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      Antiparasitic Properties of Cantharidin and the Blister Beetle Berberomeloe majalis (Coleoptera: Meloidae)

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          Abstract

          Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. Great Bustards, Otis tarda, eat CTD-containing Berberomeloe majalis blister beetles, and it has been hypothesized that beetle consumption by these birds reduces parasite load (a case of self-medication). We examined this hypothesis by testing diverse organisms against CTD and extracts of B. majalis hemolymph and bodies. Our results show that all three preparations (CTD and extracts of B. majalis) were toxic to a protozoan ( Trichomonas vaginalis), a nematode ( Meloidogyne javanica), two insects ( Myzus persicae and Rhopalosiphum padi) and a tick ( Hyalomma lusitanicum). This not only supports the anti-parasitic hypothesis for beetle consumption, but suggests potential new roles for CTD, under certain conditions.

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          Most cited references52

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          Medical uses of mylabris in ancient China and recent studies.

          Mylabris is the dried body of the Chinese blister beetle. The species used in medicine are Mylabris phalerata and M. cichorii. The use of mylabris as a traditional medicine in China can be traced back more than 2000 years, and it is still used as a folk medicine today. In recent studies, it has been found that mylabris possesses antitumor properties, increases the number of leucocytes, and has irritant effects on the urinary organs. The active constituent of mylabris is cantharidin. The synthesis of cantharidin is rather difficult. In order to find a less toxic analogue of cantharidin, its hydrolytic compound, disodium cantharidate, and its demethylated form, norcantharidin, were prepared. By biochemical and biological methods, it was found that these compounds may affect cancer cells in several ways. In clinical studies, antihepatoma effectiveness sequentially increased from cantharidin to disodium cantharidate to norcantharidin. Disodium cantharidate showed less urinary irritation than cantharidin while norcantharidin showed little to no such irritation. It appears that the two methyl groups of cantharidin are not the main functional groups for antitumor activity and for the stimulation of bone marrow but are associated with urinary irritation. Hydrocantharidimide, methylcantharidimide and dehydronorcantharidin have also been studied. All these compounds, except the last one, have been produced as antitumor agents in China. Since demethylated cantharidin may be prepared by total synthesis, it may be more suitable for medical investigation than cantharidin itself.
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            Cantharidin, another natural toxin that inhibits the activity of serine/threonine protein phosphatases types 1 and 2A.

            R Honkanen (1993)
            Cantharidin, a natural toxicant of blister beetles, is a strong inhibitor of protein phosphatases types 1 (PP1) and 2A (PP2A). Like okadaic acid, cantharidin inhibits the activity of the purified catalytic subunit of PP2A (IC50 = 0.16 microM) at a lower concentration than that of PP1 (IC50 = 1.7 microM) and only inhibits the activity of protein phosphatase type 2B (PP2B) at high concentrations. Dose-inhibition studies conducted with whole cell homogenates indicate that cantharidin also inhibits the native forms of these enzymes. Thus, cantharidin, which is economical and readily available, may be useful as an additional probe for studying the functions of serine/threonine protein phosphatases.
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              Cantharidin revisited: a blistering defense of an ancient medicine.

              Cantharidin, a vesicant produced by beetles in the order Coleoptera, has a long history in both folk and traditional medicine. In dermatology, topical cantharidin has long been used to treat warts and molluscum. In 1962, cantharidin lost Food and Drug Administration (FDA) approval owing to the failure of its manufacturers to submit data attesting to cantharidin's efficacy. However, it is expected that the FDA will soon include cantharidin on its "Bulk Substances List," which would permit physicians or pharmacists to compound cantharidin to be used in the office for individual patients. A comprehensive discussion of the origins, folk uses, current FDA status, current dermatologic uses, and effects of cantharidin poisoning has been compiled herein. No cases of systemic intoxication or scarring have been reported with the proper use of cantharidin by a physician. Cantharidin is a safe and valuable medication and should be readded to the dermatologic therapeutic armamentarium.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                22 April 2019
                April 2019
                : 11
                : 4
                : 234
                Affiliations
                [1 ]School of Biological Sciences, Illinois State University, Normal, IL 61790, USA; dwwhitm@ 123456ilstu.edu
                [2 ]Instituto de Ciencias Agrarias, CSIC, Serrano 115-dpdo, 28006 Madrid, Spain; mafay@ 123456ica.csic.es
                [3 ]Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Arzobispo Morcillo S/N, 28029 Madrid, Spain; rafael.martinez@ 123456uam.es
                [4 ]Facultad de Farmacia, Universidad Complutense de Madrid (UCM), CEI Campus Moncloa, 28040 Madrid, Spain; alexandraibanez@ 123456ucm.es
                [5 ]Facultad de Veterinaria, Universidad Complutense (UCM), 28040 Madrid, Spain; angeles@ 123456ucm.es
                Author notes
                [* ]Correspondence: azu@ 123456ica.csic.es ; Tel.: +34-917-452-500
                Author information
                https://orcid.org/0000-0002-8687-1100
                https://orcid.org/0000-0001-5124-664X
                Article
                toxins-11-00234
                10.3390/toxins11040234
                6521026
                31013660
                caa4e173-3602-447b-baab-8c12196444e8
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 April 2019
                : 18 April 2019
                Categories
                Article

                Molecular medicine
                cantharidin,blister beetle,berberomeloe majalis,nematicide,ixodicide,antifeedant
                Molecular medicine
                cantharidin, blister beetle, berberomeloe majalis, nematicide, ixodicide, antifeedant

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