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      Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity

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          Abstract

          Coumarin (2 H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further.

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          Coumarin Metabolism, Toxicity and Carcinogenicity: Relevance for Human Risk Assessment

          B.G Lake (1999)
          The metabolism, toxicity and results of tests for carcinogenicity have been reviewed with respect to the safety for humans of coumarin present in foodstuffs and from fragrance use in cosmetic products. Coumarin is a natural product which exhibits marked species differences in both metabolism and toxicity. The majority of tests for mutagenic and genotoxic potential suggest that coumarin is not a genotoxic agent. The target organs for toxicity and carcinogenicity in the rat and mouse are primarily the liver and lung. Moreover, the dose-response relationships for coumarin-induced toxicity and carcinogenicity are non-linear, with tumour formation only being observed at high doses which are associated with hepatic and pulmonary toxicity. Other species, including the Syrian hamster, are seemingly resistant to coumarin-induced toxicity. There are marked differences in coumarin metabolism between susceptible rodent species and other species including humans. It appears that the 7-hydroxylation pathway of coumarin metabolism, the major pathway in most human subjects but only a minor pathway in the rat and mouse, is a detoxification pathway. In contrast, the major route of coumarin metabolism in the rat and mouse is by a 3,4-epoxidation pathway resulting in the formation of toxic metabolites. The maximum daily human exposure to coumarin from dietary sources for a 60-kg consumer has been estimated to be 0.02 mg/kg/day. From fragrance use in cosmetic products, coumarin exposure has been estimated to be 0.04 mg/kg/day. The total daily human exposure from dietary sources together with fragrance use in cosmetic products is thus 0.06 mg/kg/day. No adverse effects of coumarin have been reported in susceptible species in response to doses which are more than 100 times the maximum human daily intake. The mechanism of coumarin-induced tumour formation in rodents is associated with metabolism-mediated, toxicity and it is concluded that exposure to coumarin from food and/or cosmetic products poses no health risk to humans.
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            Natural and Synthetic Coumarin Derivatives with Anti-Inflammatory / Antioxidant Activities

            Konstantina Fylaktakidou, Konstantinos Litinas, Demetrios Nicolaides … (2004)
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              Biosynthesis of coumarins in plants: a major pathway still to be unravelled for cytochrome P450 enzymes

              F Bourgaud, A Hehn, R. Larbat … (2006)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date (Print): 2013
                Publication date (Electronic): 24 March 2013
                Volume: 2013
                Electronic Location Identifier: 963248
                Affiliations
                1Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa
                2Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South Africa
                Author notes

                Academic Editor: Paul W. Doetsch

                Article
                DOI: 10.1155/2013/963248
                PMC ID: 3622347
                PubMed ID: 23586066
                SO-VID: 897ba517-e474-42f8-89be-ad4ca9cb12ee
                Copyright © Copyright © 2013 K. N. Venugopala et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 October 2012
                Date accepted : 4 February 2013
                Categories
                Subject: Review Article

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