Abstract
Astilbin is a flavonoid compound isolated from the rhizome of Smilax china L. The effects and possible mechanisms of astilbin on hyperuricemia and nephropathy
rats were elucidated in this study. Different dosages of astilbin (1.25, 2.5, and
5.0 mg/kg) were administered to 10 % fructose-induced hyperuricemic rats. The results
demonstrated that astilbin significantly decreased the serum uric acid (Sur) level
by increasing the urinary uric acid (Uur) level and fractional excretion of urate
(FEUA) but not inhibiting the xanthine oxidase (XOD) activity. In addition, kidney
function parameters such as serum creatinine (Scr) and blood urea nitrogen (BUN) were
recovered in astilbin-treated hyperuricemic rats. Further investigation indicated
that astilbin prevented the renal damage against the expression of transforming growth
factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) and also exerted a renal protective
role by inhibiting formation of monosodium urate (MSU) and production of prostaglandin
E2 (PGE2) and interleukin-1 (IL-1). These findings provide potent evidence for astilbin as
a safe and promising lead compound in the development of a disease-modifying drug
to prevent hyperuricemia and nephropathy.
Key words
astilbin - hyperuricemia - connective tissue growth factor - interleukin-1 - nephropathy
-
Smilax china
- Smilaceae
References
- 1
Wortmann R L.
Gout and hyperuricemia.
Curr Opin Rheumatol.
2002;
14
281-286
- 2
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J.
Gout-associated uric acid crystals activate the NALP3 inflammasome.
Nature.
2006;
440
237-241
- 3
Kang D H, Nakagawa T.
Uric acid and chronic renal disease: possible implication of hyperuricemia on progression
of renal disease.
Semin Nephrol.
2005;
25
43-49
- 4
Zhou X Y, Matavelli L, Frohlich E D.
Uric acid: its relationship to renal hemodynamics and the renal renin-angiotensin
system.
Curr Hypertens Rep.
2006;
8
120-124
- 5
Horiuchi H, Ota M, Nishimura S, Kaneko H, Kasahara Y, Ohta T, Komoriya K.
Allopurinol induces renal toxicity by impairing pyrimidine metabolism in mice.
Life Sci.
2000;
66
2051-2070
- 6 State Administration of Traditional Chinese Medicine of People's Republic of China
.Zhong-hua-ben-cao. Shanghai: Shanghai Science and Technology Publisher; 1999: 157-160
- 7
Chen Y, Wang Q, Li B, Li L, Pan L N, Huang Y.
Study on identification and quality for Smilax china L. of compound gout granules.
Asia-Pacific Tradit Med.
2008;
4
237-239
- 8
Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H.
Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test.
Planta Med.
2000;
66
3-6
- 9
Wang J, Zhao Y, Xu Q.
Astilbin prevents concanavalin A-induced liver injury by reducing TNF-α production and T lymphocytes adhesion.
J Pharm Pharmacol.
2004;
56
495-502
- 10
Cai Y, Chen T, Xu Q.
Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes.
Inflamm Res.
2003;
52
334-340
- 11
Li G S, Jiang W L, Yue X D, Qu G W, Tian J W, Wu J, Fu F H.
Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro.
Planta Med.
2009;
75
1470-1475
- 12
Chen T, Li J, Cao J, Xu Q, Komatsu K, Namba T.
A new flavanone isolated from Rhizoma Smilacis glabrae and the structural requirements of its derivatives for preventing immunological hepatocyte
damage.
Planta Med.
1999;
65
56-59
- 13
Perez-Ruiz F, Calabozo M, Garcia Erauskin G, Ruibal A, Herrero-Beites A M.
Renal underexcretion of uric acid is present in patients with apparent high urinary
uric acid output.
Arthritis Care Res.
2002;
47
610-613
- 14
Mo S F, Zhou F, Lv Y Z, Hu Q H, Zhang D M, Kong L D.
Hypouricemic action of selected flavonoids in mice: structure–activity relationships.
Biol Pharm Bull.
2007;
30
1551-1556
- 15
Nakagawa T, Hu H, Zharikov S, Tuttle K R, Short R A, Glushakova O, Ouyang X, Feig D I,
Block E R, Herrera-Acosta J, Patel J M, Johnson R J.
A causal role for uric acid in fructose-induced metabolic syndrome.
Am J Physiol Renal Physiol.
2006;
290
F625-F631
- 16
Hallfrisch J.
Metabolic effects of dietary fructose.
FASEB J.
1990;
4
2652-2660
- 17
Fields M, Lewis C G, Lure M D.
Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies
the signs associated with copper deficiency in rats fed fructose.
Free Radic Biol Med.
1996;
20
595-600
- 18
Shimada M, Johnson R J, May Jr. W S, Lingegowda V, Sood P, Nakagawa T, Van Q C, Dass B,
Ejaz A A.
A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome.
Nephrol Dial Transplant.
2009;
24
2960-2964
- 19
Chen C J, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock K L.
MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated
by monosodium urate crystals.
J Clin Invest.
2006;
116
2262-2271
- 20
Guan Z, Buckman S Y, Miller B W, Springer L D, Morrison A R.
Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both
c-Jun NH2-terminal kinase and p 38 MAPK signal pathways in rat renal mesangial cells.
J Biol Chem.
1998;
273
28670-28676
- 21
Narumiya S, Sugimoto Y, Ushikubi F.
Prostanoid receptors: structures, properties, and functions.
Physiol Rev.
1999;
79
1193-1226
- 22
Qi W E, Chen X M, Poronnik P, Pollock C A.
Transforming growth factor-β/connective tissue growth factor axis in the kidney.
Int J Biochem Cell Biol.
2008;
40
9-13
- 23
Gupta S, Clarkson M R, Duggan J, Brady H R.
Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial
fibrosis.
Kidney Int.
2000;
58
1389-1399
- 24
Okada H, Kikuta T, Kobayashi T, Inoue T, Kanno Y, Takigawa M, Sugaya T, Kopp J B,
Suzuki H.
Connective tissue growth factor expressed in tubular epithelium plays a pivotal role
in renal fibrogenesis.
J Am Soc Nephrol.
2005;
16
133-143
- 25
Hu Q H, Wang C, Li J M, Zhang D M, Kong L D.
Allopurinol, rutin and quercetin attenuate hyperuricemia and renal dysfunction in
rats induced by fructose intake: renal organic ion transporter involvement.
Am J Physiol Renal Physiol.
2009;
297
1080-1091
Chunfeng Zhang
Key Laboratory of Modern Chinese Medicines
China Pharmaceutical University
No. 24 Tongjia Lane
Nanjing City 210009
P. R. China
Phone: +86 25 83 27 14 26
Fax: +86 25 83 27 14 26
Email: zhangchunfeng67@163.com
Zhonglin Yang
Key Laboratory of Modern Chinese Medicines
China Pharmaceutical University
No. 24 Tongjia Lane
Nanjing City 210009
P. R. China
Phone: +86 25 83 27 14 26
Fax: +86 25 83 27 14 26
Email: zlyang1950@yahoo.cn