Xanthine Oxidase Inhibitor Research Articles

Physical and Functional Properties of Powders Obtained during Spray Drying of Cyani flos Extracts.

Edible flowers are a potential source of bioactive ingredients and are also an area of scientific research. Particularly noteworthy are Cyani flos, which have a wide range of uses in herbal medicine. The below study aimed to investigate the influence of selected soluble fiber fractions on the selected properties of physical and biochemical powders obtained during spray drying a water extract of Cyani flos. The drying efficiency for the obtained powders was over 60%. The obtained powders were characterized by low moisture content (≤4.99%) and water activity (≤0.22). The increase in the addition of pectin by the amount of 2-8% in the wall material resulted in a decrease in hygroscopicity, water solubility, and protection of flavonoids and anthocyanins both before and after digestion in the tested powders in comparison to the sample with only inulin as a carrier. Additionally, it was noted that all samples were characterized by high bioaccessibility when determining antioxidant properties and xanthine oxidase inhibition.

Allopurinol: Clinical Considerations in the Development and Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Other Associated Drug Reactions.

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, requiring cessation of the medication with initial signs of rash or other early manifestations of SJS/TEN. One major consideration in the increased risk of allopurinol-mediated or modulated SJS/TEN is the need to have a lower dose in the setting of renal disease. The purpose of this review is not only to examine the involvement of allopurinol in SJS/TEN but also to provide detailed information about the drug, allopurinol, and general features and characteristics of SJS/TEN and other associated drug reactions.

A phenome-wide association and factorial Mendelian randomization study on the repurposing of uric acid-lowering drugs for cardiovascular outcomes

Uric acid has been linked to various disease outcomes. However, it remains unclear whether uric acid-lowering therapy could be repurposed as a treatment for conditions other than gout. We first performed both observational phenome-wide association study (Obs-PheWAS) and polygenic risk score PheWAS (PRS-PheWAS) to identify associations of uric acid levels with a wide range of disease outcomes. Then, trajectory analysis was conducted to explore temporal progression patterns of the observed disease outcomes. Finally, we investigated whether uric acid-lowering drugs could be repurposed using a factorial Mendelian randomization (MR) study design. A total of 41 overlapping phenotypes associated with uric acid levels were identified by both Obs- and PRS- PheWASs, primarily cardiometabolic diseases. The trajectory analysis illustrated how elevated uric acid levels contribute to cardiometabolic diseases, and finally death. Meanwhile, we found that uric acid-lowering drugs exerted a protective role in reducing the risk of coronary atherosclerosis (OR = 0.96, 95%CI: 0.93, 1.00, P = 0.049), congestive heart failure (OR = 0.64, 95%CI: 0.42, 0.99, P = 0.043), occlusion of cerebral arteries (OR = 0.93, 95%CI: 0.87, 1.00, P = 0.044) and peripheral vascular disease (OR = 0.60, 95%CI: 0.38, 0.94, P = 0.025). Furthermore, the combination of uric acid-lowering therapy (e.g. xanthine oxidase inhibitors) with antihypertensive treatment (e.g. calcium channel blockers) exerted additive effects and was associated with a 6%, 8%, 8%, 10% reduction in risk of coronary atherosclerosis, heart failure, occlusion of cerebral arteries and peripheral vascular disease, respectively. Our findings support a role of elevated uric acid levels in advancing cardiovascular dysfunction and identify potential repurposing opportunities for uric acid-lowering drugs in cardiovascular treatment.

Inhibitiory mechanism of phloretin on xanthine oxidase and its synergistic effect with allopurinol and febuxostat

The development of natural xanthine oxidase (XO) inhibitors is an effective strategy for the treatment of hyperuricemia. In this study, the inhibition mechanism of phloretin on XO and its joint inhibition with clinical drugs (allopurinol and febuxostat) were investigated, using multispectroscopic and molecular simulation techniques. The results showed that phloretin reversibly inhibited XO in a mixed type with an IC50 value of 31.83 ± 0.32 μM. Phloretin quenched the fluorescence of XO with a static mechanism and hydrophobic interactions were the key binding force of phloretin binding to XO. Furthermore, the interaction between phloretin and XO resulted in a more relaxed structure and less stable of the enzyme with a reduction in the α-helix content from 21.5% to 11.3%. The heatmap analysis showed that a combination of phloretin (15 μM) and allopurinol (10 μM) or phloretin (30 μM) and febuxostat (0.01 μM) exhibited the strongest synergistic effect on XO inhibition in a mixed manner. The combination of phloretin and allopurinol/febuxostat enhanced the binding affinity with XO compared to the inhibitors individually. Molecular docking indicated that phloretin, allopurinol and febuxostat bound to different sites of XO to produce a synergistic inhibition by preventing substrate access to the Mo activity center and affecting electron transfer. This study may provide theoretical references for the development of phloretin and its formulation with clinical drugs as uric acid-lowering food functional factor or drug.

Investigation of in vitro biological activity of young Hordeum vulgare leaf in correlation with its bioactive compounds.

Young shoots of cereals are widely regarded as superfoods with health benefits attributed to their potential antioxidant activity and antioxidant-related effects (e.g. anticancer). The current study aimed to examine the chemical characteristics of Hordeum vulgare methanolic and aqueous extracts and assess their antioxidant activity using the DDPH and ORAC. Furthermore, the inhibitory effect of xanthine oxidase was screened. TLC bioautography was employed to determine the polarity of the compounds present in the extracts that exhibited the most potent free radical scavenging activity. Total flavonoid content of the methanolic and aqueous extracts was 0.14mgQE/g and 0.012mgQE/g, respectively. The antioxidant activity of the methanolic extract was found to be more potent, with a value of 0.97 ± 0.13mmolTE/g than the aqueous extract which had no activity. This study presents novel findings on the xanthine inhibitory activity of H. vulgare. The methanolic extract demonstrated moderate inhibition of xanthine oxidase with a value of 23.24%. The results of our study were compared with the phytochemical and pharmacological analysis of Triticum aestivum, and further comparison was made with the data reported in the literature. Inconsistencies were observed in the chemical and pharmacological properties of H. vulgare, which could be a result of using herbal material harvested in different vegetative phases and various methods used for extraction. The findings of our study indicate that the timing of the harvest and extraction method may play crucial role in attaining the optimal phytochemical composition of H. vulgare, hence enhancing its pharmacological activity.

A study on the antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activity of the Artemisia vulgaris L. extract and its fractions

Ethnopharmacological relevanceVietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. Aim of the studyThe study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. MethodsAccording to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. ResultsThe assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 μM). ConclusionThe results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.

Quercetin as the primary xanthine oxidase inhibitor compound in Maclura tricuspidata leaf

Maclura tricuspidata (MT) leaf demonstrated various health benefits, notably the inhibition of xanthine oxidase (XOD) activity, which is crucial in the management of hyperuricaemia and many diseases related to oxidative stress. This study aimed to identify the primary compound responsible for this inhibitory effect. Through a systematic investigation, MT leaf extracts were subjected to solvent-solvent partitioning using ethyl acetate, n-hexane, n-butanol, and dichloromethane. Further purification involved adsorption and desorption using Amberlite XAD-2 resin, followed by column chromatography on Silica Gel and Sephadex LH-20. The purified compounds were analysed using UPLC-QTOF-MS coupled with NMR spectroscopy. Our findings identified quercetin, a phenolic compound, as the most significant inhibitor of XOD activity in MT leaf, with an IC50 value of 212.92 μg/ml. This is the first report of purifying and identifying a single compound responsible for XOD inhibition in MT.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

Allopurinol versus Trimetazidine for the Treatment of Angina: A Randomized Clinical Trial.

Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y.

Development and Validation of an RP-HPLC Method for the Estimation of the Selective Xanthine Oxidase Inhibitor Topiroxostat in Tablets: Greenness Analysis Using AGREE Score

ABSTRACT Background: Xanthine oxidoreductase (XOR) is a key enzyme in the breakdown of purines. It converts hypoxanthine to xanthine and then xanthine to uric acid. Excess uric acid can lead to gout, a painful type of arthritis. XOR inhibitors such as topiroxostat are used to treat gout by reducing uric acid production, preventing the formation of uric acid crystals. Aim and Objectives: A simple and sensitive analytical method was developed to quantify the xanthine oxidase inhibitor topiroxostat in tablet formulation. Materials and Methods: The analyte was seperated on a Phenomenex Luna C18 column (250 mm × 4.6 mm × 5 μm particle size) using a mobile phase of potassium dihydrogen orthophosphate pH 2.5 adjusted with orthophosphoric acid and acetonitrile (60:40 % v/v) pumped at 1.0 mL/min. Detection of the effluent was done using a UV detector at a wavelength of 215 nm. Results: The retention time for topiroxostat was 3.81 min. The drug showed linearity within the concentration range of 18–42 μg/mL. The accuracy of the method was considered satisfactory and the mean recovery percentage in the acceptable range of 99.33-100.45 %. Conclusion: The RP-HPLC method was successfully developed and validated according to ICH guidelines. The AGREE software was used to assess the environmental friendliness score of the proposed method, which was determined to be 0.79. The proposed method was simple, precise, sensitive, rapid, and robust for estimating topiroxostat in tablets.

Inhibitory capacity of xanthine oxidase, and anticancer activity of compounds from Sarcandra glabra (Thunb.) Nakai flower

The flower of Sarcandra glabra (Thunb.) Nakai (FSN) has been considered an important supplementation material in natural flower-flavoured tea products in Vietnam. The present work has considerable significance for adding pharmacological value of FSN. Two compounds, namely emodin and methyl rosmarinate, were identified for the first time from a methanolic extract of FSN from Vietnam while analysing the inhibitory capacity of xanthine oxidase and cytotoxic activities. High levels of xanthine oxidase inhibiting capacity and cytotoxicity activity against HepG2 and A549 cancer cell lines were detected from emodin, with IC50 of 4.88 ± 0.42, 13.72 ± 0.48, and 18.33 ± 0.10 µg/mL, respectively. Emodin also activated the apoptotic factors of caspase-9, Bax, and PARP in HepG2, and caspase-3/9 and p53 in A549. Our results revealed for the first time the xanthine oxidase inhibitory effect of M70 with IC50 of 34.15 ± 1.33 µg/mL, which would shed light on its potential application for developing anti-hyperuricemia agents. The present work suggested that using flower-flavoured tea product of FSN could have many health benefits for gout patients.

Substrate Influence on Enzymatic Activity in Cordyceps militaris for Health Applications

Cordyceps militaris, well known for its therapeutic potential in managing type-2 diabetes through the inhibition of α-amylase and α-glucosidase enzymes, was the central focus of this research, which investigated the influence of various cultivation substrates on its enzymatic inhibitory properties and bioactive compound content. Previous studies have primarily focused on the general pharmacological benefits of C. militaris but have not thoroughly explored how different substrates affect its bioactive profile and enzyme inhibitory activities. This study aimed to evaluate the impact of substrate selection on the enzyme inhibition activities and the levels of bioactive compounds such as cordycepin and adenosine in C. militaris, demonstrating that substrate selection markedly affects both these enzymes’ inhibition activities and bioactive compound levels. Particularly, C. militaris fruiting bodies grown on Brihaspa atrostigmella showed the highest concentrations of cordycepin (2.932 mg/g) and adenosine (1.062 mg/g). This substrate also exhibited the most potent α-glucosidase inhibition with an IC50 value of 336.4 ± 16.0 µg/mL and the most effective α-amylase inhibition with an IC50 value of 504.6 ± 4.2 µg/mL. Conversely, C. militaris cultivated on the solid residues of Gryllus bimaculatus displayed the strongest xanthine oxidase (XOD) inhibition, with the lowest IC50 value of 415.7 ± 11.2 µg/mL. These findings highlight the critical role of substrate choice in enhancing the medicinal properties of C. militaris, suggesting that optimized cultivation can enhance the bioactive properties for more effective natural therapies for diabetes and other metabolic disorders. This study not only extends the understanding of C. militaris’ pharmacological potential but also illustrates its applicability in developing customized treatment options.

Identification of Anastatica hierochuntica L. Methanolic-Leaf-Extract-Derived Metabolites Exhibiting Xanthine Oxidase Inhibitory Activities: In Vitro and In Silico Approaches.

There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification, as well as predictions of their anticancer, pharmacokinetic, and toxic properties; oral bioavailability; and endocrine disruption using SwissADMET, PASS, ProTox-II, and Endocrine Disruptome web servers. A total of 12 metabolites, with a majority of flavonoids, were identified. Rutin, quercetin, and luteolin flavonoids demonstrated the highest ranked docking scores of -12.39, -11.15, and -10.43, respectively, while the half-maximal inhibitory concentration (IC50) values of these metabolites against XO activity were 11.35 µM, 11.1 µM, and 21.58 µM, respectively. In addition, SwissADMET generated data related to the physicochemical properties and drug-likeness of the metabolites. Similarly, the PASS, ProTox-II, and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of the prominent and promising therapeutic use of A. hierochuntica methanolic-leaf-extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies.

Exploring the mechanism and inhibitory effect of robinin on xanthine oxidase using multi-spectroscopy and molecular dynamics simulation methods

Xanthine oxidase (XOD) is a key enzyme in purine metabolism that is tightly associated with hyperuricemia (HUA). Natural flavonoids can inhibit XOD activity. In this study, the inhibitory activity and mechanism of the novel flavonoid robinin on XOD were analyzed using enzyme inhibition kinetics, multispectral techniques, molecular docking, and molecular dynamics (MD) simulations. Robinin reversibly inhibited the activity of XOD in a mixed competitive manner, with an IC50 value of 31.79 ± 0.15 μg/mL. Moreover, robinin spontaneously binds to a specific site on XOD and effectively quenches its intrinsic fluorescence via a single static quenching mechanism. The combination of XOD and robinin induced secondary structure rearrangement and conformational changes in XOD and prevented the entry of substrates, thus producing a strong inhibitory effect. Molecular docking and MD simulation revealed that robinin mainly binds to XOD through hydrogen bonding and hydrophobic interactions to form more stable complexes with a binding energy of −7.4 kcal/mol. Overall, this study established a theoretical reference for robinin as a promising natural XOD inhibitor for relieving HUA.

A strategy for inhibitors screening of xanthine oxidase based on colorimetric sensor combined with affinity chromatography technology

The discovery of enzyme inhibitors from natural products is a crucial aspect in the development of therapeutic drugs. However, the complexity of natural products presents a challenge in developing simple and efficient methods for inhibitor screening. Herein, we have developed an integrated analytical model for screening xanthine oxidase (XOD) inhibitors that combines simplicity, accuracy, and efficiency. This model utilizes a colorimetric sensor and affinity chromatography technology with immobilized XOD. The colorimetric sensor procedure can quickly identify whether there are active components in complex samples. Subsequently, the active components in the samples identified by the colorimetric sensor procedure were further captured, separated, and identified through affinity chromatography. The integrated analytical model can significantly enhance the efficiency and accuracy of inhibitor screening. The proposed method was applied to screen for an activity inhibitor of XOD in five natural medicines. As a result, a potential active ingredient for XOD, polydatin, was successfully identified from Polygoni Cuspidati Rhizoma et Radix. This work is anticipated to offer new insights for the screening of enzyme inhibitors from natural medicines.

Battle of the strategies: diet versus drug therapy for gout

The best results in combating gout are achieved through a combination of diet and drug therapy. Urate-lowering therapy, which includes febuxostat, has been shown to be more effective and convenient than diet when it comes to achieving and maintaining target uric acid (UA) levels in gout patients. Febuxostat, a xanthine oxidase inhibitor, helps to reduce UA levels in the blood by blocking its formation. This helps prevent the deposition of urate crystals in joints and tissues and reduces the frequency and severity of gout attacks. At the same time, a diet of low purine foods may also have some effect on UA levels. Diet can improve the results of drug treatment by reducing the need for medications and minimizing the risk of side effects. However, without adequate drug therapy, diet will not produce the desired results. Therefore, febuxostat remains the preferred urate-lowering treatment option for gout, especially given its proven efficacy in these patients.

Preparation and Characterization of Febuxostat Nanosuspension as Fast Dissolving Oral Film

Background: Quickly dissolved oral films are a widely accepted method of delivering drugs and help patients adhere to treatment regimens. Nanosuspensions (NS) are colloidal dispersions of drug particles with a submicron size, and their large surface area enhances the solubility and dissolution of low-water-soluble drugs. Febuxostat (FXT) is a non-purine xanthine oxidase inhibitor with a low dissolution rate that limits its absorption. Objective: To develop fast-dissolving oral films (FDOFs) containing FXT NS and convert NS into solid dosage forms to ease administration and accelerate drug release. Methods: FXT NS was prepared using Soluplus as a stabilizer and Tween80 as a co-stabilizer through an anti-solvent precipitation technique. We prepared FDOFs using a solvent casting method, utilizing hydrophilic polymers like pullulan, polyvinyl alcohol (PVA), gelatin, and plasticizers like polyethylene glycol (PEG400) and glycerin. The study assessed the film's thickness, weight, folding endurance, drug content, disintegration time, and drug release. We validated the drug's compatibility using FTIR, and conducted a crystallinity study using DSC and X-ray powder diffraction. Results: F4 was the optimized formula prepared using PVA and PEG400. In just three minutes, the F4 dissolution rate increased significantly (99.63% vs. 11.23%) compared to the FXT ordinary film. Also, it had good mechanical properties. Conclusions: FXT NS were successfully loaded into FDOFs with accepted properties.

FLAVONOIDS FOR ANTI-HYPERURICEMIA: A LITERATURE REVIEW

Background: Hyperuricemia is a condition on the level of uric acid in the blood increases, it is more than 6.0 mg/dL in women and more than 7.0 mg/dL in men and is currently a public health problem because of its increasing prevalence. Hyperuricemia is believed to have contributed to an increased risk of mortality and morbidity associated with various diseases such as metabolic syndrome, kidney disease, cardiovascular disease, etc. Flavonoids in plants can be used to help treat hyperuricemia due to it is believed to have low side effects. Objective: The aim of this article was to review the effect of flavonoids on plants as anti-hyperuricemia. Design: The design used in preparing this manuscript is an integrative review by reviewing articles on the impact of flavonoids as anti-hyperuricemia. Data Sources: Sources of information were obtained from research articles from 2004-2023 which were accessed through PubMed, Scopus, Sciendirect, SpringerLink, and Google Scholar. Review Methods: In the process of selecting articles to ensure the quality of the articles used in preparing this article, the authors used the PRISMA method. Results: In this article, 15 in vivo studies related to the effect of plants containing flavonoids (kaemferol, luteolin, apigenin, rutin quercetin, morin, butein, vitexin, etc.) on reducing uric acid levels by various mechanisms from previous studies. Conclusion: Based on several studies reported that flavonoids have an effect on lowering uric acid levels by inhibiting xanthine oxidase (XO) activity, affecting the expression of uric acid transporters in the kidneys which contribute to the increase of excretion of uric acid in urine.

Elucidating the substance basis and pharmacological mechanism of Fufang Qiling granules in modulating xanthine oxidase for intervention in hyperuricemia

Ethnopharmacological relevanceFufang Qiling granules (FQG), derived from the traditional Qiling Decoction with a longstanding clinical history, is utilized for the treatment of hyperuricemia (HUA). FQG is formulated with a combination of seven Chinese herbs based on the principles of traditional Chinese medicine (TCM) theories. Clinical evidence indicates that FQG exhibits favorable therapeutic effects in reducing uric acid (UA) levels and attenuating renal damage. Aim of this studyTo elucidate the potential active components and pharmacological mechanism of FQG in the treatment of HUA, and to provide an experimental basis for the development of efficient and low-toxicity TCM for HUA treatment. Materials and methodsA HUA rat model induced by potassium oxonate and adenine was established to initially evaluate the hypouricemic effects of FQG. Chemical analyses were conducted using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to investigate the active components and mechanism of FQG in the treatment of HUA. Potential Xanthine oxidase (XOD) inhibitors were screened from FQG based on ultrafiltration liquid chromatography and mass spectrometry (UF-LC-MS). Molecular docking, surface plasmon resonance (SPR) and circular dichroism (CD) spectroscopy were applied to validate the interactions between the active components and XOD. ResultsIn comparison to the model group, treatment with FQG significantly decreased serum UA, serum creatinine (CREA), serum blood urea nitrogen (BUN), and liver XOD activity. Additionally, the FQG administration notably ameliorated HUA-induced renal injury in rats. Through the pharmacodynamics of the HUA rat models and network pharmacology, it was found that XOD was a key pathway enzyme in UA metabolism. 18 XOD inhibitors were screened from FQG by UF-LC-MS, and 11 compounds with strong affinity were verified by SPR, molecular docking and CD spectroscopy. ConclusionIn summary, flavonoids, organic acids and saponins may be the active components in FQG that alleviate HUA. The primary mechanism of FQG involves inhibiting XOD enzyme activity in the plasma to reduce UA production, alleviating renal tubular epithelial cell necrosis, tubulointerstitial injury, fibrosis, and urate deposition, ultimately exerting a therapeutic effect on HUA.

Identification and molecular docking of xanthine oxidase and α-glucosidase inhibitors in Opuntia ficus-indica fruit.

Opuntia ficus-indica fruit (OFI) is rich in bioactive compounds, which can promote human health. In this work, the purified OFI extract was prepared from OFI and its bioactivities were investigated. Xanthine oxidase (XOD) and α-glucosidase (α-Glu) inhibitors of the purified OFI extract were screened and identified by bio-affinity ultrafiltration combined with UPLC-QTRAP-MS/MS technology. The inhibitory effect of these inhibitors on enzymes were verified, and the potential mechanism of action and binding sites of inhibitors with enzymes were revealed based on molecular docking. The results showed that the total phenolic content of the purified OFI extract was 355.03mg GAE/g DW, which had excellent antioxidant activity. Additionally, the extract had a certain inhibitory effect on XOD (IC50=199.00±0.14µg/mL) and α-Glu (IC50=159.67±0.01µg/mL). Seven XOD inhibitors and eight α-Glu inhibitors were identified. Furthermore, XOD and α-Glu inhibition experiments in vitro confirmed that inhibitors such as chlorogenic acid, taxifolin, and naringenin had significant inhibitory effects on XOD and α-Glu. The molecular docking results indicated that inhibitors could bind to the corresponding enzymes and had strong binding force. These findings demonstratethat OFI contains potential substances for the treatment of hyperuricemia and hyperglycemia.