Background: Rosmarinic acid is known to be a natural phenolic compound widely distributed in Labiatae herbs such as rosemary, sweet basil, and perilla. In the present study, we evaluated the suppressive effects of rosmarinic acid on mesangioproliferative glomerulonephritis in vivo, which was induced by intravenous injection of rabbit anti-rat thymocyte serum (ATS) to rats. Methods: Rosmarinic acid was orally administered to the rats at a dose of 100 mg/kg/day from the day of ATS injection (day 0) to day 8 when rats were sacrificed. The degree of mesangial cell proliferation and matrix accumulation were evaluated by trichrome staining and by immunostaining for proliferating cell nuclear antigen (PCNA), fibronectin, type IV collagen and fibrin. Superoxide dismutase (SOD)-activity in the homogenate of renal cortex was also evaluated. Results: The number of PCNA-positive cells, staining areas of trichrome, fibronectin, collagen IV and fibrin in the glomerulus were significantly decreased, and SOD-activity of renal cortex homogenate was significantly augmented in rosmarinic acid-treated group. Conclusion: Rosmarinic acid would suppress the proliferation of mesangial cells and glomerular matrix expansion in vivo by its fibrinolytic and anti-oxidative activity.

Keywords:
Mesangioproliferative glomerulonephritis, Labiatae herbs, Mesangial cell proliferation, Fibronectin, Fibrin, Rosmarinic acid
1.
Scarpati ML, Oriente G: Isolation and constitution of rosmarinic acid from Rosmarinus officinalis. Ricerca Sci 1958;28:2329–2333.
2.
Tada H, Murakami Y, Omoto T, Shimomura K, Ishimaru K: Rosmarinic acid and related phenolics in hairy root cultures of Ocimum basilicum. Phytochemistry 1996;42:431–434.
3.
Agata I, Kusakabe H, Hatano T, Nishibe S, Okuda T: Melitric acid A and B, new trimeric caffeic acid derivatives from Melissa officinalis. Chem Pharm Bull 1993;41:1608–1611.
4.
Englberger W, Hadding U, Etshenberg E, Graf E, Leyck S, Winkelmann J, Parnham MJ: Rosmarinic acid: A new inhibitor of complement C3-convertase with anti-inflammatory activity. Int J Immunopharmacol 1988;10:729–737.
5.
Peake PW, Pussell BA, Martyn P, Timmermans V, Charlesworth JA: The inhibitory effect of rosmarinic acid on complement involves the C5 convertase. Int J Immunopharmacol 1991;13:853–857.
6.
Sahu A, Rawal N, Pangburn MK: Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. Biochem Pharmacol 1999;57:1439–1446.
7.
Yamamoto H, Sakakibara J, Nagatsu A, Sekiya K: Inhibitors of arachidonate lipoxygenase from defatted perilla seed. J Agri Food Chem 1998;46:862–865.
8.
Ito H, Miyazaki T, Ono M, Sakurai H: Antiallergic activities of rabdosiin and its related compounds: Chemical and biochemical evaluations. Bioorg Med Chem 1998;6:1051–1056.
9.
Rimando AM, Inoshiri S, Otsuka H, Kohda H, Yamazaki K, Padolina WG, Torres L, Quintana EG, Cantoria MC: Screening for mast cell histamine release inhibitory activity of Philippine medicinal plants: Active constituent of Ehretia microphylla. Shoyakugaku Zasshi 1987;41:242–247.
10.
Tada M, Matsumoto R, Yamaguchi H, Chiba K, Tada M, Matsumoto R, Yamaguchi H: Novel antioxidants isolated from Perilla frutescens Britton var. crispa (Thunb.). Biosci Biotech Biochem 1996;60:1093–1095.
11.
Nakamura Y, Ohto Y, Murakami A, Ohigashi H: Superoxide scavenging activity of rosmarinic acid from Perilla frutescens Britton var. acuta f. viridis. J Agri Food Chem 1998;46:4545–4550.
12.
Makino T, Ono T, Muso E, Yoshida H, Honda G, Sasayama S: Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial cells. Nephrol Dialysis Tramsplant 2000;15:1140–1145.
13.
Ishizaki M, Masuda Y, Fukuda Y, Sugisaki Y, Yamanaka N, Masugi Y: Experimental mesangioproliferative glomerulonephritis in rats induced by intravenous administration anti-thymocyte serum. Acta Pathol Jpn 1986;36:1191–1203.
14.
Flöege J, Johnson RJ, Gordon K, Iida H, Pritzl P, Yoshimura A, Campbell C, Alpers CE, Couser WG: Increased synthesis of extracellular matrix in mesangial proliferative nephritis. Kidney Int 1991;40:477–488.
15.
Fukui H, Yazaki K, Tabata M: Two phenolic acids from Lithospermum erythrorhizon cell suspension cultures. Phytochemistry 1984;23:2398–2399.
16.
Liu N, Ono T, Suyama K, Nogaki F, Shirakawa K, Maeda M, Kawamura T, Kamata T, Oyama A, Muso E, Sasayama S: Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy. Kidney Int 2000;58:598–606.
17.
Higuchi Y, Ono K, Sekita S: Preventive effects of Shichimotsu-koka-to on renal lesions in stroke-prone spontaneously hypertensive rats. Biol Pharm Bull 1998;21:914–918.
18.
Hattori T, Shindo S, Hisada T, Fujitsuka N, Hibino T, Terazono Y, Maruno M: Effects of Onpi-to (TJ-8117) on mesangial injury induced by anti Thy-1 antibody. Jpn J Pharmacol 1995;105:63–75.
19.
Iida J, Seifert R, Alpers CE, Gronwald GK, Phillips PE, Pritzl P, Gordon K, Gown AM, Ross R, Bowen-Pope DF, Johnson RJ: PDGF and PDGF-R are induced in mesangial proliferative nephritis in the rat. Proc Natl Acad Sci USA 1991;88:6560–6564.
20.
Okuda A, Languino LR, Ruoslahti E, Border WA: Elevated expression of TGF-β and proteoglycan production in experimental glomerulonephritis. J Clin Invest 1990;86:453–462.
21.
Bagchus WM, Hoedemaeker PJ, Rozing J, Bakker WW: Acute glomerulonephritis after intravenous injection of monoclonal anti-thymocyte antibodies in the rat. Immunol Lett 1986;12:109–113.
22.
Haraguchi M, Border WA, Huang Y, Noble NA: t-PA promotes glomerular plasmin generation and matrix degradation in experimental glomerulonephritis. Kidney Int 2001;59:2146–2155.
23.
Zou ZW, Xu LN, Tian JY: Antithrombotic and antiplatelet effects of rosmarinic acid, a water-soluble component isolated from radix Salviae miltiorrhizae (danshen). Acta Pharmac Sin 1993;28:241–245.
24.
Nakamura K, Oka M, Shirai M, Igarashi Y, Kojima K, Kaneko O, Hamada N, Mera J, Masaoka H, Nagase M: Source of reactive oxygen species in anti-thy-1 nephritis. Ren Fail 1998;20:399–405.
25.
Hamada N, Nagase M: In vivo effect of OPC15161, a superoxide scavenger, on anti-thy-1 nephritis. Eur J Pharmacol 1996;317:123–128.
26.
Ito S, Sugisaki T, Soezima K: Generation of oxygen radicals and formation of fibrin thrombi in glomerular capillaries of rats with nephrotoxic nephritis. Jpn J Nephrol 1989;31:171–177.
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2002
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