Ananya Das1*, Prema Modak1, Arghya Prosun Sarkar2, Satyajit Halder1, Bidduth Kumar Sarkar3, Anita Rani Chowdhury4, Sukalyan Kumar Kundu1
1Department of Pharmacy, Jahangirnagar University, Savar, Dhaka- 1342, Bangladesh
2Department of Pharmacy, Islamic University, Kushtia, Bangladesh
3Department of Pharmacy, Ranada Prasad Shaha University, Narayanganj, Bangladesh
4Department of Pharmacy, Jagannath University, Dhaka, Bangladesh
*Address for Corresponding Author
Ananya Das
Department of Pharmacy
Jahangirnagar University, Savar, Dhaka- 1342, Bangladesh
Abstract
Hyperuricemia ensues due to the reabsorption and diminished evacuation of uric acid which is accountable for the advancement of gout and radically concomitant with the progress of numerous long-lasting ailments for instance malignant tumor, cardiovascular ailments, and kidney failure. Underlying factors such as excessive intake of purine containing supplements, obesity, age, sex, sugar, and alcohol intake may condense the formation of uric acid and exaggerate the injurious effects of uric acid. Novel inventive pharmaceutical and curative mediations are being used for the tackling of hyperuricemia but the problem arises when patients complain about adverse reactions with serious complications that may increase the rate of developing new diseases. Medicinal and dietary plants with bioactive phytochemicals like polyphenols, flavonoids are more feasible due to less toxicity, more economical for developing countries, formulation advantages for primary healthcare, better appropriateness with human physiological conditions. To facilitate the design of plant-based alternative therapy it is a prerequisite to connecting herbal medicine with novel prescription and additional precise explorations have to be ensured for the authentication of the effectiveness and safety of herbal formulations. The existing assessment outlines production, metabolism, and excretion of uric acid, hazard influences (overabundance and low excretion of uric acid), conventional pharmacotherapy for hyperuricemia and its related complications, the use of plants, its origin; parts to be used, mechanism of actions to preclude hyperuricemia are highlighted based on of previously issued literature.
Keywords: Uric acid, hyperuricemia, dietary plants, bioactive phytochemicals, xanthine oxidase inhibitory activity
Introduction
Uric acid (UA) {C5H4N4O3 [IUPAC: 7, 9- dihydro-1H purine-2, 6, 8(3H) trione]} plays an important role in the balance of potassium, sodium, bicarbonate, or alkaline and other electrolytes which specially produced from the dead cells and purine that presents in dietary elements. It is the heterogeneous compound having C, H, N, and O in its constitutional configuration presents 3-7 mg/dL (standard level) in the blood (El Ridi and Tallima, 2017; Hafez et al., 2017).
Xanthine oxidase enzyme catalyzes the construction of uric acid (290 kDa) by the oxidation of hypoxanthine to xanthine in the manifestation of molecular oxygen specifically superoxide anions and hydrogen peroxide and consequently to uric acid (Lin and Shih, 1994; Candan, 2003).
Excessive production (≥7 mg/dL in males and ≥6 mg/dL in females) or less excretion of uric acid is responsible for hyperuricemia (HUA) which is a metabolic ailment. The prevalence of serum uric acid is short in children, higher in men than women (Desideri et al., 2014; Johnson et al., 2003).
Innumerable threats influence the production of uric acids (UA) such as age, gender; race, genetic makeup, environmental, socioeconomic factors, geographic location as well as endogenous sources like meat, seafood, and alcohol intake are associated with development of high UA formation in the blood. Additionally, hyperuricemia (HUA) correspondingly surges production of reactive oxygen species (ROS), endothelin-1 production and nitric oxide (NO) system reticence, enriched synthesis of renin-angiotensin-aldosterone system stimulation (De Oliveria and Burini, 2012; Choi and Churhan, 2007). UA starts inducing crystals in renal tubules recognized as monosodium urate crystals (NaU) ensues gout owing to the installation of urate crystals in joints that are connected with inflammation (Brook et al., 2010; Roddy and Doherty, 2010). HUA possibly will trigger numerous prolonged and acute ailments, e.g. gout, renal failure, tumor lysis syndrome (TLS), coronary heart disease, hemospermia, arterial hypertension, and metabolic syndrome (Krishnan, 2014; Gustafsson and Unwin, 2013).
In recent times newly exploited therapeutic tactics are available for HUA to persevere with certain adverse properties. In the future, alternative prescriptions or bioactive components in dietary foods like fruits and vegetables with lesser side effects as well as its antioxidant potentiality are necessary to confront HUA complaints (Yang et al., 2015; Wang et al., 2017). Consequently, the rationales of this present review are to deliver an outline of the influence of various plant parts, vegetables, fruits, and herbal products on the hyperuricemic conditions, their mode of action, and active constituents.
Production, metabolism, and elimination of uric acid
Uric acid is the natural waste product of purine degradation. It can be generated not only within the body or endogenously during cell turnover but also in association with various exogenous sources. Purine nucleotides namely two such as adenine (6-aminopurine), guanine (2-amino-6-oxypurine) which is a constitutional component present in DNA (Deoxyribonucleic acid), RNA (Ribonucleic acid), ATP (Adenosine triphosphate), AMP (Adenosine monophosphate), cyclic AMP (Cyclic Adenosine monophosphate), CGMP (Cyclic Guanosine monophosphate), GTP (Guanosine triphosphate), NADH (Nicotinamide Adenine Dinucleotide), NADPH (Nicotinamide Adenine Dinucleotide Phosphate), and coenzyme Q. Purine is mainly synthesized in the liver by de novo and salvage pathway (Itakura et al.,1981).
Xanthine oxidoreductase (XOR) is the enzyme responsible for the expression of reactive oxygen species and uric acid and predominantly existing into two versions xanthine oxidase (XO) and xanthine dehydrogenase (XDH). XOR converts to XDH and then XO. Hypoxanthine is formed from adenine by the action of adenase enzyme, which is converted into xanthine by xanthine oxidase to end with uric acid. By guanase enzyme catalysis guanine converts into xanthine.
XO is the main enzyme for the breakdown of hypoxanthine and xanthine that leads to the subsequent formation of uric acid. Purine from exogenous or dietary sources is being mainly catabolized by xanthine dehydrogenase. The cells and tissues like liver, skeletal muscle, intestine, kidney, vascular endothelial are highly capable of expressing XDH which plays a significant role in the formation of uric acid (Waring et al., 2000; Waring 2005; Maiuolo et al., 2016).
Figure 1. Production and metabolism of uric acid (Maiuolo et al., 2016; Kushiyama et al., 2016)
Uric acid is further processed to allantoin by the presence of urate oxidase (uricase) enzyme that is 5-10 times an extra soluble form of uric acid in mammals excluding primates (human and higher apes) (Yeldandi et al., 1992; Vigetti et al., 2000). Oxidative stress is measured via allantoin as a biomarker as it is formed when uric acid responds with reactive oxygen species and readily excreted through the urine (Kandar et al., 2006; Barsoum and Khatib, 2017). The kidney is responsible for the evacuation of 75% UA and the other 25% is eliminated by the gastrointestinal tract that supports to conserve the regular body uric acid levels (De Oliveria and Burini, 2012). Urate-anion transporter (URAT) l, organic anion transporter (OAT) 1, and 3 in kidneys are the key transporters for uric acid excretion (Chen et al., 2015).
Aspects amalgamate with excessive production of uric acid
Overproduction appears in fewer percentages of patients who have hyperuricemia. Circumstances that provoke excess production of uric acid
Exterior issues in the form of diet (Bobulescu and Moe, 2012; Dehgan et al., 2008)
Inner issues (Reginato and Olsen, 2007; Torres and Puig, 2007)
Metabolic syndromes (Kang et al., 2002; Choi et al., 2005; Bos et al., 2006)
Particular categories of medications (Taniguchi et al 2005; Han et al., 2013)
Other conditions (Bos et al., 2006; Bedir et al., 2003; Towiwat and Li, 2015; Robinson and Horsburgh, 2014).
Figure 2. Overproduction and underexcretion of uric acid with underlying risk factors (Ragab et al., 2017)
Underexcretion of uric acid
Underexcretion is the main reason for hyperuricemia. Kidneys separate out urate which is a salt of uric acid and exits the body across urine. Renal inadequacy happens if any inaccuracy ensues in this consistent procedure which leads to a reduced uric acid excretion (Cho et al., 2015).
Frequent polymorphisms in numerous genes (Iseki et al., 2001; Kang et al., 2002)
Several autosomal dominant conditions (Gnanenthiran et al., 2011)
Medications (Terkeltataub, 2006)
Additional conditions (Choi et al., 2005)
Pharmacotherapy for controlling hyperuricemia
Numerous management approaches are present to efficiently decline as well as conserve SUA intensities beneath the saturation point and for this purpose; several anti-hyperuricemic preparations are available in the market. These preparations generally characterized into uricostatic medicines that show inhibitory action towards urate production (allopurinol, oxypurinol, febuxostat, etc) as well as uricosuric medicines that raises the frequency of uric acid excretion (probenecid, sulphinpyrazone, benzbromarone, etc). Other medications like uricase therapy (pegloticase, rasburicase) or can be said enzymatic preparations are also prescribed frequently by physicians. They are either prescribed separately or as a mixture aimed at depressing UA production otherwise enriches UA discharge. Additionally, the medications embrace anti – hyperuricemic actions but extremely accompanying with sundry complications (Dalbeth et al., 2006; Crittenden and Pillinger, 2013). Moreover, the invention of novel medications has been expanded day by day and some of them are in the developmental state (Gliozzi et al., 2016). Feature of some conspicuous medications, their dose and dosage form, mechanism of actions and reported complications are expounded and delineated in (Table 1 and figure 3).
Table 1. Anti-hyperuricemic medications and related complications
|
Classification |
Drugs |
Dose and dosage form |
Mechanism of action |
Complications |
References |
|
Uricostatic preparations (Shows inhibitory action towards urate production) |
Allopurinol (Leading therapeutic choice due to low price and prolonged safety issues) |
300–600 mg/day (oral as well as an intravenous application) |
1. Impedes xanthine oxidase. 2.Diminishes urate construction
|
Hypersensitivity, renal and hepatic failure, skin rashes, and gastrointestinal complications are considered detrimental for the human body. |
(Terlkeltaub,2003; Dalbeth et al., 2006; Schumacher et al., 2008; Vargas and Neogi, 2017) |
|
Febuxostat
|
40 and 80-mg (orally as tablets) |
1. An innovative non- purine selective inhibitor of xanthine oxidase. 2. Hamper ONOO and reactive oxygen species (ROS) creation non-competitively. 3. Counteracts endothelial damage. |
Headache, nausea, liver abnormalities diarrhea, and even skin rashes.
|
(Perez et al., 2008; Schumacher et al., 2008; Becker et al., 2005a, 2005b ) |
|
|
Uricosuric drugs (Rises the frequency of uric acid excretion) |
Probenecid
|
Initial quantity is 250 mg/day (two times) and so subsequently rising to 500-1000 mg/day (two times) for 7-14 days orally. |
1. Block the resumption of uric acid through URAT-1
|
Hemolytic anemia with the engrossment of glucose-6 phosphate dehydrogenase insufficiency |
(Reinders et al., 2009) |
|
Sulphinpyrazone |
200-800 mg/day |
1. Abolition of uric acid through kidney |
Peptic ulcer likewise gastrointestinal complications. |
(Gliozzi et al., 2016) |
|
|
Benzbromarone |
100-200 mg/day (one time) |
1. Exerts strong uricosuric effect |
Hemolysis, peptic ulcer |
(Reinders et al., 2009; Perez et al., 1998) |
|
|
Uricase therapy
|
Pegloticase (pegylated uricase) |
The tolerated amount is approximately 8 mg/14 days dispensed intravenously |
Soluble allantoin Reduce serum uric acid |
Methemoglobinemia, hemolysis, and immunogenicity are recorded with its consumption |
(Sundy et al., 2011). |
|
Rasburicase (Chemotherapy- induced hyperuricemia) |
0.15 mg/kg/day or 0.2 mg/kg/day (5 days) Intravenously |
1. Facilitates oxygen addition to uric acid by allantoin which is not active |
Hypersensitivity reaction. |
(Bosly et al., 2003; Richette et al., 2007). |
|
|
Medications in experimental exploration |
Anakinra(IL-1 receptor competitor) Nilonacept (IL-1 receptor) Canakinumab (Monoclonal anti-IL-1beta antibody) Lesinurad (URAT1 blocker) Arhalofenate (URAT1 blocker) Levotofisopam (URAT1 blocker), RDEA3170 (URAT1 blocker), BCX4208 (Purine nucleoside phosphorylase blocker), DHNB (XO blocker) Pegadricase (Pegylated uricase) |
(Lu et al., 2013; Crittenden and Pillinger, 2013; Gliozzi et al., 2016) |
|||
Figure 3. Pharmacotherapy for controlling hyperuricemia and how they react within normal physiological condition within the human body (Azevedo et al., 2017)
Natural compounds that reduce SUA production
Established medications such to xanthine oxidase blocker in addition as urate lowering agents that are consumed to diminish SUA intensity inside the body by blocking XO produces frequent unfavorable outcomes that provide rise to other obstacles (Bustanji et al., 2011; Fagugli et al., 2008). Thus, XO blocker from plants or their metabolites requires more and more investigation because they hold greater beneficial potential with less adverse outcomes as well as discourage hyperuricemia, gout, gouty arthritis, calculus and other ailments.
Several isolated aromatic herbs from plants, medicinal plants, vegetables, fruits, cereals, nuts, legumes, seeds, spices, green and black tea hold oxygen scavenging capacity to obliterate the oxidation and inflammation reaction formed through enzyme xanthine oxidase. To dam, the formation of uric acid XO is clogged by active constituents of plant metabolites and via hydrophobic bonds produced XO-active metabolites composite besides blocked the free active site that dosen’t allow additional binding. Conspicuously, a surplus of active constituents present in plants impedes XO around alternatively over recommended medications (Sweeny et al., 2001; Alloway, 1999).
Several investigations establish that polyphenols are the foremost group amongst active constituents and others including lignans (secoisolariciresinol and matairesinol), flavonoids (flavones, apigenin, and luteolin, quercetin, naringenin), flavanols, oligomeric, catechin and epicatechin, anthocyanins (cyaniding, isoflavones, genistein), phenolic acids (chlorogenic acid, ellagic acid, vanillic acid, caffeic acid, p-coumaric acid, gallic acid, hydroxybenzoic acid and ferulic acid), curcuminoids (curcumin), stilbenes (resveratrol), chalcones (phlorizin, chalcone) and several alkaloids like costinones A, costinones B, isatinones A, isatinones B, indirubin, and trisindoline. More and more clinical investigations and research work should be performed to determine the opportunities of polyphenol for treating hyperuricemia (Vauzour et al., 2008; Gonzalez and Rodriguez, 2011; Bravo, 1998; Ahmad et al., 2010).
Table 2. Medicinal and dietary plants sources, common name, functional metabolites and mechanism of action
|
Scientific Name |
Family |
Local Name |
Parts used |
Active constituents |
Mechanism |
References |
|
Allium cepa |
Liliaceae |
Onion |
Bulbs and leaves |
Phytonutrients including phenolics and flavonoids (e.g., Sugars, fibers, vitamins, anthocyanins, quercetin, and glucosides) |
Xanthine Oxidase and xanthine dehydrogenase inhibitor |
(Ouyang et al., 2018) |
|
Allium sativum |
Liliaceae |
Garlic |
Bulbs |
Allicin and its derivatives S-allyl cysteine, diallyldisulfide, diallyltrisulfide |
Xanthine Oxidase inhibitor |
(Ghalehkandi et al., 2012) |
|
Mangifera indica |
Anacardiaceae |
Mango |
Extract of leaf |
Not reported |
Diminish serum uric acid level |
(Jiang et al., 2012) |
|
Ocimum sanctum L. |
Lamiaceae |
Ban Tulsi |
All parts including seeds |
Triterpene, ursolic acid |
Decrease level of uric acid |
(Singh et al., 2010; Kelm et al., 2000) |
|
Apium gravelens |
Umbelliferae |
Celery |
Dried powdered leaves |
Polyphenols and flavonoids |
Anti-hyperurecemic activity |
(Mohamed and Al- Okbi, 2008) |
|
Hibiscus sabdariffa
|
Malvaceae
|
Roselle |
Whole plant |
Epigallocatechin galla caffeicacid, epigallocatechin, catechin, and protocatechuic acid |
Rising uricase activity, decline uric acid levels, impact on serum and liver xanthine oxidase |
(Kuo et al., 2012) |
|
Carica papaya |
Caricaceae |
Papaya |
Unripe fruit and it’s peels and leaf extracts |
Not reported |
Inhibit xanthine oxidase and serum uric acid |
(Azmi et al., 2012; Calderon et al.,2015) |
|
Phyllanthus emblica |
Phyllanthaceae |
Indian gooseberry/ amla |
Fruits exract |
Ascorbic acid, several active tannoid principles (emblicanin A, emblicanin B, punigluconin, and pedunculagin) and other polyphenols, Flavonoids, kaempferol, ellagic acid, and gallic acid. |
Decrease serum uric acid |
(Sarvaiva et al., 2015) |
|
Prunus mume |
Rosaceae |
Japanese apricot and Chinese plum |
Fruit |
Triterpenoids such as oleanolic acid, ursolic acid, lupeol, and α-amyrin |
Decrease serum and liver uric acid and xanthine oxidase |
(YiLT et al., 2012)
|
|
Cassia fistula L. |
Caesalpiniaceae |
Badorlathi |
Leaves, Pulps, Barks |
Flavonoids |
Xanthine oxidase inhibitors |
(Argulla and Chichioco, 2014; Rahman and Debnath, 2015) |
|
Cinnamomum cassia |
Lauraceae |
Cinnamon |
Whole plants, bark, twigs |
Cinnamic acid, cinnamaldehyde, coniferaldehyde, cinnacasolide B, Ocoumaric acid, cinnamic alcohol, dihydromelilotoside, cinnacasolide A, and cinnacasolide |
Inhibits xanthine oxidase |
(Ngoc et al., 2012)
|
|
Zingiber officinale |
Zingiberaceae
|
Zinger |
Rhizomes
|
6-gingerol, 6-shogaol, 6-paradol, quercetin, glutathione |
Inhibits xanthine oxidase |
(Nile et al., 2017) |
|
Coix lachryma-jobi L. var |
Gramineae / Poaceae |
Adlay seed or Job’s tears |
Fruits and seeds |
Phenolic antioxidants, including phenolic acids such as protocatechuic acid, chlorogenic acid, vanillic acid, caffeic acid, p-coumaric acid, and ferulic acid |
Inactivation of xanthine oxidase |
(Zhao et al., 2014) |
|
Prunus cerasus L. |
Rosaceae |
Tart cherry |
Cherry juice |
Anthocyanins |
Diminish synthesis of serum uric acid |
(Bell et al., 2014) |
|
Myristica fragrans |
Myristicaceae |
Nutmeg |
Mace or aril or nut |
Phytochemicals, such as phenolics, flavonoids, alkaloids, tannins and saponins. |
Obstruct uric acid metabolism by impeding xanthine oxidase |
(Ullah, 2017) |
|
Olea europea |
Oleaceae |
Olive |
Leaves |
Luteolin‑7‑O‑β‑D‑glucoside, luteolin , caffeic acid, oleuropien, and apigenin |
Inactivate xanthine oxidase |
(Flemmig et al., 2011) |
|
Perilla frutescens |
Lamiaceae |
Perilla or Korean perilla |
Leaves |
Protocatechuic acid, chlorogenic acid, caffeic acid, 4-methoxy cinnamic acid, oleanolic acid, kaempferol-3 orutinoside, rosmarinic acid, luteolin, methyl-rosmarinic acid, apigenin, and 4,5,7-trimethoxyflavone |
Inactivate xanthine oxidase and reduce serum uric acid |
(Wang et al., 2017) |
|
Caryophyllus aromaticus |
Myrtaceae |
Clove |
Flower buds |
Polyphenols and flavonoids |
Inactivate xanthine oxidase |
(Havlik et al., 2010) |
|
Punica granatum |
Punicaceae |
Pomegranate |
Fruits, (peel, aril, seeds, and juice, leaves, roots, and stem) |
Phenolic acids, flavanols, flavones, flavanones, anthocyanidins, and anthocyanin (pelargonidin 3,5-diglucoside, pelargonidin 3-glucoside) |
Inactivate xanthine oxidase |
(Wong et al., 2014; Rummun et al., 2013) |
|
Psidium guajava Linn |
Myrtaceae |
Guava |
Root, stem bark especially leaf |
Quercetin, kaempferol, catechin, quercitrin rutin luteolin, epicatechin, caffeic acid, chlorogenic acid and gallic acid |
Incapacitate xanthine oxidase |
(Irondi et al., 2016) |
|
Pyrus elaeagnifolia |
Rosaceae |
Wild pear |
Fruits |
Not reported |
Incapacitate xanthine oxidase |
(Baltas , 2017) |
|
Litchi chinensis |
Sapindaceae |
Litchi |
End product of litchi fruit, flowers, pericarp, and seed |
Proanthocyanidins, Oligonol |
Incapacitate xanthine oxidase and reduce serum uric acid |
(Li et al., 2013) |
|
Vitis vinifera |
Vitaceae |
Grape berries |
Aqueous acetone of seeds |
Sugars, flavonoids, anthocyanins and proanthocyanins, organic acids, tannin, mineral salts, and vitamins. |
Deactivate xanthine dehydrogenase |
(Wang et al., 2004) |
|
Angelica keiskei |
Apiaceae |
Not reported |
Whole plant |
Coumarins and chalcones |
Deactivate xanthine oxidase |
(Kim et al., 2014) |
|
Persicaria hydropiper |
Polygonaceae |
Kesum/water pepper/ Biskathali |
Flower |
Flavonoids, sesquiterpenes, sesquiterpenoids, and phenylpropanoids |
Deactivate xanthine oxidase |
(Rahman and Kumar, 2015; Huq et al., 2014) |
|
Lagenaria siceraria |
Cucurbitaceae |
Ghia or ghia kaddu or bottle gourd |
Fruits |
Ascorbic acid, fructose, glucose, raffinose, caffeoylquinic acid, cucurbitacins, pectin, β-carotene, iso-fucosterol, campesterol, spinasterol, leucine, tyrosine, amaino alkanoic acid, quercetin, iso-quercetin, kaempferol, palmtic acid, oleanolic acid, and linoleic acid |
Deactivate xanthine oxidase |
(Ahmed et al.,2017) |
|
Camellia sinensis |
Theaceae |
Green tea |
Dried leaves of plant |
Polyphenolic components recognized as catechins like (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and (-)-epicatechin (EC), (-)-gallocatechingallate (GCG) and (+)-Catechin (C) |
Deactivate xanthine oxidase |
(Chen et al., 2015) |
|
Beetroot pomace |
Amaranthaceae |
Beetroot |
Peel (main), crown, flesh |
Phenolic (ferulic acid, vanillic acid, p-hydroxybenzoic acid, caffeic acid, protocatechuic acid, catechin, epicatechin, and rutin) and betalain combinations (betanin, isobetanin and vulgaxanthin I) |
Deactivate xanthine oxidase |
(Vulic et al., 2014) |
|
Aspalathus linearis |
Fabaceae |
Rooibos herbal tea |
Leaves and stems |
Orientin, rutin, and aspalathin |
Deactivate xanthine oxidase and reduce serum uric acid |
(Kondo et al., 2013) |
|
Juglans regia L. |
Juglandaceae |
Walnut |
Fruit, stem, leaf, green husk and shell |
Coumaric aldehyde, coumalic acid, cinnamic aldehyde, 4hydroxybenzaldehyde |
Deactivate xanthine oxidase and anti-hyperuricemic |
(Wang et al., 2015; Wang et al., 2016)
|
|
Dinocarpus longan Lour |
Sapindaceae |
Longan |
Water extract of seed |
Gallic acid, corilagin, ellagic acid |
Decline uric acid production and uricosuric actions |
(Hou et al., 2012) |
|
Lychnophora trichocarpha |
Asteraceae |
Malva nut |
Ethanol extract of aerial parts |
Apigenin (XO inhibition), luteolin, apigenin, lupeol, lychnopholide and eremantholide |
Anti-inflammatory and urate-depressing actions |
(DE Souza et al., 2012) |
|
Piper nigrum L. |
Piperaceae |
Black pepper |
Not reported |
Piperine |
Deactivate xanthine oxidase |
(Sabina et al., 2011) |
|
Chrysanthemum indicum |
Asteraceae |
Indian Chrysanthemum
|
Methanol extract of flowers |
Luteolin and apigenin |
Decline uric acid production |
(Kong et al., 2000) |
|
Morinda citrifolia L. |
Rubiaceae |
Noni |
Fruit juice |
Not determined |
Inactivate xanthine oxidase |
(Palu et al., 2009) |
|
Lagerstroemia speciosa (L.) Pers. |
Lythraceae |
Queen's crepe-myrtle or pride of India |
Leaves |
Valoneic acid dilactone (VAD), Ellagic acid (EA) |
Inactivate xanthine oxidase and anti-hyperuricemic |
(Unno et al., 2004)
|
|
Erythrina strica roxb |
Papilionaceae |
Coral tree |
Hydromethanolic extract of leaves |
Flavonoids, saponins, tannins, phenolics, and triterpenoids |
Obstruct xanthine oxidase (XO) and xanthine dehydrogenase (XDH) |
(Raju et al., 2012) |
|
Rhus coriaria |
Anacardiaceae |
Sicilian sumac |
Hydroalcoholic fruits extract |
Protocatechuic acid, methyl gallate, and phenolic (as gallic acid) |
Inactivate xanthine oxidase |
(Mahdabadi et al., 2013) |
|
Juniperus phoenicea |
Cupressaceae |
Juniper |
Decoction of fresh leaves in water |
Phenols |
Reduce uric acid level and antioxidant |
(Gdoura et al., 2013) |
|
Momordica charantia |
Cucurbitaceae |
Bitter gourd |
Methanol-water extract of pulp |
Phenols and Flavonoids |
Reduce xanthine oxidase |
(Alsultanee et al., 2014) |
|
Origanum majorana Linn. |
Labiatae |
Sweet majorana |
Root and stem extracts in ethanol and water
|
Saponins, phenols, flavonoids, tannins, valoneic acid dilactone triterpenoids, saponins, coumarins, polyphenols, ellagic acid |
Hinder xanthine oxidase |
(Vasudeva et al., 2014) |
|
Phyllanthus niruri Linn. |
Euphorbiaceae |
Stonebreaker |
Methanolic extract of plant |
Lignans |
Uricosoric activities and inactivate Xanthine oxidase |
(Murugaiyah and Chan, 2009) |
|
Glycine max |
Leguminosae |
Soya bean |
Plant extract |
Allantionase |
Hinder xanthine oxidase |
(Al-Masri , 2016) |
|
Biota orientalis
|
Cupressaceae
|
Westmot
|
Leaves
|
Quercetin rutin |
Hinder xanthine oxidase |
(Zhu et al., 2004) |
|
Caesalpinia sappan
|
Caesalpiniaceae
|
Pathimughom
|
Heartwood
|
Neosappanone A
|
Hinder xanthine oxidase |
(Nguyen et al., 2004) |
|
Conyza bonariensis
|
Asteraceae
|
Flax‑leaf fleabane |
Whole plant
|
Syringic acid, takakin 8 – O glucuronide |
Hinder xanthine oxidase |
(Kong et al., 2001) |
|
Petroselinum crispum |
Apiaceous |
Parsley |
Seeds and leaves
|
Flavonols (kaempferol and quercetin) and flavones (apigenin and luteolin) |
Hinder liver xanthine oxidase and xanthine dehydrogenase |
(Haidari et al., 2011) |
|
Coccinia grandis
|
Cucurbitaceae
|
Ivy Gourd
|
Leaves
|
Saponins, cardenolides, flavonoids and polyphenols |
Hinder xanthine oxidase and anti-inflamatory |
(Umamaheswari et al., 2007) |
|
Vitex negundu
|
Verbenaceae
|
Horseshoe vitex or Pochatia
|
Leaves
|
Flavonoids (vitexicarpin), triterpenoids (betulinic acid and ursolic acid), lignans (negundins, vitedonin), alkaloid (vitedoamine) and diterpene (vitedoin) |
Hinder xanthine oxidase and anti-inflamatory |
(Umamaheswari et al., 2007) |
|
Coriandrum sativum
|
Apiaceae
|
Coriander
|
Fruit
|
Polyphenols |
Hinder xanthine oxidase and anti-inflammatory |
(Havlik et al., 2010) |
|
Chamomilla recutita
|
Asteraceae
|
Pineapple weed
|
Flowers
|
Polyphenols |
Hinder xanthine oxidase and anti-inflammatory |
(Havlik et al., 2010) |
|
Gossypium herbaceum
|
Malvaceae
|
Cotton or kapas |
Leaves |
Carbohydrates, tannin, phenolic compounds, flavonoids, saponins, glycosides, steroids |
Hinder xanthine oxidase and anti-oxidant |
(Kumar et al., 2011) |
|
Vinca sp. |
Apocynaceae |
Unknown |
Plant extract |
Vinblastine alkaloid |
High potential anti-gout |
(Costantini, 1992) |
|
Colchicum sp. |
Colchicaceae |
Unknown |
Plant extract |
Colchicine alkaloid |
High potential anti-gout |
(Dalbeth et al., 2014) |
|
Azadirachta indica |
Meliaceae |
Neem |
Leaves |
Flavonoids, tannins, alkaloids and tetranortriterpenes, including nimbin, nimbinin, nimbidinin, nimbolide, and nimbidic acid |
Anti-inflammatory |
(Rahman and Kumar,2015; Mahabub et al., 2009) |
|
Adenanthera pavonina |
Fabaceae |
Rakta kombol |
Barks |
Flavonoids, steroids, saponins, and triterpenoids |
Anti-inflammatory |
(Ara et al., 2010) |
|
Curcuma longa |
Zingiberaceae |
Turmeric |
Whole plant |
Curcumin |
Decrease uric acid level |
(Mohamed and Okabi, 2008; Panahi et al., 2016) |
|
Swietenia mahagoni |
Meliaceae |
Mahagoni |
Seed |
Gallic acid, flavonoids |
Inactivate xanthine oxidase |
(Sahgal et al., 2009) |
|
Cymbopogan citrates |
Poaceae |
Lemon grass |
Leaves and stalks |
phenols |
Inactivate xanthine oxidase |
(Mirghani et al., 2012) |
|
Physalis alkekengi |
Solanaceae |
Strawberry tomato |
Leaves and tomato |
Flavonoid, phenol, and carotenoid compounds |
Inactivate xanthine oxidase |
(Hoshani et al., 2011) |
|
Solanum nigrum |
Solanaceae |
Black Nightshade |
Leaves |
Polyphenols |
Inactivate xanthine oxidase |
(Mukherjee et al., 2015) |
|
Daucus carota |
Apiaceae |
Carrot |
Roots |
Polyphenols. alkaloids, carbohydrates, flavonoids, and protein |
Inactivate xanthine oxidase |
(Patil et al., 2012) |
|
Withania somnifera |
Solanaceae |
Ashwagandha |
Roots and stem |
Sitoindosides VII–X, withaferin A, 5-dehydroxywithanolide-R, withasomniferin-A, 2,3-dihydrowithaferinA, 24,25-dihydro27-desoxywithaferinA, 1-oxo-5,6-epoxy-witha-2-ene-27- ethoxy-olide, 27-O--d-glucopyranosylphysagulin D, physagulin D, withanoside I–VII, 27-O-- d-glucopyranosylviscosalactone B, 4,16-dihydroxy5,6-epoxyphysagulin D, alkaloids, diacetylwithaferin A and viscosalactone B, withanolides, particular reducing sugars and flavonoids |
Preclude monosodium urate crystal-induced swelling |
(Rasool and Varalakshmi, 2006) |
|
Citrus aurantium L. |
Rutaceae |
Bitter orange |
Immature fruits peels are more useful |
Hesperidin, neohesperidin, naringin, naringenin, hesperetin, nobiletin, and tangeretin |
Incapacitate xanthine oxidase and relegate serum uric acid |
(Liu et al., 2016) |
Figure 4. Selected herbs with their functional metabolites configuration (Congregated from various online images) a) Withania somnifera, b) Curcuma longa, c) Azadirachta indica, d) Ocimum sanctum,e) Psidium guajava, f) Camellia sinensis, g) Cinnamomum cassia, h) Olea europea, i) Allium cepa, j) Allium sativum, k) Phyllanthus emblica, l) Myristica fragrans, m) Zingiber officinale
Conclusions
Hyperuricemia (HUA) could be a serious phenomenon which isn’t only confined in the local region but also spread globally. To beat the injurious consequences of this life-endangering disease consequential development within the medication should be brought as soon as possible in alliance with scientists and other health care professionals in various segments. Though approved anti-hyperuricemic medications are randomly prescribed by physicians, sometimes these medications don’t seem to be preferred by the patients for its side effects and even modern medications are out of reach for people in most of the developing countries because of economic problem. For this reason, physicians suggest dietary plant foods to diminish the injurious effects of elevated uric acid in addition on inhibit the supreme threatening enzyme xanthine oxidase with more brilliant effects likewise as similar pharmacologic effects of conventional medications like allopurinol. Researchers are susceptible to conduct more in vivo, in vitro studies to guage the effect of varied bioactive metabolites of plants, fruits, and vegetables that reduce the reabsorption of uric acid in intestine and enhance its excretion through urine. The mentioned plants during this review article reveal anti-hyperuricemic activity by distinctive cellular pathways, for instance, xanthine oxidase obstruction, anti-inflammatory, antioxidant, and uricosuric because of the presence of most promising functional constituents phenolic glycosides and flavonoids (quercetin, rutin, genistein, and luteolin).
Future perspective
This review outlines the crucial outcome of using conventional medications as well as the possibility to develop novel therapy in this sector by using technology. Additionally, the review also provides an overall image about the chance of traditional plants and their constituents to become a source of the management of hyperuricemia. So, more and more plant extracts screening should be conducted to judge the protection, efficacy, potency, how the metabolites react with the active site of enzyme xanthine oxidase, their synergistic effects, internal toxicity, purity, drug- constituents interactions., quality control and all the procedures should be validated consistent with guidelines. By ongoing preclinical and clinical trials, suitable formulations are often developed to motif the medications for future purposes.
Conflicts of interest declaration
The authors assert that they need no conflict of interest.
Acknowledgement
This review article is co- operated and appreciated by department of pharmacy of the Jahangirnagar University, Ranada Prasad Shaha University, Islamic University, Jagannath University of Bangladesh.
References
Ahmad I, Ijaz F, Fatima I, Ahmad N, Chen S, Afza N, Malik A. 2010. Xanthine oxidase/tyrosinase inhibiting, antioxidant, and antifungal oxindole alkaloids from Isatis costata. Pharmaceutical biology 48(6): 716-721.
Ahmed D, Dar P, Chaudhery R, Masih R. 2017. Chemical constituents of Lagenaria siceraria mesocarp and its xanthine oxidase and alpha-amylase inhibitory activities. International Journal of Fruit Science 17(3): 310-322.
Alloway JA. 1999. Gout and hyperuricemia. American family physician59: 925-934.
Al-Masri SA. 2016. Beneficial role of high plant proteins in the treatment against hyperuricemia in experimental rats. Journal of Animal and Plant Sciences 26(3): 619-26.
Alsultanee IR, Ewadh MJ, Mohammed MF. 2014. Novel natural anti gout medication extract from Momdica Charantia. Journal of Natural Sciences Research 4(17): 16-23.
Ara A, Arifuzzaman M, Ghosh CK, Hashem MA, Ahmad MU, Bachar SC, Nahar L, Sarker SD. 2010. Anti-inflammatory activity of Adenanthera pavonina L., Fabaceae, in experimental animals. Revista Brasileira de Farmacognosia 20(6): 929-932.
Argulla LE, Chichioco-Hernandez CL. 2014. Xanthine oxidase inhibitory activity of some Leguminosae plants. Asian Pacific Journal of Tropical Disease 4(6): 438-441.
Azevedo VF, Lopes MP, Catholino NM, Paiva ED, Araújo VA, Pinheiro GD. 2017. Critical revision of the medical treatment of gout in Brazil. Revista brasileira de reumatologia 57(4): 346-355.
Azmi SM, Jamal P, Amid A. 2012. Xanthine oxidase inhibitory activity from potential Malaysian medicinal plant as remedies for gout. International Food Research Journal 19(1): 159.
Baltas N. 2017. Investigation of a wild pear species (Pyrus elaeagnifolia subsp. Elaeagnifolia Pallas) from Antalya, Turkey: polyphenol oxidase properties and anti-xanthine oxidase, anti-urease, and antioxidant activity. International Journal of Food Properties 20(3): 585-595.
Barsoum R, El-Khatib M. 2017. Uric acid and life on earth. Journal of advanced research 8(5): 471.
Becker MA, Schumacher HR Jr, Wortmann RL. 2005a. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty-eight-day, multicenter, phase II, random-ized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthritis & Rheumatism 52(3): 916–923.
Becker MA, Schumacher HR Jr, Wortmann RL. 2005b. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. New England Journal of Medicine 353(23): 2450–2461.
Bedir A, Topbas M, Tanyeri F, Alvur M, Arik N. 2003. Leptin might be a regulator of serum uric acid concentrations in humans. Japanese Heart Journal 44(4): 527-536.
Bell PG, Gaze DC, Davison GW, George TW, Scotter MJ, Howatson G. 2011. Montmorency tart cherry (Prunus cerasus L.) concentrate lowers uric acid, independent of plasma cyanidin-3-O-glucosiderutinoside. Journal of Functional Foods 11: 82-90.
Bobulescu IA, Moe OW. 2012. Renal transport of uric acid: evolving concepts and uncertainties. Advances in Chronic Kidney Disease 19(6): 358-371.
Bos MJ, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM. 2006. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke 37(6):1503-1507.
Bosly A, Sonet A, Pinkerton CR, McCowage G, Bron D, Sanz MA, Van den Berg H. 2003. Rasburicase (recombinant urate oxidase) for the management of hyperuricemia in patients with cancer: report of an international compassionate use study. Cancer: Interdisciplinary International Journal of the American Cancer Society 98(5): 1048-1054.
Bravo L. 1998. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutrition Reviews 56(11): 317-333.
Brook RA, Forsythe A, Smeeding JE, Lawrence Edwards N. 2010. Chronic gout: epidemiology, disease progression, treatment and disease burden. Current Medical Research and Opinion 26(12): 2813-2821.
Bustanji Y, Hudaib M, Tawaha K, Mohammad M, Almasri I, Hamed S, Oran S. 2011. In vitro xanthine oxidase inhibition by selected Jordanian medicinal plants. Jordan Journal of Pharmaceutical Sciences 1: 1-8.
Calderon PE, San Juan C, San Pedro MG, Reyes AM, Salom PJ, Sanchez AR, Sandigan H, Sangayab HJ, Saure MC, Savilla MH, Santos D. 2015. Antihyperuricemic and Nephroprotective Effects of Carica papaya Aqueous Leaf Extract in a Murine Model of Hyperuricemia and Acute Renal Tissue Injury. InDLSU Research Congress 2015 De La Salle University (pp. 2-4).
Candan F. Effect of Rhus coriaria L. 2003. (Anacardiaceae) on superoxide radical scavenging and xanthine oxidase activity. Journal of Enzyme Inhibition and Medicinal Chemistry 18(1): 59-62.
Chen G, Tan ML, Li KK, Leung PC, Ko CH. 2015. Green tea polyphenols decreases uric acid level through xanthine oxidase and renal urate transporters in hyperuricemic mice. Journal of Ethnopharmacology 175: 14-20.
Cho SK, Kim S, Chung JY, Jee SH. 2015. Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1. BMJ open 5(11): e009360.
Choi HK, Atkinson K, Karlson EW, Curhan G. 2005. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Archives of internal medicine 165(7): 742-748.
Choi HK, Curhan G. 2007. Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey. Arthritis Care & Research: Official Journal of the American College of Rheumatology 57(5): 816-821.
Choi HK, Mount DB, Reginato AM. 2005. Pathogenesis of gout. Annals of internal medicine 143(7): 499-516.
Costantini AV. 1992. The fungal etiology of gout and hyperuricemia: the antifungal mode of action of colchicine. Biomedical Reviews 1: 47-52.
Crittenden DB, Pillinger MH. 2013. New therapies for gout. Annual review of medicine 64: 325-37.
Dalbeth N, Kumar S, Stamp L, Gow P. 2006. Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout. The Journal of Rheumatology 33(8): 1646-1650.
Dalbeth N, Lauterio TJ, Wolfe HR. 2014. Mechanism of action of colchicine in the treatment of gout. Clinical Therapeutics 36(10): 1465-1479.
De Oliveira EP, Burini RC. 2012. High plasma uric acid concentration: causes and consequences. Diabetology & metabolic syndrome 4(1): 1-7.
De Souza MR, de Paula CA, de Resende ML, Grabe-Guimarães A, de Souza Filho JD, Saúde-Guimarães DA. 2012. Pharmacological basis for use of Lychnophora trichocarpha in gouty arthritis: anti-hyperuricemic and anti-inflammatory effects of its extract, fraction and constituents. Journal of Ethnopharmacology 142(3): 845-850.
Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, Boerwinkle E, Levy D, Hofman A, Astor BC, Benjamin EJ. 2008. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. The Lancet 372(9654): 1953-1961.
Desideri G, Castaldo G, Lombardi A, Mussap M, Testa A, Pontremoli R, Punzi L, Borghi C. 2014. Is it time to revise the normal range of serum uric acid levels? European Review for Medical and Pharmacological Sciences 18(9): 1295-1306.
El Ridi R, Tallima H. 2017. Physiological functions and pathogenic potential of uric acid: A review. Journal of advanced research 8(5): 487-493.
Fagugli RM, Gentile G, Ferrara G, Brugnano R. 2008. Acute renal and hepatic failure associated with allopurinol treatment. Clinical Nephrology 70(6): 523-526.
Flemmig J, Kuchta K, Arnhold J, Rauwald HW. 2011. Olea europaea leaf (Ph. Eur.) extract as well as several of its isolated phenolics inhibit the gout-related enzyme xanthine oxidase. Phytomedicine 18(7): 561-566.
Gdoura N, Murat JC, Abdelmouleh A, Elfeki A. 2013. Effects of Juniperus phoenicea extract on uricemia and activity of antioxidant enzymes in liver, erythrocyte and testis of hyperuricemic (oxonate-treated) rats. African Journal of Pharmacy and Pharmacology 7(8): 416-425.
Ghalehkandi JG, Ebrahimnezhad Y, Nobar RS. 2012. Effect of garlic (Allium sativum) aqueous extract on serum values of urea, uric-acid and creatinine compared with chromium chloride in male rats. Annals of Biological Research 3(9): 4485-4490.
Gliozzi M, Malara N, Muscoli S, Mollace V. 2016. The treatment of hyperuricemia. International Journal of Cardiology 213: 23-27.
Gnanenthiran SR, Hassett GM, Gibson KA, McNeil HP. 2011. Acute gout management during hospitalization: a need for a protocol. Internal medicine journal 41(8): 610-617.
González-Castejón M, Rodriguez-Casado A. 2011. Dietary phytochemicals and their potential effects on obesity: a review. Pharmacological research 64(5):438-455.
Gustafsson D, Unwin R. 2013. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC nephrology 14(1): 164.
Hafez RM, Abdel-Rahman TM, Naguib RM. 2017. Uric acid in plants and microorganisms: Biological applications and genetics-A review. Journal of advanced research 8(5): 475-486.
Haidari F, Keshavarz SA, Shahi MM, Mahboob SA, Rashidi MR. 2011. Effects of parsley (Petroselinum crispum) and its flavonol constituents, kaempferol and quercetin, on serum uric acid levels, biomarkers of oxidative stress and liver xanthine oxido reductase activity in oxonate-induced hyperuricemic rats. Iranian journal of pharmaceutical research: IJPR 10(4): 811.
Han J, Liu Y, Rao F, Nievergelt CM, O'Connor DT, Wang X, Liu L, Bu D, Liang Y, Wang F, Zhang L. 2013. Common genetic variants of the human uromodulin gene regulate transcription and predict plasma uric acid levels. Kidney international 83(4): 733-740.
Havlik J, de la Huebra RG, Hejtmankova K, Fernandez J, Simonova J, Melich M, Rada V. 2010. Xanthine oxidase inhibitory properties of Czech medicinal plants. Journal of ethnopharmacology 132(2):461-465.
Hoshani M, Mianabadi M, Aghdasi M, Azim-Mohseni M. 2011. Inhibition effects of Physalis alkekengi extract on xanthine oxidase activity in different phenological stages. Clinical Biochemistry 13(44): S343.
Hou CW, Lee YC, Hung HF, Fu HW, Jeng KC. 2012. Longan seed extract reduces hyperuricemia via modulating urate transporters and suppressing xanthine oxidase activity. The American journal of Chinese medicine 40(05): 979-91.
Huq AK, Jamal JA, Stanslas J. 2014. Ethnobotanical, phytochemical, pharmacological, and toxicological aspects of Persicaria hydropiper (L.) Delarbre. Evidence-Based Complementary and Alternative Medicine 2014.
Irondi EA, Agboola SO, Oboh G, Boligon AA, Athayde ML, Shode FO. 2016. Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro. Journal of intercultural ethnopharmacology 5(2): 122.
Iseki K, Oshiro S, Tozawa M, Iseki C, Ikemiya Y, Takishita S. 2001. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertension Research 24(6): 691-97.
Itakura MI, Sabina RL, Heald PW, Holmes EW. 1981. Basis for the control of purine biosynthesis by purine ribonucleotides. The Journal of clinical investigation 67(4): 994-1002.
Jiang Y, You XY, Fu KL, Yin WL. 2012. Effects of extract from Mangifera indica leaf on monosodium urate crystal-induced gouty arthritis in rats. Evidence-Based Complementary and Alternative Medicine 2012.
Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M. 2003. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41(6): 1183-90.
Kand'ár R, Žáková P, Mužáková V. 2006. Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography. Clinica Chimica Acta 365(1-2): 249-56.
Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ. 2002. A role for uric acid in the progression of renal disease. Journal of the American Society of Nephrology 13(12): 2888-97.
Kelm MA, Nair MG, Strasburg GM, DeWitt DL. 2000. Antioxidant and cyclooxygenase inhibitory phenolic compounds from Ocimum sanctum Linn. Phytomedicine 7(1):7-13.
Kim DW, Curtis-Long MJ, Yuk HJ, Wang Y, Song YH, Jeong SH, Park KH. 2014. Quantitative analysis of phenolic metabolites from different parts of Angelica keiskei by HPLC–ESI MS/MS and their xanthine oxidase inhibition. Food chemistry 153: 20-27.
Kondo M, Hirano Y, Nishio M, Furuya Y, Nakamura H, Watanabe T. 2013. Xanthine oxidase inhibitory activity and hypouricemic effect of aspalathin from unfermented rooibos. Journal of food science 78(12): H1935-9.
Kong LD, Abliz Z, Zhou CX, Li LJ, Cheng CH, Tan RX. 2001. Glycosides and xanthine oxidase inhibitors from Conyza bonariensis. Phytochemistry 58(4): 645-51.
Kong LD, Cai Y, Huang WW, Cheng CH, Tan RX. 2000. Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout. Journal of ethnopharmacology 73(1-2): 199-207.
Krishnan E. 2014. Interaction of inflammation, hyperuricemia, and the prevalence of hypertension among adults free of metabolic syndrome: NHANES 2009–2010. Journal of the American Heart Association 3(2):e000157.
Kumar SP, Singh SS, Singh NP, Mayur P. 2011. In-vitro antioxidant activity of Gossypium herbaceum Linn. International Research Journal of Pharmacy 2(7): 166-170.
Kuo CY, Kao ES, Chan KC, Lee HJ, Huang TF, Wang CJ. 2012. Hibiscus sabdariffa L. extracts reduce serum uric acid levels in oxonate-induced rats. Journal of Functional Foods 4(1): 375-81.
Kushiyama A, Nakatsu Y, Matsunaga Y, Yamamotoya T, Mori K, Ueda K, Inoue Y, Sakoda H, Fujishiro M, Ono H, Asano T. 2016. Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis. Mediators of Inflammation 2016.
Li S, Chen L, Yang T, Wu Q, Lv Z, Xie B, Sun Z. 2013. Increasing antioxidant activity of procyanidin extracts from the pericarp of Litchi chinensis processing waste by two probiotic bacteria bioconversions. Journal of agricultural and food chemistry 61(10): 2506-12.
Lin JK, Shih CA. 1994. Inhibitory effect of curcumin on xanthine dehydrogenase/oxidase induced by phorbol-12-myristate-13-acetate in NJH3T3 cells. Carcinogenesis 15(8): 1717-21.
Liu K, Wang W, Guo BH, Gao H, Liu Y, Liu XH, Yao HL, Cheng K. 2016. Chemical evidence for potent xanthine oxidase inhibitory activity of ethyl acetate extract of Citrus aurantium L. dried immature fruits. Molecules 21(3): 302.
Lü JM, Yao Q, Chen C. 2013. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a potent inhibitor of xanthine oxidase: a potential therapeutic agent for treatment of hyperuricemia and gout. Biochemical pharmacology 86(9): 1328-37.
Mahabub-Uz-Zaman M, Ahmed NU, Akter R, Ahmed K, Aziz MS, Ahmed MS. 2009. Studies on anti-inflammatory, antinociceptive and antipyretic activities of ethanol extract of Azadirachta indica leaves. Bangladesh Journal of Scientific and Industrial Research 44(2): 199-206.
Mahdabadi MN, Zahra K, Nadia TB, Farzaneh L, Asma J, Seyed HM. 2013. RhusCoriaria effect on serum uric acid level and in vivo xanthine oxidase activity in oxonate-induced hyperuricemic mice. Journal of Pharmaceutical and Biomedical Sciences 3(12):1-6.
Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. 2016. Regulation of uric acid metabolism and excretion. International journal of cardiology 213:8-14.
Mirghani ME, Liyana Y, Parveen J. 2012. Bioactivity analysis of lemongrass (Cymbopogan citratus) essential oil. International Food Research Journal 19(2): 569-75.
Mohamed DA, Al-Okbi SY. Evaluation of anti-gout activity of some plant food extracts. Polish journal of food and nutrition sciences 58(3).
Mukherjee CH, Paul SU, Kundu RI. 2015. Comparative evaluation of antiproliferative activity of Solanum nigrummethanolic and aqueous extract on Hela, Siha and C33A cells. International Journal of Pharmacy and Pharmaceutical Sciences 7(4): 320-4.
Murugaiyah V, Chan KL. 2009. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. Journal of ethnopharmacology 124(2): 233-9.
Ngoc TM, Khoi NM, Nhiem NX, Tai BH, Van Don D, Van Luong H, Son DC, Bae K. 2012. Xanthine oxidase inhibitory activity of constituents of Cinnamomum cassia twigs. Bioorganic & medicinal chemistry letters 22(14): 4625-8.
Nguyen MT, Awale S, Tezuka Y, Le Tran Q, Kadota S. 2004. Neosappanone A, a xanthine oxidase (XO) inhibitory dimeric methanodibenzoxocinone with a new carbon skeleton from Caesalpinia sappan. Tetrahedron letters 45(46): 8519-22.
Nile SH, Nile AS, Keum YS. 2017. Total phenolics, antioxidant, antitumor, and enzyme inhibitory activity of Indian medicinal and aromatic plants extracted with different extraction methods. 3 Biotech 7(1): 76.
Ouyang H, Hou K, Peng W, Liu Z, Deng H. 2018. Antioxidant and xanthine oxidase inhibitory activities of total polyphenols from onion. Saudi Journal of Biological Sciences 25(7): 1509.
Palu A, Deng S, West B, Jensen J. 2009. Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice. Phytotherapy Research 23(12): 1790-1.
Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendía LE, Sahebkar A. 2016. Curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: a randomized controlled trial. Journal of cardiovascular pharmacology 68(3): 223-9.
Patil MV, Kandhare AD, Bhise SD. 2012. Anti-inflammatory effect of Daucus carota root on experimental colitis in rats. International Journal of Pharmacy and Pharmaceutical Sciences 4(1): 337-43.
Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, Herrero-Beites A, Garcia-Erauskin G, Ruiz-Lucea E. 1998. Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout. Annals of the rheumatic diseases 57(9): 545-9.
Perez-Ruiz F, Dalbeth N, Schlesinger N. 2008. Febuxostat, a novel drug for the treatment of hyperuricemia of gout. Future 3(5):421-7.
Ragab G, Elshahaly M, Bardin T. 2017. Gout: An old disease in new perspective–A review. Journal of Advanced Research 8(5): 495-511
Rahman AH, Debnath A. 2015. Ethno-botanical Study at the Village Pondit Para under Palash Upazila of Narsingdi District, Bangladesh. International Journal of Advanced Research 3(5): 1037-52.
Rahman AH, Kumar AK. 2015. Investigation of medicinal plants at Katakhali Pouroshova of Rajshahi District, Bangladesh and their conservation management. Applied Ecology and Environmental Sciences 3(6): 184-92.
Raju R, Joseph S, Scria S, Mathews SM, Umamheshwari M. 2012. Effect of the fractions of Erythrina stricta leaf extract on serum urate levels and Xo/Xdh activities in oxonate-induced hyperuricaemic mice. Journal of Applied Pharmaceutical Science 2(2): 89.
Rasool M, Varalakshmi P. 2006. Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: an in vivo and in vitro study. Chemico-biological interactions 164(3): 174-80.
Reginato AM, Olsen BR. 2007. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear? Current opinion in rheumatology 19(2): 134-45.
Reinders MK, Van Roon EN, Jansen TT, Delsing J, Griep EN, Hoekstra M, Van De Laar MA, Brouwers JR. 2009. Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol. Annals of the rheumatic diseases 68(1): 51-6.
Richette P, Brière C, Hoenen-Clavert V, Loeuille D, Bardin T. 2007. Rasburicase for tophaceous gout not treatable with allopurinol: an exploratory study. The Journal of rheumatology 34(10): 2093-8.
Robinson PC, Horsburgh S. 2014. Gout: joints and beyond, epidemiology, clinical features, treatment and co-morbidities. Maturitas 78(4): 245-51.
Roddy E, Doherty M. 2010. Gout. Epidemiology of gout. Arthritis research & therapy 12(6): 223.
Rummun N, Somanah J, Ramsaha S, Bahorun T, Neergheen-Bhujun VS. 2013. Bioactivity of nonedible parts of Punica granatum L. a potential source of functional ingredients. International journal of food science 2013.
Sabina EP, Nagar S, Rasool M. 2011. A role of piperine on monosodium urate crystal-induced inflammation—an experimental model of gouty arthritis. Inflammation 34(3): 184-92.
Sahgal G, Ramanathan S, Sasidharan S, Mordi MN, Ismail S, Mansor SM. 2009. In vitro antioxidant and xanthine oxidase inhibitory activities of methanolic Swietenia mahagoni seed extracts. Molecules 14(11): 4476-85.
Sarvaiya VN, Sadariya KA, Pancha PG, Thaker AM, Patel AC, Prajapati AS. 2015. Evaluation of antigout activity of Phyllanthus emblica fruit extracts on potassium oxonate-induced gout rat model. Veterinary world 8(10): 1230.
Schumacher Jr HR, Becker MA, Wortmann RL, MacDonald PA, Hunt B, Streit J, Lademacher C, Joseph‐Ridge N. 2008. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28‐week, phase III, randomized, double‐blind, parallel‐group trial. Arthritis Care & Research 59(11): 1540-8.
Singh H, Krishna G, Baske PK. 2010. Plants used in the treatment of joint diseases (rheumatism, arthritis, gout and lumbago) in Mayurbhanj district of Odisha, India. Report and opinion 2(9): 22-6.
Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vßzquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W. 2011. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. Jama 306(7): 711-20.
Sweeney AP, Wyllie SG, Shalliker RA, Markham JL. 2001. Xanthine oxidase inhibitory activity of selected Australian native plants. Journal of Ethnopharmacology 75(2-3): 273-7.
Taniguchi A, Urano W, Yamanaka M, Yamanaka H, Hosoyamada M, Endou H, Kamatani N. 2005. A common mutation in an organic anion transporter gene, SLC22A12, is a suppressing factor for the development of gout. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 52(8): 2576-7.
Terkeltaub R, Bushinsky DA, Becker MA. 2006. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Research & Therapy 8(1): S4.
Terkeltaub RA. 2003. Gout. New England Journal of Medicine 349(17): 1647-55.
Torres RJ, Puig JG. 2007. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet journal of rare diseases 2(1):48.
Towiwat P, Li ZG. 2015. The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout. International journal of rheumatic diseases 18(5): 495-501.
Ullah MF. 2017. Antioxidative and xanthine oxidase inhibitory activities and phytochemical screening of the hydro-alcoholic extract of mace, aril of Myristica fragrans: Implication as an adjuvant therapy in gout. International journal of food properties 20(3): 694-703.
Umamaheswari M, AsokKumar K, Somasundaram A, Sivashanmugam T, Subhadradevi V, Ravi TK. 2007. Xanthine oxidase inhibitory activity of some Indian medical plants. Journal of ethnopharmacology 109(3): 547-51.
Unno T, Sugimoto A, Kakuda T. 2004. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. Journal of Ethnopharmacology 93(2-3): 391-5.
Vargas-Santos AB, Neogi T. 2017. Management of gout and hyperuricemia in CKD. American Journal of Kidney Diseases 70(3): 422-39.
Vasudeva N, Prerna S, Sneha Das SK. 2014. Antigout and antioxidant activity of stem and root of Origanum majorana Linn. American Journal of Drug Discovery and Development 4(2): 102-2.
Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. 2008. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes & nutrition 3(3):115.
Vigetti D, Monetti C, Acquati F, Taramelli R, Bernardini G. 2000. Human allantoicase gene: cDNA cloning, genomic organization and chromosome localization. Gene 256(1-2): 253-60.
Vulić JJ, Ćebović TN, Čanadanović-Brunet JM, Ćetković GS, Čanadanović VM, Djilas SM, Šaponjac VT. 2014. In vivo and in vitro antioxidant effects of beetroot pomace extracts. Journal of Functional Foods 6: 168-75.
Wang H, Cheng L, Lin D, Ma Z, Deng X. 2017. Lemon fruits lower the blood uric acid levels in humans and mice. Scientia Horticulturae 220: 4-10.
Wang X, Zhao M, Su G, Cai M, Sun‐Waterhouse D, Zhou C, Lin L. 2016. Antihyperuricemic activities of an ethanolic and aqueous extract of Walnut (Juglans regia L.) shell and a new aldehyde xanthine oxidase inhibitor. International Journal of Food Science & Technology 51(2): 453-60.
Wang X, Zhao M, Su G, Cai M, Zhou C, Huang J, Lin L. 2015. The antioxidant activities and the xanthine oxidase inhibition effects of walnut (J uglans regia L.) fruit, stem and leaf. International Journal of Food Science & Technology 50(1): 233-9.
Wang Y, Zhu JX, Kong LD, Yang C, Cheng CH, Zhang X. 2004. Administration of procyanidins from grape seeds reduces serum uric acid levels and decreases hepatic xanthine dehydrogenase/oxidase activities in oxonate‐treated mice. Basic & clinical pharmacology & toxicology 94(5): 232-7.
Wang Z, Kwon SH, Hwang SH, Kang YH, Lee JY, Lim SS. 2017. Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract. Journal of Chromatography B 1048: 30-7.
Waring WS, Webb DJ, Maxwell SR. 2000. Uric acid as a risk factor for cardiovascular disease. Qjm AN INTERNATIONAL JOURNAL OF MEDICINE 93(11): 707-13.
Waring WS. 2005. An investigation of the potential influence of serum uric acid concentration on regulation of the human cardiovascular system (Doctoral dissertation, University of Edinburgh).
Wong YP, Ng RC, Chuah SP, Koh RY, Ling AP, Antioxidant and xanthine oxidase inhibitory activities of Swietenia macrophylla and Punica granatum , 4-5 Aug. 2014, International Conference on Biological, Environment and Food Engineering (Indonesia).
Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ, Wu CY, Hung SI, Chung WH. 2015. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA internal medicine 175(9): 1550-7.
Yeldandi AV, Patel YD, Liao M, Kao FT, Rao MS, Reddy JK, Le Beau MM. 1992. Localization of the human urate oxidase gene (UOX) to 1p22. Cytogenetic and Genome Research 61(2): 121-2.
Yi LT, Li J, Su DX, Dong JF, Li CF. 2012. Hypouricemic effect of the methanol extract from Prunus mume fruit in mice. Pharmaceutical biology 50(11): 1423-7.
Zhao M, Zhu D, Sun-Waterhouse D, Su G, Lin L, Wang X, Dong Y. 2014. In vitro and in vivo studies on adlay-derived seed extracts: phenolic profiles, antioxidant activities, serum uric acid suppression, and xanthine oxidase inhibitory effects. Journal of agricultural and food chemistry 62(31): 7771-8.
Zhu JX, Wang Y, Kong LD, Yang C, Zhang X. 2004. Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. Journal of ethnopharmacology 93(1): 133-40.
