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

Abstract

Context 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.

Consumption of Roasted Coffee Leads to Conjugated Metabolites of Atractyligenin in Human Plasma

“…Atractyligenin glycosides are water-soluble and abundant in Arabica coffee, which is a substantial part of coffee blends in many cases. While atractyligenin glycosides have been reported in several toxic plants and weeds, 11 they are absent in foods other than coffee. This coffee specificity and their appearance in plasma and urine after coffee suggest that atractyligenin metabolites might be exploited as potential dietary biomarkers for coffee consumption.…”

“…Atractyligenin glycosides are water-soluble and abundant in Arabica coffee, which is a substantial part of coffee blends in many cases. While atractyligenin glycosides have been reported in several toxic plants and weeds, they are absent in foods other than coffee. This coffee specificity and their appearance in plasma and urine after coffee suggest that atractyligenin metabolites might be exploited as potential dietary biomarkers for coffee consumption. − Therefore, the present investigation aimed to evaluate concentration–time profiles of atractyligenin derivatives from coffee and their metabolites in plasma after consumption of roasted coffee brew for the first time.…”

“…While their biological function for the coffee plant is unknown, their abundance is exceptionally high in Arabica coffee. It is around 0.8–1.4 mg/g ( 2 ) and 0.4–0.9 mg/g ( 3 ), respectively, while the aglycone itself ( 1 ) occurs only in traces. − While glycosides of 1 have been reported in various plants, e.g., Atractylis gummifera L. or Xanthium strumarium L., coffee is the only known food containing them in substantial amounts. This is supported by data from untargeted liquid chromatography–mass spectrometric (LC-MS) metabolomics studies with urine from coffee and noncoffee drinkers .…”