Xanthine Oxidase Inhibitory Effect Research Articles

Discovery, Characterization, and Anti-XOD Activity of Calcium Metallophore from Coix lacryma-jobi.

In this work, coixalkyne A (1), a natural polynuclear calcium complex with a novel cross-shaped molecular architecture, was isolated from Coix lacryma-jobi L. along with the undescribed analogue coixalkyne B (2). Their structures were identified by means of NMR spectroscopy, ECD calculations, and single-crystal X-ray diffraction. It is noteworthy that the calcium ligands of 1 as well as compound 2 possess rare terminal alkynes and a nor-carbon sesquiterpene (C14) framework. The antihyperuricemic activity of C. lacryma-jobi and xanthine oxidase (XOD) inhibitory effects of 1-2 were elucidated by in vivo and in vitro assays, while the possible mechanism of action was suggested by molecular docking. Different from the reported chemical synthesis and protein calcium carriers, the discovery of compounds 1 and 2 provided new proof for the natural calcium metallophore in plants with xanthine oxidase inhibitory activity.

The Effect of Xanthine Oxidase Inhibitors in the Prevention and Treatment of Stroke: A Systematic Review and Meta-Analysis.

Xanthine oxidase inhibitors (XOIs) may help prevent stroke. However, heterogeneity can be found in the conclusions of different studies. The relevant evidence was summarized in this systematic review and meta-analysis to further clarify the role of XOIs in the prevention and treatment of stroke, with a focus on evaluating the effects of XOIs in primary and secondary prevention of stroke, acute stroke treatment, and reduction of post-stroke complications. Randomized controlled trials (RCTs) or cohort studies on the effect of XOIs in the prevention and treatment of stroke were searched in PubMed, EMBASE, and Cochrane Library from inception to 3 March 2024, along with hand searching. The analyses were carried out using Review Manager 5.4. The analysis included 14 studies (115,579 patients). While XOIs did not significantly reduce the risk of stroke (RR: 0.89; 95% CI: 0.59-1.34), they improved post-stroke functional outcomes, with a reduction in the modified Rankin scale scores (mean difference: -0.6; 95% CI: -0.8 to -0.4), decreased intercellular adhesion molecule-1 levels (mean difference: -15.2 ng/mL; 95% CI: -22.3 to -8.1), improved augmentation index (AIx) by 4.2% (95% CI: 2.5-5.9%), reduced central blood pressure (mean reduction: 4.8 mmHg; 95% CI: 2.6-6.9), and delayed carotid intima-media thickness progression (mean difference: -0.05 mm/year; 95% CI: -0.08 to -0.02).

Preparation and Efficacy Evaluation of Antihyperuricemic Peptides from Marine Sources.

Marine-derived foods, often called blue foods, are promising sustainable alternatives to conventional food sources owing to their abundant amino acids and high protein content. Current treatments for hyperuricemia, a chronic condition attributed to purine metabolism disorders, are associated with various side effects. Novel peptide xanthine oxidase inhibitors have been discovered in the hydrolyzed products of marine fish and invertebrate proteins, which have demonstrated promising therapeutic potential by reducing uric acid levels in vitro and in vivo. This review explores the potential therapeutic effects of xanthine oxidase inhibitors derived from marine fish and invertebrates, summarizes the methods for extracting bioactive peptides from marine organisms, and emphasizes the impact of different proteases on the structure-activity relationship of bioactive peptides. The hypouricemic effects of these bioactive peptides warrant further verification. There is consensus on the in vitro chemical methods used to verify the xanthine oxidase inhibitory effects of these peptides. Considering several cell and animal model development strategies, this review summarizes several highly recognized modeling methods, proposes strategies to improve the bioavailability of bioactive peptides, and advocates for a diversified evaluation system. Although the screening and evaluation methods for antihyperuricemic peptides have been shown to be feasible across numerous studies, they are not optimal. This review examines the deficiencies in bioavailability, synthesis efficiency, and evaluation mechanisms in terms of their future development and proposes potential solutions to address these issues. This review provides a novel perspective for the exploration and application of marine-derived hypouricemic bioactive peptides.

Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

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.

Xanthine oxidase inhibitory constituents from the roots of Ampelopsis japonica

Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of Ampelopsis japonica resulted in the isolation of two new triterpenoids (1-2), designated Ampejaponoside A and B, along with sixteen known compounds (3-18). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds 3-18 confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity in vitro. As a result, compounds 2, 8, and 14-16 displayed significant XOD inhibitory effect, particularly 16 being the most potent with an IC50 value of 0.21 μM, superior to positive substance allopurinol (IC50 1.95 μM). Molecular docking uncovered a unique interaction mode of 16 with the active site of XOD. The current study showed that the triterpenoids and polyphenols from A. japonica could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.

Fermentation of olive pulp by Limosilactobacillus fermentumNCU001464: physicochemical properties, biological activity and bioactive phenols

SummaryOlives, which are rich in bioactive compounds, are processed into beverages in China. We investigated the effect of fermentation by Limosilactobacillus fermentum NCU001464 on the physicochemical characteristics, biological activities and phenolic compounds of olive pulp. After fermentation for 48 h, pH and individual sugar content of olive pulp decreased. Lm. fermentum NCU001464 fermentation enhanced the hydroxyl radical scavenging activity and the inhibitory effect against xanthine oxidase (XO) of olive pulp. Total phenol content was not significantly different between olive pulp fermented for 0 and 48 h. However, the fermented olive phenol extract had a lower IC50 value than the unfermented phenol extract. Fluorescence spectroscopy results revealed that the olive phenol extract had a stronger XO inhibitory effect after fermentation. The dominant binding forces between olive phenols and XO were hydrogen bonds and van der Waals forces. There were 31 different phenolic compounds between the unfermented and fermented extracts.

Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78–0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75–0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66–0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61–0.96; P = 0.020) or LDL-C of 136.90–157.40 mg/dL (OR, 0.67; 95% CI, 0.49–0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.

The Effects of Xanthine Oxidase Inhibitors on the Management of Cardiovascular Diseases

The Effects of Xanthine Oxidase Inhibitors on the Management of Cardiovascular Diseases

Lignan and Phthalide Derivatives from the Rhizome of Ligusticum chuanxiong (Rhizoma chuanxiong) and Evaluation of Their anti-Xanthine Oxidase Activities.

The previous research results showed that the extracts of ethyl acetate of the rhizome of Ligusticum chuanxiong (Rhizoma chuanxiong) possessed significant antigout effects in model mice. To explore the active ingredients responsible for the effects, phytochemical studies were performed, which led to the isolation of three rare 8', 9-linked neolignans, ligusticumins A-C (1-3), together with two novel phthalide-phenylpropanoid heterodimers, ligusticumalides A-B (4 and 5). It is noteworthy that 4 possesses an unprecedented 7-styryl phthalide skeleton. The structures and absolute configurations of 1-5 were elucidated by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy and electron-capture detector (ECD) spectroscopic methods. The bioassay results showed that compounds 1, 2, 3, and 5 presented moderate inhibitory activities against xanthine oxidase (XO) and 4 possessed a significant XO inhibitory effect with an IC50 value of 93.88 μM. This is the first time to investigate the anti-XO active ingredients of R. chuanxiong, which provides valuable information for searching for new antigout agents from natural products.

Discovery and Characterization of Moracin C as an Anti-Gouty Arthritis/Hyperuricemia Candidate by Docking-Based Virtual Screening and Pharmacological Evaluation.

In the present study, a natural product database of compounds associated with herbs traditionally verified to treat gout/hyperuricemia/arthritis was constructed. 3D-shape and docking-based virtual screening was conducted. To identify potential xanthine oxidase (XOD) inhibitors in the database, eight compounds with commercial availability were identified as high 3D-shape similarity with febuxostat (1), a known XOD inhibitor. Docking was used to further predict the possible interactions between XOD and these compounds. Moracin C (2), moracin D (3), and isoformononetin (8) exhibited higher docking scores and binding energies than other compounds. In vitro, 2 inhibited XOD with an IC50 value of 0.25 ± 0.14 μM, which is similar to that of 1 (0.16 ± 0.08 μM). In a hyperuricemic mouse model, 5-20 mg/kg 2 exhibited satisfying urate-lowering and XOD inhibitory effects. Compound 2 also exhibited antiarthritis activities. In RAW264.7 cells, 2 at 1-10 μM inhibited the expression of IL-1β and TNF-α induced by MSU. In an acute gouty arthritis model in SD rats, 5-20 mg/kg 2 significantly alleviated the toe swelling, inflammatory response, and dysfunction disorder caused by monosodium urate (MSU). Compound 2 inhibited serum IL-1β and TNF-α cytokines as well as reduced the expression of the NLRP3/ASC/caspase-1 inflammasome in joints. In summary, 2 was an effective compound for the treatment of hyperuricemia/gouty arthritis.

Role of EGF/ERK1/2/HO-1 axis in mediating methotrexate induced testicular damage in rats and the ameliorative effect of xanthine oxidase inhibitors

Objectives: Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. The current the protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Materials and methods: Thirty-two rats were randomly allocated to four groups; control (received vehicles), MTX (received single dose, 20 mg/kg, i.p.), MTX + ALL (received MTX plus ALL) and MTX + FEB (received MTX plus ALL). ALL and FEB were administered orally at 100- and 10 mg/kg, respectively for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and total nitrite/nitrate (NOx) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. Results: ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NOx, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. Conclusion: All and FEB were equally protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions. Their effects might be through activation of the EGF/ERK1/2/HO-1 pathway.

S-24-2: IMPACT OF FEBUXOSTAT ON VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY: INSIGHTS FROM THE RANDOMIZED PRIZE STUDY

Objective: Although uric acid lowering therapies, including xanthine oxidase (XO) inhibition, may reduce the absolute level of blood pressure (BP), the effect of XO inhibition on BP variability is largely unknown. The objective of the present analysis was to evaluate the impact of febuxostat, an XO inhibitor, on BP variability in a randomized trial setting. Design and method: This was a sub-analysis of the PRIZE study, a randomized trial to evaluate the potential effect of febuxostat on carotid intima-media thickness progression. Patients with hyperuricemia and carotid plaques were randomly assigned to the febuxostat or control group. During a 24-month period, office BP and pulse rate (PR) were measured 3 times or more. BP and PR variabilities were assessed with standard deviation (SD) and coefficient of variation (CV). The effect of febuxostat on BP and PR variabilities were adjusted with age, sex, and baseline BP or PR, expressed with 95% confidence intervals. Results: A total of 472 patients with hyperuricemia and carotid plaques were included into the present analysis. Overall, the median serum uric acid level was 7.6 [7.1, 8.2] mg/dl at baseline, and a history of hypertension was found in 419 (88.8%) patients. Baseline characteristics were well balanced between the febuxostat group (n = 236) and control group (n = 236). During the 24-month follow-up period, the febuxostat group had a significantly lower adjusted mean systolic BP (128.4 [126.8 to 130.0] vs. 130.7 [129.1 to 132.2] mm Hg, p = 0.04) and CV of systolic BP (7.4 [6.7 to 8.0] vs. 8.2 [7.6 to 8.8], p = 0.04) than the control group. Adjusted SD of PR was also lower in the febuxostat group than their counterpart (5.95 [4.93 to 6.97] vs. 7.33 [6.32 to 8.33], p = 0.04). Conclusions: XO inhibition with febuxostat was associated with reduced visit-to-visit BP variability as well as reduced PR variability, illustrating the potential therapeutic effect of febuxostat in patients with hyperuricemia and carotid plaques.

Molecular docking approach to identify xanthine oxidase inhibitory effect of bioactive compounds in Pogostemon cablin (Blanco) Benth

Molecular docking approach to identify xanthine oxidase inhibitory effect of bioactive compounds in Pogostemon cablin (Blanco) Benth

Hydrothermal treatment improves xanthine oxidase inhibitory activity and affects the polyphenol profile of Flos Sophorae Immaturus.

Flos Sophorae Immaturus (FSI) is rich in polyphenols and a potential uric acid-lowering food. However, the processing of FSI is greatly restricted due to the heat sensitivity and low solubility of polyphenols. In this study, hydrothermal treatment - an effective strategy - was applied to FSI processing. The variation of xanthine oxidase (XO) inhibitory effect and polyphenol composition of FSI during hydrothermal treatment were recorded. The XO inhibition rate of FSI increased from 32.42% to 89.00% after hydrothermal treatment at 220 °C for 30 min, as well as total polyphenols (from 0.66 to 1.11 mg mL-1 ) and flavonoids (from 1.21 to 1.58 mg mL-1 ). However, high thermal temperature (>160 °C) and extended thermal time (>90 min) caused the degradation of polyphenols. Rutin, kaempferol-3-O-rutinoside and narcissoside rapidly degraded and converted to quercetin, kaempferol and isorhamnetin when the temperature exceeded 160 °C. The maximum yields of quercetin, kaempferol and isorhamnetin were at 220 °C for 30 min, 90 min and 90 min, respectively. Meanwhile, the conversion kinetics conformed to the first-order model. Interestingly, these newly formed polyphenols possessed better XO inhibitory effects than their derivatives with 3-O-rutinoside. Polyphenol conversion during hydrothermal treatment was the main reason for enhancing XO inhibitory activity. Therefore, hydrothermal treatment is an appropriate method for improving the XO inhibitory effect of FSI. © 2022 Society of Chemical Industry.

Impact of febuxostat on visit-to-visit blood pressure variability: insights from the randomised PRIZE Study

ObjectivesAlthough uric acid lowering therapies, including xanthine oxidase (XO) inhibition, may reduce the absolute level of blood pressure (BP), the effect of XO inhibition on BP variability is largely unknown....

Study on the anti-hyperuricemic bioactivity and chemical components of Sterculiae lychnophorae Semen

Sterculiae lychnophorae Semen is an edible and medicinal resource and is widely used in functional foods in China. In the previous study, the S. lychnophorae′ function of anti-hyperuricemia was found, but its main functional ingredients have not been clarified. In this study, the major functional ingredients of S. lychnophorae with anti-hyperuricemic effect were determined under activity guided screening through the intervention for xanthine oxidase (XO) enzymatic reaction in vitro. The results showed EtOAc fraction (EF) of S. lychnophorae had the strongest inhibitory activity among all fractions with the inhibition rate 94.94%. Since hyperuricemia could trigger inflammation reaction, the anti-inflammation effect of mainly functional ingredient (EF) was also researched through a cell inflammation model established by using uric acid (UA) to stimulate HK-2 cells. The results showed that the expression levels of inflammatory cytokines IL-6, IL-1β and TNF-α were decreased after treatment with EF. On the meanwhile, molecular mechanistic studies revealed that EF could downregulate the phosphorylation levels of PI3K, AKT, IκBα, NF-κB proteins in HK-2 cells. These results showed that EF could potentially lower UA level and combat inflammation by inhibiting the PI3K/AKT/NF-κB signal pathway. Furthermore, the chemical components of EF were also clarified. As a result, two new compounds, ethyl 2, 3-dihydro-1, 4-benzodioxin-6-carboxylate (1) and ethyl 3-(butyryloxy)-4-hydroxybenzoate (2), together with 15 known compounds were identified from EF by extensive NMR experiments and comparison with the data reported in the literature. The XO inhibitory effects of all the compounds were analyzed. With the determination of the anti-hyperuricemic mechanism and chemical component of EF, it can be used as a raw material to develop functional foods against hyperuricemia in the future.

Synthesis of New Pyrazole Hybrids as Potential Anticancer Agents with Xanthine Oxidase Inhibitory Activity.

The study aims to synthesize hybrid molecules containing pyrazole and aryldiazenyl/arylhydrazono fragments with promising anticancer activity. The clinical effectiveness of anticancer drugs is limited by their adverse side effects and patient resistance. Therefore, the development of safer classes of drugs through rational drug design is imperative. Considering the anticancer potential of the pyrazole moiety, the study was carried out with the objective of synthesizing some hybrid pyrazole derivatives with anticancer potential. The anticancer potential of these pyrazolyl analogues were evaluated by sulforhodamine B assay using three cancer cell lines MCF-7, HepG2, and HCT-116. HCT-116 was the most sensitive cell line against these pyrazolyl analogues. Among these newly synthesised derivatives, 1-(4-((4-bromophenyl)diazenyl)-3,5-dimethyl-1H-pyrazol-1-yl)-2-(naphthalen-2-yloxy)ethan-1-one (5e) emerged as a promising anticancer agent (IC50 3.6-24.6 μM), having a xanthine oxidase inhibitory effect (IC50 10.87 μM). To obtain further insights into the binding interactions of these molecules, molecular docking studies were also carried out. In summary, our findings suggest that these hybrid pyrazolyl derivatives can be considered as potential lead molecules for anticancer agents.

In vitro xanthine oxidase inhibitory properties of Flos Sophorae Immaturus and potential mechanisms

Flos Sophorae Immaturus (FSI) possessed potential xanthine oxidase (XO) inhibitory activity as a uric acid-lowing natural product. The present work identified and quantified the free and bound polyphenols of FSI by UPLC-QTOF-MS. Then determined the primary polyphenols with XO inhibitory effect and clarified their potential mechanisms by omission experiment, interaction assay, inhibition type, and fluorescence measurements. The results revealed that nine polyphenols were detected in the free polyphenol extract and ten polyphenols were detected in the bound polyphenol extract. Meanwhile, seven polyphenols were identified as XO inhibitors, including quercetin, kaempferol, isorhamnetin, rutin, hyperoside, protocatechuic acid, and quercitrin with the IC50 values of 0.03, 0.11, 0.07, 5.62, 11.48, 22.13, and 367.82 mg/mL, but their inhibition stability was lower than 24 h. Although the content of quercetin (18.87 mg/g) was not the highest, it played a crucial role to the XO inhibitory effect of FSI. Furthermore, kaempferol and isorhamnetin alone revealed the sub-additive effect with quercetin, while the combination of other polyphenols with quercetin generated the interference or antagonism effects. Quercetin, isorhamnetin, and kaempferol were mixed-type and competitive inhibitors, which significantly quenched the fluorescence intensity of XO. Moreover, the binding processes of quercetin-XO, kaempferol-XO, and isorhamnetin-XO were spontaneous and endothermic, and the hydrophobic interaction was the key driving force. In general, quercetin, kaempferol, and isorhamnetin in FSI can be used as potential XO inhibitors.

In vitro inhibitory effects of polyphenols from Tartary buckwheat on xanthine oxidase: Identification, inhibitory activity, and action mechanism

The xanthine oxidase (XO) inhibitory activity is an important way to evaluate the anti-hyperuricemia effect of natural products. In the present work, the XO inhibitory effect of Tartary buckwheat was elucidated by polyphenols determination, omission experiment, interaction assay, inhibition types, fluorescence spectroscopy, and molecular docking. The results revealed that eight primary polyphenols were identified, including rutin (544 mg/100 g) and quercetin (261 mg/100 g). Quercetin (IC50 = 0.03 mg/mL) was a mixed-type inhibitor and exhibited the strongest inhibitory effect, followed by kaempferol (IC50 = 0.11 mg/mL). Moreover, a sub-additive effect was exhibited in the complex of quercetin-kaempferol, but the combination of quercetin and other polyphenols caused interference or antagonism effects. Furthermore, quercetin and kaempferol showed an obvious fluorescence quenching effect on XO, and the bindings were mainly driven by hydrophobic forces and hydrogen bonds. This study shows that Tartary buckwheat may be a potential functional food to inhibit XO activity.