Abstract
Hyperuricemia is associated with a number of pathological conditions, such as gout. Lowering of elevated uric acid levels in the blood could be achieved by xanthine oxidase inhibitors and inhibitors of renal urate reabsorption. Some natural compounds isolated from herbs used in traditional Chinese medicine have been previously demonstrated to act as xanthine oxidase inhibitors. In the present investigation, Paederia scandens (Lour.) Merrill (Rubiaceae) extract (PSE; 4.5, 2.25, and 1.125 g/kg) orally for 14 days was demonstrated to possess in vivo potent hypouricemic activity in hyperuricemic rats pretreated with potassium oxonate. In addition, PSE was also demonstrated to be an inhibitor of xanthine oxidase. Lineweaver-Burk analysis of the enzyme kinetics indicated that the inhibition of PSE was of a mixed type. Using an oxonate-induced hyperuricemic rat model, PSE was indeed shown to exhibit uricosuric action in vivo, which could explain, at least in part, the observed hypouricemic effect of PSE in these rats. The potential application of this compound in the treatment of conditions associated with hyperuricemia is discussed.
Abbreviations
AP: allopurinol
BEN: benzbromarone
CMC-NA: carboxymethylcellulose sodium salt
PO: potassium oxonate
PSE: P. scandens extract
XO: xanthine oxidase
Key words
Paederia scandens extract - Rubiaceae - hyperuricemia - serum uric acid - xanthine oxidase - uricosuric effect - potassium oxonate
References
-
1
Klemp P, Stansfield S A, Castle B, Robertson M C.
Gout is on the increase in New Zealand.
Ann Rheum Dis.
1997;
56
22-6
-
2
Arromdee E, Michet C J, Crowson C S, O’Fallon W M, Gabried S E.
Epidemiology of gout: is the incidence rising?.
J Rheumatol.
2002;
29
403-6
-
3
Liote F.
Hyperuricemia and gout.
Curr Rheumatol Rep.
2003;
5
27-34
-
4
Zeng Q, Wang Q, Chen R, Xiao Z, Huang S, Xu J.
Primary gout in Shantou: a clinical and epidemiological study.
Chin Med J (Engl).
2003;
116
6-9
-
5
Li Y, Stamler J, Xiao Z, Folsom A, Tao S, Zhang H.
Serum uric acid and its correlates in Chinese adult populations, urban and rural, of Beijing: The PRC-USA collaborative study in cardiovascular and cardiopulmonary epidemiology.
Int J Epidemiol.
1997;
26
88-96
-
6
Johnson R J, Kang D H, Feig D, Kivlighn S, Kanellis J, Watanabe S. et al .
Is there a pathogenic role for uric acid in hypertension and cardiovascular and renal disease?.
Hypertension.
2003;
41
183-90
-
7
Tseng C H.
Independent association of uric acid levels with peripheral arterial disease in Taiwanese patients with type 2 diabetes.
Diabet Med.
2005;
21
24-9
-
8
Marangella M.
Uric acid elimination in the urine: pathophysiological implications.
Contrib Nephrol.
2005;
147
32-48
-
9
Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha S H. et al .
Molecular identification of a renal urate anion exchanger that regulates blood urate levels.
Nature.
2002;
417
447-52
-
10
Bomalaski J S, Clark M A.
Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase.
Curr Rheumatol Rep.
2004;
6
240-7
-
11
Schlesinger N.
Management of acute and chronic gouty arthritis: present state-of-the-art.
Drugs.
2004;
64
399-416
-
12
Liu J, Liang J Y, Xie T.
Development of iridoids in recent years.
Strait Pharm J.
2004;
16
14-8
-
13
Hiroyuki I, Shuji I, Shimokawa N, Okigawa M.
Studies on monoterpene gluclucosides of Paederia scandens.
Chem Pharm Bull.
1969;
17
942-8
-
14
Xu Z, Peng S, Xin L, Bing R B, Ding L.
Sulfur-containing iridoid glucosides from Paederia scandens.
.
Fitoterapia.
2006;
77
374-7
-
15
Stavric B, Clayman S, Gadd R EA, Hebert D.
Some in vivo effects in the rat induced by chlorprothixene and potassium oxonate.
Pharmacol Res Commun.
1975;
7
117-24
-
16
Hall I H, Scoville J P, Reynolds D J, Simlot R, Bosisio E.
LC-UV-electrospray-MS-MS mass spectrometry analysis of plant constituents inhibiting xanthine oxidase.
Pharm Res.
1998;
15
936-43
-
17
Kong L D, Zhou J, Wen Y L, Li J M, Cheng C HK.
Aesculin possesses potent hypouricemic action in rodents but is devoid of xanthine oxidase/dehydrogenase inhibitory activity.
Planta Med.
2002;
68
175-8
-
18
Lowry O H, Rosebrough N J, Farr A L, Randall R J.
Protein measurement with folin phenol reagent.
J Biol Chem.
1951;
193
265-75
-
19
Kong L D, Cai Y, Huang W W, Cheng C HK, Tan R X.
Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout.
J Ethnopharmacol.
2000;
73
199-207
-
20
Kramer H M, Curhan G.
The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey, 1988 – 1994.
Am J Kidney Dis.
2002;
40
37-42
-
21
Chen S Y, Chen C L, Shen M L, Kamatani N.
Clinical features of familial gout and effects of probable genetic association between gout and its related disorders.
Metabolism.
2001;
50
1203-7
-
22
Yale S H, Yale E S, Mann D S.
Fever, rash and angioedema after a course of allopurinol.
Hosp Pract.
1996;
31
92-4
-
23
Bieber J D, Terkeltaub R A.
Gout: on the brink of novel therapeutic options for an ancient disease.
Arthritis Rheum.
2004;
50
2400-14
-
24
Terkeltaub R A.
Clinical practice: gout.
N Engl J Med.
2003;
249
1647-55
-
25
25 Yan H Y, Ma Y, Liu M, Zhou L L.
The effect of Paederia scandens extracts on mouse hyperuricemia induced by yeast.
Pharmacol Clin CMM.
2007;
23
115-8
-
26
Hayden M R, Suresh C T.
Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle.
Nutr Metab (London).
2004;
1
10-25
-
27
Cohen A, Aberdoth R, Hochstein P.
Inhibition of free radical-mediated DNA damage by uric acid.
FEBS Lett.
1984;
174
147-50
-
28
Stinefelt B, Leonard S S, Blemings K P, Shi X L, Klandorf H.
Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid.
Ann Clin Lab Sci.
2005;
35
37-45
Lanlan Zhou
Department of Pharmacology
Anhui Medical University
Hefei
Anhui 230032
People’s Republic of China
Phone: +86-551-356-8135
Fax: +86-551-516-1133
Email: lanlzhou@yahoo.com.cn