Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and...Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.展开更多
Diabetes mellitus remains a major global health issue,and great attention is directed at natural therapeutics.This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating ...Diabetes mellitus remains a major global health issue,and great attention is directed at natural therapeutics.This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating their inhibitory effects onα-glucosidase andα-amylase,two key enzymes involved in starch digestion.Six scientific databases(PubMed,Virtual Health Library,EMBASE,SCOPUS,Web of Science,and WHO Global Index Medicus)were searched until August 21,2022,for in vitro studies reporting IC50 values of purified flavonoids onα-amylase andα-glucosidase,along with corresponding data for acarbose as a positive control.A total of 339 eligible articles were analyzed,resulting in the retrieval of 1643 flavonoid structures.These structures were rigorously standardized and curated,yielding 974 unique compounds,among which 177 flavonoids exhibited inhibition of bothα-glucosidase andα-amylase are presented.Quality assessment utilizing a modified CONSORT checklist and structure-activity relationship(SAR)analysis were performed,revealing crucial features for the simultaneous inhibition of flavonoids against both enzymes.Moreover,the review also addressed several limitations in the current research landscape and proposed potential solutions.The curated datasets are available online at https://github.com/MedChemUMP/FDIGA.展开更多
The property of major cellulases from the guts of Anoplophora glabripennis larvae have been characterized. The optimal temperatures of both β 1,4 glucosidase (β glucosidase) and endo β 1,4 endoglucanase (...The property of major cellulases from the guts of Anoplophora glabripennis larvae have been characterized. The optimal temperatures of both β 1,4 glucosidase (β glucosidase) and endo β 1,4 endoglucanase (endoglucanase, Cx) are 40℃. The β glucosidase was optimally active at pH 4\^8, while the optimal activity of the endoglucanase occurred at pH 4 4 5 6 The endoglucanase was active with a wide range of pH and temperature, the levels of activity from 25℃ to 50℃ were more than 80%, and the activity remained 60% between pH 3 2 and pH 7 2. The endoglucanase exhibited higher thermal stability than β glucosidase. Both enzymes lose their activities by heat treatment at 60℃. Two isozymes of endoglucanase were detected in sodium carboxymethylcellulose polyacrymide gels (CMC gel) by chemical colorization, and purified by elution from the gel slices. The molecular weights of the two isozymes were estimated as 26kD and 39kD respectively. Moreover molecular characteristics of the two isozymes are currently underway.展开更多
Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and p...Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg～(-l).d～(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg～(-l)-d～(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)展开更多
Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, conden...Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, condensing, precipitating, exchanging with resins and rinsing. In vitro glucosidase inhibitory activities were examined by photometric bioassay derived from rats, yeast and almond of all the Chinese medicine extracts. Diabetic ICR mice models were established by intraperitoneal injection of STZ (200 mg/kg). To investigate the in vivo effect of lowering blood glucose, the mouse blood glucose level was assayed at 30 min after being given 2.5 g/kg starch and acarbose or varied concentrations of different constituents of some Chinese medicines by stomach tube. Results: The constituents of Sangye, Sangzhi, Sangbaipi, Dihuang and Yuzhu showed potent inhibitory activities against glucosidase. Furthermore, the first kind of constituents was proved to be beneficial in reducing blood glucose by in vivo glucose tolerance experiments. Conclusion: The constituents of Chinese medicines with reducing blood glucose effect have been discovered, thus providing a clue to novel drugs.展开更多
BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still e...BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.展开更多
To produce β-glucosidase by consecutive batch fermentation, a marine Aspergillus niger was immobilized on a natural carrier, towel gourd vegetable sponges. The immobilized mycelia were 0.15 g/g carrier with the immob...To produce β-glucosidase by consecutive batch fermentation, a marine Aspergillus niger was immobilized on a natural carrier, towel gourd vegetable sponges. The immobilized mycelia were 0.15 g/g carrier with the immobilized biomass percentage of over 95%. The immobilized mycelia possessed the long durability（22.5 days）. The maximum production occurred 1.5 day earlier by the immobilized mycelia than by the free mycelia. β-Glucosidase production of five consecutive batches was over 110 U/m L. At high salinity,the activity and stability of β-glucosidase from the marine A. niger increased remarkable. Immobilizing the marine A. niger on the novel natural carrier achieved the efficient production of β-glucosidase.展开更多
Objective: To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana(P. americana)(traditionally used in Cameroon against diabetes) on β-glucosidase, β-glucosidase, maltase...Objective: To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana(P. americana)(traditionally used in Cameroon against diabetes) on β-glucosidase, β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities, enzymes involved in starch digestion or diabetic complications. Methods: The methanol extracts from Piper umbellatum and P. americana were prepared by maceration. To assess relative efficacy of these extracts, the determination of concentrations that were needed to inhibit 50% of enzyme activity was done, whereas, gas chromatography-mass spectrum was used to identify components from extracts that may be responsible for the activities. Results:The tested extracts strongly inhibited β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities with IC50 ranging from(1.07 ± 0.03) to(31.77 ± 1.17) μg/mL.Among the tested extracts, P. americana was the most active against sensitive enzymes(IC50 of1.07 ± 0.03 to 15.63 ± 1.23). But, none of the extracts showed interesting inhibitory effect against β-glucosidase as their percentage inhibitions were less than 16%. From gas chromatographymass spectrum analysis, 10 and 8 compounds were identified in Piper umbellatum and P.americana extracts respectively, using NIST library 2014. Conclusions: Results of this study provide the scientific credential for a prospective usage of these plants to treat diabetes.展开更多
Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens,thereby exacerbating infections.However,there are few effective therapeutic strategies to prevent and intervene in enter...Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens,thereby exacerbating infections.However,there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections.Here,we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium(S.Tm).Subsequently,we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo.Enterococci,which are tolerant of iron-deficient environments,produceβ-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones,inhibiting S.Tm growth and ameliorating the severity of S.Tm-induced symptoms by inducing iron limitation.Overall,we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections,providing an alternative intervention to combat polymicrobial infections.展开更多
The H7N9 influenza virus poses a significant threat to human health,and the mechanism by which it infects humans remains incompletely understood.Our investigation has unveiled significant insights into the role of glu...The H7N9 influenza virus poses a significant threat to human health,and the mechanism by which it infects humans remains incompletely understood.Our investigation has unveiled significant insights into the role of glucosidase alpha,neutral C(GANC)gene in human H7N9 infections.Through whole genome sequencing(WGS),we identified five low-frequency functional and heterozygous variants of GANC strongly associated with human H7N9 infections compared to healthy controls.Furthermore,we observed a reduction in mRNA and protein expression of GANC following H7N9 virus infection in vitro and in vivo.Subsequent experiments involving GANC demonstrated the promotion of H7N9 virus replication in a stable strain with GANC overexpression.Conversely,GANC knockdown exhibited the ability to restrict influenza A virus(IAV)replication,including H7N9,H9N2,and H1N1,both in vitro and in vivo.This inhibition was mediated by GANC’s ability to promote the degradation of H7N9 hemagglutinin(HA).Moreover,we discovered that GANC knockdown facilitated the degradation of HA in a proteasome-dependent manner.The inhibition caused by GANC knockdown was mediated by promoting direct binding of HA with the proteasome 26S subunit,non-ATPase,1(PSMD1)and PSMD2.All five variants in the GANC gene reduced their ability to promote H7N9 virus replication,and also diminished the levels of GANC-induced HA protein expression.Our findings revealed a novel mechanism by which GANC inhibits the proteasome-dependent degradation of HA to promote H7N9 virus replication.These results suggest that GANC may play an important role in IAV replication.展开更多
Aims Nitrogen(N)addition could affect the rate of forest litter and soil organic matter decomposition by regulating extracellular enzyme activity(EEa).The impact of N addition on EEa may differ across different age st...Aims Nitrogen(N)addition could affect the rate of forest litter and soil organic matter decomposition by regulating extracellular enzyme activity(EEa).The impact of N addition on EEa may differ across different age stands with different organic matter quality.We were interested in whether the impact of N addition on EEa in litter and mineral soil during the growing season was dependent on stand age of a larch plantation in North China.Methods We added three levels of N(0,20 and 50 kg N ha^(−1) year^(−1))in three age stands(11,20 and 45 years old)of Larix principis-rupprech-tii plantation in North China.We measured potential activities of β-1,4-glucosidase(b),cellobiohydrolase(Cb),β-1,4-N-acetyl-glucosaminidase(Nag)and phenol oxidase(Po)in litter(organic horizon)and mineral soil(0-10 cm)during the second growing sea-son after N amendment.We also measured C and N concentrations,microbial biomass C and N,and KCl-extractable ammonium and nitrate in both litter and mineral soil.Important Findings We observed unimodal patterns of EEa during the growing season in all three stands,consistent with the seasonal variations of soil temperature.stand age had a strong effect on EEa in both litter and mineral soil,and this effect differed between litter and mineral soil as well as between different enzymes.N addition did not significantly affect the activities of b or Cb but significantly suppressed the activity of Nag in litter.We also found stand age-specific responses of Po activity to N addition in both litter and mineral soil.N addition suppressed Po activity of the high C:N ratio litters in 20-and 45-year-old stands but had no significant effect on Po activity of the low C:N ratio litter in 11-year-old stand.moreover,N addition inhibited Po activity of the high C:N ratio soil in 20-year-old stand but had no significant impact on Po activity of the low C:N ratio soils in 11-and 45-year-old stands.overall,stand age had a greater effect on EEa in litter and mineral soil compared to 2 years of N addition.moreover,the effect of N addition on Po activity is stand age dependent,which may affect the long-term soil carbon storage in this forest.展开更多
EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to...EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to the endoplasmic reticulum quality control （ERQC） machinery for the correct folding and proper assembly in order to reach its final destination. Genetic studies have demonstrated that ERD2b, a counterpart of the yeast or mammalian HDEL receptor ERD2 for retaining proteins in the endoplasmic reticulum （ER） lumen, is required for EFR function in plants （Li et al., 2009）. In this study, we characterized the Arabidopsis glucosidase Ⅱ β--subunit via the H DEL motif against the non-redundant protein database. Data mining also revealed that the glucosidase Ⅱ β--subunit gene has a highly similar expression pattern to ERD2b and the other known ERQC components involved in EFR biogenesis. Importantly, the T-DNA insertion lines of the glucosidase Ⅱ β-subunit gene showed that EFR-controlled responses were substantially reduced or completely blocked in these mutants. The responses include seedling growth inhibition, induction of marker genes, MAP kinase activation, and callose deposition, trigged by peptide elf18, a full mimic of E F-Tu. Taken together, ourdata indicate a requirement of the glucosidase Ⅱ β-subunitfor EFR function.展开更多
This study aimed to explore the effect of enzymatic hydrolysis conditions(enzyme types and hydrolysis time)of date seed protein hydrolysates(DSPH)on in-vitro inhibition of molecular markers related with diabetic and h...This study aimed to explore the effect of enzymatic hydrolysis conditions(enzyme types and hydrolysis time)of date seed protein hydrolysates(DSPH)on in-vitro inhibition of molecular markers related with diabetic and hypercholesteremia.The DSPH was prepared using alcalase,bromelain,papain,and protease at different hydrolysis time(HT)(2,4 and 6 h).Higher degree of hydrolysis was observed for papain at 6 h HT.The results showed that alcalase and bromelain generated DSPHs at 6 h HT greatly improved the pancreatic lipase inhibition activity while the cholesterol esterase inhibition activity was greatly enhanced with alcalase and protease at 6 h HT and papain generated DSPHs at 4 h HT.Bromelain generated DSPH displayed the highest inhibition of dipeptidyl peptidase-IV(DPP-IV)and amylase at 6 and 2 h hydrolysis time,respectively.All the enzymes at 2 h HT except that of papain showed the highestα-glucosidase inhibitory activities.These results revealed that the DSPH displayed enhanced inhibitory activities towards molecular markers related with diabetes and obesity and thus have promising potential to be used as health-promoting ingredients in the fabrication of functional foods.展开更多
In this study, jabuticaba peel purified phenolic extracts were studied regarding their potential inhibitory effects on digestive enzymes linked to diabetes mellitus (DM) and obesity, inhibitory activities towards glyc...In this study, jabuticaba peel purified phenolic extracts were studied regarding their potential inhibitory effects on digestive enzymes linked to diabetes mellitus (DM) and obesity, inhibitory activities towards glycation of bovine serum albumin (BSA), and antioxidant activities. The impact of in vitro gastrointestinal digestion (GID) on the stability of anthocyanins and bioactivities was also evaluated. The analyzed extracts exhibited significant inhibitory activities of α-glucosidase (IC_(50): 0.47–5.20 mg/mL), α-amylase (IC_(50): 0.45–1.88 mg/mL), and lipase (IC_(50): 13.52–111.51 mg/mL). The extracts also inhibited the glycation of BSA (IC50: 0.23–7.07 mg/mL) and showed relevant antioxidant activities. The correlation analysis indicated anthocyanins as one of the main contributing compounds to the bioactivities studied. Cyanidin-3-glucoside was the major anthocyanin identified in the extracts by HPLC analysis. After GID, there was a decrease in the total anthocyanin content (72.77% ± 1.67%) and, consequently, a reduction in the inhibitory activities of carbohydrate digestive enzymes and BSA glycation. This research provided scientific data about the functional properties of jabuticaba peel extracts, which may be a source of dietary compounds with hypoglycaemic, antiglycation, and antioxidant effects.展开更多
Objective To establish a simple and rapid method for the determination of 1,3-dideoxygalactonojirimycin in Bombycis Faeces,a potent glucosidase inihibitor,by HPLC.Methods A RP-HPLC method with fluorescence detection h...Objective To establish a simple and rapid method for the determination of 1,3-dideoxygalactonojirimycin in Bombycis Faeces,a potent glucosidase inihibitor,by HPLC.Methods A RP-HPLC method with fluorescence detection has been developed.Results The HPLC method developed in this research has a good reliability including accuracy and precision.The detection limit was less than 72 ng.Conclusion This method is sufficiently sensitive for determining 1,3-dideoxygalactonojirimycin in Bombycis Faeces and other related products.展开更多
A simple and efficient HPLC method was developed for quality analysis of flavonoids from Impatiens balsamina L.(IBL)flowers,which were collected from Xingjiang,Anhui,Henan,and Hubei provinces in China.The flavonoids s...A simple and efficient HPLC method was developed for quality analysis of flavonoids from Impatiens balsamina L.(IBL)flowers,which were collected from Xingjiang,Anhui,Henan,and Hubei provinces in China.The flavonoids substances in IBL were determined by HPLC through methyl alcohol ultrasonic extraction.A mixture of展开更多
基金support by Universidad Nacional de Rosario(80020180300114UR and 80020180100128UR)CONICET(PIP No 11220200102423)FONCYT(PICT2019-02232 and PICT2021-1034)for the development of this work.
文摘Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.
基金funded by the University of Medicine and Pharmacy at Ho Chi Minh City under grant number 162/2019/HĐ-ĐHYD for Thanh-Dao Tran.
文摘Diabetes mellitus remains a major global health issue,and great attention is directed at natural therapeutics.This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating their inhibitory effects onα-glucosidase andα-amylase,two key enzymes involved in starch digestion.Six scientific databases(PubMed,Virtual Health Library,EMBASE,SCOPUS,Web of Science,and WHO Global Index Medicus)were searched until August 21,2022,for in vitro studies reporting IC50 values of purified flavonoids onα-amylase andα-glucosidase,along with corresponding data for acarbose as a positive control.A total of 339 eligible articles were analyzed,resulting in the retrieval of 1643 flavonoid structures.These structures were rigorously standardized and curated,yielding 974 unique compounds,among which 177 flavonoids exhibited inhibition of bothα-glucosidase andα-amylase are presented.Quality assessment utilizing a modified CONSORT checklist and structure-activity relationship(SAR)analysis were performed,revealing crucial features for the simultaneous inhibition of flavonoids against both enzymes.Moreover,the review also addressed several limitations in the current research landscape and proposed potential solutions.The curated datasets are available online at https://github.com/MedChemUMP/FDIGA.
文摘The property of major cellulases from the guts of Anoplophora glabripennis larvae have been characterized. The optimal temperatures of both β 1,4 glucosidase (β glucosidase) and endo β 1,4 endoglucanase (endoglucanase, Cx) are 40℃. The β glucosidase was optimally active at pH 4\^8, while the optimal activity of the endoglucanase occurred at pH 4 4 5 6 The endoglucanase was active with a wide range of pH and temperature, the levels of activity from 25℃ to 50℃ were more than 80%, and the activity remained 60% between pH 3 2 and pH 7 2. The endoglucanase exhibited higher thermal stability than β glucosidase. Both enzymes lose their activities by heat treatment at 60℃. Two isozymes of endoglucanase were detected in sodium carboxymethylcellulose polyacrymide gels (CMC gel) by chemical colorization, and purified by elution from the gel slices. The molecular weights of the two isozymes were estimated as 26kD and 39kD respectively. Moreover molecular characteristics of the two isozymes are currently underway.
文摘Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg～(-l).d～(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg～(-l)-d～(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)
文摘Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, condensing, precipitating, exchanging with resins and rinsing. In vitro glucosidase inhibitory activities were examined by photometric bioassay derived from rats, yeast and almond of all the Chinese medicine extracts. Diabetic ICR mice models were established by intraperitoneal injection of STZ (200 mg/kg). To investigate the in vivo effect of lowering blood glucose, the mouse blood glucose level was assayed at 30 min after being given 2.5 g/kg starch and acarbose or varied concentrations of different constituents of some Chinese medicines by stomach tube. Results: The constituents of Sangye, Sangzhi, Sangbaipi, Dihuang and Yuzhu showed potent inhibitory activities against glucosidase. Furthermore, the first kind of constituents was proved to be beneficial in reducing blood glucose by in vivo glucose tolerance experiments. Conclusion: The constituents of Chinese medicines with reducing blood glucose effect have been discovered, thus providing a clue to novel drugs.
基金Supported by National Science and Technology Major Project,No.2014ZX09101046-004(to Chen L)National Natural Science Foundation of China,Nos.81873543 and 81570468(to Wang JS).
文摘BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.
文摘To produce β-glucosidase by consecutive batch fermentation, a marine Aspergillus niger was immobilized on a natural carrier, towel gourd vegetable sponges. The immobilized mycelia were 0.15 g/g carrier with the immobilized biomass percentage of over 95%. The immobilized mycelia possessed the long durability（22.5 days）. The maximum production occurred 1.5 day earlier by the immobilized mycelia than by the free mycelia. β-Glucosidase production of five consecutive batches was over 110 U/m L. At high salinity,the activity and stability of β-glucosidase from the marine A. niger increased remarkable. Immobilizing the marine A. niger on the novel natural carrier achieved the efficient production of β-glucosidase.
基金supported by the 2016 CIIT-TWAS Postdoctoral Fellowship(grant number:3240293205)
文摘Objective: To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana(P. americana)(traditionally used in Cameroon against diabetes) on β-glucosidase, β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities, enzymes involved in starch digestion or diabetic complications. Methods: The methanol extracts from Piper umbellatum and P. americana were prepared by maceration. To assess relative efficacy of these extracts, the determination of concentrations that were needed to inhibit 50% of enzyme activity was done, whereas, gas chromatography-mass spectrum was used to identify components from extracts that may be responsible for the activities. Results:The tested extracts strongly inhibited β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities with IC50 ranging from(1.07 ± 0.03) to(31.77 ± 1.17) μg/mL.Among the tested extracts, P. americana was the most active against sensitive enzymes(IC50 of1.07 ± 0.03 to 15.63 ± 1.23). But, none of the extracts showed interesting inhibitory effect against β-glucosidase as their percentage inhibitions were less than 16%. From gas chromatographymass spectrum analysis, 10 and 8 compounds were identified in Piper umbellatum and P.americana extracts respectively, using NIST library 2014. Conclusions: Results of this study provide the scientific credential for a prospective usage of these plants to treat diabetes.
基金supported by the National Key Research and Development Program of China(2022YFD1801600)National Natural Science Foundation of China(32230106).
文摘Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens,thereby exacerbating infections.However,there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections.Here,we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium(S.Tm).Subsequently,we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo.Enterococci,which are tolerant of iron-deficient environments,produceβ-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones,inhibiting S.Tm growth and ameliorating the severity of S.Tm-induced symptoms by inducing iron limitation.Overall,we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections,providing an alternative intervention to combat polymicrobial infections.
基金supported by the National Key Research and Development Program of China(grant number:2021YFC2300100,2021YFC2300102,and 2021YFC2300103)the Shenzhen science and Technology program(grant number:JCYJ20200109142438111,KQTD20200820145822023,KCXFZ20211020172545006,and ZDSYS20230626091203007)+6 种基金the High-Level Project of Medicine in Nanshan,Shenzhenthe Sanming Project of Medicine in Shenzhen(grant number:SZSM202103008)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant number:2022-RC310-02)the Guangdong Basic and Applied Basic Research Foundation(grant number:2023A1515011767)the Guangdong Provincial Science and Technology Program(grant number:2019B030301009)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(grant number:24qnpy175)the Shenzhen Medical Research Fund(grant number:B2403004).
文摘The H7N9 influenza virus poses a significant threat to human health,and the mechanism by which it infects humans remains incompletely understood.Our investigation has unveiled significant insights into the role of glucosidase alpha,neutral C(GANC)gene in human H7N9 infections.Through whole genome sequencing(WGS),we identified five low-frequency functional and heterozygous variants of GANC strongly associated with human H7N9 infections compared to healthy controls.Furthermore,we observed a reduction in mRNA and protein expression of GANC following H7N9 virus infection in vitro and in vivo.Subsequent experiments involving GANC demonstrated the promotion of H7N9 virus replication in a stable strain with GANC overexpression.Conversely,GANC knockdown exhibited the ability to restrict influenza A virus(IAV)replication,including H7N9,H9N2,and H1N1,both in vitro and in vivo.This inhibition was mediated by GANC’s ability to promote the degradation of H7N9 hemagglutinin(HA).Moreover,we discovered that GANC knockdown facilitated the degradation of HA in a proteasome-dependent manner.The inhibition caused by GANC knockdown was mediated by promoting direct binding of HA with the proteasome 26S subunit,non-ATPase,1(PSMD1)and PSMD2.All five variants in the GANC gene reduced their ability to promote H7N9 virus replication,and also diminished the levels of GANC-induced HA protein expression.Our findings revealed a novel mechanism by which GANC inhibits the proteasome-dependent degradation of HA to promote H7N9 virus replication.These results suggest that GANC may play an important role in IAV replication.
基金National Natural Science Foundation of China(#41171202,41125004).
文摘Aims Nitrogen(N)addition could affect the rate of forest litter and soil organic matter decomposition by regulating extracellular enzyme activity(EEa).The impact of N addition on EEa may differ across different age stands with different organic matter quality.We were interested in whether the impact of N addition on EEa in litter and mineral soil during the growing season was dependent on stand age of a larch plantation in North China.Methods We added three levels of N(0,20 and 50 kg N ha^(−1) year^(−1))in three age stands(11,20 and 45 years old)of Larix principis-rupprech-tii plantation in North China.We measured potential activities of β-1,4-glucosidase(b),cellobiohydrolase(Cb),β-1,4-N-acetyl-glucosaminidase(Nag)and phenol oxidase(Po)in litter(organic horizon)and mineral soil(0-10 cm)during the second growing sea-son after N amendment.We also measured C and N concentrations,microbial biomass C and N,and KCl-extractable ammonium and nitrate in both litter and mineral soil.Important Findings We observed unimodal patterns of EEa during the growing season in all three stands,consistent with the seasonal variations of soil temperature.stand age had a strong effect on EEa in both litter and mineral soil,and this effect differed between litter and mineral soil as well as between different enzymes.N addition did not significantly affect the activities of b or Cb but significantly suppressed the activity of Nag in litter.We also found stand age-specific responses of Po activity to N addition in both litter and mineral soil.N addition suppressed Po activity of the high C:N ratio litters in 20-and 45-year-old stands but had no significant effect on Po activity of the low C:N ratio litter in 11-year-old stand.moreover,N addition inhibited Po activity of the high C:N ratio soil in 20-year-old stand but had no significant impact on Po activity of the low C:N ratio soils in 11-and 45-year-old stands.overall,stand age had a greater effect on EEa in litter and mineral soil compared to 2 years of N addition.moreover,the effect of N addition on Po activity is stand age dependent,which may affect the long-term soil carbon storage in this forest.
文摘EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to the endoplasmic reticulum quality control （ERQC） machinery for the correct folding and proper assembly in order to reach its final destination. Genetic studies have demonstrated that ERD2b, a counterpart of the yeast or mammalian HDEL receptor ERD2 for retaining proteins in the endoplasmic reticulum （ER） lumen, is required for EFR function in plants （Li et al., 2009）. In this study, we characterized the Arabidopsis glucosidase Ⅱ β--subunit via the H DEL motif against the non-redundant protein database. Data mining also revealed that the glucosidase Ⅱ β--subunit gene has a highly similar expression pattern to ERD2b and the other known ERQC components involved in EFR biogenesis. Importantly, the T-DNA insertion lines of the glucosidase Ⅱ β-subunit gene showed that EFR-controlled responses were substantially reduced or completely blocked in these mutants. The responses include seedling growth inhibition, induction of marker genes, MAP kinase activation, and callose deposition, trigged by peptide elf18, a full mimic of E F-Tu. Taken together, ourdata indicate a requirement of the glucosidase Ⅱ β-subunitfor EFR function.
基金United Arab Emirates University for funding this research through a research grant(Fund code-31R214 and 12R055)awarded to the principal investigator Sajid Maqsood.
文摘This study aimed to explore the effect of enzymatic hydrolysis conditions(enzyme types and hydrolysis time)of date seed protein hydrolysates(DSPH)on in-vitro inhibition of molecular markers related with diabetic and hypercholesteremia.The DSPH was prepared using alcalase,bromelain,papain,and protease at different hydrolysis time(HT)(2,4 and 6 h).Higher degree of hydrolysis was observed for papain at 6 h HT.The results showed that alcalase and bromelain generated DSPHs at 6 h HT greatly improved the pancreatic lipase inhibition activity while the cholesterol esterase inhibition activity was greatly enhanced with alcalase and protease at 6 h HT and papain generated DSPHs at 4 h HT.Bromelain generated DSPH displayed the highest inhibition of dipeptidyl peptidase-IV(DPP-IV)and amylase at 6 and 2 h hydrolysis time,respectively.All the enzymes at 2 h HT except that of papain showed the highestα-glucosidase inhibitory activities.These results revealed that the DSPH displayed enhanced inhibitory activities towards molecular markers related with diabetes and obesity and thus have promising potential to be used as health-promoting ingredients in the fabrication of functional foods.
基金We gratefully acknowledge Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Finance Code 001)-Brazil,Conselho Nacional de Desenvolvimento Científico e Tecnol´ogico(CNPq)-Brazil and Fundaç˜ao de Amparo`a Pesquisa do Estado de Minas Gerais(FAPEMIG)-Brazil for financial supportBioclin,for the donation of kits for analyses.PCS,LLO,BRCLJ,and SAF are supported by Research Fellowships from CNPq.
文摘In this study, jabuticaba peel purified phenolic extracts were studied regarding their potential inhibitory effects on digestive enzymes linked to diabetes mellitus (DM) and obesity, inhibitory activities towards glycation of bovine serum albumin (BSA), and antioxidant activities. The impact of in vitro gastrointestinal digestion (GID) on the stability of anthocyanins and bioactivities was also evaluated. The analyzed extracts exhibited significant inhibitory activities of α-glucosidase (IC_(50): 0.47–5.20 mg/mL), α-amylase (IC_(50): 0.45–1.88 mg/mL), and lipase (IC_(50): 13.52–111.51 mg/mL). The extracts also inhibited the glycation of BSA (IC50: 0.23–7.07 mg/mL) and showed relevant antioxidant activities. The correlation analysis indicated anthocyanins as one of the main contributing compounds to the bioactivities studied. Cyanidin-3-glucoside was the major anthocyanin identified in the extracts by HPLC analysis. After GID, there was a decrease in the total anthocyanin content (72.77% ± 1.67%) and, consequently, a reduction in the inhibitory activities of carbohydrate digestive enzymes and BSA glycation. This research provided scientific data about the functional properties of jabuticaba peel extracts, which may be a source of dietary compounds with hypoglycaemic, antiglycation, and antioxidant effects.
文摘Objective To establish a simple and rapid method for the determination of 1,3-dideoxygalactonojirimycin in Bombycis Faeces,a potent glucosidase inihibitor,by HPLC.Methods A RP-HPLC method with fluorescence detection has been developed.Results The HPLC method developed in this research has a good reliability including accuracy and precision.The detection limit was less than 72 ng.Conclusion This method is sufficiently sensitive for determining 1,3-dideoxygalactonojirimycin in Bombycis Faeces and other related products.
文摘A simple and efficient HPLC method was developed for quality analysis of flavonoids from Impatiens balsamina L.(IBL)flowers,which were collected from Xingjiang,Anhui,Henan,and Hubei provinces in China.The flavonoids substances in IBL were determined by HPLC through methyl alcohol ultrasonic extraction.A mixture of
