FOOD HYDROCOLLOIDS
·
2020
·
IF 7.053
Mengting Ni,Xing Hu,Deming Gong,Guowen Zhang
Vitexin, a C-glycosylated flavonoid , is abundant in numerous foods . In this study, vitexin was determined as an uncompetitive α-glucosidase inhibitor and its binding site was different from the active site. It possessed a remarkably higher inhibitory activity than acarbose with its IC 50 value of 52.80 ± 1.65 μM. Interestingly, the combination of acarbose with vitexin showed a strong synergistic inhibition effect. The stable complex between vitexin and α-glucosidase was mainly formed by hydrogen bonds and hydrophobic forces. The presence of vitexin induced a looser conformation of α-glucosidase and decreased its surface hydrophobicity. Computational docking and chemical modification of α-glucosidase found that residues Glu, Asn, Lys, and Thr were essential for the binding course and their importance order was Glu, Asn > Lys > Thr. Molecular dynamics simulation results revealed the molecular mechanism of the interaction between vitexin and α-glucosidase and verified the above experimental results. This work proposed rewarding findings in functional research of vitexin as a potential α-glucosidase inhibitor.
研究领域:
食品科学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-12
·
IF 15.7
Huang Jiayong,Shen Zhuanglin,Xiao Xiaoyun,Wang Lanteng,Zhang Jiwen,Zhou Jiahai,Gu Yang
The clinical efficacy of the antidiabetic drug acarbose is hampered by degradation by the acarbose-preferred glucosidase (Apg) from K. grimontii TD1. Understanding the catalytic mechanism of Apg can aid the design of next-generation hypoglycemic pharmaceuticals acarbose analogs. Here, we determine several crystal structures of Apg to identify the catalytic residues and the ligand-binding pocket of Apg. Structural analyses and computational modeling reveal D448 as the active nucleophile, contrasting with prior studies that assumed D336 to be the nucleophile. In addition to E373 proposed as the proton donor in previous reports, we find that R334 might be an alternative proton donor. Our experimental and computational analyses indicate the two-ring product acarviosine is the two-step hydrolyzed product, where the second hydrolysis is the rate-limiting step. Additionally, further investigation of the acarbose analogs acarstatins A and B that are resistant to Apg is conducted by computational analysis. Overall, our studies provide perspectives into the intricacies of Apg’s catalytic mechanism, contributing to the design of next-generation hypoglycemic pharmaceuticals.
研究领域:
结构生物学
·
酶学
·
计算生物学
·
药物化学
·
糖尿病研究
✓ 已验证
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2023
·Vol. 24
·期 1
·1-19
·
IF 5.8
Liu Lin,Fan Haiyang,Li Liang,Fan Yunping
Background Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections (RTIs) have become the primary cause of death for T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa RTI in T2DM individuals and elucidate its underlying mechanism. Methods High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a RTI model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa RTI were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. Results We found that P. aeruginosa RTI was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa RTI in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa RTI by acarbose in nondiabetic mice. Conclusions This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.
研究领域:
药理学
·
微生物学
·
传染病学
·
糖尿病学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jingjing Cui,Di Lian,Yuan Li,Yutong Du,Zihan Qu,Xue Zhang,Li Li
Coreopsin is a flavonoid from Coreopsis tinctoria . The inhibition of coreopsin and synergy with acarbose against α-amylase (PPA) or α-glucosidase (SCG) were explored. As a result, coreopsin exhibited stronger inhibition on PPA/SCG than that of acarbose. Combination of coreopsin (4.11 μM) with acarbose (132.77 μM) had significant synergistic effect on PPA, while combination of coreopsin (5.76 μM) and acarbose (121.7 μM) had significant synergy on SCG. Coreopsin, acarbose and acarbose-coreopsin inhibited PPA in mixed-type mode. Acarbose competitively inhibited SCG, whereas coreopsin and acarbose-coreopsin inhibited SCG in mixed-type mode. Fluorescence analysis conformed that coreopsin could synergize with acarbose by increasing the binding ability of acarbose to PPA/SCG. Compared with acarbose or coreopsin, acarbose-coreopsin complexes resulted in more conformational changes of PPA/SCG, revealing that the complexes had stronger inhibitory ability than acarbose or coreopsin alone. The detail binding information of coreopsin, acarbose or acarbose-coreopsin to PPA /SCG was revealed by computer simulation.
研究领域:
药理学
·
生物化学
·
酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Spectroscopy
·
2026
·Vol. 2026
·期 1
·5791311
·
IF 1.7
Xue Zhang,Di Lian,Yuan Li,Yutong Du,Zihan Qu,YuXin Cui,Li Li
Studies indicated that some active flavonoids combined with acarbose could reduce the side effects of acarbose and enhance its efficacy. Isorhamnetin-3-O-rutinoside (IOR) is a flavonoid found in many edible herbs. In this work, the synergistic effects of IOR and acarbose on α -amylase/α-glucosidase (PA/AG) were evaluated using ZIP score analysis. In the presence of IOR, the binding constant K b values of acarbose with PA/AG were significantly improved, indicating that IOR exhibited synergistic effect with acarbose by increasing its K b values. Furthermore, in the presence of IOR, acarbose resulted in greater changes in microenvironment and secondary structure of PA/AG. The docking analysis confirmed that IOR and acarbose bound to the different sites of PA/AG. Compared with pure enzyme, the complexes formed by IOR/acarbose with two enzymes were more stable based on dynamics simulations. This study suggested that IOR might be used as a potential synergistic inhibitor of acarbose.
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yuan Li,Yutong Du,Xue Zhang,Zihan Qu,Di Lian,Jingjing Cui,Li Li
Isoginkgetin is an edible biflavone from ginkgo biloba leaves with many bioactivities. In this work, the inhibition and synergistic effect of isoginkgetin with miglitol or acarbose on saccharomyces cerevisiae α-glucosidase (α-SCG) were tracked via various spectroscopic techniques and computer simulations. Compared with miglitol or acarbose, isoginkgetin displayed more remarkable inhibition effect on α-SCG. In the presence of isoginkgetin, miglitol and acarbose exhibited stronger inhibitory effect on α-SCG than miglitol and acarbose alone. Isoginkgetin exerted the synergistic inhibitory effect by significantly increasing the binding affinity of acarbose or miglitol with α-SCG, leading to larger structural changes in α-SCG. The best binding mode, the stability of the formed complex, and the contribution of key amino acids to the binding were deeply analyzed via dynamics simulation. Isoginkgetin can be used as a strong inhibitor of α-SCG and synergistic inhibitor of miglitol or acarbose.
研究领域:
药理学
·
生物化学
·
酶学
·
计算生物学
·
天然产物研究
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2019
·
IF 5.657
Xiao-Xue Li,Sun-Kai Ling,Ming-Yue Hu,Yu Ma,Yuan Li,Pei-Lin Huang
The cardiovascular efficacy of glucose-lowering drugs is needed due to the cardiovascular complication in type 2 diabetes mellitus (T2DM). Acarbose is an α-glucosidase inhibitor that suppresses postprandial hyperglycemia , however, the cardiovascular protection of acarbose has still remained controversial. NLRP3 inflammasome activation mediated tight junction disruption, a hallmark event of endothelial barrier dysfunction leading to endothelial hyperpermeability in diabetes. Given the anti-inflammatory property of acarbose, it was investigated that acarbose protected against vascular endothelial barrier dysfunction through inhibiting NLRP3 inflammasome in vascular endothelial cells in T2DM rats. The rat aortic endothelial cells (RAECs) were incubated with high glucose (HG, 30 mM) for 24 h in vitro. It was found that HG significantly induced the formation and activation of NLRP3 inflammasome, which was markedly blocked by acarbose treatment. Furthermore, acarbose blocked the Nox4-dependent superoxide (O 2 .- ) generation, which regulated NLRP3 inflammasome in RAECs. Importantly, we found that acarbose remarkably enhanced the junction protein expression of ZO-1 and VE-Cadherin and consequently abolished vascular hyperpermeability, which was associated with inhibiting NLRP3 inflammasome in RAECs. In vivo, acarbose intervention relieved vascular leakage in the heart of diabetic rats injected with Evans blue dye and the vasodilatory response to acetylcholine , which was accompanied with the restoration of ZO-1, VE-Cadherin, Nox4 and NLRP3 inflammasome in the aortal endothelium of diabetic rats. Taken together, our data indicated that acarbose ameliorated endothelial barrier dysfunction by directly inhibiting NLRP3 inflammasome which was dependent on inhibiting Nox4 oxidase-dependent O 2 .- production. These properties might carry a potential significance for acarbose in cardiovascular protection in diabetic patients.
研究领域:
药理学
·
心血管科学
·
糖尿病研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 138
·期 48
·51553
·
IF 3.125
Ju-Zhen Yi,Kunhua Lin,Hao Wu,Xuhong Mao,Li-Ming Zhang,Liqun Yang
A hydrogel comprising covalently modified carboxylated pullulan and concanavalin A (CPUL-ConA) was prepared with glucose-sensitivity in a simulated small intestinal fluid containing glucose. The acarbose-encapsulated CPUL-ConA (Acar/CPUL-ConA) hydrogel, with an acarbose encapsulation ratio of 0.63, was prepared by immersing the dried CPUL-ConA hydrogel in an acarbose/PBS (pH 7.2) solution. In the simulated gastric fluid, less than 20% acarbose was released from the Acar/CPUL-ConA hydrogel, which could be beneficial to protecting the stomach. In contrast, more than 80% acarbose was smartly controlled released from the Acar/CPUL-ConA hydrogel in the simulated small intestine fluid containing glucose. Scanning electron microscopy provided further evidence of the smart release of acarbose from the Acar/CPUL-ConA hydrogel in simulated gastrointestinal fluids, which is advantageous to inhibiting α-glucosidase activity and subsequently reducing the postprandial blood glucose levels, as well as helpful for reducing the gastrointestinal dysfunction of acarbose. Rheological analysis indicated that the Acar/CPUL-ConA hydrogel showed characteristics of chemical crosslinked hydrogels. There was no obvious shear thinning behavior, suggesting that the Acar/CPUL-ConA hydrogel could be stable under gastric and intestinal peristalsis. Therefore, the Acar/CPUL-ConA hydrogel is anticipated to improve the therapeutic efficacy of postprandial hyperglycemia and type 2 diabetes.
研究领域:
药学
·
材料科学
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 2.6
Xudong Xia,Rongrui Lu,Nanxing Zhao,Hongming Kong,Fang Yuan,Hesheng Liu,Lianliang Liu,Xiangyang Qi,Qiuping Chen
Summary α-Glycosidase, a critical therapeutic target in type 2 diabetes mellitus (T2DM), can be modulated by inhibitors to reduce postprandial blood glucose levels. This study investigated the inhibitory effects of vine tea ( Ampelopsis grossedentata ) and its key compounds on α-glycosidase. The results demonstrated that fifteen varieties of vine tea extracts inhibited α-glycosidase in a dose-dependent manner, with IC 50 values ranging from 5.25 to 35.8 μg mL −1 . HPLC analysis revealed dihydromyricetin (DHM) as the main compound in vine tea, with an IC 50 value of 262.50 μM. Notably, the synergistic combination of DHM and the antidiabetic drug acarbose (ABS) significantly enhanced inhibitory effectiveness, with the optimal ratio (1:125) yielding a potentiation index (CI) of 0.09. Fluorescence and molecular docking analyses supported the hypothesis that DHM enhanced ABS's inhibitory effect through complex formation and specific interactions, offering a promising option for safer and more effective diabetes therapy.
研究领域:
药理学
·
糖尿病研究
·
植物化学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Jichen Yang,Xiaoli Wang,Chuanying Zhang,Lun Ma,Tao Wei,Yajing Zhao,Xin Peng
Flavonoid compounds have anti-diabetic activity, which can control blood glucose levels by inhibiting α-glucosidase activity. In this paper, the inhibition mechanisms between four flavonoid compounds and α-glucosidase were studied by multispectroscopic methods and molecular docking . The results showed that the inhibitory activities of flavonoid compounds were higher than that of acarbose , and the sequence of inhibition effect was scutellarein > nepetin > apigenin > hispidulin > acarbose. Also, the synergistic effects of flavonoid compounds combined with acarbose on inhibiting α-glucosidase activity were observed. The fluorescence results showed that flavonoid compounds combined with α-glucosidase to form a stable complex. And the spectral analysis indicated that the microenvironmental and secondary structure of α-glucosidase were changed. The present study demonstrated that the molecular structure of flavonoid compounds played an important role in the inhibition process, namely, scutellarein with more hydroxyl groups on the A-ring might serve as the most effective α-glucosidase inhibitor.
研究领域:
药理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jichen Yang,Huan Li,Xiaoli Wang,Chuanying Zhang,Guo Feng,Xin Peng
As a natural flavonolignan, silibinin is reported to possess multiple biological activities, while the inhibitory potential of silibinin on carbohydrate-hydrolyzing enzymes is still unclear. Therefore, in this study, the inhibitory effect and underlying mechanism of silibinin against α-amylase/α-glucosidase were investigated. The results indicated that silibinin showed a strong inhibitory efficiency against α-amylase/α-glucosidase in noncompetitive manners and exhibited synergistic inhibition against α-glucosidase with acarbose. However, interestingly, the inhibitory effect of silibinin was significantly hindered in various milk protein-rich environments, but this phenomenon disappeared after simulated gastrointestinal digestion of milk proteins in vitro. Furthermore, silibinin could combine with the inactive site of α-amylase/α-glucosidase and change the microenvironment and secondary structure of the enzymes, thereby influencing the catalytic efficiency of enzymes. This research suggested that silibinin could be used as a novel carbohydrate-hydrolyzing enzyme inhibitor, and milk beverages rich in silibinin had the potential for further application in antidiabetic dietary or medicine.
研究领域:
食品科学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Qin Zhou,Yishi Wei,Yijing Liao,Xing Hu,Deming Gong,Guowen Zhang
Identification of new α -glucosidase ( α -Glu) inhibitors from natural sources is very important to the management of type 2 diabetes. In this work, liquiritigenin (LTG), a flavonoid compound derived from liquorice, was found to have excellent inhibition of α -Glu (IC 50 = 27.91 ± 3.48 μM) in a mixed manner. LTG reduced the endogenous fluorescence of α -Glu in a static mode by spontaneously forming stable complexes with the α -Glu-substrate through hydrophobic forces and hydrogen bonding. LTG decreased the α -helix and β -sheet contents of α -Glu while increasing the β -turn and random coil contents. Computer simulation showed that LTG interacted non-covalently with Gly161, Glu422, Glu429, and Asn235 residues of α -Glu, causing structural unfolding of the enzyme, which affected the substrate-enzyme interaction and ultimately reduced the release of the product. While acarbose, a competitive inhibitor of α -Glu, spontaneously hydrogen-bonded Tyr158, His280, Asp242, and Asp352 residues of the LTG− α -Glu complex. Moreover, a combination of LTG (6.00 μM) and acarbose (30.00 μM) had a remarkable synergistic inhibition on α -Glu, which may be because LTG made the structure of α -Glu loosening and reduced its catalytic activity through allosteric effect. And the occupation of the active cavity by acarbose may lead to a conformational change in the LTG− α -Glu complex, which effectively hindered the binding between the substrate and α -Glu. These findings may offer a new theoretical foundation for the development of LTG as a glucose-lowering ingredient in functional foods.
研究领域:
药理学
·
生物化学
·
计算生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）