Natural Products and Extracts as Xantine Oxidase Inhibitors – A Hope for Gout Disease?

2020 ◽  
Vol 26 ◽  
Author(s):  
Ilkay Erdogan Orhan ◽  
Fatma Sezer Senol Deniz
Keyword(s):  
Natural Products ◽  
Uric Acid ◽  
Waste Product ◽  
Acid Synthesis ◽  
Intermediate Compound ◽  
Living System ◽  
Ginsenoside Rd ◽  
Drug Classes ◽  
Urate Crystal ◽  
High Concentrations

: Xanthine oxidase (EC 1.17.3.2) (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+ ), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy include XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist; intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.

scholarly journals The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

1972 ◽  
Vol 128 (5) ◽  
pp. 1057-1067 ◽  
Author(s):  
E. D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fat Cells ◽  
Glyceride Synthesis ◽  
Glucose Incorporation ◽  
High Concentrations ◽  
Stimulation Of

1. 0.5mm-Palmitate stimulated incorporation of [U-14C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.

Effect of Riboflavin Deficiency on the Metabolism of Oxypurines in Chicks

1971 ◽  
Vol 49 (12) ◽  
pp. 1059-1062 ◽  
Author(s):  
S. T. Chou
Keyword(s):  
Uric Acid ◽  
Acid Synthesis ◽  
Xanthine Dehydrogenase ◽  
Broiler Chicks ◽  
Uric Acid Concentration ◽  
Riboflavin Deficiency ◽  
Deficient Diet ◽  
High Incidence ◽  
Liver And Kidney ◽  
Riboflavin Deficient

Day-old broiler chicks of both sexes were used in three experiments to determine the effect of riboflavin deficiency on oxypurine metabolism catalyzed by xanthine dehydrogenase, a riboflavin-containing enzyme. Chicks fed a riboflavin-deficient diet (1.38 mg/kg) for 3 weeks exhibited depressed growth and a high incidence of curled-toe paralysis (higher than 80%) as compared to control chicks (15.1 mg riboflavin per kilogram diet; no incidence of curled-toe paralysis). In addition, the precursors of uric acid, hypoxanthine and/or xanthine, accumulated in the liver and kidney of deficient chicks showing curled-toe paralysis. These observations show that dietary riboflavin being incorporated into xanthine dehydrogenase is essential for oxypurine metabolism. Moreover in the chick, the liver and the kidney may be important sites of uric acid synthesis. The low uric acid concentration in the plasma of the deficient chicks appeared to be indicative of a disturbance in uric acid synthesis in the liver and kidney.

scholarly journals Light and electron microscopical observations of the effects of high-density lipoprotein on growth of Plasmodium falciparum in vitro

Parasitology ◽  
2004 ◽  
Vol 128 (6) ◽  
pp. 577-584 ◽  
Author(s):  
H. IMRIE ◽  
D. J. P. FERGUSON ◽  
M. CARTER ◽  
J. DRAIN ◽  
A. SCHIFLETT ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Density Lipoprotein ◽  
Light And Electron Microscopy ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
High Density ◽  
High Concentrations ◽  
Electron Microscopical ◽  
Necessary And Sufficient

Human serum high-density lipoprotein (HDL) is necessary and sufficient for the short-term maintenance of Plasmodium falciparum in in vitro culture. However, at high concentrations it is toxic to the parasite. A heat-labile component is apparently responsible for the stage-specific toxicity to parasites within infected erythrocytes 12–42 h after invasion, i.e. during trophozoite maturation. The effects of HDL on parasite metabolism (as determined by nucleic acid synthesis) are evident at about 30 h after invasion. Parasites treated with HDL show gross abnormalities by light and electron microscopy.

Metabolism of the Black Snake Embryo

1953 ◽  
Vol 30 (4) ◽  
pp. 492-501 ◽  
Author(s):  
HUGH CLARK
Keyword(s):  
Energy Source ◽  
Uric Acid ◽  
Acid Synthesis ◽  
K Value ◽  
Embryonic Tissues ◽  
Hatching Time ◽  
Urea Content ◽  
Foetal Liver ◽  
Liver And Kidney ◽  
Post Deposition

1. Post-deposition growth of the black snake embryo is characterized by k values as follows: days 1-11, 0.46; days 11-34, 0.057; days 34-67, 0.039. 2. Total excreted nitrogen is 12.55 mg. occurring successively in development as ammonia, urea and uric acid; k value of total nitrogen production is 0.062, days 11-67, which in comparison with those of growth during this period suggest that stored protein is an energy source during a large part of development. 3. Urea is excreted into the albumen which is the principal storage reservoir and into the yolk; that which is excreted into the yolk is reabsorbed after the 45th day and re-deposited in the albumen as urea, and is in part (22%) converted to uric acid. 4. Concentration of urea in the yolk and yolk-sac continues to increase at the same rate after the 11th day (k = 0.024), although the actual amount declines after the 45th day; concentration in the embryonic tissues increases to the 58th day, then decreases sharply to hatching time; concentration in the albumen increases throughout development, reaching a concentration of approximately 500 mg.%. 5. Uric acid synthesis is believed to be preceded by urea formation, and the presence of urease in the foetal liver and kidney suggest that the urea is hydrolysed to ammonia which is then incorporated into uric acid. Site of the transformation is uncertain, though the early and persistent localization of uric acid in the chorio-allantoic membrane points to this as the organ of synthesis. Decrease in total urea content is quantitatively identical with increase in uric acid. 6. The significance of these findings in relation to development of the vertebrate cleidoic egg is discussed.

scholarly journals Effectiveness of Sirsak Fruit Juice Therapy to Decreasing Elderly Acid Acid Levels in Tresna Werdha Social Beach Pagar Dewa Bengkulu

2019 ◽  
Vol 26 (1) ◽  
pp. 26-34
Author(s):  
Dian Dwiana ◽  
Santoso Ujang Effendi ◽  
Vusva Vaudyah
Keyword(s):  
Uric Acid ◽  
Fruit Juice ◽  
Waste Product ◽  
Sampling Technique ◽  
The Elderly ◽  
Social Institution ◽  
Before And After ◽  
Acid Acid

Uric acid is the end product or a waste product resulting from the metabolism/ breakdown of purines .. The purpose of this study was to determine the effectiveness of Soursop fruit juice therapy to decrease uric acid levels in the Elderly Social Institution Tresna Werdha Pagar Dewa Bengkulu year 2018. The design of this Penenlitian pre- experimental. The population in this study who had the Uric Acid in Elderly Social Institution Tresna Pagar Dewa Bengkulu which amount 17 people. The sampling technique used Total sampling technique. Collecting data in this study is the observation uric acid levels before and after therapy soursop juice for 2 minggu..Hasil research showed: (1) there are 17 people (100%) with high levels of uric acid 6 mg / dl; (2) there are 13 people (76.5%) had decreased levels of uric acid, and 4 (23, 5%) who did not experience decreased levels of uric acid; (3) No effect Soursop fruit juice therapy to decrease uric acid levels in the Elderly Social Institution Tresna Werdha Pagar Dewa Bengkulu. Keywords: elderly, uric acid, soursop juice

scholarly journals Influence of testosterone on purine metabolism and gout

2021 ◽  
Vol 22 (3) ◽  
pp. 11-17
Author(s):  
T. S. Panevin
Keyword(s):  
Uric Acid ◽  
Sex Hormones ◽  
Metabolic Disorders ◽  
Purine Metabolism ◽  
The Body ◽  
Uric Acid Concentration ◽  
Androgen Deficiency ◽  
Inflammatory Processes ◽  
High Concentrations ◽  
Pro Inflammatory Cytokines

Many different factors are involved in the regulation of purine metabolism. An important role is played by the level of sex hormones: high concentrations of androgens lead to a higher, and estrogen – to a lower level of uric acid. However, according to the results of numerous studies, it has been shown that the effect of sex hormones is not limited only to the uric acid concentration. Sex hormones affect inflammatory processes in the body by modulating the production of pro-inflammatory cytokines and regulating the corresponding signaling pathways. Androgen deficiency can lead to obesity and metabolic disorders, which can contribute to the development and course of gout. This review examines the effect of testosterone, as well as the effect of changes in its concentration on the dynamics of purine metabolism and gout.

Aestivation and Ionic Regulation in Two Species of Pomacea (Gastropoda, Prosobranchia)

1968 ◽  
Vol 48 (3) ◽  
pp. 569-585
Author(s):  
COLIN LITTLE
Keyword(s):  
Uric Acid ◽  
Ionic Composition ◽  
Posterior Chamber ◽  
Freshwater Gastropods ◽  
Normal Value ◽  
Weight Losses ◽  
Relative Composition ◽  
Loss Of Weight ◽  
Wet Weight ◽  
High Concentrations

1. The ionic composition of the haemolymph, and the concentrations of uric acid and protein, have been determined for the amphibious prosobranchs Pomacea lineata and P. depressa. Ionic composition of the haemolymph is similar to that of freshwater gastropods. 2. The urine is decidedly hypo-osmotic to the haemolymph, reabsorption of ions occurring in the anterior chamber of the kidney. The rate of production of urine is approximately 1 µl./g./min. at 25° C. 3. The onset of aestivation appears to be related to a loss of 20% of the normal wet weight of the tissues. The loss of weight during aestivation averages 0.009% of the initial wet weight/hr., and aestivation may continue for over 400 days. 4. During aestivation the osmotic pressure of the haemolymph may rise to twice its normal value; but this is 30 mM/l. NaCl less than that predicted from weight losses. The relative composition of the haemolymph alters little, except that the percentages of sodium and chloride increase. 5. Uric acid accumulates round the blood vessels during aestivation, especially in the lung. Relatively little accumulates in the two chambers of the kidney, and only that in the posterior chamber is excreted later. Since the volume of fluid in the posterior chamber falls to about 10% of its normal value, while the total loss of weight of the snail is about 50%, the fluid in the posterior chamber acts as a water reserve. 6. Recovery from aestivation occurs in about 24 hr., when the snails are placed in water. The posterior chamber of the kidney excretes high concentrations of uric acid during this time. 7. The characteristics of aestivation are discussed, and compared with those shown by the Pulmonata.

Medicinal Plants and Their Bioactive Compounds for the Management and Treatment of Gout

2021 ◽  
pp. 267-287
Author(s):  
Bui Thanh Tung
Keyword(s):  
Natural Products ◽  
Uric Acid ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Inflammatory Arthritis ◽  
Natural Compound ◽  
Complex Form ◽  
Compound Structure ◽  
Anti Inflammatory

Gout is a complex form of arthritis which is characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the joints. Gout is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Natural products offer many options to reduce the progress and symptoms of diseases, including gout. Natural compound structure including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids have anti-inflammatory, antioxidant, and XO activities. In this chapter, the authors present medicinal plants and isolated compounds which are used to prevent and reduce the pathogenesis of gout.

scholarly journals Effects of Conventional Uric Acid–Lowering Therapy on Monosodium Urate Crystal Deposits

2019 ◽  
Vol 72 (1) ◽  
pp. 150-156 ◽  
Author(s):  
Hanna Ellmann ◽  
Sara Bayat ◽  
Elizabeth Araujo ◽  
Bernhard Manger ◽  
Arnd Kleyer ◽  
...  
Keyword(s):  
Uric Acid ◽  
Monosodium Urate ◽  
Lowering Therapy ◽  
Urate Crystal
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