Bioavailability and Biological Effects of 2-O-β-d-Glucopyranosyl-carboxyatractyligenin from Green Coffee in Caenorhabditis elegans

Abstract

Targeted analysis of Coffea arabica and Coffea canephora green coffees (total sample size n = 57) confirmed 2-O-β-d-glucopyranosyl-carboxyatractyligenin (6) as the quantitatively dominating carboxyatractyligenin derivative. Its abundance in Arabicas (2425 ± 549 nmol/g, n = 48) exceeded that in Robustas (34 ± 12 nmol/g, n = 9) roughly by a factor of 70. Coffee processing involving heat (e.g., steam treatment and decaffeination) reduced concentrations of 6 and increased those of the decarboxylated derivative. The bioavailability of compound 6 in Caenorhabditis elegans was demonstrated by ultraperformance liquid chromatography-tandem mass spectrometry analysis of extracts prepared from nematode cultures incubated in a liquid medium containing 6. A toxicity assay performed to assess the impact of 6 in vivo showed a 20-fold higher median lethal dose (LD50 = 11.7 ± 1.2 mM) concentration compared to that of the known phytotoxic adenine-nucleotide transporters inhibitor carboxyatractyloside (2, LD50 = 0.61 ± 0.05 mM), whereas 1 mM 6 and 0.1 mM 2 were sufficient to decrease the survival of wild type C. elegans, already 10–20-fold lower doses reduced reproduction. Because the insulin/insulin-like growth factors signaling cascade (IIS) is a key regulator of life span and stress resistance, the impact of compound 6 on the survival of long-living daf-2 C. elegans was tested. As the susceptibility of these nematodes to 6 was as high as that in wild type, an impact on central metabolic processes independent of IIS was suggested. Analysis of the in vivo adenosine triphosphate (ATP) content of adult C. elegans revealed no changes after 1 and 24 h, but a 50% reduction after treatment with 1 mM 6 during the entire postembryonic development. These data speak for a developmental-stage-dependent modulation of the ATP pool by 6.

Identification of Phytochemical Compounds in Coffea arabica Whole Coffee Cherries and Their Extracts by LC-MS/MS

“…2- O- β - d -Glucopyranosyl-carboxyatractyligenin was previously identified as the major carboxyatractyligenin derivative in green coffee . On the other hand, the carboxy-derivative could not be detected in roasted coffee samples but instead contained atractyligenin at levels ranging from 225 to 279 nmol/g .…”

“…On the other hand, the carboxy-derivative could not be detected in roasted coffee samples but instead contained atractyligenin at levels ranging from 225 to 279 nmol/g . This showed that 2- O- β - d -glucopyranosyl-carboxyatractyligenin was initially present in the raw coffee, but was subsequently degraded during the roasting process, resulting in decarboxylation to generate atractyligenin, 2- O- β - d -glucopyranosylatractyligenin, and 3′- O-β- d -glucopyranosyl-2′- O- isovaleryl-2β-(2-desoxy-atractyligenin)-β- d -glucopyranoside. , …”

“…7 Coffee also contains atractyligenin and carboxyatractyligenin derivatives. 8,9 Byproducts of these are toxic sulfoglucosides that inhibit the adenine nucleotide translocase (ANT) in mitochondria, thereby obstructing the oxidative phosphorylation process. 8 Similar to the sulfo-glucosides, Lang et al 8 noticed that 2-O-β-D-glucopyranosyl-carboxyatractyligenin isolated from raw coffee also inhibited phosphorylation through ANT blockage.…”

“…8 This showed that 2-O-β-D-glucopyranosyl-carboxyatractyligenin was initially present in the raw coffee, but was subsequently degraded during the roasting process, resulting in decarboxylation to generate atractyligenin, 2-O-β-D-glucopyranosylatractyligenin, and 3′-O-β-D-glucopyranosyl-2′-O-isovaleryl-2β-(2-desoxy-atractyligenin)-β-D-glucopyranoside. 8,9 Global research has greatly improved our understanding of the physiological benefits of coffee and its diverse products. Yet, the number of phytonutrients reported in previous studies for coffee do not encompass all classes and types of chemicals and their metabolites.…”

Alternative model organisms for toxicological fingerprinting of relevant parameters in food and nutrition

“…An overview is given in Table 1. The main assays used to study C. elegans comprise brood-size (number of eggs producedtotal progeny), growth and reproduction, life-span and oxidative stress (Liao 2018;Piechulek and Mikecz 2018;Moyson et al 2019;Spanier et al 2019;Wang et al 2020). Compared to rats and rabbits, in a large-scale evaluation of the developmental toxicity of chemicals in the ToxCast TM library, C. elegans was found to be very accurate for predicting developmental toxicity.…”