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      Suppressive Effects of Rosmarinic Acid on Mesangioproliferative Glomerulonephritis in Rats

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          Abstract

          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.

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          Most cited references 10

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          Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b.

          Rosmarinic acid has been reported to inhibit complement activation in vivo as well as in vitro. Previous studies suggested that the inhibitory effect was due to inhibition of C3/C5 convertases, but inhibition of C3b attachment would yield the same results. Recent work in our laboratory demonstrated that compounds with polyhydroxylated phenyl rings are highly reactive with the thioester bond in nascent C3b. These compounds block complement activation by preventing attachment of C3b to the activating surface. Because rosmarinic acid contains two 3,4-dihydroxyphenyl groups, the current study was undertaken to re-examine the mechanism of inhibition by analyzing the effect of rosmarinic acid on C3b attachment. In assays using purified complement proteins, rosmarinic acid inhibited covalent attachment of C3b to cells with an 1C50 = 34 microM. Inhibition of C5 convertase activity required 1500 microM rosmarinic acid, and no significant inhibition of the C3 convertase enzyme, which produces C3b from C3, was observed at 10,000 microM. In hemolytic assays using human serum, rosmarinic acid was shown to inhibit activation of both the classical (IC50 = 180 microM) and the alternative (IC50 = 160 microM) pathways of complement. Rosmarinic acid concentrations up to 10,000 microM did not cause direct inactivation of C3. Radioiodination of rosmarinic acid was used to demonstrate covalent activation-dependent incorporation of rosmarinic acid specifically into the thioester-containing alpha'-chain of nascent C3b. These findings indicate that inhibition of complement activation by rosmarinic acid is due to the reaction of rosmarinic acid with the activated thioester of metastable C3b, resulting in covalent attachment of the inhibitor to the protein.
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            Superoxide Scavenging Activity of Rosmarinic Acid fromPerilla frutescensBritton Var.acutaf.viridis

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              Rosmarinic acid: A new inhibitor of complement C3-convertase with anti-inflammatory activity

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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                October 2002
                18 October 2002
                : 92
                : 4
                : 898-904
                Affiliations
                aDepartment of Pharmacognosy, Graduate School of Pharmaceutical Sciences, and bDivision of Nephrology, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto; cDivision of Nephrology, Tazuke-Kofukai, Medical Research Institute Kitano Hospital, Osaka, Japan
                Article
                65457 Nephron 2002;92:898–904
                10.1159/000065457
                12399637
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 8, References: 26, Pages: 7
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/65457
                Categories
                Original Paper

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