In vitro Evaluation of Antiproliferative, Lipoxygenase and Xanthine Oxidase Inhibitory Activities of Artemisia nilagirica (C.B.Clarke) Pamp. Leaf Extracts

S-allyl cysteine as potent anti-gout drug: Insight into the xanthine oxidase inhibition and anti-inflammatory activity

Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and gout

Xanthine oxidase (XO) is an enzyme that has an improtant role in the synthesis of uric acid. XO is an enzyme allowscatalyzing the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid. These are two reactions in the final stage of metabolism of the purines in the body. Offal, XO enzyme inhibitors reduce biosynthesis of uric acid have been used to prevent and treat gout. In this study, Gompherena celosiodes is extracted by ultrasonic with ethanol 80 % (EtOH)solvents and fractionated with n-hexane, ethyl acetate (EtOAc) and n-butanol (n-BuOH) solvents. These fractions were evaluated xanthine oxidase inhibitory activities in vitro. The results show that n-BuOH fraction from roots bark had the strongest XO enzyme inhibitory activity (IC50: 27,39 ± 0,31µg/mL), followed by EtOH fraction (IC50: 47,37 ± 0,26 µg/mL) and EtOAc fraction (IC50: 33,36 ± 0,51µg/mL) and the lowest is n-hexan fraction (IC50: 81,59 ± 0,21µg/mL). The research results indicated that the n-BuOH fraction and the EtOAc fraction from tree-hatched soil have a potential in the prevention and treatment of gout.

Chemical and biological characteristics of Sri Lankan white tea

A series of 2-(substituted benzylamino)-4-methylthiazole-5-carboxylic acid was designed and synthesized as structural analogue of febuxostat. A methylene amine spacer was incorporated between the phenyl ring and thiazole ring in contrast to febuxostat in which the phenyl ring was directly linked with the thiazole moiety. The purpose of incorporating methylene amine was to provide a heteroatom which is expected to favour hydrogen bonding within the active site residues of the enzyme xanthine oxidase. The structure of all the compounds was established by the combined use of FT-IR, NMR and MS spectral data. All the compounds were screened in vitro for their ability to inhibit the enzyme xanthine oxidase as per the reported procedure along with DPPH free radical scavenging assay. Compounds 5j, 5k and 5l demonstrated satisfactory potent xanthine oxidase inhibitory activities with IC50 values, 3.6, 8.1 and 9.9 μm, respectively, whereas compounds 5k, 5n and 5p demonstrated moderate antioxidant activities having IC50 15.3, 17.6 and 19.6 μm, respectively, along with xanthine oxidase inhibitory activity. Compound 5k showed moderate xanthine oxidase inhibitory activity as compared with febuxostat along with antioxidant activity. All the compounds were also studied for their binding affinity in active site of enzyme (PDB ID-1N5X).

Tea, from Camellia sinensis, is second only to water in global consumption. Tea germplasm in Sri Lanka consists of over 600 tea cultivars, and currently, 70 of them are recommended for commercial tea cultivation. However, the biological activities of Sri Lankan tea cultivars have not been documented. The present study investigated the in vitro enzyme inhibitory activities, viz., lipase, α-amylase, xanthine oxidase, α-glucosidase, and acetylcholinesterase, as well as antioxidant activity in black tea and tea leaves harvested from 15 different tea cultivars during the major seasons in Sri Lanka. The remarkable α-glucosidase, xanthine oxidase, and acetylcholinesterase inhibitory activities in black tea and tea leaves of tea cultivars were observed, with the IC50 of black tea ranging from 5.77 to 104.10 ppm, 0.55 to 36.75 ppm, and 28.37 to 184.06 ppm, respectively. Additionally, some tea cultivars have exhibited moderate α-amylase and lipase inhibitory activities. The radical scavenging activities of DPPH (1,1-diphenyl-2-picrylhydrazyl) and nitric oxide on black tea and tea leaves were exhibited with the IC50 of black tea ranging from 14.03–67.23 ppm and 76.22 to 251.35 ppm, respectively.

3,4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a potent inhibitor of xanthine oxidase: A potential therapeutic agent for treatment of hyperuricemia and gout

A strategy to boost xanthine oxidase and angiotensin converting enzyme inhibitory activities of peptides via molecular docking and module substitution

BACKGROUND: Uric acid is a final result of purine catabolism, the enzymatic reactions in the body cells from amino acids or ribonucleotide dinucleotide. Peperomia pellucida L. (P. pellucida), Acalypha indica L. (A. indica) and Momordica charantia L. (M. charantia) are plants which have efficacy to reduce levels of uric acid excess. The aim of this research is to find out the effect of ethanol extract of P. pellucida, A. indica and M. charantia in preventing the formation of uric acid excess by inhibiting the action of the enzyme xanthine oxidase and comparing the inhibition activity of xanthine oxidase on treatments.METHODS: The study design is experimental and conducted using the enzyme xanthine oxidase, xanthine (substrate), pH 7.5 phosphate buffer, samples (P. pellucida, A. indica and M. charantia ethanol extracts) and HCL as reaction breaker. Inhibition of xanthine oxidase was determined enzymatically and unreacted xanthine was measured by UV spectrophotometer at 290 nm. The data were expressed as percent inhibition and the inhibitory concentration (IC)50 were determined using linear regresion of inhibition activity vs. concentration.RESULTS: The IC50 of P. pellucida, A. indica and M. charantia ethanol extracts in inhibiting xanthine oxidase were 19.5 ppm, 77.6 ppm and 17.8 ppm, respectively. IC50 of allopurinol was 1.99 μg/ml, and negative control (combination of enzyme and substrate) has absorbance value of 0.75026.CONCLUSION: Ethanol extract of M. charantia showed the most potent inhibition toward xanthine oxidase compared to the other two extracts.KEYWORDS: xanthine oxidase, Peperomia pellucida L., Acalypha indica L., Momordica charantia L.

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.

Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol

The purpose of this study was to evaluate the antioxidant activities, tyrosinase inhibitory effects on the fruiting bodies of Pleurotus salmoneostramineus extracted with acetone, methanol and hot water. The antioxidant activities were performed on β-carotene-linoleic acid, reducing power, DPPH, ferrous ions chelating abilities, and xanthine oxidase inhibitory activities. In addition to this, phenolic compounds were also detected. Acetonic, methanolic and hot water extracts of P. salmoneostramineus showed the similar pattern of β-carotene-linoleic acid inhibition. At 8 mg/ml, methanolic extract showed a high reducing power of 1.62. The scavenging effects on DPPH, acetonic and methanolic extracts were effective than hot water extract. The strongest chelating effect was obtained from the acetonic and methanolic extracts at 1.0 mg/ml. Gallic acid, protocatechuic acid, chlorogenic acid, formononetin, and biochanin-A were detected from acetonitrile and 0.1N hydrochloric acid (5:1) solvent extract. The xanthine oxidase and tyrosinase inhibitory activities of the acetonic, methanolic, and hot water extracts increased with increasing concentration. The results suggested that fruiting bodies of P. salmoneostramineus may have potential as a natural antioxidants. Key words: Antioxidant, phenolic compounds, Pleurotus salmoneostramineus, tyrosinase inhibition, xanthine oxidase.

Background:Cervical cancer has been linked to human papillomavirus (HPV) types 16 and 18. Essential oils (EOs) are vital natural products of plants with various therapeutic and biological properties.Objectives:The purpose of this study is to investigate and assess Tanacetum sinaicum essential oil’s possible antiviral and anticancer properties, with a focus on its in vitro effects on human cervical cancer and human breast adenocarcinoma cell lines. Materials and Methods:Tanacetum sinaicum EO was extracted via hydrodistillation (HD) and characterized using gas chromatography-mass spectrometry (GC-MS). MTT assay was used to determine the cell viability of Hela (a human epithelial cervical cancer) and MCF-7 (human breast adenocarcinoma) cell lines. Quantitative real-time polymerase chain reaction (PCR) was utilized to assess the antiviral efficacy of EO against HPV-16 and 18, and anti-metastatic characteristics. The biological activity of EO was assessed using Autophage and Cell genotoxicity via the comet assay.Results: EO is mostly composed of chrysanthenyl acetate, thujone, and verbenol. The cell viability was reduced after 24 hours of incubation at doses from 100 to 400 µg/ml. Concentrations of 800 to 3,200 µg/ml significantly inhibit cell growth. After a 24-hour incubation period, doses ranging from 100 to 400 µg/ml reduced cell viability from 62 to 72%. Concentrations of 800 to 3,200 µg/ml significantly suppress cell growth by over 95%. In MCF7 and HeLa cell lines, EO lowered virus copy numbers in a dose-dependent manner, with higher concentrations of the oil inhibiting virus replication more effectively. EO treatment increased the number of autophagosomes/autolysosomes and acidic vesicular organelles in both cell lines. On the HeLa and MCF7 cell lines, EO demonstrated antiproliferative and antimetastatic effects. The results demonstrated that EO had dose-dependent genotoxic effects on both cancer cell lines, as evidenced by DNA damage. Conclusion:Tanacetum sinaicum EO is a prospective source of natural bioactive compounds that can be employed in pharmaceutical and medicinal applications due to its antiviral, antiproliferative, anti-metastatic and genotoxic properties.

Hyperuricemia is linked to a variety of disorders that can have serious consequences for human health. Peptides that inhibit xanthine oxidase (XO) are expected to be a safe and effective functional ingredient for the treatment or relief of hyperuricemia. The goal of this study was to discover whether papain small yellow croaker hydrolysates (SYCHs) have potent xanthine oxidase inhibitory (XOI) activity. The results showed that compared to the XOI activity of SYCHs (IC50 = 33.40 ± 0.26 mg/mL), peptides with a molecular weight (MW) of less than 3 kDa (UF-3) after ultrafiltration (UF) had stronger XOI activity, which was reduced to IC50 = 25.87 ± 0.16 mg/mL (p < 0.05). Two peptides were identified from UF-3 using nano-high-performance liquid chromatography-tandem mass spectrometry. These two peptides were chemically synthesized and tested for XOI activity in vitro. Trp-Asp-Asp-Met-Glu-Lys-Ile-Trp (WDDMEKIW) (p < 0.05) had the stronger XOI activity (IC50 = 3.16 ± 0.03 mM). The XOI activity IC50 of the other peptide, Ala-Pro-Pro-Glu-Arg-Lys-Tyr-Ser-Val-Trp (APPERKYSVW), was 5.86 ± 0.02 mM. According to amino acid sequence results, the peptides contained at least 50% hydrophobic amino acids, which might be responsible for reducing xanthine oxidase (XO) catalytic activity. Furthermore, the inhibition of the peptides (WDDMEKIW and APPERKYSVW) against XO may depend on their binding to the XO active site. According to molecular docking, certain peptides made from small yellow croaker proteins were able to bind to the XO active site through hydrogen bonds and hydrophobic interactions. The results of this work illuminate SYCHs as a promising functional candidate for the prevention of hyperuricemia.

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.