Xanthine Oxidase Inhibitory Activity Research Articles

Natural Bioactive Compounds: Emerging Therapies for Hyperuricemia.

Hyperuricemia is a crucial feature of metabolic syndrome, characterized by elevated uric acid that causes urate crystal deposits in joints, kidneys, and subcutaneous tissues, resulting in gout and hyperuricemic nephropathy. The primary causes of uric acid metabolism disorder include overproduction and reduced excretion. The majority of uric acid in human body is derived from the breakdown of purine nucleotides. Overproduction of uric acid can result from increased concentration or activity of xanthine oxidase, the key enzyme responsible for uric acid synthesis. Alterations in the activity of proteins responsible for uric acid reabsorption and excretion can also affect serum uric acid. Many bioactive compounds derived from natural plants have been shown to inhibit xanthine oxidase activity to reduce uric acid production, modulate the activity of transport proteins to promote uric acid excretion, or alleviate oxidative stress and inflammation through various signaling pathways. These properties have garnered significant attention from researchers. In this paper, we first introduce the pathophysiological mechanisms of hyperuricemia, then summarize bioactive compounds with urate-lowering effects, and discuss their potential applications in treating hyperuricemia and its complications.

Insight into Sequential Extrusion and Cysteine Treatment for Improving Rheological Characteristics and In Vitro Digestibility of Whey Protein Isolate.

The effects of sequential cold extrusion and cysteine (Cys) treatment on the rheological characteristics and in vitro digestibility of whey protein isolate (WPI) were researched in this work. Cold extrusion and Cys treatment increased the apparent viscosity, shear stress, Péclet number, and viscoelasticity of WPI. Furthermore, the emulsifying activity index enhanced in the order of WPI, Cys-treated WPI (Cys-WPI), cold-extruded WPI (CWPI), and extrusion-Cys treated WPI (Cys-CWPI). The emulsion stability index of Cys-CWPI was increased by 29.69% higher than that of WPI. Besides, the α-glucosidase inhibitory rate and xanthine oxidase inhibitory activity in the digests of Cys-CWPI were markedly increased compared with digests of WPI. The synergism of cold extrusion and Cys provides an effective approach for the application of whey protein-based thickeners and emulsifiers; meanwhile, its digestive products may assist in the development of hypoglycemic and uric acid-lowering foods.

Phyllanthi Fructus ameliorates hyperuricemia and kidney injure via inhibiting uric acid synthesis, modulating urate transporters, and alleviating inflammation

Phyllanthi Fructus, known as Yuganzi (YGZ), is a unique medicine and food homologous fruit with both medicinal and nutritional properties. Its historical use in treating hyperuricemia (HUA) and gout is well-documented. However, the precise therapeutic effects and potential molecular mechanisms remain unclear. In this study, an experimental rat modelling by a high-fat/high-sugar diet and potassium oxonate/adenine oral administration was used to evaluate the pharmacodynamic effects of YGZ. Network pharmacology, molecular docking and molecular dynamics simulation were utilized to elucidate the potential mechanisms. Supplementation with YGZ effectively ameliorated HUA by inhibiting xanthine oxidase activity, and enhancing uric acid excretion through up-regulating of OAT1 and ABCG2, while down-regulating of URAT1. Furthermore, YGZ supplementation enhanced superoxide dismutase activity, reduced malondialdehyde content, and inhibited the secretion of IL1B, IL6, TNFα, ICAM1, VCAM1, TGFβ1, and NF-κB protein expression. Network pharmacology analysis indicated that YGZ influences 138 targets, modulating the disease network via lipid and atherosclerosis, insulin resistance, HIF-1, TNF, IL-17, TLRS, and NF-κB signaling pathways. Molecular docking analysis suggested that organic acids (e.g. ellagic acid, gallic acid) and flavonoids (e.g. quercetin, delphinidin, luteolin, epigallocatechin gallate) exhibited superior binding abilities to key targets (e.g. XDH, ABCG2, URAT1, OAT1, IRS1, PTGS2, TLR4). Noteworthy, molecular dynamics simulations confirmed that epigallocatechin gallate binds to URAT1 with the greatest stability. These results provide substantial evidence for the therapeutic efficacy of YGZ and establish a theoretical foundation for the development of natural products in treating hyperuricemia.

Regulation of ROS metabolism in macrophage via xanthine oxidase is associated with disease progression in pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) exacerbation can lead to respiratory failure, multi-organ failure, and symptoms related to central nervous system diseases. The purpose of this study is to screen biomarkers and metabolic pathways that can predict the progression of PTB, and to verify the role of the metabolic enzyme xanthine oxidase (XO) in the progression of PTB. To explore the biomarkers and mechanisms underlying the progression of PTB, plasma metabolomics sequencing was conducted on patients with severe PTB, non-severe PTB, and healthy individuals. Screening differential metabolites and metabolic pathways that can predict the progression of PTB, and verifying the function and mechanism of action of XO through experiments. The purine metabolism, sphingolipid metabolism, and amino acid metabolism between the three groups differ. In patients with severe PTB, the levels of xanthosine and hypoxanthine are increased, while the levels of D-tryptophan, dihydroceramide and uric acid are decreased. Inhibition of XO activity has been observed to reduce the levels of tumor necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as to suppress the production of reactive oxygen species (ROS) and the activation of the NF-κB pathway, while also promoting the growth of MTB within cells. D-tryptophan, xanthosine, and dihydroceramide can be utilized as biomarkers for progression of PTB, assisting in the evaluation of disease progression, and XO stands out as a potential therapeutic target for impeding the progression of PTB.

Antioxidant potential and xanthine oxidase inhibition of flavonol glycosides from Phyllanthus emblica L. leaves

Context: Hyperuricemia is the cause of gout in the inflammatory joint condition. The xanthine oxidase enzyme is a therapeutic target for gout treatment because it plays a role in the generation of uric acid. Allopurinol is used to treat gout. It prevents the xanthine oxidase enzyme from producing as much uric acid. When selecting a medication, one must consider the various adverse effects of allopurinol. Phyllanthus emblica plants are among the medicinal plants that can be used as an alternative treatment for gout. Aims: To evaluate isolated compounds from the Phyllanthus emblica as antihyperuricemia candidates. Methods: The isolated compounds were characterized using High-Performance Liquid Chromatography Analysis and Thin Layer Chromatography-Densitometry. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cupric ion (CUPRAC) antioxidant capacity procedures were used to develop the antioxidant activity index. The ability to inhibit xanthine oxidase was determined using a spectrophotometer. Results: Compound 1 was indicated as rutin having antioxidant capacity with an antioxidant activity index (AAI) DPPH value of 7.89 ± 0.03 and AAI CUPRAC value of 15.83 ± 0.04 stronger than compound 2 (quercitrin) with an AAI DPPH value of 3.72 ± 0.01 and AAI CUPRAC 3.24 ± 0.03. The IC50 for quercitrin's inhibition of xanthine oxidase is 23.85 ± 2.04, which was higher than rutin’s IC50 value of 32.77 ± 4.49 µg/mL. Conclusions: Flavonol glycosides present in the ethanol extract of Phyllanthus emblica leaves gave potent xanthine oxidase inhibitory activity stronger than the extract. Quercitrin gave stronger xanthine oxidase inhibitory activity, but this compound has weaker antioxidant capacity compared to rutin.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment

Ethnopharmacological relevanceHyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. Aim of the studyThis study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. Materials and methodsHyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. ResultsPoria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. ConclusionsPoria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

Network Pharmacology Combined with Experimental Validation to Investigate the Mechanism of the Anti-Hyperuricemia Action of Portulaca oleracea Extract.

Hyperuricemia (HUA) is a common metabolic disease caused by purine metabolic disorders in the body. Portulaca oleracea L. (PO) is an edible wild vegetable. In this study, the regulatory effect of PO on HUA and its potential mechanism were initially elucidated through network pharmacology and experimental validation. The results showed that PO from Sichuan province was superior to the plant collected from other habitats in inhibiting xanthine oxidase (XOD) activity. Berberine and stachydrine were isolated and identified from PO for the first time by UPLC-Q-Exactive Orbitrap MS. The potential molecular targets and related signaling pathways were predicted by network pharmacology and molecular docking techniques. Molecular docking showed that berberine had strong docking activity with XOD, and the results of in vitro experiments verified this prediction. Through experimental analysis of HUA mice, we found that PO can reduce the production of uric acid (UA) in the organism by inhibiting XOD activity. On the other hand, PO can reduce the body 's reabsorption of urate and aid in its excretion out of the body by inhibiting the urate transporter proteins (GLUT9, URAT1) and promoting the high expression of urate excretory protein (ABCG2). The results of H/E staining showed that, compared with the positive drug (allopurinol and benzbromarone) group, there was no obvious renal injury in the middle- and high-dose groups of PO extract. In summary, our findings reveal the potential of wild plant PO as a functional food for the treatment of hyperuricemia.

High-Efficiency Enzyme Assay and Screening of Enzyme-Inhibiting Nanomaterials Using Capillary Electrophoresis with Hierarchically Porous Metal-Organic Framework-Based Immobilized Enzyme Microreactor.

Enzyme-inhibiting nanomaterials have significant potential for regulating enzyme activity. However, a universal and efficient method for systematically screening and evaluating the inhibitory effects of various nanomaterials on drug target enzymes has not been established. While the integrated technique of immobilized enzyme microreactor (IMER) with capillary electrophoresis (CE) serves as an effective tool for enzyme analysis, it still faces challenges such as low enzyme loadability, unsatisfactory stability, and limited applicability. Herein, hierarchical porous metal-organic frameworks (HP-MOFs) were explored as high-performance enzyme immobilization carriers and stationary phases to develop a novel HP-MOFs-based IMER-CE microanalysis system for efficient online enzyme assay and systematic screening of enzyme-inhibiting nanomaterials. As a proof-of-concept demonstration, the model enzyme xanthine oxidase (XOD) was immobilized on a HP-UiO-66-NH2 coated capillary, serving as an efficient and durable IMER for screening potential XOD-inhibiting nanomaterials. The hierarchically micro- and mesoporous structure and superior enzyme loadability of as-prepared HP-UiO-66-NH2-IMER was intensively characterized, followed by systematic evaluation of the separation performance of HP-UiO-66-NH2 coated column and the enzyme kinetics of the immobilized XOD. Compared to the microporous UiO-66-NH2-IMER, the HP-UiO-66-NH2-IMER-CE system showed significant improvements in enzyme loading, maximum reaction rate, repeatability, and long-term stability. Furthermore, the established method was effectively employed to screen the XOD inhibitory activity of various nanomaterials, revealing that graphene oxide, single wall carbon nanotube and three other nanomaterials exhibited inhibitory potentials. The HP-MOFs-based microanalysis system can be easily expanded by modifying the types of immobilized enzymes and holds the potential to accelerate the identification and rational design of effective enzyme-inhibiting nanomaterials.

Xanthine oxidase inhibitors: Virtual screening and mechanism of inhibition studies

Xanthine oxidase (XO), which plays a key role in purine metabolism, is an important target enzyme for the prevention and treatment of hyperuricemia. Inhibitory activity against XO is a common criterion for the screening of compounds with potential anti-hyperuricemic activity. In this study, 22 XO inhibitors were used to construct a 3D-QSAR pharmacophore model. Subsequently, molecular docking and in vitro activity evaluations were used to identify strong XO inhibitors from a list of 2000 natural compounds. The interaction mechanisms of these compounds with XO were analyzed based on inhibition kinetics and multi-spectral analyses. The pharmacophore model was composed of three hydrogen bond receptors and a hydrophobic center. The screened compounds — Diosmetin, Fisetin, and Genistein — all showed good XO inhibitory activity, with IC50 values of 1.86 ± 0.11 μM, 5.83 ± 0.08 μM, and 7.56 ± 0.10 μM, respectively. Kinetic analysis, fluorescence quenching assays, and molecular docking experiments showed that Diosmetin, Fisetin, and Genistein docked near the same active site of XO, mainly affecting the microenvironment of tryptophan residues. These molecules showed static binding to XO via hydrogen bonds, hydrophobic interactions, and van der Waals forces. Diosmetin and Genistein were competitive inhibitors, whereas Fisetin was a mixed inhibitor. Infrared spectroscopy showed that Diosmetin, Fisetin, and Genistein increased the α-helix content of XO from 7.4 % to 16.6 %, 21.4 %, and 11.2 %, respectively, thereby enhancing its stability. In summary, the pharmacophore model constructed in this study was accurate. The flavonoids Diosmetin, Fisetin, and Genistein effectively inhibited the activity of XO, and the amino acid residues LEU257, ILE353, and VAL259 played a key role in the interaction between the flavonoids and XO. These findings are of great significance for the screening and development of new XO inhibitors.

Antioxidant and Xanthine oxidase inhibitory activities of the tea (Camellia sinensis) flower

The major purpose of this study was to investigate the DPPH radical scavenging activity, hydroxyl radical scavenging activity, superoxide radical scavenging activity, reducing power, ferrous ion chelating activity, and xanthine oxidase activity for research of antioxidant and xanthine oxidase inhibitory activities using a variety of extracts of tea (Camellia sinensis) flower. Among the several extracts, when 800 μg/mL of the ethanol extract was used, the maximum DPPH radical scavenging activity was obtained, 79.2%, which was approximately 80.8% compared to L-ascorbic acid, the maximum hydroxyl radical scavenging activity, 71.3%, which was approximately 73.2% compared to BHA, and the maximum super oxide radical scavenging activity, 89.4%, which was, approximately 90.6% compared to BHT, and the maximum reducing power, 1.94 at an OD of 700 nm, which was approximately 49.2% compared to L-ascorbic acid, respectively. On the other hand, when 800 μg/mL of the hot water extract was used, the maximum activity of ferrous ion chelate was obtained, 28.6%, which was approximately 48.4% compared to EDTA and the maximum xanthine oxidase inhibitory activity, 61.4%, approximately 63.8% compared to catechin, respectively. These results indicated the application potential for industries that can produce new biomaterials that can compensate for the shortcomings of existing synthetic antioxidants and use discarded tea flower as food, pharmaceutical, and cosmetic materials.

Design, synthesis, and evaluation of chalcone derivatives as xanthine oxidase inhibitors

Xanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton. We introduced a carboxyl group and a hydroxyl group to the B ring and modified the A ring. 35 chalcone derivatives were designed and synthesized. All the 35 derivatives exhibited higher XO inhibition activities (IC50 = 0.064–0.559 μM) compared with allopurinol (IC50 = 2.588 μM). Their high affinity was attributed to strong hydrogen bond interactions formed between the introduced carboxyl and hydroxyl groups with key amino acid residues in XO. SAR analysis disclosed that carboxyl, hydroxyl, ethyl (12c), methylamino (12h), dimethylamino (12i), indolin (13k), and indol (13l) groups played important roles in improving the whole molecules’ inhibition potency against XO. ADME predictions and cytotoxicity assays suggested their pharmacokinetic characteristics and biocompatibility were desirable. Additionally, 12c exhibited a significant hypouricemic effect on potassium oxonate-induced hyperuricemia rats after orally administrated at a dose range of 10–40 mg/kg, representing a promising anti-hyperuricemia potential for further optimization and development.

Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Fruits of Chaenomeles speciosa (Sweet) Nakai.

Chaenomeles speciosa (Sweet) Nakai (C. speciosa) is a traditional Chinese herbal medicine that possesses not only abundant nutritional value but also significant medicinal properties. The extracts of C. speciosa fruits effectively reduce urate levels, but the specific chemical constituents responsible for this effect in C. speciosa fruits are still unknown. Therefore, this study aims to investigate and analyze the structure-activity relationships of these constituents to better understand their ability to lower uric acid. Activity-guided fractionation and purification processes were used to isolate compounds with xanthine oxidase (XO) inhibitory activity from C. speciosa fruits, resulting in three extracts: petroleum ether, ethyl acetate, and n-butanol. The ethyl acetate and n-butanol fractions showed strong activity and underwent further separation and purification using chromatographic techniques. Twenty-four compounds were isolated and identified, with nine showing potent activity, including chlorogenic acid, methyl chlorogenate, butyl chlorogenate, ethyl chlorogenate, cryptochlorogenic acid methyl ester, caffeic acid, p-coumaric acid, benzoic acid and protocatechuic acid. The docking analysis showed that these compounds interacted with amino acid residues in the active site of XO through hydrogen bonding and hydrophobic interactions. These findings suggest that these compounds help reduce uric acid in C. speciosa, supporting further investigation into their mechanism of action.

Design, Synthesis, and Xanthine Oxidase Inhibitory Activity of 4-(5-Aminosubstituted-4-cyanooxazol-2-yl)benzoic Acids.

Xanthine oxidase is a known therapeutic target for the treatment of hyperuricemia and related diseases. Despite the availability of current drugs such as allopurinol and febuxostat, the search for new compounds to effectively inhibit this enzyme remains relevant. In our study, 75 virtual structures of 4-(5-aminosubstituted-4-cyanooxazol-2-yl)benzoic acids with structural similarity to febuxostat were designed for evaluation of their potency against xanthine oxidase. After molecular docking simulations, eight compounds were selected for synthesis and in vitro testing. The synthesized compounds were found to exhibit in vitro xanthine oxidase inhibitory activity in the nanomolar concentration range. The most effective inhibitors with 4-benzylpiperidin-1-yl or 1,2,3,4-tetrahydroisoquinolin-2-yl substituents at position 5 of the oxazole ring had IC50 values close to that of febuxostat. The kinetic data suggest a mixed-type inhibition when the inhibitor binds preferentially to the free enzyme rather than to the enzyme-substrate complex. Molecular docking and molecular dynamic simulations were carried out to get insight into the key interactions of the inhibitors bound to the xanthine oxidase active site.

Rhododendron luteum Sweet Flower Supercritical CO2 Extracts: Terpenes Composition, Pro-Inflammatory Enzymes Inhibition and Antioxidant Activity.

Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential.

Presence of Flazin in Miso and Identification of Four Tryptophan-Derived ß-Carbolines Formed during Fermentation.

In miso, due to the substantial presence of genistein, flazin is often overlapped and masked by genistein in HPLC analysis. Flazin in the miso extracts could be resolved with genistein through medium-pressure liquid chromatography run under a nonacidified methanol-water system and subsequently fractionated by semipreparative HPLC and identified by NMR spectroscopic analysis. As referenced, flazin was detected in all 11 locally marketed miso products, with contents ranging from 3.5 to 124.8 μg/g. In lab-made miso fermented at 28 and 37 °C for 8 weeks, flazin formed faster at 37 °C than at 28 °C. Based on the time-dependent HPLC chromatographic changes of the miso extracts during fermentation, the presence of tryptophan-derived ß-carboline intermediates was deduced. Tryptophan was then supplemented for miso fermentation, and four peak substances were targeted for isolation by sophisticated approaches. Four ß-carbolines were purified and instrumentally identified, i.e., P1: 1-(1,3,4,5-tetrahydroxypentyl)-9H- pyrido[3,4-b]indole, P2 (diastereomer of P1): 1-(1*,3,4,5-tetrahydroxypentyl)- 9H-pyrido[3,4-b]indole, and Miso 101: 1-(1,3,4,5-tetrahydroxypentyl)-9H- pyrido[3,4-b]indole 3-carboxylic acid, and Miso 111 (diastereomer of Miso 101): 1-(1*,3,4,5-tetrahydroxypentyl)-9H-pyrido[3,4-b]indole 3-carboxylic acid. Each of the purified β-carbolines along with tryptophan and flazin exhibited varied ABTS·+ scavenging and xanthine oxidase inhibitory activities.

Rationally designed febuxostat-based hydroxamic acid and its pH-Responsive nanoformulation elicits anti-tumor activity

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability.

Phytochemical Analysis, and Antioxidant and Hepatoprotective Activities of Chamaerops humilis L. Leaves; A Focus on Xanthine Oxidase.

Chamaerops humilis L. is clumping palm of the family Arecaceae with promising health-promoting effects. Parts of this species are utilized as food and employed in folk medicine to treat several disorders. This study investigated the phytochemical constituents of C. humilis leaves and their antioxidant and xanthine oxidase (XO) inhibitory activities in vitro and in vivo in acetaminophen (APAP)-induced hepatotoxicity in rats. The chemical structure of the isolated phytochemicals was determined using data obtained from UV, MS, IR, and 1H-, 13C-NMR spectroscopic tools as well as comparison with authentic markers. Eleven compounds, including tricin 7-O-β-rutinoside, vicenin, tricin, astragalin, borassoside D, pregnane-3,5,6,16-tetrol, oleanolic acid, β-sitosterol and campesterol were isolated from C. humilis ethanolic extract (CHEE). CHEE and the butanol, n-hexane, and dichloromethane fractions exhibited in vitro radical scavenging and XO inhibitory efficacies. The computational findings revealed the tendency of the isolated compounds towards the active site of XO. In vivo, CHEE ameliorated liver function markers and prevented tissue injury induced by APAP in rats. CHEE suppressed hepatic XO, decreased serum uric acid and liver malondialdehyde (MDA), and enhanced reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in APAP-treated rats. CHEE ameliorated serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β in APAP-treated rats. Thus, C. humilis is rich in beneficial phytochemicals that possess binding affinity towards XO. C. humilis exhibited potent in vitro antioxidant and XO inhibitory activities, and prevented APAP hepatotoxicity by attenuating tissue injury, oxidative stress and inflammation.

Methanol extract of black garlic protects against hyperuricemia by xanthine oxidase inhibitory activity in-vitro

Garlic (Allium sativum L.) has been used as a medicative food for a long time. However, some individuals are averse to raw garlic owing to its pungent taste and aroma. As a result, a variety of garlic formulations have been created to minimize these characteristics without reducing their functions. Extensive in vitro and in vivo research has shown that black garlic has several benefits, including anti-oxidant, anti-inflammatory, anticancer, anti-obesity, anti-diabetic, anti-allergic, cardioprotective, and hepatoprotective characteristics. However, it remains unclear which compounds are active ingredients in the extract and the contributions of the main identified compounds to the extract's XO inhibitory activity are unknown. This study aims to look into the potent XO inhibitors found in black garlic methanol extract. The research methodology is experimental, involving the inhibition of xanthine oxidase activity, specifically measuring the amount of uric acid formed during the reaction catalyzed by xanthine oxidase. This is accomplished in vitro via enzymatic reactions and spectrophotometric measurements. The Maillard reaction is responsible for the production of black color in garlic, and it is influenced by heating temperature, humidity, and fermentation time. Starting on the 17th day of the fermentation process, the brownish intensity of the garlic samples heated at 70 ° C and 90% humidity changed to brown. The optimum concentration is 0.3 units/mL at an optimum temperature of 30oC and an optimum pH of 8.0 at a substratum concentration of 0.30 mM at a wavelength of 284 nm. The activity of the xanthine oxidase enzyme was inhibited by allopurinol at various concentrations, with allopurinol having the highest percentage inhibition value of 78.74 percent at a concentration of 10 ppm. The present study showed that meanwhile, the highest inhibition occurred on the 29th day of fermentation, with a percentage value of 68.01 percent, and decreased the next day

Xanthine Oxidase Inhibitory Activity and Uric Acid Dissolution Power of Some Plant Extracts: In Vitro Therapeutical Approach for Gout Treatment

Xanthine Oxidase Inhibitory Activity and Uric Acid Dissolution Power of Some Plant Extracts: In Vitro Therapeutical Approach for Gout Treatment

Synthesis and Biological Evaluation of Novel Chlorogenic Acid-Apigenin Conjugates as Anti-acute Gout Agents.

Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.