Baicalin inhibits the expression of monocyte chemoattractant protein-1 and interleukin-6 in the kidneys of apolipoprotein E-knockout mice fed a high cholesterol diet

Liu,Lihua; Liao,Pingping; Wang,Bin; Fang,Xin; Li,Wei; Guan,Siming

doi:10.3892/mmr.2015.3186

Baicalin inhibits the expression of monocyte chemoattractant protein-1 and interleukin-6 in the kidneys of apolipoprotein E-knockout mice fed a high cholesterol diet

Authors:
- Lihua Liu
- Pingping Liao
- Bin Wang
- Xin Fang
- Wei Li
- Siming Guan
View Affiliations

Affiliations: Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: January 13, 2015 https://doi.org/10.3892/mmr.2015.3186
Pages: 3976-3980

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hyperlipidemia is considered an independent risk factor for renal dysfunction and induces a significant increase in the expression of inflammatory mediators, which can be used to evaluate the degree of renal injury. Baicalin is widely used in traditional Chinese herbal medicine and has multiple pharmacological effects. The present study investigated whether baicalin can attenuate the expression of vascular cell adhesion molecule 1 (VCAM‑1) via a reduction in the expression of monocyte chemoattractant protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) in the kidney of apolipoprotein E (ApoE)‑knockout (KO) mice fed a high cholesterol diet. These mice were used as a model of atherosclerosis and were treated with baicalin (100 mg/kg/day) daily by gavage for a period of 12 weeks. By contrast, wild‑type male C57BL/6J mice were fed a standard diet. Blood samples were obtained from the angular veins of the mice to measure the total cholesterol (TC) and the expression levels of VCAM‑1, MCP‑1 and IL‑6 in the kidney tissues of the mice were analyzed using reverse transcription quantitative polymerase chain reaction and western blot analysis. Following oral administration of baicalin, no significant difference was observed in the TC in the baicalin group compared with the high cholesterol diet control group. The TC was significantly higher in the AopE‑KO mice compared with the wild‑type male C57BL/6J mice. The expression levels of VCAM‑1, MCP‑1 and IL‑6 in the kidney tissues of the baicalin group were lower compared with those in the high cholesterol diet control group. The results suggested that baicalin decreased the expression levels of pro‑inflammatory mediators and prevented kidney dysfunction in the ApoE‑KO mice fed a high cholesterol diet.

View Figures

View References

1	Moorhead JF, Chan MK, El-Nahas M and Varghese Z: Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet. 2:1309–1311. 1982. View Article : Google Scholar : PubMed/NCBI
2	uan XZ, Varghese Z and Moorhead JF: An update on the lipid nephrotoxicity hypothesis. Nat Rev Nephrol. 5:713–721. 2009. View Article : Google Scholar
3	Kim E, Tolhurst AT, Qin LY, Chen XY, Febbraio M and Cho S: CD36/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury. J Neurosci. 28:4661–4670. 2008. View Article : Google Scholar : PubMed/NCBI
4	Sultan A, Strodthoff D, Robertson AK, et al: T cell-mediated inflammation in adipose tissue does not cause insulin resistance in hyperlipidemic mice. Circ Res. 104:961–968. 2009. View Article : Google Scholar : PubMed/NCBI
5	Perez de Lema G, Maier H, Nieto E, et al: Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol. 12:1369–1382. 2001.PubMed/NCBI
6	Anders HJ, Belemezova E, Eis V, et al: Late onset of treatment with a chemokine receptor CCR1 antagonist prevents progression of lupus nephritis in MRL-Fas(lpr) mice. J Am Soc Nephrol. 15:1504–1513. 2004. View Article : Google Scholar : PubMed/NCBI
7	Rovin BH, Rumancik M, Tan L and Dickerson J: Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis. Lab Invest. 71:536–542. 1994.PubMed/NCBI
8	Zoja C, Liu XH, Donadelli R, et al: Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice. J Am Soc Nephrol. 8:720–729. 1997.PubMed/NCBI
9	Tesch GH, Schwarting A, Kinoshita K, Lan HY, Rollins BJ and Kelley VR: Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest. 103:73–80. 1999. View Article : Google Scholar : PubMed/NCBI
10	Chow F, Ozols E, Nikolic-Paterson DJ, Atkins RC and Tesch GH: Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney Int. 65:116–128. 2004. View Article : Google Scholar
11	He X, Schoeb TR, Panoskaltsis-Mortari A, et al: Deficiency of P-selectin or P-selectin glycoprotein ligand-1 leads to accelerated development of glomerulonephritis and increased expression of CC chemokine ligand 2 in lupus-prone mice. J Immunol. 177:8748–8756. 2006. View Article : Google Scholar : PubMed/NCBI
12	Tashiro K, Koyanagi I, Saitoh A, et al: Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal. 16:1–4. 2002. View Article : Google Scholar : PubMed/NCBI
13	Kanamori H, Matsubara T, Mima A, et al: Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochem Biophys Res Commun. 360:772–777. 2007. View Article : Google Scholar : PubMed/NCBI
14	Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Rollin BJ and Tesch GH: Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney Int. 69:73–80. 2006. View Article : Google Scholar
15	Garibotto G, Sofia A, Balbi M, et al: Kidney and splanchnic handling of interleukin-6 in humans. Cytokine. 37:51–54. 2007. View Article : Google Scholar : PubMed/NCBI
16	Li C, Lin G and Zuo Z: Pharmacological effects and pharmacokinetics properties of Radix scutellariae and its bioactive flavones. Biopharm Drug Dispos. 32:427–445. 2011. View Article : Google Scholar : PubMed/NCBI
17	Baylor NW, Fu T, Yan YD and Ruscetti FW: Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7-glucuronic acid, 5,6-dihydroxyflavone). J Infect Dis. 165:433–437. 1992. View Article : Google Scholar : PubMed/NCBI
18	Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW and Wang JM: Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochem Biophys Res Commun. 276:534–538. 2000. View Article : Google Scholar : PubMed/NCBI
19	Zeng Y, Song C, Ding X, Ji X, Yi L and Zhu K: Baicalin reduces the severity of experimental autoimmune encephalomyelitis. Braz J Med Biol Res. 40:1003–1010. 2007. View Article : Google Scholar : PubMed/NCBI
20	Zhang XP, Tian H, Wu DJ, et al: Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and octreotide. Hepatobiliary Pancreat Dis Int. 8:85–92. 2009.PubMed/NCBI
21	Zhang X, Tian H, Wu C, et al: Effect of baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis. Pancreas. 38:732–738. 2009. View Article : Google Scholar : PubMed/NCBI
22	Zwai M, Chen R, Li Z, et al: Deletion of angiotensin II type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice. Circulation. 112:1636–1643. 2005. View Article : Google Scholar
23	Kim DH, Kim HK, Park S, et al: Short-term feeding of baicalin inhibits age-associated NF-kappaB activation. Mech Ageing Dev. 127:719–725. 2006. View Article : Google Scholar : PubMed/NCBI
24	Zhang Y, Gao Z, Liu J and Xu Z: Protective effects of baicalin and quercetin on an iron-overloaded mouse: comparison of liver, kidney and heart tissues. Nat Prod Res. 25:1150–1160. 2011. View Article : Google Scholar : PubMed/NCBI
25	Zhang XP, Tian H, Lai YH, et al: Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis. World J Gastroenterol. 13:5079–5089. 2007.PubMed/NCBI
26	Lv SS, Liu G, Wang JP, et al: Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting macrophage infiltration. Int Immunopharmacol. 17:275–282. 2013. View Article : Google Scholar : PubMed/NCBI
27	Tesch GH, Maifert S, Schwarting A, Rollins BJ and Kelley VR: Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. J Exp Med. 190:1813–1824. 1999. View Article : Google Scholar : PubMed/NCBI
28	Fu CP, Lee IT, Sheu WH, et al: The levels of circulating and urinary monocyte chemoattractant protein-1 are associated with chronic renal injury in obese men. Clin Chim Acta. 413:1647–1651. 2012. View Article : Google Scholar : PubMed/NCBI
29	Wu T, Xie C, Wang HW, et al: Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol. 179:7166–7175. 2007. View Article : Google Scholar : PubMed/NCBI
30	Bolton CH, Downs LG, Victory JG, et al: Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant. 16:1189–1197. 2001. View Article : Google Scholar : PubMed/NCBI
31	Cottone S, Mule G, Amato F, et al: Amplified biochemical activation of endothelial function in hypertension associated with moderate to severe renal failure. J Nephrol. 15:643–648. 2002.PubMed/NCBI
32	Zhu L, Shi S, Liu L, Lv J and Zhang H: Increased plasma sVCAM-1 is associated with severity in IgA nephropathy. BMC Nephrol. 14:212013. View Article : Google Scholar : PubMed/NCBI
33	Nelson CL, Karschimkus CS, Dragicevic G, et al: Systemic and vascular inflammation is elevated in early IgA and type 1 diabetic nephropathies and relates to vascular disease risk factors and renal function. Nephrol Dial Transplant. 20:2420–2426. 2005. View Article : Google Scholar : PubMed/NCBI
34	Bruneval P, Bariety J, Belair MF, Mandet C, Heudes D and Nicoletti A: Mesangial expansion associated with glomerular endothelial cell activation and macrophage recruitment is developing in hyperlipidaemic apoE null mice. Nephrol Dial Transplant. 17:2099–2107. 2002. View Article : Google Scholar : PubMed/NCBI