On-chip assay for determining the inhibitory effects and modes of action of drugs against xanthine oxidase

Naoghare, Pravin K.; Kwon, Ho Taik; Song, Joon Myong

doi:10.1016/j.jpba.2009.07.020

Cited by 13 publications

(4 citation statements)

References 33 publications

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“…Chao et al [ 27 ] considered that naringenin had a stronger inhibitory effect toward iNOS and COX-2 than did an equal concentration of vitamin C. Another study showed the possible interaction between naringenin and XO. Naoghare et al [ 28 ] proposed that XO was also inhibited by naringenin because the concomitant hydrophilicity and hydrophobicity within the naringenin molecule helped it to bind the active site of XO more strongly, thereby reducing the activity of XO. In the present study, the pharmacological network built showed that naringenin interacted with iNOS and XO.…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

Liu

Fěng

2015

Evidence-Based Complementary and Alternative Medicine

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Zhi-Zi-Da-Huang decoction (ZZDHD), a classic traditional Chinese medicine (TCM) formula, has been used for centuries to treat alcoholic liver disease. Reliable therapeutics of ZZDHD has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the antioxidative mechanism of ZZDHD as an effective therapeutic approach to treat alcoholic liver disease. Multiple active compounds of ZZDHD were screened based on four key original enzymes (cytochrome P450 2E1, xanthine oxidase, inducible nitric oxide synthase, and cyclooxygenase-2) involved in ethanol-induced oxidative stress damage. A drug-target network was constructed through network pharmacology analysis, which predicted the relationships of active ingredients to the targets. Some results had been verified by the previous experimental pharmacological studies; meanwhile, it was first reported that xanthine oxidase and eriocitrin, neoeriocitrin, isorhoifolin, and poncirin had interactions. The network pharmacology strategy used provided a forceful tool for searching the mechanism of action of TCM formula and novel bioactive ingredients.

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Section: Resultsmentioning

confidence: 99%

Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

Liu

Fěng

2015

Evidence-Based Complementary and Alternative Medicine

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“…However, the IC 50 of naringenin (206.3 μM) is much lower than allopurinol (14.67 μM) (Naoghare et al, 2010;Umamaheswari et al, 2013). Dong et al (2016) stated that pinobanksin was a mixed-type inhibitor XO, with an IC 50 of 125.1 μM.…”

Section: In Vitro Structure-activity Relationship Analysis Of Flavanonesmentioning

confidence: 99%

“…Naringenin contains hydrophilic and hydrophobic groups, which contribute to its ability to tightly bind to the active region of XO, thereby decreasing XO activity. However, the IC 50 of naringenin (206.3 μM) is much lower than allopurinol (14.67 μM) (Naoghare et al., 2010; Umamaheswari et al., 2013). Dong et al.…”

Section: Mechanism Of Xo Activity and Hua Inhibition By Flavonoidsmentioning

confidence: 99%

Mechanism of flavonoids inhibiting xanthine oxidase and alleviating hyperuricemia from structure–activity relationship and animal experiments: A review

Xue

Gong

et al. 2023

Food Frontiers

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Hyperuricemia (HUA) is a metabolic disease caused by excessive uric acid in patients. Flavonoids have attracted extensive attention due to their safety, effectiveness, and little side effects in the treatment of HUA and inhibition of xanthine oxidase (XO) activity. In this paper, the studies on the treatment of HUA and the inhibition of XO activity by flavonoids (including flavones, flavonols, flavanones, flavanols, isoflavonoids, anthocyanins, and chalcones) were comprehensively reviewed from the aspects of structure–activity relationship and animal experiments. Results showed that hydrogen bonds and hydrophobic interactions were the two most important forces involved in the interaction between flavonoids and XO. Flavonoids could combine with the hydrophobic cavity of XO to cause changes in XO structure and influence the action of enzyme and substrate, thereby decreasing the catalytic activity of XO. Moreover, flavonoids undergo a series of metabolic reactions in the organism, which plays a role in alleviating HUA by affecting the expression of related genes and proteins (e.g., glucose transporter 9, urate transporter 1, and organic anion transporter 1) in the kidneys, liver, and intestinal tract of the organism and changing the internal environment in organs. In addition, this paper provides new perspectives on the shortcomings of the current research, to promote the in‐depth development and application of flavonoids.

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“…Xanthine oxidase (XOD) is a metalloprotein that catalyzes the purine catabolism and also of major medical interest as a target of many drugs against several diseases in humans, such as gout, hyperuricaemia and chronic heart failure [12]. Although XOD has been implicated as a key oxidative enzyme to construct electrochemical sensors for the determination of hypoxanthine and xanthine [13–15], no electrochemical investigation has been performed on the studies of the drug metabolism by XOD.…”

Section: Introductionmentioning

confidence: 99%

Study of Drug Metabolism by Xanthine Oxidase

Zhao

Yang

et al. 2012

IJMS

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In this work, we report the studies of drug metabolism by xanthine oxidase (XOD) with electrochemical techniques. Firstly, a pair of stable, well-defined and quasi-reversible oxidation/reduction peaks is obtained with the formal potential at −413.1 mV (vs. SCE) after embedding XOD in salmon sperm DNA membrane on the surface of pyrolytic graphite electrode. Then, a new steady peak can be observed at −730 mV (vs. SCE) upon the addition of 6-mercaptopurine (6-MP) to the electrochemical system, indicating the metabolism of 6-MP by XOD. Furthermore, the chronoamperometric response shows that the current of the catalytic peak located at −730 mV increases with addition of 6-MP in a concentration-dependent manner, and the increase of the chronoamperometric current can be inhibited by an XOD inhibitor, quercetin. Therefore, our results prove that XOD/DNA modified electrode can be efficiently used to study the metabolism of 6-MP, which may provide a convenient approach for in vitro studies on enzyme-catalyzed drug metabolism.

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On-chip assay for determining the inhibitory effects and modes of action of drugs against xanthine oxidase

Cited by 13 publications

References 33 publications

Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

Network Pharmacology-Based Antioxidant Effect Study of Zhi-Zi-Da-Huang Decoction for Alcoholic Liver Disease

Mechanism of flavonoids inhibiting xanthine oxidase and alleviating hyperuricemia from structure–activity relationship and animal experiments: A review

Study of Drug Metabolism by Xanthine Oxidase

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