scholarly journals Natural Xanthine Oxidase Inhibitor 5-O-Caffeoylshikimic Acid Ameliorates Kidney Injury Caused by Hyperuricemia in Mice

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7307
Author(s):  
Dong Zhang ◽  
Mojiao Zhao ◽  
Yumei Li ◽  
Dafang Zhang ◽  
Yong Yang ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
In Silico ◽  
Active Sites ◽  
Kidney Injury ◽  
Oxidase Inhibitor ◽  
Mice Model ◽  
Xanthine Oxidase Inhibitor ◽  
Sgr A

Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50 of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of −8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

scholarly journals Standardization of Diploid Codonopsis laceolata Root Extract as an Anti-Hyperuricemic Source

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2065
Author(s):  
Seung-Yub Song ◽  
So-Hyeon Bok ◽  
Sung-Ho Lee ◽  
Min-Hee Kim ◽  
Hee-Ock Boo ◽  
...  
Keyword(s):  
Quality Control ◽  
Xanthine Oxidase ◽  
Ethanolic Extract ◽  
Functional Materials ◽  
Extraction Methods ◽  
Oxidase Inhibitor ◽  
Root Extract ◽  
Xanthine Oxidase Inhibitor

Codonopsis lanceolate exerts various medicinal effects and has been used as a traditional medicine for inflammation, asthma, gastritis, and liver disease. Recently, we reported the xanthine oxidase inhibitory activity of C. lanceolata extract and that lobetyolin, one of the key components, was a xanthine oxidase inhibitor. Lobetyolin showed anti-hyperuricemic activity in vitro and in vivo. In this study, we prepared various types of C. lanceolata extracts for the development of functional materials and natural drugs. We present the optimal analytical approach for the quality control and extraction optimization of C. lanceolata preparations. We established and validated a HPLC analysis for easy separation and quantification of the lobetyolin biomarker. Solvent extracts of C. lanceolata root were prepared and the profiles of the active marker and the optimal extraction methods were evaluated. The 100% ethanolic extract demonstrated the highest lobetyolin content. The validated HPLC method confirmed that lobetyolin was present in C. lanceolata root extracts. We suggest that the anti-hyperuricemic activities of C. lanceolata extract could be attributed to this marker compound. The results proposed that the 100% ethanolic extract could be used for the prevention of hyperurecemia, and that this analytical method and biomarker could be useful for the quality control of C. lanceolata preparations.

scholarly journals Optimization of the Extraction Conditions and Biological Evaluation of Dendropanax morbifera H. Lev as an Anti-Hyperuricemic Source

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3313 ◽  
Author(s):  
Seung-Sik Cho ◽  
Seung-Hui Song ◽  
Chul-Yung Choi ◽  
Kyung Park ◽  
Jung-Hyun Shim ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Ethanol Extract ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Dendropanax Morbifera ◽  
Hexane Extracts ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Ethanol Extracts

Dendropanax morbifera H. Levis a medicinal plant native to South Korea, East Asia, and South America. Among some 75 species, one species grows in Korea. In previous studies, D. morbifera extracts with anti-oxidant, anti-inflammatory, anti-complementary and anti-cancer activities were reported. The present study aims to investigate optimization of extraction and evaluation of anti-hyperuricemic effects of D. morbifera leaf and the phytochemicals contained therein. Ethanol and hexane extract were found to display the best xanthine oxidase inhibition among six types of solvent and water extract. The antioxidant effect of the ethanol extract was superior to that of the hexane extract. The DPPH radical scavenging effect of the ethanol and hexane extracts were 81.52 ± 1.57% and 2.69 ± 0.16. The reducing power of the ethanol and hexane extracts were 9.71 ± 0.15 and 0.89 ± 0.01 mg/g equivalent of gallic acid. Total phenols of the ethanol and hexane extracts were 6.53 ± 0.16 and 0.63 ± 0.001 mg/g equivalent of gallic acid. In addition, we compared the two marker compounds from D. morbifera, chlorogenic acid and rutin, which were determined in the ethanol extract at 0.80 ± 0.03% and 0.52 ± 0.01%, respectively. We found that the ethanol extracts showed better xanthine oxidase inhibition than hexane extracts. Especially, ethanol extracts showed higher antioxidant activity than hexane extracts. Based on these results, we selected the ethanol extract as an effective xanthine oxidase inhibitor and confirmed whether ethanol extracts showed xanthine oxidase inhibition in animal experiments. The in vivo mouse study demonstrated that ethanol extract of D. morbifera leaf at the dose of 300 mg/kg could inhibit blood/hepatic xanthine oxidase activity and this result shows that the xanthine oxidase inhibitory activity in vitro is reproduced in vivo. The present study showed that ethanol extract was optimal xanthine oxidase inhibitor which can be applied to prevent diseases related to hyperuricemia.

scholarly journals Absorption of Hemoglobin Iron: The Role of Xanthine Oxidase in the Intestinal Heme-Splitting Reaction

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 94-103 ◽  
Author(s):  
R. BEN DAWSON ◽  
SHEILA RAFAL ◽  
LEWIS R. WEINTRAUB
Keyword(s):  
Epithelial Cell ◽  
Xanthine Oxidase ◽  
Intestinal Epithelial Cell ◽  
Oxidase Inhibitor ◽  
Small Intestinal Mucosa ◽  
Intestinal Epithelial ◽  
Sephadex Column ◽  
Xanthine Oxidase Inhibitor

Abstract Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.

scholarly journals [18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations

2019 ◽  
Vol 12 (1) ◽  
pp. 58-71 ◽  
Author(s):  
Suchitil Rivera-Marrero ◽  
Laura Fernández-Maza ◽  
Samila León-Chaviano ◽  
Marquiza Sablón-Carrazana ◽  
Alberto Bencomo-Martínez ◽  
...  
Keyword(s):  
In Silico ◽  
Specific Activity ◽  
Senile Plaques ◽  
Coupling Reaction ◽  
In Vitro Assays ◽  
Mice Model ◽  
Wild Mice ◽  
In Silico Studies

Background: Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. </p><p> Methods: Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/A&#223; plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. </p><p> Results: The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the A&#946;-peptide, mainly through &#960;-&#960; interactions. According to a dynamic simulation study the ligand-A&#946; peptide complexes are stable in simulation-time (&#916;G = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to A&#946; plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11&#177;0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. </p><p> Conclusion: The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of A&#946; senile plaques.

Xanthine oxidase inhibitory activity of nicotino/isonicotinohydrazides: A systematic approach from in vitro , in silico to in vivo studies

2017 ◽  
Vol 25 (8) ◽  
pp. 2351-2371 ◽  
Author(s):  
Humaira Zafar ◽  
Muhammad Hayat ◽  
Sumayya Saied ◽  
Momin Khan ◽  
Uzma Salar ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Systematic Approach ◽  
In Vivo Studies

scholarly journals Allopurinol inhibits excess glucose-induced trophoblast IL-1β and ROS production

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Masaru Negi ◽  
Melissa J Mulla ◽  
Christina S Han ◽  
Vikki M Abrahams
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Human Trophoblast ◽  
Xanthine Oxidase Inhibitor ◽  
Adverse Pregnancy ◽  
Excess Glucose ◽  
Trophoblast Cell Line

Pre-gestational diabetes is a risk factor for preeclampsia, a condition associated with inflammatory markers, a dysregulated angiogenic profile, and impaired placentation. Using an in vitro model, we previously reported that hyperglycemic levels of glucose induced a pro-inflammatory (IL-1β, IL-8, RANTES, GRO-α), anti-angiogenic (sFlt-1) and anti-migratory profile in a human trophoblast cell line. The IL-1β response to excess glucose was mediated by uric acid-induced activation of the NLRP3 inflammasome. Allopurinol is a xanthine oxidase inhibitor that inhibits uric acid and reactive oxygen species (ROS) production. Thus, we sought to test the effects of allopurinol on the IL-1β and other inflammatory, angiogenic and migratory responses that are triggered in the trophoblast by excess glucose. Under excess glucose conditions, allopurinol significantly inhibited trophoblast secretion of inflammatory IL-1β; caspase-1 activity; IL-8; RANTES; and GRO-α. Allopurinol also significantly inhibited excess glucose-induced trophoblast secretion of anti-angiogenic sFlt-1. The presence of IL1Ra significantly inhibited excess glucose-induced trophoblast IL-8 and GRO-α secretion but had no effect on RANTES or sFlt-1. Conversely, DPI, a ROS inhibitor, significantly inhibited excess glucose-induced trophoblast GRO-α and sFlt-1 secretion, but had no effect on IL-8 or RANTES. Together, our findings indicate that the xanthine oxidase inhibitor allopurinol inhibited excess glucose-induced trophoblast IL-1β secretion. Additionally, through its inhibition of both IL-1β and ROS production by the trophoblast, allopurinol reduced the additional pro-inflammatory and anti-angiogenic responses to excess glucose. Thus, allopurinol may be a candidate medication to prevent placental dysfunction and adverse pregnancy outcomes, such as preeclampsia, in pregnant women with diabetes.

scholarly journals Delphinidin-3-O-sambubioside: a novel xanthine oxidase inhibitor identified from natural anthocyanins

2020 ◽  
Author(s):  
Jiahong Xie ◽  
Haoxin Cui ◽  
Yang Xu ◽  
Lianghua Xie ◽  
Wei Chen
Keyword(s):  
Fluorescence Quenching ◽  
Xanthine Oxidase ◽  
Conformational Changes ◽  
Inhibitory Activity ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Computational Docking ◽  
Inhibitory Activities ◽  
Monomeric Anthocyanins

Abstract Objectives This study was conducted to investigate the xanthine oxidase (XO) inhibitory activities of 18 monomeric anthocyanins from berry fruits and roselle, and to illustrate the underlying mechanism of the most active anthocyanin delphinidin-3-O-sambubioside. Materials and Methods 18 monomeric anthocyanins were prepared and purified in our lab. The inhibitory properties of anthocyanins were investigated by in vitro inhibitory activity studies and fluorescence quenching studies; the inhibitory mechanism were explored through kinetic studies, fluorescence quenching studies, circular dichroism analysis and computational docking simulations. Results XO inhibitory activities of anthocyanins were related to the structures of B rings and glycosides. Among all the tested anthocyanins, delphinidin-3-O-sambubioside showed the most potent inhibitory activity with an IC50 of 17.1 μM, which was comparable to the positive control allopurinol. Spectroscopic results revealed that delphinidin-3-O-sambubiosid could spontaneously interact with XO and induce conformational changes. Computational docking study indicated that delphinidin-3-O-sambubioside could bind to XO with a proper orientation, stably formed π-π interactions and hydrogen bonds with key residues, thus preventing the substrate from entering the active pocket. Conclusions In brief, our study identified delphinidin-3-O-sambubioside as a potent XO inhibitor from natural anthocyanins, which is potentially applicable for prevention and treatment of hyperuricemia.

In vitro and in vivo activities of imipenem combined with BLI-489 against class D β-lactamase-producing Acinetobacter baumannii

2020 ◽  
Author(s):  
Yung-Chih Wang ◽  
Shu-Wei Huang ◽  
Ming-Hsien Chiang ◽  
I-Ming Lee ◽  
Shu-Chen Kuo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Active Sites ◽  
Synergistic Effects ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Class D ◽  
Time Kill

Abstract Background According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like β-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). Objectives In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D β-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. Methods A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time–kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. Results Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time–kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. Conclusions Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

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