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OPEN ACCESS Journal of Biological Sciences
ISSN 1727-3048
DOI: 10.3923/jbs.2018.468.474
Research Article
Anti-hyperuricemic, Uricosuric and Xanthine-oxidase Inhibitory
Activities of Watermelon Powder in a Rat Gout Model
Basim Jasim Hameed, Falah Hassan Shari and Usama Hamid Ramadhan
Department of Clinical Laboratories Sciences, College of Pharmacy, University of Basrah, Basrah, Iraq
Abstract
Background and Objective: Gout is a common metabolic disorder around the world. It characterized by elevation of uric acid levels in
the blood, leading to increase the deposition of urate crystals in the joints and kidneys. The current study was carried out to investigate
the efficacy and mechanism action of watermelon powder as antihyperuricemic agent. Materials and Methods: Enzyme assay was done
by using bovine milk xanthine oxidase (XO). The XO inhibitory activity
in vitro
was performed by using different doses of watermelon
powder and the degree of XO inhibition was expressed as IC50. The antihyperuricemic and uricosuric activity of watermelon were tested
in the potassium oxonate-induced hyperuricemic rats for seven consecutive days of oral treatment of 25, 50 and 100 mg kgG1 doses.
Results: The results of the study revealed that the watermelon has a moderate activity of XO inhibition with IC50 =95.24 µg mLG1. In
addition, these results showed that all doses of watermelon powder were able to significant reduce serum uric acid levels in the
hyperuricemic rats. Moreover, the results of uricosuric activity assay showed that the watermelon significantly increased the urinary
excretion of uric acid. Conclusion: The watermelon powder showed significant effects on the evaluated models and therefore it may be
promising agent for the treatment of gout since it possesses a moderate xanthine oxidase inhibitory and a potent of both
antihyperuricemic and uricosuric effects.
Key word: Watermelon powder, xanthine oxidase, antihyperuricemic, uricosuric, gout, hyperuricemic, urate crystals
Received: September 01, 2018 Accepted: September 27, 2018 Published: October 15, 2018
Citation: Basim Jasim Hameed, Falah Hassan Shari and Usama Hamid Ramadhan, 2018. Anti-hyperuricemic, uricosuric and xanthine-oxidase inhibitory
activities of watermelon powder in a rat gout model. J. Biol. Sci., 18: 468-474.
Corresponding Author: Basim Jasim Hameed, Department of Clinical Laboratories Sciences, College of Pharmacy, University of Basrah, Basrah, Iraq
Copyright: © 2018 Basim Jasim Hameed
e t a l
. This is an open access article distributed under the terms of the creative commons attribution License, which
permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Competing Interest: The authors have declared that no competing interest exists.
Data Availability: All relevant data are within the paper and its supporting information files.
J. Biol. Sci., 18 (8): 468-474, 2018
INTRODUCTION
Gout is a widespread metabolic disorder around the
world, characterized by elevation of uric acid levels in the
blood, leading to increased accumulation of needle-like urate
crystals in the joints and kidneys1. The accumulation of urate
crystals in the tissues activates the inflammatory sequence,
followed by acute inflammatory response such as swelling,
warmth and quite pain2,3. In humans, the uric acid is the
ultimate product of metabolic pathway of purines. Most of the
uric acid pool attributed to the breakdown of endogenous
purines while the remaining quantity resulted from dietary
(exogenous) purines4. Unfortunately, human is the only being
of the rest of the other mammals cannot convert uric acid to
a more soluble substance, allantoin because of the absence of
the uricase enzyme5. Consequently, the altitude of uric acid
levels in the blood due to the hepatic overproduction of uric
acid or renal underexcretion of it or both will lead to the
occurrence of hyperuricemia and gout respectively6.
There are two types of urate-lowering drugs in the gout
treatment: Xanthine oxidase inhibitors and uricosurics. The
first type of drugs such as allopurinol is indicated for the
patients who suffer from the increased in the uric acid
production, whereas the uricosurics drugs such as febuxostat
are indicated for the patients who are suffering from the
underexcretion of urates. The mechanism action of xanthine
oxidase inhibitors through inhibition the action of xanthine
oxidase, which is responsible on the conversion of xanthine
into hypoxanthine and of hypoxanthine to uric acid6,7. The
action of uricosurics drugs via the enhancing the renal
excretion of uric acid by inhibition of set of proteins involved
in the renal tubules are called urate transport-related
proteins8. However, the use of these drugs will not be without
serious health complications such as hepatotoxicity, renal
toxicity and severe allergic reactions and sometimes may
lead to renal failure9,10. Therefore, the search for new
antihyperuricemic drugs, including more safety and efficacy
would be very useful in treatment of the gout and related
diseases11.
The use of herbal plants is earning new interest in the
treatment of diseases due to their low sensitivity and side
effects12. Plants contain a large amount of potential
antioxidants and bioactive substances, making them a target
for the search for new drugs13. It has been demonstrated that
the many plant-derived antioxidants can be regulated uric
acid through either increasing uric acid excretion (uricosuric
activity) or by reducing the production of uric acid (inhibition
of xanthine oxidase) to reduce the risk of gout14.
Watermelon (
Citrullus lanatus
) commonly consumed in
the summer as a refreshing fruit all over the world and in the
Middle East specifically due to the very hot climate15,16.
Watermelon consists of more than 90% water and hence it is
called watermelon. Watermelon is a rich natural source for
many bioactive materials such as A, C, E and B-complex
vitamins and it contains amino acid citrulline, cucurbitacin,
triterpenes, alkaloids and many different minerals17-19. The red
colour of watermelon flesh is as result of an excellent quantity
of the potent antioxidant carotenoid, lycopene. Many
studies have shown that watermelon juice has numerous
beneficial therapeutic effects such as potent antioxidant,
anti-inflammatory, antimicrobial, laxative, anti-giardial and
anti-hyperlipidemic activity20-22. The protective effect of
watermelon for several different tissues such as liver, kidneys
and nerves have been reported23, 24. The fruit is very effective
in the treatment of, dropsy and infections and stones of
urinary tract25. Th e pr esent study was de sign ed t o eva lua te
the anti-hyperuricemic activity of
Citrullus lanatus
(watermelon) and investigation the mechanism action of
urate-lowering effect through either by increasing of uric acid
excretion and/or by decreasing of uric acid production via the
inhibition of xanthine oxidase enzyme.
MATERIALS AND METHODS
Reagents and chemical: Uric acid kit was purchased from
Biolabs Company (Maizy, France). Xanthine oxidase from
bovine milk (Grade I), xanthine and allopurinol were provided
from Sigma-Aldrich (Dorset, England). All other chemicals
were supplied from Merck (Darmstadt, Germany). All
chemicals and reagents used in this study were of analytical
grade.
Pl a n t m a te r ia l an d p re p ar a ti o n o f wa t e rm e lo n po w de r : R ip e
fruit of red-fleshed watermelon (
Citrullus lanatus
) was
purchased in May, 2018 from a local market of Basrah, Iraq.
The fresh watermelon fruit was washed under tap water and
the rinds were peeled by using a stainless knife, then the seeds
were removed from the fruit flesh. The flesh was sliced using
slicer and then the slices were dried by hot-air oven (Lab-Line,
USA) at 40EC for two days. The dried watermelon slices were
then grinded by an electric mill (Silver Crest, Germany) into a
fine powder, kept in a sealed glass container and stored in the
refrigerant before use26. This study was conducted during
May-June of 2018 at the Faculty of Pharmacy, University of
Basrah, Basrah, Iraq.
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J. Biol. Sci., 18 (8): 468-474, 2018
Animals: This study included the use of male Wistar rats
(150-180 g), were supplied from the unit of animals house at
college of Pharmacy, Basrah University. The rats were
separated into different groups (n = 6), then the animals were
accommodated in isolated plastic cages and kept in the
animals room under a regulated condition at temperature
25±2EC and humidity 30±15% with 12-h dark/12-h light
cycle for a week before being used for acclimatization.
The animals were consumed standard chow and water ad
libitum. Animal Ethics committee, University of Basrah, Iraq
(No. 2013/32), authorized all of dealing procedures with
animals that described in this study.
In vitro
XO inhibitory activity: The xanthine oxidase (XO)
inhibitory effect of watermelon powder was assessed
spectrophotometrically at 290 nm according to
Sunarni
et al
.27 and Yumita
et al
.28 with minor changes. The
mixture assay consists of 0.9 mL of 0.05 M sodium phosphate
buffer (pH 7.5 at 25EC), 1 mL of watermelon powder
(100 µg mLG1 in DMSO) and 0.1 mL of XO enzyme solution
(0.1 unit mLG1 in phosphate buffer, pH 7.5) was prepared in
cold buffer directly before using. After a 15 min pre-incubation
at 25EC, then the reaction was allowed to start by addition of
2000 µL of freshly prepared solution of substrate (0.15 mM
xanthine solution). Next, a further incubation process was
achieved for the reaction mixture at 25EC for 30 min. After
addition of 1 mL of 1N HCl solution into assay mixture for
stopping the reaction, the absorbance was recorded at wave
length 290 nm by using UV/Vis spectrophotometer (Chrom
Tech, USA) against the blank which is prepared in the same
procedure but with replacement of enzyme solution by
phosphate buffer. The positive control solution was prepared
by using allopurinol (100 µg mLG1) in DMSO. The inhibitory
activity against the XO was stated as the percentage of
inhibition (%):
XO inhibition (%) = 1 100
where, " represents the activity of XO in absence of the tested
substance (watermelon powder) and $ is the activity of
XO with presence of watermelon powder. Different
concentrations of both watermelon powder and allopurinol
(1, 2, 3, 4, 5, 10, 25, 50 and 100 µg mLG1) were used
for evaluation of XO inhibitory activities and then the
dose-response logarithmic curve was applied to determine
the median maximum inhibitory concentration IC50.
Drug administration: Allopurinol, benzbromarone and
watermelon powder were suspended in 0.5% sodium salt
of car box ymeth ylc ell ulose , CM C-N a (v ehi cle ). P ota ssium
oxonate, uricase inhibitor (250 mg kgG1) was suspended in the
solution of 0.9% sterile saline. All solutions were prepared
freshly before use for
in vivo
experiments.
Evaluation of anti-hyperuricemic and uricosuric activity:
The anti-hyperuricemic and uricosuric activity of watermelon
powder was investigated by using the potassium oxonate-
induced hyperuricemia in the rats model according to
Qin
et al
.29 and Ferrari
et al
.30 with modifications. Animals
were fasted by withdrawing of food and water 2 h before
drugs administration. Experimental animals (rats) were divided
randomly into seven groups (n = 6). The uricase inhibitor
(Potassium oxonate) at a dose of 250 mg kgG1 was injected
intraperitoneally (i.p.) to rats of groups (2-7) in the 1st, 3rd and
7th days, of the experiment period. Rats groups were
administered with oral treatments of the vehicle, allopurinol,
benzbromarone and watermelon powder solutions by oral
gavage 1 h. after the administration of potassium oxonate,
once daily for seven consecutive days of experiment.
Animals of normal control (group 1) and hyperuricemic
control (group 2) were received only vehicle via oral
administration. Allopurinol and benzbromarone groups
(group 3-4) treated orally with allopurinol and benzbromarone
in a dose (10 mg kgG1) respectively. Sample groups (5-7)
treated orally with watermelon powder at the doses 25, 50
and 100 mg kgG1, respectively once a day, throughout the
days of the experiment. At the 6th day of experiment, the
animals were transferred to the metabolic cages for the urine
collection over 24 h. The urine samples then centrifuged at
2000 rpm to get the supernatant for uric acid assay. The
collection of whole blood samples from each rat was achieved
by cutting tail vein 2 h. After last administration of tested
drugs the blood samples were permitted for 0.5 h at room
temperature for clotting and 5 min for centrifugation at
3500 rpm to get the serum. The sera and urine samples were
stored at -20EC until the uric acid is assayed.
Uric acid assay: The enzymatic-colorimetric method was
employed to determine the serum uric acid levels by using a
standard diagnostic kit.
Statistical analysis: The results of all trials in this study are
stated as Mean±SEM. Statistical analysis was carried out by
one-way ANOVA pursued by the Dennetts t-test. The values
of probability (P) less than 0.05 were considered as statistically
significant.
RESULTS
In vitro
XO inhibitory activity: The inhibitory effects of
watermelon and allopurinol for bovine milk xanthine oxidase
470
J. Biol. Sci., 18 (8): 468-474, 2018
100
90
80
70
60
50
40
30
20
10
0
Inhibi tion (%)
0.0 0.5 1.0 1.5 2.0 2.5
Log (concentration)
Allopurinol IC = 1.83 µg mL
50
G
1
Watermelon IC
50
= 95.24 µg mL
G
1
at different concentrations were represented in Table 1. Each
has revealed more than 50% of XO inhibition at the
concentration 100 µg mLG1. At highest concentration
100 µg mLG1, the watermelon resulted in 58% of XO
inhibition activity, whereas the standard XO inhibitor,
allopurinol demonstrated 95% of XO inhibition activity at
the same concentration. The xanthine oxidase inhibitory
effects for both watermelon and allopurinol were also stated
in the term of IC50, which is represent the concentration of
standard drug or tested sample that is required for 50%
inhibition of xanthine oxidase activity under the same
experimental co ndi tion s. T he IC50 v alues wer e cal cul ated
Fig. 1: Xanthine oxidase inhibitory activity and IC50 values of
watermelon acid and allopurinol
Table 1: Xanthine oxidase inhibitory activity of watermelon and allopurinol at
different concentrations
XO inhibitory activity (%)
---------------------------------------------------------------
Concentration (µg mLG1) Allopurinol Watermelon
100 95±1.5 58±2.2
50 90±0.6 41±0.7
25 81±1.1 33±1.8
10 72±2.1 28±1.4
5 68±2.0 22±0.3
4 62±0.4 19±0.2
3 56±0.6 16±1.1
2 52±1.6 12±0.8
1 42±1.2 10±0.7
according to the dose-response logarithmic curve by using
GraphPad Prism V 6.05 program (GraphPad Prism software,
Inc., USA), Where the value was equal to 1.834 µg mLG1 for
allopurinol and 95.243 µg mLG1 for watermelon respectively as
shown in Fig. 1.
Anti-hyperuricemic and uricosuric activity: To assess the
existence of anti-hyperuricemic effect of the watermelon,
the potassium oxonate-induced hyperuricemic rats model
was used in this study. As exposed in the Table 2, the
intraperitoneal administration of uricase inhibitor, potassium
oxonate (250 mg kgG1) significantly raised (p<0.001) the uric
acid concentrations in the serum of rats compared to healthy
normouricemic control group. The administration of standard
xanthine oxidase inhibitor, allopurinol and standard uricosuric
drug, benzbromarone in a does (10 mg kgG1, p.o), permitted
to considerably reduction in the urate levels of hyperuricemic
rats to values close of normal control. The c onsecutive
7 day treatment of rats with watermelon at the dose 25,
50 and 100 mg kgG1 significantly reduce the serum uric acid
levels as compared with hyperuricemic control group in all
doses above. Administration of potassium oxonate for rats
caused a significant elevation in the output urine volumes,
also treatments of rats with each of allopurinol,
benzbromarone and the different doses (25, 50 and
100 mg kgG1) of watermelon powder led to a significant raise
in the volumes of urine output as compared with normal
control. Treatments of animals with allopurinol and
benzbromarone as well as the watermelon powder were able
significantly (p<0.001) to increase the excretion of uric acid in
the urine as compared towards the rats of normal control
group.
DISCUSSION
Although, gout and hyperuricemia are widespread,
the therapeutic agents for reduction the uric acid in the
blood are very few in numbers at pr esent and their u se
Table 2: Effect of watermelon powder on urine output, urine uric acid and serum uric acid in hyperuricemic rats
Groups Dose (mg kgG1) Urine output (mL/24 h) Urine uric acid (mg/24 h) Serum uric acid (mg dLG1)
Normouricemic control - 3.25±0.58 1.28±0.54 1.25±0.21
Hyperuricemic control - 5.10±0.57a4.86±0.28b4.42±0.85c
Allopurinol 10 5.62±0.57b6.37±1.24b1.34±0.27c
Benzbromarone 10 7.21±0.68b11.64±1.15b1.65±0.41c
Watermelon 25 5.74±1.09b7.23±0.95b2.65±0.62c
50 6.12±0.65b8.65±0.85b2.14±0.54c
100 6.68±0.86b9.94±0.79b1.87±0.37c
Values are expressed as Mean±SEM for 6 rats, ap<0.01, bp<0.001, significant difference compared to normal control, cp<0.0001 significant difference compared to
hyperuricemic control
471
J. Biol. Sci., 18 (8): 468-474, 2018
is s ometimes li mited due to un desir able s ide effects.
Therefore, natural products represent a potential source
of novel anti-hyperuricemic agents31,32. This study is the
first to investigate that the watermelon powder exerts
antihyperuricemic effect in potassium oxonate-induced
hyperuricemic rats. Furthermore, the underlying mechanism
of watermelon powder might be through inhibiting of
xanthine oxidase activity and of uricosuric activity, increasing
of uric acid excretion in urine.
In the present study, hyperuricemia status was induced in
rats model by intraperitoneal administration of potassium
oxonate in a dose (250 mg kgG1) for 7 days. The induction of
hyperuricemia in rats caused a significant increase in urine
secretion and significant increase the concentration of uric
acid in both blood and urine. These results confirm that the
model used was effective in stimulating hyperuricemia and are
in agreement with previous reports29-33. Administration of
watermelon powder caused a significant reduction in the
blood uric acid levels in hyperuricemic animals. Moreover, the
same administration resulted in a significant increase the
excretion and clearance of uric acid in hyperuricemic rats.
Watermelon powder increased each of urinary excretion,
clearance of uric acid and reduction of blood uric acid in a
dose-dependent manner. Watermelon powder at 100 mg kgG1
dose manifested similar influence of both benzbromarone
(10 mg kgG1) and allopurinol (10 mg kgG1), which indicated to
the importance of watermelon as a potent antihyperuricemic
and uricosuric agent32,34.
The watermelon fruit is a rich source for many natural
antioxidants such as vitamin C, lycopene, cucurbitacin,
citrulline and other polyphenols15,19-25. The presence of such
constituents, especially vitamin C, supports the hypothesis
that the watermelon is an effective diet in the prevention and
treatment of gout 35-38. The previous studies has been reported
that the vitamin C can reduce the uric acid in blood through
either the direct uricosuric potential, which is due to a
competitive inhibition of renal reabsorption of uric acid via an
anion-exchange transport system at the proximal tubule in
nephron or through enhancing the glomerular filtration rate.
Moreover, as a potent antioxidant, vitamin C is able to
diminish the oxidative stress and inflammation in the body
cells, thereby reducing the synthesis and ultimately blood
level of uric acid39-41.
The uricosuric effect of watermelon powder may be of
great interest the treatment of gout and related diseases,
taking into account that the more than 90% of gouty
patients are resulted from the underexcretion of uric acid32,33.
Unlike standard uricosuric drugs, it was rep ort ed t hat th e
watermelon possesses hepato and nephroprotective
effects18,24. The property of antiurolithic that caused by the use
of watermelon exhibits a further advantage over uricosuric
effect, which may reduce the risk of deposition of uric acid in
the renal tubules that commonly occurred with use of
uricosuric drugs42.
Another probable mechanism that any material can
reduce of uric acid in the blood is by inhibiting the activity of
xanthine oxide enzyme, which in turn reduces the production
of uric acid. The watermelon powder revealed a mild
in vitro
xanthine oxidase inhibitory activity. It has been reported
that watermelon contain many bioactive materials like
polyphenols. Previous studies have indicated that these
substances showed a good inhibitory activity towards
xanthine oxidase. The viewed xanthine oxidase inhibitory
activity of watermelon powder may be attributed to the
existence of these polyphenols at low concentrations43-47.
This study has limitations that will be addressed in
our next experiments. First, isolation, purification and
identification of the active constituents of the watermelon
powder in order to investigate their anti-hyperuricemic effect
on potassium oxonate-induced hyperuricemic rats. Second,
study the effect of watermelon powder on the inhibitory
activity of xanthine oxidase
in vivo
.
CONCLUSION
Based on the findings of the present study, the
watermelon powder significantly reduced the uric acid levels
i n t he b lo od o f t h e p ot a ss i um ox o na t e- i nd u c ed h yp e ru r ic e mi c
rats via the synergistic effect of both xanthine oxidase
inhibitory and uricosuric activities. The same findings clearly
demonstrated that the antihyperuricemic activity of
watermelon powder might be attributable mainly to the
uricosuric nature and partially to the xanthine oxidase
inhibitory activity.
SIGNIFICANCE STATEMENT
This study confirmed that the watermelon red-fleshed
works to reduce the levels of uric acid in the blood through
the synergistic effect of both increasing the uric acid excretion
in the urine and inhibition of uric acid synthesis. The uric
acid-lowering effect for melon may be due to the presence of
many natural antioxidants, especially vitamin C. It is very
important to increase the consumption of melon for gout
patients as food and alternative treatment to promote human
health and reduce the risk of gout and related diseases.
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J. Biol. Sci., 18 (8): 468-474, 2018
ACKNOWLEDGMENT
This study was performed at Clinical Laboratories
Sciences, College of Pharmacy, University of Basrah, Basrah,
Iraq. Authors are grateful to Head of department for providing
the necessary facilities.
REFERENCES
1. Haidari, F., M.R. Rashidi, S.A. Keshavarz, S.A. Mahboob,
M.R. Eshraghian and M.M. Shahi, 2008. Effects of onion
on serum uric acid levels and hepatic xanthine
dehydrogenase/xanthine oxidase activities in hyperuricemic
rats. Pak. J. Biol. Sci., 11: 1779-1784.
2. Silva, C.R., J.K. Frohlich, S.M. Oliveira, T.N. Cabreira and
M.F. Rossato
et al
., 2013. The antinociceptive and
anti-inflammatory effects of the crude extract of
Jatropha
isabellei
in a rat gout model. J. Ethnopharmacol.,
145: 205-213.
3. Zhao, P., K.L. Chen, G.L. Zhang, G.R. Deng and J. Li, 2017.
Pharmacological basis for use of
Selaginella moellendorffii
in gouty arthritis: Antihyperuricemic, anti-inflammatory and
xanthine oxidase inhibition. Evidence-Based Complement.
Altern. Med., Vol. 2017. 10.1155/2017/2103254.
4. Maiuolo, J., F. Oppedisano, S. Gratteri, C. Muscoli and
V. Mollace, 2016. Regulation of uric acid metabolism and
excretion. Int. J. Cardiol., 213: 8-14.
5. Saigal, R. and A. Agrawal, 2015. Pathogenesis and
clinical management of gouty arthritis. J. Assoc. Phys. India,
63: 56-63.
6. Dalbeth, N., T.R. Merriman and L.K. Stamp, 2004. Gout. Lancet,
388: 2039-2052.
7. Li, E.K., 2004. Gout: A review of its aetiology and treatment.
Hong Kong Med. J., 10: 261-270.
8. Hu, Q.H., J.X. Zhu, J. Ji, L.L. Wei, M.X. Miao and H. Ji, 2013.
Fructus gardenia extract ameliorates oxonate-induced
hyperuricemia with renal dysfunction in mice by
regulating organic ion transporters and mOIT3. Molecules,
18: 8976-8993.
9. De Souza, M.R., C.A. de Paula, M.L.P. de Resende,
A. Grabe-Guimaraes, J.D. de Souza Filho and
D.A. Saude-Guimaraes, 2012. Pharmacological basis for use
of
Lychnophora trichocarpha
in gouty arthritis: Anti-
hyperuricemic and anti-inflammatory effects of its
extract, fraction and constituents. J. Ethnopharmacol.,
142: 845-850.
10. Mishra, D., G. Ghosh, P.S. Kumar and P.K. Panda, 2011. An
experimental study of analgesic activity of selective COX-2
inhibitor with conventional NSAIDs. Asian J. Pharm. Clin. Res.,
4: 78-81.
11. Ahmad, N.S., M. Farman, M.H. Najmi, K.B. Mian and A. Hasan,
2008. Pharmacological basis for use of
Pistacia integerrima
leaves in hyperuricemia and gout. J. Ethnopharmacol.,
117: 478-482.
12. Unno, T., A. Sugimoto and T. Kakuda, 2004. Xanthine oxidase
inhibitors from the leaves of
Lagerstroemia speciosa
(L.)
Pers. J. Ethnopharmacol., 93: 391-395.
13. Gautam, M., M. Chandel and W. Azmi, 2012. Therapeutic role
of L-DOPA produced as a secondary metabolite from
different legumes and plant sources. Ann. Phytomed.,
1: 1-8.
14. Umamaheswari, M., K. As okKu mar, A. S omas undaram,
T. Sivashanmugam, V. Subhadradevi and T.K. Ravi, 2007.
Xanthine oxidase inhibitory activity of some Indian medical
plants. J. Ethnopharmacol., 109: 547-551.
15. Kim, S.J., Y. Matsushita, K. Fukushima, D. Aoki, S. Yagami,
H.G. Yuk and S.C. Lee, 2014. Antioxidant activity of a
hydrothermal extract from watermelons. LWT-Food Sci.
Technol., 59: 361-368.
16. Olaniyan, M.F., B.O. Odejobi and S.A. Oke, 2016. Changes in
creatinine, urea, glutathione-S transferase and uric acid
levels in acetaminophen extra overdosed rabbits treated
with watermelon juice (
Citrullus lanatus
). Eur. Acad. Res.,
4: 6613-6627.
17. Balakrishnan, N., T. Varughese and S.P. Mathew, 2015. A
review on
Citrullus lanatus
Thu nb. Int. J. Pharm. Sci . Let t.,
5: 558-562.
18. Altas, S., G. Kizil, M. Kizil, A. Ketani and P.I. Haris, 2011.
Protective effect of Diyarbak2r watermelon juice on carbon
tetrachloride-induced toxicity in rats. Food Chem. Toxicol.,
49: 2433-2438.
19. Tlili, I., C. Hdider, M.S. Lenucci, R. Ilahy, H. Jebari and
G. Dalessandro, 2011. Bioactive compounds and antioxidant
activities during fruit ripening of watermelon cultivars.
J. Food Compos. Anal., 24: 923-928.
20. Arshiya, S., 2013. The antioxidant effect of certain fruits:
A review. J. Pharm. Sci. Res., 5: 265-268.
21. Abdel-Wahab, S.I., L.E. Hassan, H.M. Sirat, S.M. Yagi and
W.S. Koko
et al
., 2011. Anti-inflammatory activities of
cucurbitacin E isolated from Citrullus lanatus var.
citroides: Role of reactive nitrogen species and
cyclooxygenase enzyme inhibition. Fitoterapia,
82: 1190-1197.
22. Hong, M.Y., N. Hartig, K. Kaufman, S. Hooshmand, A. Figueroa
and M. Kern, 2015. Watermelon consumption improves
inflammation and antioxidant capacity in rats fed an
atherogenic diet. Nutr. Res., 35: 251-258.
23. Asadi-Samani, M., N. Kafash-Farkhad, N. Azimi, A. Fasihi,
E. Alinia-Ahandani and M. Rafieian-Kopaei, 2015. Medicinal
plants with hepatoprotective activity in Iranian folk medicine.
Asian Pac. J. Trop. Biomed., 5: 146-157.
473
J. Biol. Sci., 18 (8): 468-474, 2018
24. Oyenihi, O.R., B.A. Afolabi, A.B. Oyenihi, O.J. Ogunmokun and
O.O. Oguntibeju, 2016. Hepato-and neuro-protective effects
of watermelon juice on acute ethanol-induced oxidative
stress in rats. Toxicol. Rep., 3: 288-294.
25. Erhirhie, E.O. and N.E. Ekene, 2013. Medicinal values on
Citrullus lanatus
(Watermelon): Pharmacological review.
Int. J. Res. Pharm. Biomed. Sci., 4: 1305-1312.
26. Ho, L.H., M.A. Suhaimi, I. Ismail and K.A. Mustafa, 2016. Effect
of diff erent dry ing con dition s on proxim ate compos itions
of red-and yellow-fleshed watermelon rind powders.
J. Agrobiotechnol., 7: 1-12.
27. Sunarni, T., I. Fidrianny, M.I. Iwo and K.R. Wirasutisna, 2017.
Constituent and antihyperuricemic activity of
Stelechocarpus
burahol
lea ves su bfrac tions. A sian J . Phar m. Clin. Res.,
10: 435-439.
28. Yumita, A., A.G. Suganda and E.Y. Sukandar, 2013. Xanthine
oxidase inhibitory activity of some Indonesian medicinal
plants and active fraction of selected plants. Int. J. Pharm.
Pharm. Sci., 5: 293-296.
29. Qin, Z., S. Wang, Y. Lin, Y. Zhao and S. Yang
et al
., 2018.
Antihyperuricemic effect of mangiferin aglycon derivative
J99745 by inhibiting xanthine oxidase activity and urate
transporter 1 expression in mice. Acta Pharm. Sin. B,
8: 306-315.
30. Ferrari, F.C., R.D.C.L. Lima, Z.S.F. Filha, C.H. Barros,
M.C.D.P.M. Ar au jo an d D .A . S au de -G ui ma ra es , 2016. Effects
of
Pimenta pseudocaryophyllus
extracts on gout: Anti-
inflammatory activity and anti-hyperuricemic effect through
xantine oxidase and uricosuric action. J. Ethnopharmacol.,
180: 37-42.
31. Dincer, H.E., A.P. Dincer and D.J. Levinson, 2002.
Asymptomatic hyperuricemia
: To treat or not to treat.
Cleveland Clin. J. Med., 69: 594-608.
32. Murugaiyah, V. and K.L. Chan, 2009. Mechanisms of
antihyperuricemic effect of
Phyllanthus niruri
and its lignan
constituents. J. Ethnopharmacol., 124: 233-239.
33. Yu, Z., W.P. Fong and C.H.K. Cheng, 2006. The dual actions of
morin (3, 5, 7, 2, 4 -pentahydroxyflavone) as a hypouricemic
agent: Uricosuric effect and xanthine oxidase inhibitory
activity. J. Pharmacol. Exp. Ther., 316: 169-175.
34. Bell, P.G., D.C. Gaze, G.W. Davison, T.W. George, M.J. Scotter
and G. Howatson, 2014. Montmorency tart cherry (
Prunus
cerasus
L.) concentrate lowers uric acid, independent of
plasma cyanidin-3-O-glucosiderutinoside. J. Funct. Foods,
11: 82-90.
35. Kensara, O.A., 2013. Protective effect of vitamin C
supplementation on oxonate-induced hyperuricemia and
renal injury in rats. Int. J. Nutr. Metab., 5: 61-68.
36. Gao, X., G. Curhan, J.P. Forman, A. Ascherio and H.K. Choi,
2008. Vitamin C intake and serum uric acid concentration in
men. J. Rheumatol., 35: 1853-1858.
37. Sarvaiya, V.N., K.A. Sadariya, P.G. Pancha, A.M. Thaker,
A.C. Patel and A.S. Prajapati, 2015. Evaluation of
antigout activity of
Phyllanthus emblica
fruit extracts on
potassium oxonate-induced gout rat model. Vet. World,
8: 1230-1236.
38. Krishnaveni, M. and S. Mirunalini, 2010. Therapeutic potential
of
Phyllanthus emblica
(amla): The ayurvedic wonder. J. Basic
Clin. Physiol. Pharmacol., 21: 93-105.
39. Juraschek, S.P., E.R. Miller III and A.C. Gelber, 2011. Effect of
oral vitamin C supplementation on serum uric acid: A meta
analysis of randomized controlled trials. Arthritis Care Res.,
63: 1295-1306.
40. Choi, H.K., X. Gao and G. Curhan, 2009. Vitamin C intake and
the risk of gout in men: A prospective study. Arch. Internal
Med., 169: 502-507.
41. Kensarah, O.A. and F.S. Azzeh, 2012. Implementing high
vitamin C treatments to decrease blood uric acid levels in
hyperuricemic Saudi patients. J. Am. Sci., 8: 462-467.
42. Siddiqui, W.A., M. Shahzad, A. Shabbir and A. Ahmad, 2018.
Evaluation of anti-urolithiatic and diuretic activities of
watermelon (
Citrullus lanatus
) using
in vivo
and
in vitro
experiments. Biomed. Pharmacother., 97: 1212-1221.
43. Araujo, M.C.P.M., Z.S. Ferraz-Filha, F.C. Ferrari and
D.A. Saude-Guimaraes, 2016.
Campomanesia velutina
leaves extracts exert hypouricemic effects through
inhibition of xanthine oxidase and ameliorate inflammatory
response triggered by MSU crystals. Rev. Bras. Farmacogn.,
26: 720-727.
44. Lavelli, V., C. Peri and A. Rizzolo, 2000. Antioxidant activity of
tomato products as studied by model reactions using
xanthine oxidase, myeloperoxidase and copper-induced lipid
peroxidation. J. Agric. Food Chem., 48: 1442-1448.
45. Mohamed Isa, S.S.P., A. Ablat and J. Mohamad, 2018. The
antioxidant and xanthine oxidase inhibitory activity of
Plumeria rubra
flowers. Molecules, Vol. 23, No. 2.
10.3390/molecules23020400.
46. Borghi, C. and G. Desideri, 2016. Urate-lowering drugs
and prevention of cardiovascular disease: The emerging
role of xanthine oxidase inhibition. Hypertension,
67: 496-498.
47. Valentao, P., E. Fernandes, F. Carvalho, P.B. Andrade,
R.M. Seabra and M.L. Bastos, 2001. Antioxidant activity of
Centaurium erythraea
infusion evidenced by its superoxide
radical scavenging and xanthine oxidase inhibitory activity.
J. Agric. Food Chem., 49: 3476-3479.
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