Xanthine Oxidase Activity Research Articles

Effects of Duloxetine on Oxidant-Antioxidant System in Rat Brain Tissues

Objective: After the relationship between depression and oxidative stress (OS) was demonstrated, the effect of antidepressant drugs on OS has become important. In this study, we aimed to determine the effects of the antidepressant duloxetine on the activities of the superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) enzymes as well as the lipid peroxidation (LP) product malondialdehyde (MDA) and nitric oxide (NO) levels in rat brains. 
 Material and Method: Twenty male Sprague-Dawley rats were used for the study. The first group was the control group (n=10) and the second group was the duloxetine group (n=10). Duloxetine was administered intragastrically once a day at a dose of 10 mg/kg for two weeks in the second group. Water was administered intragastrically once a day for two weeks in the first group. Rats were sacrificed at the end of the fourteenth day. The brain tissues were collected and then analyzes were performed.
 Results: As a result of this study, we found that duloxetine increased the SOD (P=0.026) activity and decreased the ADA (P=0.041), XO (P=0.034) and CAT (P=0.006) activities significantly compared to the control group. We also found an increase in the GSH-Px enzyme activity and decrease in the NO and MDA levels at non-significant rates in the duloxetine group brain tissues.
 Conclusion: The significant increase in the activity of the antioxidant enzyme SOD, the significant decrease in the activities of the XO and ADA enzymes, which can cause the formation of reactive oxygen products in the organism, and the insignificant decrease in the LP indicator MDA suggest that duloxetine can positively change the antioxidant status in rat brain tissues.

SCREENING FOR ANTI-HYPERURICEMIA POTENTIAL OF SOME INDONESIAN MEDICINAL PLANTS THROUGH XANTHINE OXIDASE INHIBITION IN VITRO ASSAY

Objective: This study aimed to examine the in vitro xanthine oxidase inhibitory activity of 12 plants commonly used as gout medicines by the Indonesian people.
 Methods: The measurement of xanthine oxidase enzyme inhibitory activity was using UV spectrophotometry. The in vitro assessment of xanthine oxidase inhibition activity was tested on extracts from Eleutherine bulbosa (Mill.) Urb. Bulbs, Pandanus amaryllifolius Roxb. leaves, Alyxia reinwardtii Blume stem barks, Ruta angustifolia Pers aerial parts, Dioscorea hispida Dennst tubers, Plantago major L. leaves, Symphytum officinale L. roots, Euphorbia hirta L. aerial parts, Chromolaena odorata L. leaves, Solanum torvum Sw fruits, Peperomia pellucida L. Kunth. aerial parts and Strobilanthes crispa L. Blume leaves.
 Results: The results of this study showed that all tested plant extracts can inhibit xanthine oxidase activity with IC50 values varying from 27.80 µg/ml to 47.14 µg/ml. The IC50 value of allopurinol, used as positive control, was 1.24 µg/ml. Among all the tested plant extracts, Strobilanthes crispa L. Blume leaves extract has the best inhibitory activity against xanthine oxidase enzyme with IC50 value of 27.80 µg/ml.
 Conclusion: Strobilanthes crispa L. Blume leaves extract has the best inhibitory activity against xanthine oxidase, so It has the potential to be developed into herbal medicine to treat hyperuricemia. This study provides scientific support for the anti-hyperuricemia activity of these herbs, which are empirically used to treat gout.

Phytochemical screening and biological evaluation of Greek sage (Salvia fruticosa Mill.) extracts

This study explores the influence of extraction solvents on the composition and bioactivity of Salvia fruticosa extracts. Ultrasound-assisted extraction with water, ethanol and their mixtures in variable proportions was used to produce four different extracts. An untargeted UPLC/MS‑based metabolomics was performed to discover metabolites profile variation between the extracts. In the analyzed samples, 2704 features had been detected, of which 95 were tentatively identified. The concentrations of the important metabolites, namely, caffeic acid, carnosic acid, carnosol, rosmarinic acid, salvianolic acid B and scutellarin, were determined, using UPLC-PDA methods. Rosmarinic acid was the dominant metabolite and antioxidant in all tested extracts, except the aqueous extract, in which scutellarin was the most abundant compound. The extracts and standards were examined for antioxidant activity and xanthine oxidase (XO) inhibitory activity. The most diverse in terms of chemical composition and rich in antioxidant compounds was 70% ethanolic extract and the strongest antioxidant was caffeic acid. All analyzed extracts showed the ability to inhibit XO activity, but the highest value was recorded for 30% ethanolic extract. Among tested standards, the most potent XO inhibitor was caffeic acid. The results suggest that the leaves of Greek sage are a source of natural XO inhibitors and may be an alternative to drugs produced by chemical synthesis.

Understanding Hyperuricemia: Pathogenesis, Potential Therapeutic Role of Bioactive Peptides, and Assessing Bioactive Peptide Advantages and Challenges.

Hyperuricemia is a medical condition characterized by an elevated level of serum uric acid, closely associated with other metabolic disorders, and its global incidence rate is increasing. Increased synthesis or decreased excretion of uric acid can lead to hyperuricemia. Protein peptides from various food sources have demonstrated potential in treating hyperuricemia, including marine organisms, ovalbumin, milk, nuts, rice, legumes, mushrooms, and protein-rich processing by-products. Through in vitro experiments and the establishment of cell or animal models, it has been proven that these peptides exhibit anti-hyperuricemia biological activities by inhibiting xanthine oxidase activity, downregulating key enzymes in purine metabolism, regulating the expression level of uric acid transporters, and restoring the composition of the intestinal flora. Protein peptides derived from food offer advantages such as a wide range of sources, significant therapeutic benefits, and minimal adverse effects. However, they also face challenges in terms of commercialization. The findings of this review contribute to a better understanding of hyperuricemia and peptides with hyperuricemia-alleviating activity. Furthermore, they provide a theoretical reference for developing new functional foods suitable for individuals with hyperuricemia.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1−2), two new geranyl glucosides (3−4), and nine known compounds (5–13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Polyphenol Composition, Antioxidant Capacity and Xanthine Oxidase Inhibition Mechanism of Furong Plum Fruits at Different Maturity Stages.

An experiment was conducted on the polyphenol content, flavonoid content, anthocyanin content, and antioxidant capacity of Furong plum (Prunus salicina Lindl. cv. "furong") at different maturity stages to determine the most suitable maturity stage. The inhibition of plum polyphenols on xanthine oxidase (XOD) was measured, and its kinetics were studied to reveal the inhibitory mechanism. The experimental results showed that the polyphenol, flavonoid and anthocyanin contents of plums at the ripe stage were the highest, reaching 320.46 mg GAE/100 g FW, 204.21 mg/100 g FW, and 66.24 mg/100 g FW, respectively, in comparison those of the plums at the immature and mid-ripe stages. The antioxidant capacity of the ripe plums was stronger than it was during the other stages of the plums growth. Among them, the total polyphenols of the ripe plums exhibited the strongest antioxidant capacity (IC50 values against DPPH and hydroxyl radicals were 28.19 ± 0.67 μg/mL and 198.16 ± 7.55 μg/mL, respectively), which was between the antioxidant capacity of the free polyphenols and bound polyphenols. The major phenolic monomer compounds of plum polyphenols were flavan-3-ols (epicatechin, catechin, proanthocyanidin, and procyanidin B2), flavonols (myricetin), and phenolic acids (chlorogenic acid, ferulic acid, and protocatechuic acid). Additionally, plum polyphenols exhibited a strong inhibitory effect on XOD, with an IC50 value of 77.64 μg/mL. The inhibition kinetics showed that plum polyphenols are mixed-type inhibitors that inhibit XOD activity and that the inhibition process is reversible. The calculated values of Ki and α were 16.53 mmol/L and 0.26, respectively.

Anti-hyperuricemic properties and mechanism of Lactiplantibacillus plantarum X7023

The study conducted on Lactiplantibacillus plantarum X7023, a novel strain isolated from stinky tofu brine, aimed to investigate its effects on hyperuricemia. The strain demonstrated high in vitro gastrointestinal survivability and purine-lowering ability (guanine, xanthine and adenine decreased by 21.4%, 93.9% and 11.5%, respectively). The anti-hyperuricemia effects of the strain have been studied in potassium oxonate and hypoxanthine induced hyperuricemia mice. The serum uric acid (UA) levels of hyperuricemic mice were significantly reduced by 38.8% and 19.0% after treatment with low and high dose of L. plantarum X7023 treatment, respectively. Additionally, the levels of creatinine and blood urea nitrogen were decreased by 19.6% and 21.2% respectively in low dose of L. plantarum X7023 group. The anti-hyperuricemic mechanism of L. plantarum X7023 might be its inhibiting xanthine oxidase (XOD) activity, and regulating the expression of renal UA transporters. According to kidney inflammatory cytokines and histopathological analysis, L. plantarum X7023 could also alleviate the kidney inflammation and protect the kidney. Therefore, L. plantarum X7023 is a potential probiotic strain for the amelioration of hyperuricemia. This study further demonstrated that there are significant correlations among UA level, oxidative stress, kidney inflammation, XOD activity and UA transporter expressions in hyperuricemic mice.

Amelioration of hyperuricemia by Lactobacillus acidophilus F02 with uric acid-lowering ability via modulation of NLRP3 inflammasome and gut microbiota homeostasis

Hyperuricemia is a metabolic disease caused by disturbances in purine metabolism and imbalances in the formation and excretion of uric acid. It is closely related to the gut microbiota, which is considered a therapeutic target. Some lactic acid bacteria with a uric acid lowering effect have the potential to ameliorate hyperuricemia in the host. However, the mechanism of action remains unclear. Here, we screened a strain of Lactobacillus acidophilus F02 that efficiently degrades uric acid precursors (inosine and guanosine) and further investigated its underlying mechanism on the alleviation of hyperuricemia in high fructose-adenine induced mice. Results showed that L. acidophilus F02 administration reduced serum uric acid levels in hyperuricemia mice by inhibiting xanthine oxidase and adenosine deaminase activity, while protecting hepatorenal injury and systemic inflammation by regulating the relative expression of NLRP3 inflammasome. Most importantly, it restored gut microbial homeostasis and the abundance of bacterial taxa (i.e., a balance in the relative abundance of Firmicutes and Actinobacteria and an increase in the abundance of Bacteroides, Ruminococcus and Lactobacillus). Furthermore, the ability of L. acidophilus F02 to lower uric acid and suppress NLRP3 inflammasome expression was confirmed in the HK-2 cell model, as well as the multiple immunomodulatory effects on RAW264.7 cells. Taken together, we speculate that fructose-adenine induced hyperuricemia triggers hepatorenal injury and gut microbiota dysbiosis, which is ameliorated by L. acidophilus F02. Collectively, the results suggest that lowering uric acid synthesis, increasing uric acid excretion and reducing NLRP3-related IL-1β levels are effective strategies to ameliorate hyperuricemia. Such information could inform future studies on the ecology of L. acidophilus and guide the use of this species for dietary applications in the food industry.

Assessment of the In Vitro Effects of Six Selected Plant Extracts on Xanthine Oxidase

Background: Gouty arthritis is one of the most prevalent forms of arthritis caused by the deposition of uric acids mostly in joints, due to hyperuricemia. Xanthine oxidase (XO) is a key enzyme of the purine degradation pathway, catalysing the oxidation of hypoxanthine to xanthine and further to uric acid; increased activity leads to hyperuricemia hence a need to control XO activity. Commonly used therapeutic approach is the use of XO inhibitors. This study aimed to investigate if Vitis vinifera, Malus sylvestris fruit peels, Cymbopogon citratum leaves, Mucuna Pruriens leaves, Zanha africana roots and leaves, Mimosa pudica roots extracts have a Xanthine Oxidase inhibitory potential in vitro. Methodology: Air dried samples were crushed into powder using a mortar and pestle. Maceration and percolation extraction methods were used to obtain active secondary metabolites from plant materials at 10%w/v. Spectrophotometric assays methods were used for Xanthine Oxidase activity and inhibition studies. Results: The results of the current study showed that all aqueous plant extracts showed the presence of flavonoids. The experimental data showed significant inhibitory effects on XO activity. C. citratum inhibited XO activity by an average of 71%. M. sylvestris exhibited 68%, 61% and 64% at 15, 30 and 45 minutes respectively. V. vinifera exhibited 75%, 66% and 77% XO inhibitory activity at 15, 30 and 45 minutes respectively. Z. Africana exhibited 73%, 65% and 74% at 15, 30 and 45 minutes respectively. M. pudica exhibited 74%, 77% and 78% XO inhibitory activity at 15, 30 and 45 minutes respectively. M. pruriens exhibited 65%, 69% and 71% XO inhibitory activity at 15, 30 and 45 minutes respectively. Conclusion: The results obtained from the current study indicates that the flavonoids present in all plant extracts under study could be potential anti-gout agents by their inhibitory activities on Xanthine Oxidase activity

Synergistic co-catalytic nanozyme system for highly efficient one-pot colorimetric sensing at neutral pH: Combining molybdenum trioxide and Fe(III)-Modified covalent triazine framework

This study investigates the co-catalytic capabilities of MoO3 nanosheets in enhancing the enzyme-like catalytic activity of a two-dimensional ultrathin Fe(III)-modified covalent triazine framework (Fe-CTF) under neutral pH conditions. The unique physicochemical surface properties and two-dimensional structures of Fe-CTF enable the direct immobilization of native enzymes (glucose oxidase (GOD) and xanthine oxidase (XOD)) through adsorption, eliminating the need for chemical processes. Efficient immobilization of the native enzymes within the Fe-CTF/GOD(XOD) hybrid is achieved through multipoint attachment involving various interactions. The Fe-CTF/MoO3 co-catalytic system exhibits enzyme-mimicking activity at neutral pH and, when combined with the high catalytic activity of the immobilized native enzymes, enables the development of a colorimetric method for glucose detection. This method demonstrates excellent facilitation, rapidity, sensitivity, and selectivity, with a linear detection range of 50–1000 μM and a limit of detection of 8.8 μM for glucose. Furthermore, a straightforward one-pot colorimetric method is established for screening XOD inhibitors. The inhibitory potential of a crude extract derived from Chinese water chestnut peel on XOD activity is evaluated using this method. The findings of this study pave the way for the utilization of nanozyme/native enzyme hybrids in pH-neutral conditions for one-pot colorimetric sensing. This work contributes to the advancement of enzyme-based sensing technologies and holds promise for various applications in biosensing and biomedical research.

Comparative studies of influence of palm oil on activity of xanthine oxidase and free radicals in liver and blood: Diabetes and metabolic syndrom

Diabetes is a chronic metabolic disease, which has affected approximately 10.5% of the global population [1]. The most frequent types of diabetes are type-1 and type-2. The third frequent type is gestational diabetes. The pathogenicity of diabetes is multifactorial and involves various factors such as genetic, food, stress, environmental pollutants, and others, in most of the cases combination of two or more factors are noticed. Comparative studies of the influence of palm oil on the activity of xanthine oxidase (XOD) and free radicals in liver and blood. The research compared the effect of palm oil on carbohydrate metabolism in male rats: in young rats and adult rats. The research compared the effect of palm oil on free radicals in male rats: in adults and juvenile rats. Experimental animal body weight change research, 30 days after palm oil treatment. For this scientific research we utilized experimental animals of the male genus: mice of the Wistar type, small mice (45-60 g) and large mice (160-180 g). Experimental animals were divided into groups of six-eight experimental mice and details are shown in the corresponding part of the results. The results are shown in six figures and two tables. Results indicate an increase in the formation of free radicals in blood plasma, both in experimental juvenile mice and in experimental large mice under the influence of palm oil. Palm oil increases the activity of XOD in blood, both in small animals and in large experimental animals. Palm oil increases the formation of XOD in the black liver in both elderly groups. In all groups during the experiment there was an increase in body weight. Results from studies of the effect of palm oil on carbohydrate metabolism showed changes in glucose tolerance test. Current studies for the first time convincingly demonstrate the risk of using palm oil. Analysis of the results of two studies on XOD and carbohydrate metabolism showed a correlation between increased XOD levels and the development of prediabetes.

Abstract 12479: Cardiovascular Stroke Nursing Best Abstract Award: Sex Differences in Relationships Between Inflammation and Symptoms in Persons With Heart Failure

Background: Heart failure (HF) is a complex syndrome involving interplay of pathologic processes, such as inflammation and myocardial remodeling. Sex differences in cardiac remodeling and function are linked to differences in inflammation. Female hearts show a pro-inflammatory shift and increased cytokine expression with aging not seen in male hearts. Yet, sex is not often considered in HF interventions. Previous studies suggest sex may moderate the relationship between inflammation and symptoms in cardiometabolic disease, but the relationship in HF is unknown. Purpose: To examine sex differences in inflammation and symptoms in Black adults living with HF. Methods: Black adults living with HF (N=41) were enrolled in this pilot study. Physical symptoms were measured with PROMIS Dyspnea, Heart Failure Somatic Perception Scale (HFSPS), and Multidimensional Fatigue Inventory (MFI). Mood symptoms were measured with Center for Epidemiological Studies Depression Scale (CESD), State-Trait Anxiety Inventory (STAI), and Perceived Stress Scale (PSS). Inflammatory biomarkers were measured via multiplex immunoassay. Xanthine oxidase (XO) activity, an indicator of oxidative stress, was measured via ELISA. Pearson correlations were stratified by sex. Results: The mean age was 57 ± 11 years, and 66% were female. Dyspnea was positively associated with XO activity in both groups. Among females, dyspnea was positively associated with matrix metalloproteinase (MMP)-12 (r=.519, p=.033), interleukin (IL)-6 (p=.564, p=.018), [C-C motif chemokine ligand(CCL)-3, (r=.509, p=.037), and CCL-11 (r=.520, p=.032). HFSPS was positively associated with XO activity among females only (r=.445, p=.014). CCL-11 was positively associated with MFI (r=.616, p=.008), PSS (p=.0537, r=.032), STAI (r=.714, p=.001), and CESD (r=.635, p=.008) symptoms among females but not males. Conclusions: While physical symptoms were associated with similar inflammatory pathways, fatigue and mood symptoms were associated with inflammation among females only. Women may be more vulnerable to inflammation-induced mood changes and fatigue. Further work is needed to better understand how sex modulates the relationship between inflammation and symptoms in persons with HF.

Antihyperuricemic activity and inhibition mechanism of xanthine oxidase inhibitory peptides derived from whey protein by virtual screening

Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and β-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.

Enhanced hypoxanthine utilization and antioxidant capacity for cAMP salvage synthesis efficiently by Arthrobacter sp. CCTCC 2013431 with glutathione addition

When hypoxanthine was used to activate the salvage pathway for cAMP synthesis, reactive oxygen species would generate in quantity resulting in low cAMP yields. cAMP fermentations with/without glutathione addition on the basis of hypoxanthine feeding were conducted. Owing to 200 mg/L glutathione added at 24 h, cAMP concentration reached 7.38 g/L with an increment of 85.89%, and cAMP conversions from hypoxanthine were improved significantly when compared with control. Intracellular ROS and malonaldehyde levels were reduced obviously, at the same time, cell viability, respiratory intensity and ATP/AMP were improved notably suggesting that glutathione relieved oxidative stress and cell damage leading to higher cell viability and energy metabolism. Moreover, xanthine oxidase activities and byproducts contents were decreased obviously, meanwhile, the expression contents and genes transcription levels of PUP and HPRT were increased significantly, indicating that glutathione enhanced hypoxanthine uptake for cAMP synthesis and decreased hypoxanthine decomposition resulting in higher cAMP yields and conversion ratios.

Inhibiting Hepatocyte Uric Acid Synthesis and Reabsorption Ameliorates Acetaminophen-Induced Acute Liver Injury in Mice

Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

Ameliorative Effect of a Vanadium-thiosemicarbazone Complex on Oxidative Stress in Stomach Tissue of Experimental Diabetic Rats

Recently, we have shown that oral administrations of an oxidovanadium (IV) complex, VOL, with tetradentate thiosemicarbazone ligand normalizes hyperglycemia of streptozotocin-induced diabetic rats (STZ-rats). For the development of vanadium compounds that exhibit insulin-like behavior, it is essential to know some of the pharmacokinetic properties of these complexes. The goal of the current research is to examine the healing effect of new sythesed VOL complex on the oxidative stress parameters of diabetic stomac tissue. Rats used in the experiments were divided as control, VOL+control, diabetic and diabetic+VOL. The rats were sacrificed after 12 days of the experimental period. The levels of glutathione, lipid peroxidation, non-enzymatic glycosylation, advanced oxidized protein products levels and the activities of some enzymes were measured in stomach tissue of all the experimental animals. Although VOL treatment to diabetic rats increased the stomach glutathione levels; lipid peroxidation, non-enzymatic glycosylation and advanced oxidized protein products levels were decreased. Also, the activities of catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and carbonic anhydrase were increased in VOL treated diabetic group. Whereas, lactate dehydrogenase and xanthine oxidase activities were decreased. According to the obtained outcomes, it can be said that VOL treatment has a healing effect on the stomach tissue of diabetic rats. This effect provided by VOL is most likely due to the insulin-like and antioxidant activity of the complex. In conclusion, we can say that VOL may be a suitable candidate for diabetes treatment.

Cinnamon essential oil based on NLRP3 inflammasome and renal uric acid transporters for hyperuricemia

Cinnamon is widely used as a medicinal herb and a culinary spice. The major bioactive component of cinnamon is cinnamon essential oil (CEO). CEO has been reported to have anti-inflammatory and antioxidant effects, but its mechanism of action is not known. In this study, metabolomics was combined with “weighting coefficients” from network pharmacology to identify key pathways and targets, differential metabolites and key metabolic pathways for the therapeutic effects of CEO on Hyperuricemia (HUA), and to precisely investigate the molecular mechanisms of the therapeutic effects of CEO on HUA. Metabolomic analysis revealed that abnormal l-glutamate metabolism and dysregulation of Arachidonic acid (AA) metabolic pathways exacerbated inflammatory responses and oxidative stress, subsequently mediating pathological changes in HUA and exacerbating renal tissue damage. Pharmacodynamic validation showed that CEO alleviated the renal inflammatory response by inhibiting hepatic xanthine oxidase activity, upregulating superoxide dismutase and glutathione peroxidase levels, and downregulating malondialdehyde levels, synergistically inhibiting NLRP3 inflammasome activation, suppressing downstream inflammatory Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) secretion, and enhancing antioxidant levels. Additionally, CEO exerted renal protective effects by upregulating the renal transporters OAT1 and ABCG2 and downregulating the GLUT9 and URAT1 levels, resulting in the downregulation of uric acid production and the alleviation of renal tubular lesions. This suggests that CEO could be considered as a potential functional food for kidney damage caused by hyperuricemia.

New xanthine oxidase inhibitor from white mulberry (Morus alba L.) – anti-gout prospective study

Abstract In recent years, Morus sp. (mulberry) has acquired a special importance due to its phytochemical composition and its beneficial effects on human health, including antioxidant, anticancer, antidiabetic and immuno-modulatory effects. The various parts of Morus sp., such as its fruits, leaves, twigs, and roots, are recognized as abundant sources of secondary metabolites, with the leaves containing significant amounts of glycosylated flavonols like quercetin and kaempferol, along with chlorogenic acid as the primary phenolic compound. Overall, it can be considered a multi utility plant and can be exploited as an alternative therapy in various ailments. Xanthine oxidase (XO) is the key enzyme for high serum urate levels which is the main cause of developing gout. Under the urate lowering therapy, allopurinol and febuxostat are the main XO inhibitors used to treat gout. However, mild to severe side effects of these synthetic XO inhibitors lead to finding an effective natural alternative without having any side effects. The present study was designed to find out phytochemical analysis and antigout properties of leaves of white mulberry plant. The phytochemical analysis was performed on quantitative and qualitative basis. The qualitative basis indicated the presence of alkaloids, glycosides, flavonoids, steroids, tannins, saponins and Anthraquinone. Biochemical regulation of extracts on anti-gout property using XO inhibition study. Microbial XO was isolated from the Bacillus pumilus to study the anti-gout effects of plant extracts qualitatively on xanthine – NBT plate. Additionally, image analysis studies revealed more clear aspects toward the inhibition studies by plant extracts. The XO activity observed varied from 2.89 to 13.80 μM of uric acid formed/min/ml of enzyme used. Ethanolic extract of mulberry leaves (EEML) showed higher XO inhibition than allopurinol. This is associated with its total polyphenol content, which ranged from 81.25 to 103.12 mg GAE/g of dried extract used, as reported in the case of EEML. The present study is the very first report of relating polyphenol content of EEML with the anti-gout property. EEML is a potential candidate for anti-gout property due to the presence of higher amounts of total polyphenol content and B. pumilus is the best source to extract microbial XO.

Activation of xanthine oxidase by 1,4-naphthoquinones: A novel potential research topic for diet management and risk assessment.

Oral intake of 1,4-naphthoquinones could be a potential risk factor for hyperuricemia and gout via activation of xanthine oxidase (XO). Herein, 1,4-naphthoquinones derived from food and food-borne pollutants were selected to investigate the structure and activity relationship (SAR) and the relative mechanism for activating XO in liver S9 fractions from humans (HLS9) and rats (RLS9). The SAR analysis showed that introduction of electron-donating substituents on the benzene ring or electron-withdrawing substituents on the quinone ring improved the XO-activating effect of 1,4-naphthoquinones. Different activation potential and kinetics behaviors were observed for activating XO by 1,4-naphthoquinones in HLS9/RLS9. Molecular docking simulation and density functional theory calculations showed a good correlation between -LogEC50 and docking free energy or HOMO-LUMO energy gap. The risk of exposure to the 1,4-naphthoquinones was evaluated and discussed. Our findings are helpful to guide diet management in clinic and avoid adverse events attributable to exposure to food-derived 1,4-naphthoquinones.