Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly...Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5e35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 mM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.展开更多
The unusual fused b-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase.In this study,a structure-based lead optimiza...The unusual fused b-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase.In this study,a structure-based lead optimization of vibralactone resulted in three series of 104 analogs,among which compound C1 exhibited the most potent inhibition of pancreatic lipase,with an IC50 value of 14 nM.This activity is more than 3000-fold higher than that of vibralactone.The effect of compound C1 on obesity was investigated using high-fat diet(HFD)-induced C57BL/6 J obese mice.Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity,primarily through the improvement of metabolic parameters,such as triglyceride levels.展开更多
Background:Obesity is a lifestyle disease that involves an excessive amount of body fat deposition.Cetilistat is being used to treat obesity.It mainly inhibits human pancreatic lipase,an enzyme that helps to break dow...Background:Obesity is a lifestyle disease that involves an excessive amount of body fat deposition.Cetilistat is being used to treat obesity.It mainly inhibits human pancreatic lipase,an enzyme that helps to break down the oil into small molecules of glycerol and fatty acids in the intestine.Therefore,pancreatic lipase inhibition is a potential therapeutic approach for obesity control and treatment.Methods:cetilistat’s binding mode and interaction with human pancreatic lipase are not well understood.In this study,the human pancreatic lipase inhibitory activity of cetilistat was investigated by employing molecular docking and molecular dynamics simulation.Human pancreatic lipase has two states:closed state and open state which is controlled by a surface loop i.e.“lid region”which normally undergoes conformational changes only upon addition of lipids and then breakdown into glycerol and fatty acid.In the present study,open state conformation of the human pancreatic lipase structure was used(2OXE.pdb).The docking study reveals that the cetilistat prefers to bind at the“lid region”of pancreatic lipase.Furthermore,molecular dynamics simulation reveals that the cetilistat affects the structure and dynamics of human pancreatic lipase.Mainly,cetilistat affects the conformational changes in the“lid region”of pancreatic lipase which is important for the breakdown of lipids.Furthermore,the radius of gyration(Rg)and solvent-accessible surface area shows that the cetilistat-bound pancreatic lipase affects the compactness of the lipase structure.Thus,our computational modeling study reveals the inhibitory action of cetilistat with human pancreatic lipase and may be further useful for the design and development of anti-obesity drugs.Results:To explore the binding mode and interaction of HPL with cetilistat,we employed molecular docking,a molecular dynamics simulation study.The details of which are discussed below.Conclusion:Thus,our computational modeling study reveals the inhibitory action of cetilistat with human pancreatic lipase and may be further useful for the design and development of anti-obesity drugs.展开更多
Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibi...Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.展开更多
Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elu...Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.展开更多
The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, an...The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.展开更多
This study aimed to elucidate the inhibition mechanism of apigenin against porcine pancreatic lipase(PPL),and,moreover,to comprehensively reveal the molecular basis of its anti-obesity via network pharmacology approac...This study aimed to elucidate the inhibition mechanism of apigenin against porcine pancreatic lipase(PPL),and,moreover,to comprehensively reveal the molecular basis of its anti-obesity via network pharmacology approach.The results showed that apigenin inhibited PPL with an IC50 value of 0.377±0.041 mM.Spectroscopic techniques combined molecular docking suggested that apigenin could bind into the PPL active pocket,affecting its normal spatial conformation.Moreover,molecular dynamic(MD)simulations revealed that the open conformation of PPL tended to transit to the closed in the presence of apigenin,which might one important reason for the inhibition of PPL catalytic ability.Network pharmacology analysis revealed that a total of 49 proteins could be identified as potential targets for the anti-obesity effects of apigenin.According to the protein-protein interaction(PPI)network analysis,six hub targets were extracted including IGF1,ESR1,MMP9,PPARA,MAPK14 and NR3C1.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment indicated that the 49 potential targets could be mapped to 30 pathways(p<0.05).Among them,PI3K-Akt signaling pathway and insulin resistance can be considered as two major pathways regulated by apigenin.Further docking studies indicated that apigenin can bind into the binding pocket of the six hub target proteins identified according to the PPI network.The results indicated that in addition to inhibiting PPL,apigenin could exhibit anti-obesity benefit through the molecular mechanisms uncovered by network pharmacology.This study proposes a new strategy to reveal the mechanisms of dietary polyphenols at the level of network pharmacology.展开更多
Transesterification between methyl-butyrate and 1-butanol in nonaqueous systems was catalyzed by porcine pancreatic lipase which was immobilized on cross- linked polystyrene. Organic solvents, substrate concentration,...Transesterification between methyl-butyrate and 1-butanol in nonaqueous systems was catalyzed by porcine pancreatic lipase which was immobilized on cross- linked polystyrene. Organic solvents, substrate concentration, contents of water and other parameters which affect the immobilized enzyme activity were studied. Lipase immobilized on hydrophobic crosslinked polystyrene can reduce its diffusion limit in the reaction. It was found that the activity of immobilized lipase in organic systems was two times as high as that of free lipase.展开更多
The brown planthopper(BPH),Nilaparvata lugens,an important rice insect pest,can enhance its virulence to BPH-resistant rice within as short a span as several generations.Here,we cloned a pancreatic triglyceride lipase...The brown planthopper(BPH),Nilaparvata lugens,an important rice insect pest,can enhance its virulence to BPH-resistant rice within as short a span as several generations.Here,we cloned a pancreatic triglyceride lipase(PTL)gene(NlPTL)in N.lugens,and found that its mRNA level was higher in the high virulence population(fed on variety Rathu Heenati,P-RH)than in the low virulence population(fed on variety Taichung Native 1,P-TN1).Knocking down NlPTL caused BPH individuals to spend more time in non-penetration and the pathway phases and less time feeding on the phloem of rice plants;these changes consequently decreased food intake,lipid content,survival rate,and fecundity in the insects.These findings reveal for the first time that PTL in BPH is involved in its virulence to rice plants.展开更多
Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was perfo...Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.展开更多
Two new 2H-pyran-2-one glucosides,cuscutarosides A(1)and B(2),and one new steroidal glucoside,7β-methoxy-β-sitosterol 3-O-β-glucopyranoside(3),together with 12 known compounds(4-15)were isolated from the whole plan...Two new 2H-pyran-2-one glucosides,cuscutarosides A(1)and B(2),and one new steroidal glucoside,7β-methoxy-β-sitosterol 3-O-β-glucopyranoside(3),together with 12 known compounds(4-15)were isolated from the whole plant of Cuscuta reflexa(Convolvulaceae)collected from Myanmar.The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis.The antiobesity activity of these isolates was evaluated using porcine pancreatic lipase(PPL),and the antiplatelet aggregation activity was screened using rabbit platelets induced by thrombin,platelet-activating factor(PAF),arachidonate(AA),or collagen.7β-Methoxy-β-sitosterol 3-O-β-glucopyranoside(3)showed weak PPL inhibitory activity.Cuscutaroside A(1),its acetylated derivative(1a),and scrophenoside B(8)showed weak inhibitory activity against rabbit platelet aggregation induced by collagen.Compound 1a also showed inhibitory activity against rabbit platelet aggregation induced by AA.展开更多
The chemical composition and biological activity of Sanghuangporus vaninii solid culture treated by static magnetic field were studied.The compounds were isolated and purified using ultrasonic extraction and semi-prep...The chemical composition and biological activity of Sanghuangporus vaninii solid culture treated by static magnetic field were studied.The compounds were isolated and purified using ultrasonic extraction and semi-preparative liquid chromatography.Their structures were identified through spectral data,and the inhibitory activities againstα-amylase,α-glucosidase and pancreatic lipase were evaluated.Three compounds,5,7-dihydroxy-3,4'-dimethoxyflavone(1),D-(+)-Trehalose(2),pinolenic acid(3),were extracted from the petroleum ether layer.Comparison of peak heights indicated a significantly higher content of compounds subjected to a 4 mT static magnetic field compared to those untreated.Activity tests revealed that compounds 1 and 2 exhibited strong anti-α-amylase and anti-α-glucosidase activities.Specifically,compound 1 had inhibition rates of(65.37±0.05)%and(73.81±0.12)%after 4 mT treatment,compared to(57.26±0.11)%and(65.33±0.14)%without.Compound 2 showed inhibition rates of(68.61±0.12)%and(65.38±0.09)%with the magnetic field,versus(60.71±0.06)%and(56.18±0.02)%without.Compound 3 displayed a notable inhibitory effect on pancreatic lipase,with rates of(60.83±0.03)%after 4 mT treatment and(53.77±0.09)%without.This study demonstrates that the static magnetic field enhances the chemical content and bioactivity of Sanghuangporus vaninii solid culture,providing a basis for its further development and application.展开更多
Objective:To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.Methods:A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects....Objective:To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.Methods:A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects.The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements.The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method.On the other hand,effects of oolong...展开更多
Obesity is a prominent global public health challenge.This study is aimed to explore the inhibition properties of organic and aqueous extracts of Hibiscus sabdariffa against the major enzymes associated with obesity(...Obesity is a prominent global public health challenge.This study is aimed to explore the inhibition properties of organic and aqueous extracts of Hibiscus sabdariffa against the major enzymes associated with obesity(α-amylase,α-glucosidase,and pancreatic lipase).Extraction was carried out using water and organic solvents(methanol,ethanol and ethyl acetate)and inhibitory effect of these extracts on above-mentioned enzymes was carried out using in vitro method.All four extracts showed different yet significant potential to inhibit these enzymes.The organic extracts showed much stronger inhibitory effect on the enzymes than aqueous extract as the former were richer in polyphenols.The potassium hydroxycitrate,which is a salt of major organic acid of H.sabdariffa,did not hinhibit any of these enzymes.The combination of polyphenol-rich extract with potassium hydroxycitrate did not bring about additional inhibition indicating that inhibition potential of H.sabdariffa extract against the above-mentioned enzymes is due to the polyphenolic compounds.The molecular docking approach showed that the phenolic compounds of H.Sabdariffa,particularly catechin hydrate and rutin hydrate,have higher affnity to bind at the active sites of these enzymes,generate hydrogen bonds and thus inhibit their enzymatic activity.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82160739,81922070,81973286,and 81973393)Sailing Special Project of Shanghai Rising-Star Program(Grant No.:22YF1441500)+6 种基金Program for Innovative Leading Talents of Qinghai Province(2018&2019)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202004)Shanghai Science and Technology Innovation Action Plans(Grant Nos.:20S21901500 and 20S21900900)supported by the Shanghai Science and Technology CommitteeProject of the National Multidisciplinary Innovation Team of Traditional Chinese Medicine supported by the National Administration of Traditional Chinese MedicineKey R&D and Transformation Science and Technology Cooperation Project of Qinghai Province(Grant No.:2019-HZ-819)Basic Public Welfare Research Program of Zhejiang Province(Grant No.:LGF22H280012).
文摘Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5e35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 mM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.
基金The authors are grateful to the National Natural Science Foundation of China(81102348,U1132607,81373289).
文摘The unusual fused b-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase.In this study,a structure-based lead optimization of vibralactone resulted in three series of 104 analogs,among which compound C1 exhibited the most potent inhibition of pancreatic lipase,with an IC50 value of 14 nM.This activity is more than 3000-fold higher than that of vibralactone.The effect of compound C1 on obesity was investigated using high-fat diet(HFD)-induced C57BL/6 J obese mice.Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity,primarily through the improvement of metabolic parameters,such as triglyceride levels.
文摘Background:Obesity is a lifestyle disease that involves an excessive amount of body fat deposition.Cetilistat is being used to treat obesity.It mainly inhibits human pancreatic lipase,an enzyme that helps to break down the oil into small molecules of glycerol and fatty acids in the intestine.Therefore,pancreatic lipase inhibition is a potential therapeutic approach for obesity control and treatment.Methods:cetilistat’s binding mode and interaction with human pancreatic lipase are not well understood.In this study,the human pancreatic lipase inhibitory activity of cetilistat was investigated by employing molecular docking and molecular dynamics simulation.Human pancreatic lipase has two states:closed state and open state which is controlled by a surface loop i.e.“lid region”which normally undergoes conformational changes only upon addition of lipids and then breakdown into glycerol and fatty acid.In the present study,open state conformation of the human pancreatic lipase structure was used(2OXE.pdb).The docking study reveals that the cetilistat prefers to bind at the“lid region”of pancreatic lipase.Furthermore,molecular dynamics simulation reveals that the cetilistat affects the structure and dynamics of human pancreatic lipase.Mainly,cetilistat affects the conformational changes in the“lid region”of pancreatic lipase which is important for the breakdown of lipids.Furthermore,the radius of gyration(Rg)and solvent-accessible surface area shows that the cetilistat-bound pancreatic lipase affects the compactness of the lipase structure.Thus,our computational modeling study reveals the inhibitory action of cetilistat with human pancreatic lipase and may be further useful for the design and development of anti-obesity drugs.Results:To explore the binding mode and interaction of HPL with cetilistat,we employed molecular docking,a molecular dynamics simulation study.The details of which are discussed below.Conclusion:Thus,our computational modeling study reveals the inhibitory action of cetilistat with human pancreatic lipase and may be further useful for the design and development of anti-obesity drugs.
基金the National Key Research and Development Program of China (Nos.2017YFC1700200,2017YFC1702000)NSF of China (Nos.81922070, 81973286, 81973393, 81773687)+4 种基金Natural Science Foundation of Liaoning Province (No.20180530025)Program of Shanghai Academic/Technology Research Leader (No. 18XD1403600)Shuguang Program (No. 18SG40) supported by Shanghai Education Development Foundation and Shanghai Municipal Education CommissionInnovative Entrepreneurship Program of High-level Talents in Dalian (No. 2017RQ121)Undergraduate Training Program for Innovation and Entrepreneurship from Shanghai University of Traditional Chinese Medicine (No. 2017101419803010904)。
文摘Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.
基金supported by the National Natural Science Foundation of China(Nos.81803397 and 81522050)the Science and Technology program of Qinghai Province(No.2018-ZJ-739)+1 种基金the Drug Innovation Major Project(Nos.2018ZX09711001-001-001,2018ZX09711001-001-003,and 2018ZX09711001-001-008)the Special Research Fund for Central Universities,Peking Union Medical College(No.3332018088)
文摘Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.
基金supported by the Graduate Students Scientific Research Innovation Projects of Jiangsu Province(No:CXZZ11-0804)
文摘The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
基金supported by[National Natural Science Foundation of China](Grant number 32001702).
文摘This study aimed to elucidate the inhibition mechanism of apigenin against porcine pancreatic lipase(PPL),and,moreover,to comprehensively reveal the molecular basis of its anti-obesity via network pharmacology approach.The results showed that apigenin inhibited PPL with an IC50 value of 0.377±0.041 mM.Spectroscopic techniques combined molecular docking suggested that apigenin could bind into the PPL active pocket,affecting its normal spatial conformation.Moreover,molecular dynamic(MD)simulations revealed that the open conformation of PPL tended to transit to the closed in the presence of apigenin,which might one important reason for the inhibition of PPL catalytic ability.Network pharmacology analysis revealed that a total of 49 proteins could be identified as potential targets for the anti-obesity effects of apigenin.According to the protein-protein interaction(PPI)network analysis,six hub targets were extracted including IGF1,ESR1,MMP9,PPARA,MAPK14 and NR3C1.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment indicated that the 49 potential targets could be mapped to 30 pathways(p<0.05).Among them,PI3K-Akt signaling pathway and insulin resistance can be considered as two major pathways regulated by apigenin.Further docking studies indicated that apigenin can bind into the binding pocket of the six hub target proteins identified according to the PPI network.The results indicated that in addition to inhibiting PPL,apigenin could exhibit anti-obesity benefit through the molecular mechanisms uncovered by network pharmacology.This study proposes a new strategy to reveal the mechanisms of dietary polyphenols at the level of network pharmacology.
文摘Transesterification between methyl-butyrate and 1-butanol in nonaqueous systems was catalyzed by porcine pancreatic lipase which was immobilized on cross- linked polystyrene. Organic solvents, substrate concentration, contents of water and other parameters which affect the immobilized enzyme activity were studied. Lipase immobilized on hydrophobic crosslinked polystyrene can reduce its diffusion limit in the reaction. It was found that the activity of immobilized lipase in organic systems was two times as high as that of free lipase.
基金This work was funded by the National Key Research and Development Program of China(2017YFD0200900)the Natural Science Foundation of Guangdong Province,China(2017A030310210).
文摘The brown planthopper(BPH),Nilaparvata lugens,an important rice insect pest,can enhance its virulence to BPH-resistant rice within as short a span as several generations.Here,we cloned a pancreatic triglyceride lipase(PTL)gene(NlPTL)in N.lugens,and found that its mRNA level was higher in the high virulence population(fed on variety Rathu Heenati,P-RH)than in the low virulence population(fed on variety Taichung Native 1,P-TN1).Knocking down NlPTL caused BPH individuals to spend more time in non-penetration and the pathway phases and less time feeding on the phloem of rice plants;these changes consequently decreased food intake,lipid content,survival rate,and fecundity in the insects.These findings reveal for the first time that PTL in BPH is involved in its virulence to rice plants.
文摘Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.
基金supported by the Southeast Asia Biodiversity Research Institute,Chinese Academy of Sciences(Grant Nos.2015CASEABRIRG001 and Y4ZK111B01)the International Partnership Program of Chinese Academy of Sciences(Grant No.153631KYSB20160004)+2 种基金the National Natural Science Foundation of China(31960480)the Joint Special Project of Local Undergraduate Universities in Yunnan Province,China(Grant No.2018FH001-024)the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program of Ministry of Science and Technology of the People’s Republic of China(Grant No.2019QZKK0502).
文摘Two new 2H-pyran-2-one glucosides,cuscutarosides A(1)and B(2),and one new steroidal glucoside,7β-methoxy-β-sitosterol 3-O-β-glucopyranoside(3),together with 12 known compounds(4-15)were isolated from the whole plant of Cuscuta reflexa(Convolvulaceae)collected from Myanmar.The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis.The antiobesity activity of these isolates was evaluated using porcine pancreatic lipase(PPL),and the antiplatelet aggregation activity was screened using rabbit platelets induced by thrombin,platelet-activating factor(PAF),arachidonate(AA),or collagen.7β-Methoxy-β-sitosterol 3-O-β-glucopyranoside(3)showed weak PPL inhibitory activity.Cuscutaroside A(1),its acetylated derivative(1a),and scrophenoside B(8)showed weak inhibitory activity against rabbit platelet aggregation induced by collagen.Compound 1a also showed inhibitory activity against rabbit platelet aggregation induced by AA.
基金supported by the Natural Science Foundation of Jilin Province(20220402050 GH,JJKH20220826KJ)Natural Science Foundation of Changchun Normal University(2020004).
文摘The chemical composition and biological activity of Sanghuangporus vaninii solid culture treated by static magnetic field were studied.The compounds were isolated and purified using ultrasonic extraction and semi-preparative liquid chromatography.Their structures were identified through spectral data,and the inhibitory activities againstα-amylase,α-glucosidase and pancreatic lipase were evaluated.Three compounds,5,7-dihydroxy-3,4'-dimethoxyflavone(1),D-(+)-Trehalose(2),pinolenic acid(3),were extracted from the petroleum ether layer.Comparison of peak heights indicated a significantly higher content of compounds subjected to a 4 mT static magnetic field compared to those untreated.Activity tests revealed that compounds 1 and 2 exhibited strong anti-α-amylase and anti-α-glucosidase activities.Specifically,compound 1 had inhibition rates of(65.37±0.05)%and(73.81±0.12)%after 4 mT treatment,compared to(57.26±0.11)%and(65.33±0.14)%without.Compound 2 showed inhibition rates of(68.61±0.12)%and(65.38±0.09)%with the magnetic field,versus(60.71±0.06)%and(56.18±0.02)%without.Compound 3 displayed a notable inhibitory effect on pancreatic lipase,with rates of(60.83±0.03)%after 4 mT treatment and(53.77±0.09)%without.This study demonstrates that the static magnetic field enhances the chemical content and bioactivity of Sanghuangporus vaninii solid culture,providing a basis for its further development and application.
文摘Objective:To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.Methods:A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects.The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements.The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method.On the other hand,effects of oolong...
基金the scholarship support provided to her by RMIT University.
文摘Obesity is a prominent global public health challenge.This study is aimed to explore the inhibition properties of organic and aqueous extracts of Hibiscus sabdariffa against the major enzymes associated with obesity(α-amylase,α-glucosidase,and pancreatic lipase).Extraction was carried out using water and organic solvents(methanol,ethanol and ethyl acetate)and inhibitory effect of these extracts on above-mentioned enzymes was carried out using in vitro method.All four extracts showed different yet significant potential to inhibit these enzymes.The organic extracts showed much stronger inhibitory effect on the enzymes than aqueous extract as the former were richer in polyphenols.The potassium hydroxycitrate,which is a salt of major organic acid of H.sabdariffa,did not hinhibit any of these enzymes.The combination of polyphenol-rich extract with potassium hydroxycitrate did not bring about additional inhibition indicating that inhibition potential of H.sabdariffa extract against the above-mentioned enzymes is due to the polyphenolic compounds.The molecular docking approach showed that the phenolic compounds of H.Sabdariffa,particularly catechin hydrate and rutin hydrate,have higher affnity to bind at the active sites of these enzymes,generate hydrogen bonds and thus inhibit their enzymatic activity.
