Review Articles

2020  |  Vol: 6(4)  |  Issue: 4 (July- August)  |  https://doi.org/10.31024/ajpp.2020.6.4.5
Promising actions of certain medicinal and dietary plants for the management of hyperuricemia as a natural remedy: A review

Ananya Das1*, Prema Modak1, Arghya Prosun Sarkar2, Satyajit Halder1, Bidduth Kumar Sarkar3Anita 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)

  • Foods associated with excessive purine meat from animal or marine origin, organ foods or legumes, beverages, alcohol intake (beer), fructose foods, and juices.

Inner issues (Reginato and Olsen, 2007; Torres and Puig, 2007)

  • Enhanced purine cessation.
  • Lack of enzymes participating in purine digestion (hypoxanthine–guanine phosphoribosyltransferase, uricase).
  • Overabundance of phosphoribosyl pyrophosphate synthetase.
  • Dearth of Glucose-6-phosphatase.

Metabolic syndromes (Kang et al., 2002; Choi et al., 2005; Bos et al., 2006)

  • Lesch-Nyhan syndrome, tumor lysis syndrome (a tricky situation of cancer chemotherapy), cardiovascular disorder, Type 2 diabetes, gout, hypertension, myocardial infarction, stroke, and renal disease, Kelley- seegmiller syndrome.

Particular categories of medications (Taniguchi et al 2005; Han et al., 2013)

  • Loop diuretics, angiotensin-converting enzyme (ACE) inhibitors, thiazide, b-blockers, minute amount aspirin (<1 g per day), and non-losartan angiotensin II receptor blocker, cyclosporine, levodopa, ethambutol, pyrazinamide, lead, nicotinic acid, vitamin B12, radiographic contrast agents, etc.

Other conditions (Bos et al., 2006; Bedir et al., 2003; Towiwat and Li, 2015; Robinson and Horsburgh, 2014).

  • When cell casualty occurs in cancer, heamatological and inflammatory complications are liable for uric acid acceleration.
  •  Sunstroke, overweightness indicate the improved formation of uric acid exaggerating the risk of hyperuricemia.
  • Leptin was noticed to raise serum altitudes of urate.

 

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)

  • Genes participating in renal UA transportation, comprising SLC2A9, ABCG2, SLC17A3, and SLC22A12.

Several autosomal dominant conditions (Gnanenthiran et al., 2011)

  • In the thick ascending limb of the loop of Henle a gene called uromodulin controls water penetrability. If any transformations happen in the uromodulin gene the normal process will be prohibited, which sequentially enhances SUA.

Medications (Terkeltataub, 2006)

  • Pyrazinamide, nicotinate, and lactate rise urate reabsorption via performing on URAT1

Additional conditions (Choi et al., 2005)

  • Renal insufficiency, acidosis (alcoholic ketoacidosis, lactic acidosis, starvation acidosis and diabetic ketoacidosis), metabolic disorder, hypertension, pre-eclampsia, and eclampsia, hypothyroidism, hyperparathyroidism, sarcoidosis, trisomy 21, obesity, insulin resistance lessen flux of uric acid through urine and subsequently elevate serum UA.

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


1. Uric acid

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.

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