Natural compounds with xanthine oxidase inhibitory activity: A review

Mehmood, Arshad; Ishaq, Muhammad; Zhao, Lei; Safdar, Bushra; Rehman, Ashfaq‐ur; Munir, Masooma; Raza, Ali; Nadeem, Muhammad; Iqbal, Waheed

doi:10.1111/cbdd.13437

Cited by 105 publications

(59 citation statements)

References 132 publications

(230 reference statements)

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“…Hence, alternative medicines with fewer side effects are required to tackle UA disorders. Plants have been used as a medicinal source, and natural medicines have the potential to perform beneficial functions with fewer side effects than synthetic drugs; thus, researchers have focused on natural derivatives for the development of novel XOR inhibitors [152,153]. Flavones, coumarins, and curcumin represent the class of secondary metabolites possessing xanthine oxidase inhibitory potential [154,155].…”

Section: Febuxostatmentioning

confidence: 99%

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

Liu

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.

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Section: Febuxostatmentioning

confidence: 99%

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

Liu

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Many enzyme inhibitors have been identified and isolated from the extracts of vegetables and herbs (Liu et al., 2018, 2019; Zhang et al., 2011). Various bioactive compounds, including polyphenols, saponins, terpenoids, phenylethanoid glycosides, and alkaloids, have been reported to be effective XO inhibitors (Amessis‐Ouchemoukh et al., 2017; Mehmood et al., 2019; Shi, Chen, Bao, Zeng, & Cai, 2019; Zhu et al., 2017). Among them, polyphenols have attracted most of the attentions from researchers because of their huge amounts and diverse biological activities such as antioxidation, antitumor, anti‐inflammatory, antiviral, antihypertensive, hypoglycemic, and enzyme inhibitory effects (Cao et al., 2019; Xie, Yang, Chen, & Xiao, 2014; Xie, Yang, Tang, Chen, & Ren, 2015; Zhao et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Advances in structures required of polyphenols for xanthine oxidase inhibition

et al. 2020

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Polyphenols have been used as natural medicaments for the management of hyperuricemia for a long history. They have been attracted many interests because of the little side effects in curing hyperuricemia, which is an important advantage over the antihyperuricemic drugs. In this review, the structure-activity relationships for polyphenols as xanthine oxidase (XO) inhibitors were discussed. It is concluded that the presence of hydroxyl groups, which influences the inhibitory effects, is closely related to whether the substitutions increase the steric hindrance or disturb the interaction of flavonoid with the catalytic site of XO, and the increased size of the molecule after glycosylation may increase the steric hindrance between flavonoid and XO, and consequently reducing the competitive inhibition behaviors. However, there is no obtained simple general rule that can comprehensively describe the effects of structural alteration on the inhibition activity because the results are varied among different subclasses of polyphenols. In addition, the inhibition mechanisms are mainly assumed as polyphenol binding to the active site of XO and hindering the entrance of xanthine or the discharge of uric acid and diffusion of O 2− radical.

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“…In addition to these clinically used drugs, over the years, several other molecules with XO inhibitory activity have been described [6][7][8][9]. Despite the existence of some reviews in this topic [6,7,[9][10][11], it is necessary to complement these works with a study focusing on the hit to lead evolution in the development of new XO inhibitors with improved potency and safety when compared with the clinically used drugs. Interestingly, as can be seen in this review, natural molecules and semisynthetic analogues and derivatives constitute a large group of compounds being explored at the moment in this context.…”

Section: Introductionmentioning

confidence: 99%

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

Serrano

Figueiredo

Almeida

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Hyperuricemia is characterized by elevated uric acid (UA) levels on blood, which can lead to gout, a common pathology. These high UA levels are associated with increased purine ingestion and metabolization and/or its decreased excretion. In this field, xanthine oxidase (XO), by converting hypoxanthine and xanthine to UA, plays an important role in hyperuricemia control. Based on limitations and adverse effects associated with the use of allopurinol and febuxostat, the most known approved drugs with XO inhibitory effect, the search for new molecules with XO activity is growing. However, despite the high number of studies, it was found that the majority of tested products with relevant XO inhibition were left out, and no further pharmacological evaluation was performed. Thus, in the present review, available information published in the past six years concerning isolated molecules with in vitro XO inhibition complemented with cytotoxicity evaluation as well as other relevant studies, including in vivo hypouricemic effect, and pharmacokinetic/pharmacodynamic profile was compiled. Interestingly, the analysis of data collected demonstrated that molecules from natural sources or their mimetics and semisynthetic derivatives constitute the majority of compounds being explored at the moment by means of in vitro and in vivo animal studies. Therefore, several of these molecules can be useful as lead compounds and some of them can even have the potential to be considered in the future clinical candidates for the treatment of hyperuricemia.

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Natural compounds with xanthine oxidase inhibitory activity: A review

Cited by 105 publications

References 132 publications

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

Advances in structures required of polyphenols for xanthine oxidase inhibition

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

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