Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H+ leak

Autor: Andrzej M. Woyda-Ploszczyca
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceutical Biology, Vol 61, Iss 1, Pp 372-390 (2023)
Druh dokumentu: article
ISSN: 13880209
1744-5116
1388-0209
DOI: 10.1080/13880209.2023.2168704
Popis: AbstractContext The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins.Objective This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs.Methods Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and 'Xanthium'.Results In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous.Conclusions Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium-derived extracts and purified toxins, is needed.
Databáze: Directory of Open Access Journals
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