Aim To screen for α-glucosidase inhibitor from Glyeyrrhiza uralensis Fisch.. Methods Glycyrrhizic acid, glycyrrhetinic acid, flavonoids of glycyrrhiza, alkaloids of glycyrrhiza, and glycyrrhiza polysaccharides were i...Aim To screen for α-glucosidase inhibitor from Glyeyrrhiza uralensis Fisch.. Methods Glycyrrhizic acid, glycyrrhetinic acid, flavonoids of glycyrrhiza, alkaloids of glycyrrhiza, and glycyrrhiza polysaccharides were isolated from the root of Glycyrrhiza uralensis Fisch. respectively. Three compounds were isolated from the flavonoids of glycyrrhiza as guided by the α-glucosidase inhibitory test in vitro. Moreover, the characteristics of inhibitory kinetics of glycyrol and glycyrrhetinic acid were investi- gated. Results The flavonoids of glycyrrhiza and glycyrrhetinic acid had the strongest α-glucosidase inhibitory activity. Glycyrol,β-sitosterol and liquifitin were isolated and identified. Glycyrol was a fast- binding, reversible, noncompetitive α-glucosidase inhibitor, showing IC50 at 0.26 μg·mL^-1 Glycyrrhetinic acid was a fast-binding, irreversible α-glucosidase inhibitor, showing IC50 at 102.4 μg·mL^-1. Conclusion Glycyrol is an effective α-glucosidase inhibitor.展开更多
The mulberry juice contains high concentrations of α-glucosidase inhibitors that affect glycometabolism and cause diarrhea in animals, thereby affecting the de-velopment and application of mulberry (Morus alba L.) ...The mulberry juice contains high concentrations of α-glucosidase inhibitors that affect glycometabolism and cause diarrhea in animals, thereby affecting the de-velopment and application of mulberry (Morus alba L.) as feedstuff resources. ln this study, the effects of mulberry leaf extract with and without removal of mulberry juice on starch metabolism were analyzed and compared. The results showed that mul-berry leaf extract with removal of mulberry juice exhibited significantly lower inhibi-tion rate on starch metabolism compared with mulberry leaf extract without removal of mulberry juice. ln animal feeding trials, piglet feedstuff was added with 10% mul-berry leaf powder; compared with mulberry leaf powder without removal of mulberry juice, experimental piglets fed with mulberry leaf powder with removal of mulberry juice exhibited significantly improved weight gain and significantyl reduced diarrhea rate.展开更多
A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylu...A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.展开更多
Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu ...Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)were partitioned with petroleum ether,ethyl acetate,n-butanol,and water.The assay forα-glucosidase inhibitory activity revealed strongα-glucosidase inhibitory activity in the ethyl acetate fraction,and the bioactive compounds present in this fraction were identified by the HPLCESI-QTOF-MS/MS method.Results A total of 29 compounds were determined,among the identified bioactive components;these included 12 phenylethanoid glycosides(compounds 5,6,17,20-22,24),7 flavonoids(compounds 10,19,23,25-28),5 phenolic acids(compounds 2-4,7,9),and 5 other compounds.Compounds 2-4,7,9-10,12-13,15,19,and 26,with a potentialα-glucosidase inhibitory activity,have been reported previously.Conclusions Our results show that the methodology used in this study is feasible,credible,and rapid in identifying known compounds and also for characterizing new natural glucosidase inhibitory candidates from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹).展开更多
The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with ...The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with quadrupole time of flight tandem mass spectrometry (LC-Q/TOF-MS/MS) determination to screen a-glucosidase inhibitors in complex Scutellaria baicalensis Georgi (SBG) extract. By adding a second filter to the screening process, the level of non-specific binding of Compounds 1, 3, 10 and 11 was significantly decreased, and the level of non-specific binding of Compounds 5 and 15 also was reduced. As a result, five flavonoids identified as baicalein, baicalein, wogonin, chrysin, and oroxylin A, were rapidly found to interact with α-glucosidase and possess potent anti-a-glueosidase aetivity in vitro. Specific binding of ligands to a-glucosidase was demonstrated though the proposed method and the ligands could be ranked in order of affinity for α-glucosidase, which were corresponded to the order of inhibitory activity in vitro. In conclusion, our results indicated that the developed method is a rapid and effective screening method for rat intestinal α-glucosidase inhibitors from complex herbal medicines such as SBG.展开更多
OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthaml~ on lipopolysaccharide in- duced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase act...OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthaml~ on lipopolysaccharide in- duced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase activity. The total flavonoid content of the extracts was also determined. METHODS: Cytotoxicity of the extracts to RAW 264.7 cells was evaluated by the ATPliteTM method. Inhibitory effects of the extracts on NO production were evaluated by Griess assay. Curcumin was used as a positive control. Screening of extracts for po- tential a-glucosidase inhibitors was done by a fiuo- rometric assay. The assay was based on the hydroly- sis of 4-methylumbelliferyl-a-D-glucopyranoside toform the fluorescent product, 4-methylumbellifer- one. Acarbose was used as a positive control. The total t3avonoid content was tested using kaempfer- ol as the standard. RESULTS: There were significant inhibitory effects on NO production when the extracts were 25-100 μg/ mL (P〈0.05) and curcumin was 2-4 μg/mL (P〈 0.001). The extracts showed an inhibitory effect on a-glucosidase activity at the concentrations of 15.6-125 μg/mL with a half maximal (50%)inhibito- ry concentration (ICs0) of (32.8± 5.7) μg/mL, com- pared with the ICs0 of acarbose at (1.8±0.4) μg/mL. There was a significant difference between the two IC50 values (P〈0.001). The total content of flavo- noids per gram of dried herb was 1.14 mg. CONCLUSION: Honghua (Flos Carthami) showed in- hibitory effects on NO production in activated RAW 264.7 macrophage cells and an inhibitory effect on yeast a-glucosidase. There might be a relationship between these pharmacological effects and its fla- vonoid content.展开更多
Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism ca...Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.展开更多
Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is s...Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.展开更多
文摘Aim To screen for α-glucosidase inhibitor from Glyeyrrhiza uralensis Fisch.. Methods Glycyrrhizic acid, glycyrrhetinic acid, flavonoids of glycyrrhiza, alkaloids of glycyrrhiza, and glycyrrhiza polysaccharides were isolated from the root of Glycyrrhiza uralensis Fisch. respectively. Three compounds were isolated from the flavonoids of glycyrrhiza as guided by the α-glucosidase inhibitory test in vitro. Moreover, the characteristics of inhibitory kinetics of glycyrol and glycyrrhetinic acid were investi- gated. Results The flavonoids of glycyrrhiza and glycyrrhetinic acid had the strongest α-glucosidase inhibitory activity. Glycyrol,β-sitosterol and liquifitin were isolated and identified. Glycyrol was a fast- binding, reversible, noncompetitive α-glucosidase inhibitor, showing IC50 at 0.26 μg·mL^-1 Glycyrrhetinic acid was a fast-binding, irreversible α-glucosidase inhibitor, showing IC50 at 102.4 μg·mL^-1. Conclusion Glycyrol is an effective α-glucosidase inhibitor.
文摘The mulberry juice contains high concentrations of α-glucosidase inhibitors that affect glycometabolism and cause diarrhea in animals, thereby affecting the de-velopment and application of mulberry (Morus alba L.) as feedstuff resources. ln this study, the effects of mulberry leaf extract with and without removal of mulberry juice on starch metabolism were analyzed and compared. The results showed that mul-berry leaf extract with removal of mulberry juice exhibited significantly lower inhibi-tion rate on starch metabolism compared with mulberry leaf extract without removal of mulberry juice. ln animal feeding trials, piglet feedstuff was added with 10% mul-berry leaf powder; compared with mulberry leaf powder without removal of mulberry juice, experimental piglets fed with mulberry leaf powder with removal of mulberry juice exhibited significantly improved weight gain and significantyl reduced diarrhea rate.
文摘A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.
基金the funding support from the China National Natural Science Foundation Funding Project(NO.81503452)Natural Science Foundation of Hunan Province,China(No.14JJ4066)
文摘Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)were partitioned with petroleum ether,ethyl acetate,n-butanol,and water.The assay forα-glucosidase inhibitory activity revealed strongα-glucosidase inhibitory activity in the ethyl acetate fraction,and the bioactive compounds present in this fraction were identified by the HPLCESI-QTOF-MS/MS method.Results A total of 29 compounds were determined,among the identified bioactive components;these included 12 phenylethanoid glycosides(compounds 5,6,17,20-22,24),7 flavonoids(compounds 10,19,23,25-28),5 phenolic acids(compounds 2-4,7,9),and 5 other compounds.Compounds 2-4,7,9-10,12-13,15,19,and 26,with a potentialα-glucosidase inhibitory activity,have been reported previously.Conclusions Our results show that the methodology used in this study is feasible,credible,and rapid in identifying known compounds and also for characterizing new natural glucosidase inhibitory candidates from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹).
基金supported by the National Key Scientific and Technological Special Projects(2012ZX09103-101-007)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT-IRT1193)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with quadrupole time of flight tandem mass spectrometry (LC-Q/TOF-MS/MS) determination to screen a-glucosidase inhibitors in complex Scutellaria baicalensis Georgi (SBG) extract. By adding a second filter to the screening process, the level of non-specific binding of Compounds 1, 3, 10 and 11 was significantly decreased, and the level of non-specific binding of Compounds 5 and 15 also was reduced. As a result, five flavonoids identified as baicalein, baicalein, wogonin, chrysin, and oroxylin A, were rapidly found to interact with α-glucosidase and possess potent anti-a-glueosidase aetivity in vitro. Specific binding of ligands to a-glucosidase was demonstrated though the proposed method and the ligands could be ranked in order of affinity for α-glucosidase, which were corresponded to the order of inhibitory activity in vitro. In conclusion, our results indicated that the developed method is a rapid and effective screening method for rat intestinal α-glucosidase inhibitors from complex herbal medicines such as SBG.
基金Supported by Shanxi Scholarship Council of China(No.2010-102)
文摘OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthaml~ on lipopolysaccharide in- duced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase activity. The total flavonoid content of the extracts was also determined. METHODS: Cytotoxicity of the extracts to RAW 264.7 cells was evaluated by the ATPliteTM method. Inhibitory effects of the extracts on NO production were evaluated by Griess assay. Curcumin was used as a positive control. Screening of extracts for po- tential a-glucosidase inhibitors was done by a fiuo- rometric assay. The assay was based on the hydroly- sis of 4-methylumbelliferyl-a-D-glucopyranoside toform the fluorescent product, 4-methylumbellifer- one. Acarbose was used as a positive control. The total t3avonoid content was tested using kaempfer- ol as the standard. RESULTS: There were significant inhibitory effects on NO production when the extracts were 25-100 μg/ mL (P〈0.05) and curcumin was 2-4 μg/mL (P〈 0.001). The extracts showed an inhibitory effect on a-glucosidase activity at the concentrations of 15.6-125 μg/mL with a half maximal (50%)inhibito- ry concentration (ICs0) of (32.8± 5.7) μg/mL, com- pared with the ICs0 of acarbose at (1.8±0.4) μg/mL. There was a significant difference between the two IC50 values (P〈0.001). The total content of flavo- noids per gram of dried herb was 1.14 mg. CONCLUSION: Honghua (Flos Carthami) showed in- hibitory effects on NO production in activated RAW 264.7 macrophage cells and an inhibitory effect on yeast a-glucosidase. There might be a relationship between these pharmacological effects and its fla- vonoid content.
基金Beijing Excellent Talents Training Assistance(Grant No.2017000082595G244)the Health and Research Bureau of Tongzhou District(Grant No.TWKY-2016-QN-01-58)。
文摘Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.
基金financially supported by the National Natural Science Foundation of China (21807073, 31771036 and 51703132)the Basic Research Program of Shenzhen (JCYJ20170818144745087, JCYJ20180507182413022 and JCYJ20170412111100742)+2 种基金Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)China Postdoctoral Science Foundation (2018M630987 and 2019T120752)
文摘Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.