Xanthine Oxidase Inhibitory Activity Research Articles

Extracts of Andrographis paniculata (Burm.f.) Nees Leaves Exert Anti-Gout Effects by Lowering Uric Acid Levels and Reducing Monosodium Urate Crystal-Induced Inflammation.

Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.

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.

Effects and underlying mechanisms of food polyphenols in treating gouty arthritis: A review on nutritional intake and joint health.

Gouty arthritis, one of the most severe and common forms of arthritis, is characterized by monosodium urate crystal deposition in joints and surrounding tissues. Epidemiological evidence indicates that gouty arthritis incidence is sharply rising globally. Polyphenols are found in many foods and are secondary metabolites in plant foods. The anti-inflammatory and antioxidant effects of food polyphenols have been extensively studied in many inflammatory chronic diseases. Research has suggested that many food polyphenols have excellent anti-gouty arthritis effects. The mechanisms mainly include (a) inhibiting xanthine oxidase activity; (b) reducing the levels of inflammatory cytokines and chemokines; (c) inhibiting the activation of signaling pathways and the NLRP3 inflammasome; and (d) reducing oxidative stress. This paper reviews the research progress and pathogenesis of gouty arthritis and introduces the mechanisms of food polyphenols in treating gouty arthritis, which aims to explore the potential of functional foods in the treatment of gouty arthritis. PRACTICAL APPLICATIONS: The incidence rate of gouty arthritis has increased sharply worldwide, which has seriously affected people's quality of life. According to the current research progress, food polyphenols alleviate gouty arthritis through anti-inflammatory and antioxidant effects. This paper reviews the research progress and molecular pathogenesis of gouty arthritis and introduces the mechanisms of food-derived polyphenols in the treatment of gouty arthritis, which is helpful to the prevention and treatment of gouty arthritis.

Protective effects of Quercus acuta Thunb. fruit extract against UVB-induced photoaging through ERK/AP-1 signaling modulation in human keratinocytes

BackgroundQuercus acuta Thunb. (Fagaceae) or Japanese evergreen oak is cultivated as an ornamental plant in South Korea, China, Japan, and Taiwan and used in traditional medicine. The acorn or fruit of Quercus acuta Thunb. (QAF) is the main ingredient of acorn jelly, a traditional food in Korea. Its leaf was recently shown to have potent xanthine oxidase inhibitory and anti-hyperuricemic activities; however, there have been no studies on the biological activity of QAF extracts. Solar ultraviolet light triggers photoaging of the skin, which increases the production of reactive oxygen species (ROS) and expression of matrix metalloproteinase (MMPs), and destroys collagen fibers, consequently inducing wrinkle formation. The aim of this study was to investigate the effect of water extracts of QAF against UVB-induced skin photoaging and to elucidate the underlying molecular mechanisms in human keratinocytes (HaCaT).MethodsIn this study, we used HPLC to identify the major active components of QAF water extracts. Anti-photoaging effects of QAF extracts were evaluated by analyzing ROS procollagen type I in UVB-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-diphenyl-1-picrylhydrazyl and 2,20-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assays. The expression of MMP-1 was tested by western blotting and ELISA kits. QAF effects on phosphorylation of the MAPK (p38, JNK, and ERK) pathway and transcription factor AP-1, which enhances the expression of MMPs, were analyzed by western blots.ResultsWe identified two major active components in QAF water extracts, gallotannic acid and ellagic acid. The QAF aqueous extracts recovered UVB-induced cell toxicity and reduced oxidative stress by inhibiting intracellular ROS generation in HaCaT cells. QAF rescued UVB-induced collagen degradation by suppressing MMP-1 expression. The anti-photoaging activities of QAF were associated with the inhibition of UVB-induced phosphorylation of extracellular signal-regulated kinase (ERK) and activator protein 1 (AP-1). Our findings indicated that QAF prevents UVB-induced skin damage due to collagen degradation and MMP-1 activation via inactivation of the ERK/AP-1 signaling pathway. Overall, this study strongly suggests that QAF exerts anti-skin-aging effects and is a potential natural biomaterial that inhibits UVB-induced photoaging.ConclusionThese results show that QAF water extract effectively prevents skin photoaging by enhancing collagen deposition and inhibiting MMP-1 via the ERK/AP-1 signaling pathway.

Phytochemical screening of Solanum xanthocarpum and its xanthine oxidase inhibitory activity

Pharmacological features and chemical compounds derived from Solanum xanthocarpum are often investigated. S. xanthocarpum has been widely used to treat a variety of ailments as traditional medicine. Different parts of the plant are being studied to find more new uses for the herb. Xanthine oxidase inhibition is important in many vascular, renal, and bone disorders as this super enzyme causes an increase in uric acid formation and oxidative stress. With this perspective and current literature, further studies are required to be conducted to highlight new features that may be derived from the plant. This study aimed to explore the fruits of Solanum xanthocarpum for their phytochemical constituents and their xanthine oxidase inhibitory activity. Fruits from S. xanthocarpum were identified and collected. We performed alcoholic extraction in the Soxhlet apparatus and fractionation using column chromatography. Furthermore, we analyzed phytochemical properties using fingerprinting chromatography, NMR (Nuclear magnetic resonance), Mass-spectrometry, Ultraviolet (UV), and infrared (IR) spectroscopy. The NMR spectrum revealed new chemical moieties which were validated using mass spectrometry. Later on, we conducted bioassays for xanthine oxidase Inhibitory activity on individual fractions. Three new chemical compounds were discovered (Eicosa -11, 14-dienoic acid, Docosa-7, 10, 13, 16, 19-pentanoic acid, and Glyceryl Tri Palmitoleate). These compounds were fatty acids in nature. Bioassay results obtained were positive and encouraging. Our study findings provide evidence of new chemical compounds that can be derived from Solanum xanthocarpum and can be used to treat renal diseases and gout by inhibiting excessive enzyme catalyzation of xanthine oxidase. The results suggest S. xanthocarpum as a possible candidate for a new therapeutic approach.

Identification and molecular docking of two novel peptides with xanthine oxidase inhibitory activity from Auxis thazard

Auxis thazard meat was hydrolyzed by alkaline protease. Auxis thazard hydrolysate (ATH) obtained was isolated by ultrafiltration, size exclusion chromatography and reversed-phase high-performance liquid chromatography. Two peptides with high XOD inhibitory activity purified from ATH were identified as Pro-Asp-Leu (PDL, 344.87 Da) and Ser-Val-Gly-Gly-Ala-Leu (SVGGAL, 504.26 Da) by UPLC-MS/MS, which possessed high in vitro XOD inhibitory activity with the IC50 values of 4.37 ± 0.11 mg mL-1 and 5.59 ± 0.09 mg mL-1, respectively. Molecular simulation indicated that PDL and SVGGAL binded to XOD mainly through hydrogen bond and hydrophobic interaction, thereby inhibiting XOD activity. The research results suggested that the two peptides had potential application prospects as a safe XOD inhibitor substance for hyperuricemia treatment.

Xanthine Oxidase Inhibitory Mechanism of Fisetin and Hesperitin

Fisetin and hesperitin are two common flavonoids in plant medicines. In this paper, the mechanism of xanthine oxidase (XO) inhibition was systematically studied by combining experimental and theoretical methods. The HPLC results suggested that the XO inhibitory activity of fisetin (IC50, 0.140 mM) was superior to that of hesperitin (IC50, 0.635 mM). The spectrofluorimetry results showed flavonoids could induce the static fluorescence quenching of XO, indicating that they played the inhibitory activity by forming the complexes with XO. We showed the paramount force of fisetin and XO was hydrophobic; in the complex of hesperidin and XO, hydrogen bonding and van der Waals force were crucial forces. We used Autodock software for molecular docking. The results suggested that both fisetin and hesperitin entered the active pocket of XO, and the complexes were maintained by hydrogen bonding and hydrophobic interaction, which coincided with the experimental results.

Medicinal plants of Pakistan and their xanthine oxidase inhibition activity to treat gout: a systematic review

Gout is the most prevalent form of arthritis that arises due to hyperuricemia. Xanthine oxidase inhibitors (XOI) are usually prescribed to treat gout. Although treatment options are available, these therapies are associated with side effects, and natural remedies may be proven helpful in this regard. This systematic review aims to present consolidated information on the xanthine oxidase inhibition potential of the plants located in Pakistan. An extensive literature review reveals that no such study that systematically summarizes existing data is currently available. The present study is registered with PROSPERO (ID: CRD42021247416) and performed according to PRISMA guidelines. Several databases were searched (from January 2000 to April 2021) for the keywords, including "hyperuricemia", "xanthine oxidase inhibitory activity", ?medicinal plants", "gout", "Pakistan", "in vivo", and "in vitro". The SYRCLE?s RoB tool was used to assess the risk of bias. Total 22 articles met the inclusion criteria. Following plants had higher XO inhibitory activity (>75%); Bryophyllum pinnatum, Zingiber officinale, Laggera aurita, Trachyspermum ammi, Tribulus terrestris, Trianthema triquetra, and Croton sparsiflorus. Numerous phytochemicals were also identified, and the followings had potent activity; acacetin 1 (11.92 ± 0.01 µM), ranuncoside (IC50 = 11.69 µM), chrysin 2 (IC50= 73.74 ± 0.02 µM), methyl-3,4,5-trihydroxybenzoate (IC50= 59.5 µM), costinone A (IC50= 90.3 ± 0.06 µM), and umbelliferone (IC50= 97.12 ± 0.01 µM). This study will provide beneficial insight into medicinal plants and serve as a reference for future studies on gout treatment. A rigorous pharmacological and clinical evaluation of medicinal plants is required to gauge their efficacy and safety.

Preliminary Phytochemical Analysis of Anti Hyperlipidimic and Xanthine Oxidase Inhibitory Activities of Malus domestica

Introduction: Malus domestica is a well known plant commonly known as apple belonging to the family Rosaceae. The fruit is rich in flavonoids and many other phytochemicals. The fruit is also reported to have many therapeutic properties.
 Aim: The aim of this study is to analyse phytochemical constituents and to evaluate antihyperlipidemic and xanthine oxidase inhibitory activities of Malus domestica aqueous extract.
 Materials and Methods: The phytochemical screening, and assessment of in vitro anti cholesterol and xanthine oxidase inhibitory activity were done in aqueous extract of Malus domestica using standard procedures.
 Results and Discussion: Many phytochemical elements, such as alkaloids, proteins, amino acids, terpenoids, flavonoids, carbohydrates, saponins, and steroids, were found in Malus domesticus extract. The extract also has anticholesterol effect in vitro, according to the findings. The extract is also efficient in inhibiting the xanthine oxidase inhibitory activity in a concentration dependent manner. The results obtained in the study show that Malus domestica has significant anti cholesterol and antioxidant activities.
 Conclusion: The present study established the potent in vitro anti cholesterol and xanthine oxidase inhibitory potential of Malus domestica.

Accumulation of betacyanin in Hylocereus undatus rind: Pigment stability analysis and its role in xanthine oxidase inhibition

BackgroundBetalain pigments are water soluble natural pigments that contain nitrogen. Betacyanin have been reported to possess several biological properties MethodIn the present work, the pigment from the rind of Hylocereus undatus was analyzed for its stability upon elevated temperature, pH, time, light period, and metal ions. Further, the effect of betacyanin pigment on xanthine oxidase enzyme inhibition was studied. Further to retain the betacyanin stability, encapsulation with different encapsulating agents was assessed ResultsIt was observed that betacyanin pigment was evenly distributed throughout the cells of Hylocereus undatus rind, which was intact in the vacuole. The betacyanin content present in the rind was estimated to be 95±0.873 mg/g fresh weight of peel. The pigment extract was stable upon treatment with ascorbic acid and citric. Betacyanin inhibited xanthine oxidase activity with an IC50 of 9 mM. Kinetics study depicts competitive inhibition mode. Betacyanin quenched the fluorescence intensities of XO, proving its interaction with the amino acid residues of XO. Docking analysis proved a higher binding affinity of betacyanin in the active site residues of XO supported by simulation studies. Starch encapsulation showed greater efficiency in stabilizing betacyanin content. ConclusionBetacyanin pigment was extracted from Hylocereus undatus rind. Betacyanin thus serves as a xanthine oxidase inhibitor preventing Uric acid elevated diseases.

Three new isopimaric acid diterpenoids from the bark of Cryptomeria japonica and their xanthine oxidase inhibitory activity

• Three new isopimaric acid diterpenoids were isolated from the bark of Cryptomeria japonica . • Structures of these isolates were elucidated by spectroscopic methods. • Some isolates exhibited xanthine oxidase inhibitory activities. Three new isopimaric acid diterpenoids, 6-oxoisopimaric acid ( 1 ), 6α-hydroxyisopimaric acid ( 2 ), and isopimara-7,9(11),15-trien-18-oic acid ( 4 ), together with two known isopimaric acid diterpenoids, isopimaric acid ( 3 ), and 8(14),15-isopimaradien-18-oic acid ( 5 ), were isolated from the bark of Cryptomeria japonica D. Don. Their structures were determined by analysis of spectroscopic data and comparison with the spectral data of known analogues. At the concentration of 50 μM, compounds 1 – 5 inhibited xanthine oxidase activity by 17.3, 16.5, 2.6, 30.5, and 24.5 %, respectively.

Xanthine oxidase targeted model setup and its application for antihyperuricemic compounds prediction by in silico methods

To achieve potential alternatives for hyperuricemia therapeutics, a novel structure‐docking energy relationship model was established for high‐throughput screening inhibitors of xanthine oxidase (XO). Molecular docking was performed between XO and 311 natural compounds from 6 traditional Chinese herbs. Then, structure‐docking energy relationship model was simulated between molecular docking energy and 63 molecular descriptors by multiple linear regressions (MLR), principal component regression (PCR), and artificial neural network (ANN), respectively. The results showed that the ANN model was the best model to predict the docking energy of XO with the coefficient of determination (R2) and mean squared error (MSE) at 0.8746 and 0.9414, respectively. The data of XO inhibitory activity were consistent with the prediction in vitro, which was also further confirmed by hyperuricemia cell model. The results suggested that the structure‐docking energy relationship model provides a paradigm framework for the screening of XO inhibitors.

Xanthine Oxidase Enzyme Inhibitory Effects of Combination Kumis Kucing (Orthosiphon aristatus L.) and Sidaguri Extract (Sida rhombifolia L.)

Hyperuricemia is a high level of uric acid in the blood and can cause gout. One of the drugs used to treat hyperuricemia is allopurinol with a mechanism of inhibiting the activity of xanthine oxidase (XO). The use of these drugs can cause various side effects if used for a long period of time. Sidaguri and kumis kucing plants are known to contain flavonoids and are proven to treat gout with each plant can reduce uric acid levels in the blood and increase its excretion in urine. This study was carried out to test the combination of sidaguri and kumis kucing extracts with certain ratios in inhibiting the activity of the xanthine oxidase enzyme.
 In this study, a combination of extracts was made using maceration method. The inhibition of xanthine oxidase activity by ethanol extract in vitro was determined by decreasing the production of uric acid monitored with a spectrophotometer at (λ) 292nm with xanthine as a substrate. Then determined the best IC50. As a comparison allopurinol is used.
 Based on the results of in vitro tests, the best comparison of the combination of kumis kucing extract and sidaguri extract can inhibit the activity of XO enzymes with the best IC50 in a row is the combination of kumis kucing and sidaguri extracts 1:1 (20.99ppm), 1:2 (39.64ppm), and 1:0.5 (52.28ppm).

Screening of bioactivity-oriented extraction approach and quality control standards of lotus leaf extracts with dual functions

In the present study, various lotus leaf extracts were prepared by multiple methods, characterized by 12 alkaloids, 14 flavonoids, and superoxide anion radical scavenging (OS) and xanthine oxidase inhibitory (XOI) activities, and divided into 3/4 groups with different characteristics. Both alkaloids and flavonoids contributed to XOI activity of representative lotus leaf extract. Norcoclaurine, O-nornuciferine, N-nornuciferine, nuciferine, luteolin, diosmetin, quercetin, and quercetin-3-O-glucuronide were defined as quality control standards for lotus leaf extracts with dual OS and XOI activities. Enzymatic hydrolysis coupled with ultrasound-assisted extraction method using 50% (v/v) ethanol was the most favorable approach for preparing food-grade lotus leaf extract with dual functions. Network pharmacology revealed that this extract having abundant alkaloids and flavonoids (especially flavonoid aglycones) could improve hyperuricemia by multiple actions on uric acid synthesis and transport, inflammation response, oxidative stress and lipid metabolism. Our study provided crucial data about clear quality control standards for plant-based functional food with potential hypouricemic effect.

Chemical Compounds, Antioxidant Activities, and Inhibitory Activities Against Xanthine Oxidase of the Essential Oils From the Three Varieties of Sunflower (Helianthus annuus L.) Receptacles.

Background/Aim: Essential oils of sunflower receptacles (SEOs) have antibacterial and antioxidant potential. However, the differences of biological activities from the different varieties of sunflowers have not been studied till now. The purpose of this study was to compare the differences of chemical compounds, antioxidant activities, and inhibitory activities against xanthine oxidase (XO) of SEOs from the three varieties of sunflowers including LD5009, SH363, and S606.Methods: SEOs were extracted by using the optimal extraction conditions selected by response surface methodology (RSM). Chemical compounds of SEOs were identified from the three varieties of sunflowers by gas chromatography-mass spectrometry (GC-MS). Antioxidant activities of SEOs were detected by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and iron ion reduction ability. Inhibitory activities of SEOs against XO were measured by using UV spectrophotometer. XO inhibitors were selected from the main chemical compounds of SEOs by the high-throughput selections and molecular simulation docking.Results: The extraction yields of SEOs from LD5009, SH363, and S606 were 0.176, 0.319, and 0.580%, respectively. A total of 101 chemical compounds of SEOs were identified from the three varieties of sunflowers. In addition, the results of inhibitory activities against XO showed that SEOs can reduce uric acid significantly. Eupatoriochromene may be the most important chemical compounds of SEOs for reducing uric acid. The results of antioxidant activities and inhibitory activities against XO showed that SEOs of LD5009 had the strongest antioxidant and XO inhibitory activities. The Pearson correlation coefficient (r > 0.95) showed that γ-terpinene, (E)-citral, and L-Bornyl acetate were highly correlated with the antioxidant activities and XO inhibitory ability.Conclusion: SEOs had antioxidant activities and XO inhibitory ability. It would provide more scientific information for utilization and selection of varieties of sunflowers, which would increase the food quality of sunflowers and incomes of farmers.

Standardization of Diploid Codonopsis laceolata Root Extract as an Anti-Hyperuricemic Source

Codonopsis lanceolate exerts various medicinal effects and has been used as a traditional medicine for inflammation, asthma, gastritis, and liver disease. Recently, we reported the xanthine oxidase inhibitory activity of C. lanceolata extract and that lobetyolin, one of the key components, was a xanthine oxidase inhibitor. Lobetyolin showed anti-hyperuricemic activity in vitro and in vivo. In this study, we prepared various types of C. lanceolata extracts for the development of functional materials and natural drugs. We present the optimal analytical approach for the quality control and extraction optimization of C. lanceolata preparations. We established and validated a HPLC analysis for easy separation and quantification of the lobetyolin biomarker. Solvent extracts of C. lanceolata root were prepared and the profiles of the active marker and the optimal extraction methods were evaluated. The 100% ethanolic extract demonstrated the highest lobetyolin content. The validated HPLC method confirmed that lobetyolin was present in C. lanceolata root extracts. We suggest that the anti-hyperuricemic activities of C. lanceolata extract could be attributed to this marker compound. The results proposed that the 100% ethanolic extract could be used for the prevention of hyperurecemia, and that this analytical method and biomarker could be useful for the quality control of C. lanceolata preparations.

Systematic investigation of the amino acid profiles that are correlated with xanthine oxidase inhibitory activity: Effects, mechanism and applications in protein source screening

This study aimed to investigate the dipeptide amino acid profiles correlated with xanthine oxidase (XOD) inhibitory activity and guide screening to determine suitable sources for XOD inhibitor protein hydrolysate preparation. The XOD inhibitory activities of 400 dipeptides were predicted via molecular docking and measured in vitro, and amino acids containing aromatic structures and charged residues were correlated with high XOD inhibitory properties. Subsequently, the effects of Cys-Glu and Lys-Glu, which showed the highest in vitro activities, were examined in hyperuricaemic mice, and were found to alleviate hyperuricaemia and modulate the gut microbiota. Furthermore, a suitable protein from Oreochromis mossambicus with high contents of charged (8.6%) and aromatic (1.67%) amino acids was screened, and the in vitro inhibitory rates of protein hydrolysate prepared from O. mossambicus against XOD were found to be 21.90% and 44.51% at 40 and 100 mg/ml, respectively. This study provides a strategy for screening protein hydrolysate sources with certain activities based on amino acid profiles.

Antioxidant activity, xanthine oxidase inhibition and acute oral toxicity of Dillenia philippinensis Rolfe (Dilleniaceae) leaf extract

Context: Hyperuricemia is a metabolic syndrome characterized by a high serum uric acid level with an increased risk of gout, diabetes, cardiovascular and renal disease. Allopurinol is a widely known xanthine oxidase inhibitor that lowers serum uric acid production. Documented adverse effects of the drug raise the need for a natural alternative for xanthine oxidase inhibitor that is safe and effective. This research is driven to address the need by capitalizing on previous studies made on the Dillenia species showing nephroprotective and antihyperuricemic activity. Aims: To evaluate the antioxidant capacity, xanthine oxidase inhibitory activity, and acute toxicity of Dillenia philippinensis; a plant locally known as Katmon and endemic to the Philippines. Methods: The D. philippinensis ethanolic leaf extract (DPELE) was partitioned using solvents of different polarities, hexane, ethyl acetate, and butanol. The antioxidant activity of the DPELE and the sub-extracts was assessed using nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging assays against ascorbic acid, while the xanthine oxidase inhibitory activity was examined against allopurinol as a standard. The acute toxicity was performed using Sprague-Dawley rats following OECD 425 guidelines. Results: The D. philippinensis ethyl acetate fraction (DPEAF) had the highest scavenging activity of nitric oxide, hydrogen peroxide, and hydroxyl (IC50 = 210.00, 70.92 and 59.88 µg/mL) free radicals, respectively. Also, the xanthine oxidase dose-dependent inhibitory activity was observed to be highest in the DPEAF with an IC50 = 23.09 µg/mL. Lastly, neither toxicity nor mortalities were observed in rats treated with the DPELE and the DPEAF for 14 days. The approximate lethal dose for DPELE and DPEAF was higher than 2000 mg/kg BW. Conclusions: This study shows that the DPELE and DPEAF are potential sources of natural antioxidants and xanthine oxidase inhibitors, which may be used in the treatment of hyperuricemia and are presumed safe to be used orally.

The Stem Infusate and Ethanol Extract of Physalis angulata Inhibitory Activities against a-Glucosidase and Xanthine Oxidase

Background: Infusate of the whole plant of Physalis angulata is used traditionally for the remedy of various diseases including diabetes and gout. This study focused on the stem of P. angulata. The objectives of this study were to investigate the potential of the stem infusate (INPA) and ethanol extract (EEPA) of P. angulata as inhibitors of α-glucosidase and xanthine oxidase.Materials and Methods: INPA and EEPA were determined for their α-glucosidase and xanthine oxidase inhibition activities in vitro, whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Reference inhibitors were used for comparison. The total phenolic compounds were also estimated.Results: EEPA had more concentrated phenolic than INPA which were 7.96 and 0.08 mgGAE/g dried biomass, respectively. INPA and EEPA inhibited α-glucosidase considerably, with IC50 of 149.11 and 409.86 µg/mL, respectively (acarbose was 130.66 µg/mL). However, they inhibited xanthine oxidase weakly, with IC50 of 0.546 and 2.643 mg/mL, respectively, compared with allopurinol 0.005 mg/mL. EEPA scavenged DPPH radicals very weakly (16.04 mg/mL) compared to BHT (0.021 mg/mL), whereas no activity was observed for INPA.Conclusion: The stem infusate and ethanol extract of P. angulata are able to inhibit the activity of α-glucosidase, thus can be further explored for sources of bioactive compounds with α-glucosidase inhibition activity.Keywords: α-glucosidase, infusate, ethanol extract, Physalis angulata, stem, xanthine oxidase

Four New Acyclic Diterpenes From Siegesbeckia orientalis

Four new acyclic diterpenes, siegetalises A-D (1-4), were isolated from the aerial parts of Siegesbeckia orientalis. Their chemical structures were elucidated by extensive analysis of high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectral data. The effects of the isolated compounds on the activity of xanthine oxidase were evaluated by the oxidative reaction with xanthine as a substrate. At a concentration of 50 µM, compounds 1-4 exhibited xanthine oxidase inhibitory activity at levels of 13.59% ± 0.51%, 19.64% ± 1.54%, 17.45% ± 1.26%, and 21.36% ± 1.40%, respectively.