JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2013
·
IF 1.495
Weiqiang Lu,Junsheng Zhu,Shien Zou,Xi Li,Jin Huang
Human skin fibroblast collagenase also known as Matrix Metalloproteinase-1 (MMP-1) is a key enzyme in remodeling and degradation of extracellular matrix, and the inhibitors of human MMP-1 are effective drug candidates for the treatment of cancer. In this study, we report an improved method for high-level expression of soluble human MMP-1 catalytic domain (cd-MMP-1) in E.coli. The enzymatic activity is found maximum at pH 7.5 and temperature 40°C with a Km value of 13.02 µM. Effects of 17 structure-related flavonoids on MMP-1 activity are evaluated using a fluorescent assay, 6 inhibitors are identified with IC50 < 10 µM. Fisetin is the most active agent with an IC50 value of 1.35 µM and is identified as a mixed type inhibitor. Our improved soluble cd-MMP-1 expression method provides a basis for inhibitors identification and may be beneficial to discover novel anti-cancer agent targeting human MMP-1.
研究领域:
生物化学
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分子生物学
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药理学
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癌症研究
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高影响因子
MOLECULES
·
2019
·Vol. 24
·期 9
·1661
·
IF 3.06
Mengmeng Xia,Yajing Fang,Weiwei Cao,Fuqiang Liang,Siyi Pan,Xiaoyun Xu
P-glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance (MDR) in cancer cells. In order to enhance the uptake of chemotherapy drugs, larger amounts of P-gp inhibitors are required. Besides several chemically synthesized P-gp inhibitors, flavonoids as P-gp inhibitors are being investigated, with their advantages including abundance in our daily diet and a low toxicity. The cytotoxicity of daunorubicin (as a substrate of P-gp) to KB/MDR1 cells and the parental KB cells was measured in the presence or absence of flavonoids. A two-dimensional quantitative structure–activity relationship (2D-QSAR) model was built with a high cross-validation coefficient (Q2) value of 0.829. Descriptors including vsurf_DW23, E_sol, Dipole and vsurf_G were determined to be related to the inhibitory activity of flavonoids. The lack of 2,3-double bond, 3′-OH, 4′-OH and the increased number of methoxylated substitutions were shown to be beneficial for the inhibition of P-gp. These results are important for the screening of flavonoids for inhibitory activity on P-gp.Keywords:flavonoids;P-gp;inhibitory activity;QSAR
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MEDICAL SCIENCE MONITOR
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2018
·
IF 1.894
Hong Jiang,Chen Zhang,Wen He
Background Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and Uighur traditional medicine used to treat various disorders such as hypertension, lung heat, cough, and bronchitis; it has good antioxidant activity. Previous studies have shown that DHBF can reduce blood pressure in renovascular hypertensive rats, improve left ventricular systolic and diastolic function, and improve myocardial contractility. Therefore, we aimed to study the effect of DHBF on cardiomyocyte hypertrophy in cultured cells. Material/Methods Neonatal rat cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang II), with or without varying concentrations of the DHBF extract. Cell Counting Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA levels, confocal laser scanning microscopy was used to measure cell surface area and intracellular Ca 2+ concentrations ([Ca 2+ ] i ), and colorimetric assays were used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity. Results Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of controls. Ang II treatment also increased cell surface area; increased mRNA expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC); increased [Ca 2+ ] i ; and reduced NOS activity and NO production. DHBF treatment could reverse these effects in a concentration-dependent manner. Conclusions These results showed that DHBF can ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the downregulation of cardiac hypertrophy genes ( ANP , BNP , and β -MHC ) and reduction in cell surface area. The mechanism may be related to NO release and [Ca 2+ ] I regulation.
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Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 2
·1795-1801
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IF 1.261
Qiang Zhang,Guangdong Cheng,Hongbin Qiu,Yuexin Wang,Jingtao Wang,Hui Xu,Tao Zhang,Lixin Liu,Ye Tao,Zhongjuan Ren
Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer cases and may be a potential therapeutic target in the treatment of prostate cancer. The present study evaluated the cytotoxicity of three flavonoids (genistein, luteolin and quercetin) towards DU145 prostate cancer cells, and investigated the effect of these flavonoids on PSCA expression. The results demonstrated that genistein, luteolin and quercetin inhibited the growth of DU145 cells in a dose-dependent manner (P<0.05) and induced morphological changes characteristic of apoptosis in DU145 cells. Flow cytometry analysis also indicated that the flavonoids induced S phase cycle arrest in DU145 cells. Notably, it was observed that expression of PSCA was inhibited at the mRNA (P<0.05) and protein levels in DU145 cells following flavonoid treatment compared with the control. These results suggest that flavonoids may be potential therapeutic agents in the treatment and prevention of prostate cancer.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2016
·
IF 3.169
Bo Zhuang,Li-Li Dou,Ping Li,E-Hu Liu
Deep eutectic solvents (DESs) are emerging as alternatives to conventional ionic liquids and organic solvents due to their unique advantages. In the present study, the tuneability of DESs as tailor-made solvents to efficiently extract polar and non-polar bioactive compounds from Platycladi Cacumen was detailedly investigated. Totally 12 types of choline chloride-, betaine-, and l-proline-based DESs were synthesized for initial screening, and extraction conditions was optimized by single-factor experiment. Experiments with different DESs and principal components analysis demonstrated that the extractability of both flavonoid glycosides and aglycones was greater with certain designed DESs than conventional solvents. In addition, the water content in DESs led to significantly different extraction yields of flavonoid compounds. The target compounds were recovered from DESs by macroporous resin LX-38 with a satisfactory yield between 77.44% and 98.92%. The knowledge acquired in this study could contribute to further DES application in extraction of bioactive compounds from natural sources.
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Food Bioscience
·
2025
·
IF 5.9
Cheng-Hai Yan,Ding Wang,Ruo-Xi Mei,Lu Tan,Yi-Jiang-Cheng Li,Richard Ansah Herman,Yan Xu,Lu-Chan Gong,Jun Wang
Natural flavonoids exhibit diverse physiological effects and are used as functional factors, antioxidants and pigments in food as well as pharmaceutical and cosmetic applications. However, their poor solubility and stability, result in low bioavailability. Biomodification through deglycosylation effectively enhances their bioactivity. This study developed two surface display strategies in Escherichia coli , anchoring α -L-rhamnosidase RhaB1-ΔN to the cell surface using the anchoring protein Lpp-OmpA. Immunofluorescence and proteinase K sensitivity tests confirmed the successful construction of surface-displaying strains E. coli Lpp-OmpA-RhaB1-ΔN and E. coli RhaB1-ΔN-SpyCatcher-SpyTag. Enzymatic property studies revealed improved temperature and pH stability of the whole-cell catalysts with surface compared to free enzymes. After 6 catalytic cycles, E. coli Lpp-OmpA-RhaB1-ΔN retained higher activity than E. coli RhaB1-ΔN. In flavonoid hydrolysis, E. coli Lpp-OmpA-RhaB1-ΔN increased yields of isoquercitrin and kaempferol-3- O -glucuronide by 20.25% and 10.99%, respectively, compared with that in whole-cell catalyst with intracellular enzyme ( p < 0.05). In addition, it should be noted that although the enzyme expression of E. coli RhaB1-ΔN-SpyCatcher-SpyTag is reduced, its hydrolysis ability of flavonoids is comparable to that of E. coli RhaB1-ΔN due to the efficient catalytic ability of extracellular enzymes. This study establishes reliable whole-cell catalysts with surface-displayed α -L-rhamnosidase for efficient natural flavonoid modification, with potential applications in the food and pharmaceutical industries.
研究领域:
生物化学
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食品科学
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制药工程
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高影响因子
ULTRASONICS SONOCHEMISTRY
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2025
·
IF 9.7
Liang Ye,Yixin Pan,Wenfang Wang,Shixin Li,Bing Yang,Xiaobin Jia,Liang Feng
This study aimed to developed an integrated ultrasound-assisted approach that incorporates ultrasound into both the enzymatic biotransformation and resin-based purification steps for the efficient preparation of secondary flavonoid glycosides (SFGs) from Epimedium. Ultrasound pretreatment was first applied to cellulase to enhance the deglycosylation of parent flavonoid glycosides (PFGs), followed by ultrasound-assisted purification using ADS-17 resin, while kinetic modeling, adsorption–desorption profiling, and morphological examinations were conducted to elucidate the underlying mechanisms of ultrasonic intensification. Kinetic analysis showed that ultrasonic pretreatment (50 W) significantly accelerated the enzymatic reaction, increasing the first-order rate constant (k 1 from 0.0129 to 0.0287 min –1 ) and reducing the time to 99 % conversion (t 99 ) from 356 to 161 min. During purification, pseudo-second-order kinetic modeling confirmed that ultrasound (150 W) enhanced adsorption by increasing the rate constant and raising the equilibrium capacity from 77.58 to 99.06 mg/g, while pseudo-first-order modeling described the accelerated desorption process, in which t 95 was shortened by ∼ 40 %. The purified SFGs achieved > 80 % purity as verified by UPLC–Q–TOF–MS. In ovariectomized rats, ultrasound-prepared SFGs markedly improved trabecular microarchitecture, biochemical markers, and OPG/RANKL/RANK signaling, exhibiting superior anti-osteoporotic efficacy compared with crude PFGs. Overall, this work develops a dual-stage ultrasound-intensified strategy that integrates biotransformation with resin purification, providing a green, efficient, and scalable approach for producing high-value natural flavonoids.
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INDUSTRIAL CROPS AND PRODUCTS
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2018
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IF 3.849
Jun Ni,Lixiang Dong,Zhifang Jiang,Xiuli Yang,Zhehang Sun,Jiaxun Li,Yuhuan Wu,Maojun Xu
Flavonoids play important roles in plant immune responses, but the molecular mechanism and influencing factors on flavonoid accumulation during Ginkgo immune responses are largely unknown. In this research, post-harvest Ginkgo leaves cultured in the dark were treated with salicylic acid (SA). A transcriptome analysis and total flavonoid measurement showed decreased flavonoid biosynthesis and accumulation in leaves. Experiments carried out in seedlings, young and adult trees, showed increased flavonoid content under light conditions but decreased content under dark conditions after treatment with SA. A detailed analysis of individual flavonoids showed similar changes for most of their contents, although some showed different change trends. Single-colored light experiments revealed that red and far-red light, but not blue light, were required in SA-induced flavonoid accumulation. The results clarified the importance of light in SA-induced flavonoid accumulation and provided valuable information to the Ginkgo related pharmaceutical industry.
研究领域:
植物学
·
分子生物学
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International Journal of Nanomedicine
·
2023
·
IF 8
Jianbo Li,Yang Yang,Likang Lu,Qiujin Ma,Jinjie Zhang
Background Morin, one of the most widely distributed flavonoids in plants, has been identified as a potent antihyperuricemic agent. Its poor water solubility and fast in vivo clearance, however, have limited its application in the treatment of hyperuricemia. In this study, a novel amphiphilic polymer (hydroxyethyl starch-deoxycholic acid [HES-DOCA]) was synthesized to overcome these limitations.Methods HES-DOCA conjugates with various substitution degrees were prepared by chemical grafting DOCA to HES through ester formation. The structures of the conjugates were confirmed by infrared spectroscopy and 1H-NMR. Physicochemical characterizations of HES-DOCA nanoparticles-loaded Morin (Morin/HES-DOCA-NPs) were studied using dynamic light scattering and transmission electron microscopy (TEM). In vitro release studies were performed to evaluate the release properties of Morin from the NPs. Subsequently, in vivo pharmacokinetic parameters of Morin/HES-DOCA-NPs were investigated in Wistar rats through intravenous administration (2 mg/kg, equivalent to Morin). Antihyperuricemic efficacy of the NPs was evaluated in a rat hyperuricemic model.Results The optimized HES-based amphiphilic polymer contained approximately 10 DOCA groups per 100 anhydroglucose units of HES, which can spontaneously self-assemble to form spherical NPs as demonstrated by TEM images. Morin/HES-DOCA-NPs were monodispersed (polydispersity index = 0.05) with a mean diameter of 197 nm and exhibited a zeta potential of −14 mV. The use of DOCA as the polymer’s hydrophobic segment enabled high drug loading efficiency (15.6%). After systemic administration, Morin/HES-DOCA-NPs exhibited significantly longer half-life and higher systemic exposure (elimination half-life and area under the plasma concentration–time curve) compared with free drug Morin. In a rat hyperuricemic model, treatment with Morin/HES-DOCA-NPs demonstrated superior therapeutic efficacy over Morin in decreasing serum uric acid level, increasing the uricosuric action, as well as attenuating hyperuricemia-associated inflammation in kidney of rats.Conclusion Collectively, these findings suggest that the novel HES-based NP formulation of Morin may have great potential for clinical treatment of hyperuricemia.
研究领域:
药剂学
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生物医学工程
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代谢病研究
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Ruiying Zhang,Yufei Liu,Yiqiao Gao,Dengfeng Peng,Qian Luan,Ziliang Li,Xiaoyang Xia,Xia Xiang
Sesame leaves contain rich phenolic acids and flavonoids. However, their potential in nanozyme synthesis has not been investigated yet. Herein, we report the preparation of flavonoid-rich sesame leaf extract (SLE), composition identification, and its use in the construction of iron (Fe)-based nanozymes (Fe-SLE CPNs). SLE was obtained with an extraction yield of ∼14.5% with a total flavonoid content (TFC) of ∼850.85 mg RE/g. There were 83 flavonoid compounds in SLE, primarily including scutellarin, apigenin-7-glucuronid, narcissin, and hyperoside. Fe-SLE CPNs exhibited nanodot morphology with a hydrodynamic size of 79.34 nm and good stability in various physiological solutions, pH levels, and temperatures. The Fe-SLE CPNs were more efficient in the scavenging ability of reactive oxygen species (ROS) than SLE alone. Furthermore, a stronger anti-inflammatory effect of the Fe-SLE CPNs was shown by modulating the MyD88-NF-κB-MAPK signaling pathways. These findings imply that SLE-based nanozymes hold great potential for diverse applications.
研究领域:
植物化学
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纳米生物学
·
药理学
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Toxics
·
2024
·Vol. 12
·期 8
·591
·
IF 3.9
Peng Tian,Yu-Xi Feng,Yan-Hong Li
The presence of thiocyanate (SCN−) in irrigation water has adverse effects on both plant growth and crop output. Hydrogen sulfide (H2S) is an important gaseous signaling molecule that can alleviate SCN−stress. Flavonoids are secondary compounds produced by plants and are ubiquitous in the plant kingdom. They play important roles in several physiological and biochemical processes. To investigate the effect of exogenous H2S on the growth of early rice plants under SCN−stress, we carried out a hydroponic experiment focusing on the interaction of exogenous H2S with flavonoids. In this study, a hydroponic experiment was performed to investigate the behavior of SCN−when subjected to varying effective doses (EC20: 24.0 mg/L; EC50: 96.0 mg/L; and EC75: 300.0 mg/L). The findings indicated that the relative growth rate (RGR) of the plants treated with H2S + SCN−was greater than that of the plants treated with SCN−alone. Higher amounts of flavonoids were detected in the shoots than in the roots, with more variability in the shoots. The early warning level results showed that most of the flavonoids were present at levels I and II, while quercetin was present at level IV. Genetic expression variation factor (GEVF) analyses revealed an increase in the quantity of “promoter genes” with increasing SCN−concentration in both rice tissues. Furthermore, administering external H2S while exposing rice tissues to SCN−resulted in a considerable decrease in the levels of reactive oxygen species. This study provides novel insights into the regulation of flavonoid levels in rice plants by exogenous H2S, facilitating enhanced resistance to SCN−stress and promoting sustainable agriculture.
研究领域:
植物学
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环境科学
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分子生物学
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PLoS Pathogens
·
2026
·Vol. 22
·期 7
·e1014425
·
IF 4.9
Hanbo Li,Yu Li,Bowen Yin,Xinming Zhang,Zheng Xu,Changxu Song,Kang Li,Ling Tian
Quercetin is recognized for diverse pharmacological activities. However, the mechanism underlying its broad-antiviral effects has not been elucidated. Herein, we identified quercetin as a potent inhibitor of both double-stranded DNA virus Bombyx mori nucleopolyhedrovirus (BmNPV) and single-stranded RNA virus porcine reproductive and respiratory syndrome virus (PRRSV). Surface plasmon resonance (SPR) revealed that quercetin targets host ubiquitin-activating enzyme 1 (Uba1) homologs. Uba1 knockdown reduced viral proliferation and enhanced the antiviral effect of quercetin, whereas Uba1 overexpression functioned oppositely. Quercetin bound Uba1 homologs with high affinity. Notably, mutation of two binding residues, Q977 and G978, significantly disrupted the binding between BmUba1 and quercetin, and abolished quercetin’s antiviral activity. Quercetin obstructed the transfer of ubiquitin from Uba1 to the E2 enzyme Ubc6, impairing the ubiquitination process. Similarly, quercetin inhibited PRRSV proliferation via targeting Uba1 in mammals. These findings elucidate the molecular mechanism underlying the pharmacological effects of quercetin, providing a theoretical basis for the development of novel antiviral agents against both DNA and RNA viruses.
Focusing on BmNPV and PRRSV, this study reveals that quercetin inhibits both DNA and RNA viruses by targeting Uba1 homologs, disrupting ubiquitin transfer between E1 and E2 enzymes. Mutations in key residues on Uba1 impair the binding with quercetin, thus lost the antiviral effect of quercetin. The conserved mechanism across species underscores quercetin’s broad-spectrum antiviral potential, providing a theoretical basis for developing effective antiviral drugs against diverse viral infections.
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