried out to evaluate the reliability of this study.Western blotting and RT-PCR were used to detect mTOR,4E-BP1,p70s6k protein expression and Mtor mRNA expression in DN rats,respectively.AKT1,TP53,ESR1 and PTEN protein expression in MPC-5 cells were detected by Western blotting.Results:Twenty-four compounds and 217 targets were selected from Gynostemma pentaphyllum,of which 36 targets overlapped with DN were taken for the potential targets.The results showed that Quercetin,Rhamnazin,Isofucosterol and 3′-methyleriodictyol corresponded to more targets,AKT1,TP53,MYC,ESR1,PTEN were more active.36 potential targets were mainly involved in autoimmunity,inflammatory response,metabolism and autophagy.In vivo and in vitro experiments showed that GP might protect the podocytes of DN rats by decreasing the protein expression of mTOR,4EBP1,p70s6k,as well as the mRNA expression of Mtor,and it had the function in regulating the potential targets through decreasing the protein expression of AKT1,TP53 and ESR1 and increasing the expression of PTEN.Conclusion:This research demonstrates that various compounds of Gynostemma pentaphyllum may intervenes in DN through targets of multiple signaling pathways,which involves a large number of biological processes.It can provide novel insights for further research of the mechanism of GP in the treatment of DN.
文摘<正> Seven polystyrene-type adsorbents (Ⅰ—Ⅶ) were synthesized by the modification of styrene-divinylbenzene copolymer respectively with hydroxymethyl, aminomethyl, methoxymethyl, phenoxymethyl, (4-hydroxy phenoxy)methyl, (4-acetylphenoxy)methyl, and acetyl groups. Their structures were characterized with chemical methods and physical techniques. The adsorption capacities of the adsorbents to stevioside and gypenosides were determined via batch test in which the HPLC method was used for the analysis of Saponin concentration of solution. The results showed that all the adsorbents could adsorb these saponins to a certain extent, but Ⅵ and Ⅶ had large capacities owing to their moderate polarities.
基金supported by the National Natural Science Foundation of China(No.82174498,82174141)the National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Support Project,the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(China)(No.2020YLXK013)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(No.KYCX21_1796).
文摘Opioid abuse can suppress the lymphatic system function,and produce severe immunosuppression that poses a significant risk of opportunistic infections such as methicillinresistant Staphylococcus aureus(MRSA)pneumonia.^(1,2)Gypenosides(Gps)are the most important immunomodulator components in the Chinese herbal medicine Gynostemma pentaphyllum.
基金supported by the National Research Foundation of Korea,grant No.2016R1D1A3B03930722(to MKL),Republic of Korea
文摘Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease(PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53 T α-synuclein transgenic mouse models of PD(A53 T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53 T mice for 20 weeks.α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53 T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase(ERK1/2), Bcl-2-associated death promoter(Bad) at Ser112, and c-Jun N-terminal kinase(JNK1/2) due to α-synuclein overexpression. In the A53 T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53 T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University(approval No. CBNUA-956-16-01) on September 21, 2016.
基金supported by the National Key R&D Program(No.2018YFC1707900)the National Natural Science Foundation of China(No.22177052)+1 种基金Jiangsu Provincial Science and Technology Development Project of Chinese Medicine(No.ZD202002)Jiangsu postgraduate scientific research innovation program(No.KYCX21_1721).
文摘Gypenosides,structurally analogous to ginsenosides and derived from a sustainable source,are recognized as the principal active compounds found in Gynostemma pentaphyllum,a Chinese medicinal plant used in the treatment of the metabolic syndrome.By bioactive tracking isolation of the plants collected from different regions across China,we obtained four new gypenosides(1−4),together with nine known gypenosides(5−13),from the methanol extract of the plant.The structures of new gypenosides were elucidated by one-dimensional(1D)and two-dimensional(2D)nuclear magnetic resonance(NMR)spectra,complemented by chemical degradation experiments.Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cαactivity assays,we established a definitive structure-activity relationship for these dammarane-type triterpenoids,affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix(ECM)deposition within hepatic stellate cells.Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration.These results underscore the potential of dammarane-type triterpenoids as prospective antifibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.
