scholarly journals In Vitro and In Silico Study of 5-[(4-Methylpiperazin-1-yl) methyl]dehydrozingerone and 5-(Morpholin-4-ylmethyl) dehydrozingerone as Lipoxygenase and Xanthine Oxidase Inhibitor

2021 ◽  
Vol 83 (5) ◽  
Author(s):  
Hayun Hayun ◽  
Razanah Hanifati ◽  
Annisa Diana Pratiwik
Keyword(s):  
Xanthine Oxidase ◽  
In Silico ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
In Silico Study

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 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 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.

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.

Isolation of a bioactive flavonoid from Spilanthes calva D.C. in vitro xanthine oxidase assay and in silico study

2014 ◽  
Vol 4 (4) ◽  
pp. 481-484 ◽  
Author(s):  
P. Jayaraj ◽  
Bijo Mathew ◽  
B. Parimaladevi ◽  
V. Alex Ramani ◽  
R. Govindarajan
Keyword(s):  
Xanthine Oxidase ◽  
In Silico ◽  
In Silico Study

scholarly journals Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nor-Ashila Aladdin ◽  
Khairana Husain ◽  
Juriyati Jalil ◽  
Carla Wulandari Sabandar ◽  
Jamia Azdina Jamal
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Oxidase Inhibitor ◽  
Bone Diseases ◽  
Spectroscopic Techniques ◽  
Xanthine Oxidase Inhibitor ◽  
Margaric Acid ◽  
Bioassay Guided Fractionation

Abstract Background In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds. Method Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques. Results The most active dichloromethane extract of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL). Conclusion This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.

Beneficial Effects of Xanthine Oxidase Inhibitor, Topiloxostat, on Experimental Diabetic Neuropathy in Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 549-P
Author(s):  
HIROKI MIZUKAMI ◽  
REMINA KOYAMA ◽  
KAZUHISA TAKAHASHI ◽  
SHO OSONOI ◽  
SAORI OGASAWARA ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Beneficial Effects ◽  
Experimental Diabetic Neuropathy
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