An improved LC‐MS/MS method for simultaneous determination of 1,5‐dicaffeoylquinic acid and its active metabolites in human plasma and its application to a pharmacokinetic study in patients

Liu, Jianglin; Dou, Guifang; Dong, Xiaona; Yuan, Dan; Ji, Xiwei; Wu, Zhuona; Zhang, Meng

doi:10.1002/bmc.1388

Cited by 7 publications

(4 citation statements)

References 6 publications

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“…In humans administered coffee, intact mono- and di-CQAs were reported to be found in high levels in plasma [ 82 , 83 ]. Following oral administration of purified 1,5-diCQA, both intact 1,5-diCQA and its methylated metabolite, 1,5-diferuloylquinic acid, were detected in human plasma [ 84 ]. However, when artichoke extracts are administered, which also contain mono- and di-CQAs, intact CQAs were not seen in the plasma [ 85 ], and the same was observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial

et al. 2022

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Centella asiatica is reputed in Eastern medicine to improve cognitive function in humans. Preclinical studies have demonstrated that aqueous extracts of C. asiatica improve cognition in mouse models of aging and Alzheimer’s disease (AD) through the modulation of mitochondrial biogenesis and nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response genes. This randomized, double-blind, crossover Phase I trial explored the oral bioavailability and pharmacokinetics of key compounds from two doses (2 g and 4 g) of a standardized C. asiatica aqueous extract product (CAP), over 10 h, in four mildly demented older adults on cholinesterase inhibitor therapy. The analysis focused on triterpenes (TTs) and caffeoylquinic acids (CQAs), which are known to contribute to C. asiatica’s neurological activity. The acute safety of CAP and the effects on NRF2 gene expression in peripheral blood mononuclear cells were evaluated. Single administration of 2 g or 4 g of CAP was safe and well-tolerated. The TT aglycones, asiatic acid and madecassic acid, were identified in plasma and urine, while the parent glycosides, asiaticoside and madecassoside, although abundant in CAP, were absent in plasma and had limited renal excretion. Similarly, mono- and di-CQAs showed delayed absorption and limited presence in plasma or urine, while the putative metabolites of these compounds showed detectable plasma pharmacokinetic profiles and urinary excretion. CAP elicited a temporal change in NRF2 gene expression, mirroring the TT aglycone’s pharmacokinetic curve in a paradoxical dose-dependent manner. The oral bioavailability of active compounds or their metabolites, NRF2 target engagement, and the acute safety and tolerability of CAP support the validity of using CAP in future clinical studies.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial

et al. 2022

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“…In humans, high plasma levels of intact mono and diCQAs were reported following coffee consumption (Farah et al 2008; Monteiro et al 2007) (Farah et al 2008). Both 1,5-diCQA and its methylated metabolite, 1,5-diferuloylqunic acid, were measured in human plasma following oral administration of 1,5-diCQA (Liu et al 2010). DiCQAs were also found in rat plasma after oral administration of Ainsliaea fragrans extract containing 1,5-, 3,4-, 3,5- and 4,5 diCQA (Su et al 2014).…”

Section: Absorption Distribution Metabolism and Elimination (Adme) mentioning

confidence: 99%

Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement

et al. 2017

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This review describes in detail the phytochemistry and neurological effects of the medicinal herb Centella asiatica (L.) Urban. C. asiatica is a small perennial plant that grows in moist, tropical and sub-tropical regions throughout the world. Phytochemicals identified from C. asiatica to date include isoprenoids (sesquiterpenes, plant sterols, pentacyclic triterpenoids and saponins) and phenylpropanoid derivatives (eugenol derivatives, caffeoylquinic acids, and flavonoids). Contemporary methods for fingerprinting and characterization of compounds in C. asiatica extracts include liquid chromatography and/or ion mobility spectrometry in conjunction with high-resolution mass spectrometry. Multiple studies in rodent models, and a limited number of human studies support C. asiatica’s traditional reputation as a cognitive enhancer, as well as its anxiolytic and anticonvulsant effects. Neuroprotective effects of C.asiatica are seen in several in vitro models, for example against beta amyloid toxicity, and appear to be associated with increased mitochondrial activity, improved antioxidant status, and/or inhibition of the pro-inflammatory enzyme, phospholipase A2. Neurotropic effects of C. asiatica include increased dendritic arborization and synaptogenesis, and may be due to modulations of signal transduction pathways such as ERK1/2 and Akt. Many of these neurotropic and neuroprotective properties of C.asiatica have been associated with the triterpene compounds asiatic acid, asiaticoside and madecassoside. More recently, caffeoylquinic acids are emerging as a second important group of active compounds in C. asiatica, with the potential of enhancing the Nrf2-antioxidant response pathway. The absorption, distribution, metabolism and excretion of the triterpenes, caffeoylquinic acids and flavonoids found in C. asiatica have been studied in humans and animal models, and the compounds or their metabolites found in the brain. This review highlights the remarkable potential for C. asiatica extracts and derivatives to be used in the treatment of neurological conditions, and considers the further research needed to actualize this possibility.

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“…Nevertheless, some unchanged mono-acyl quinic acids ( i.e. , 5-caffeoylquinic acid, 3-caffeoylquinic acid, 5-feruloylquinic acid, and 4-feruloylquinic acid) and 1,5-dicaffeoylquinic acid presented T max values <3 h (Feliciano et al, 2017 ; Liu et al, 2010 ; Mena et al, 2021 ), suggesting absorption in the small intestine.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids

Pede

Mena

Bresciani

et al. 2024

Antioxidants & Redox Signaling

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Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports. Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C 6 -C 3 cinnamic acids. C 6 -C 3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [C max ] = 423 n M ), with time to reach C max (T max ) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%). Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent. Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma C max concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations. Antioxid. Redox Signal. 40, 510–541.

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An improved LC‐MS/MS method for simultaneous determination of 1,5‐dicaffeoylquinic acid and its active metabolites in human plasma and its application to a pharmacokinetic study in patients

Cited by 7 publications

References 6 publications

Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial

Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial

Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids

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