Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterisation of botanical extracts: application to extracts of <scp><i>Centella asiatica</i></scp> (L.) Urban

SUMMARY Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg‐to‐gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti‐inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase‐type p‐coumaric acid 3‐hydroxylase enzyme were discovered. More recently, a new GDSL lipase‐like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant‐based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono‐, di‐, tri‐, and tetraCQAs.

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“…Furthermore, we found similar concentrations for 3,4‐, 1,5‐, and 3,5‐diCQAs (Alcazar Magana et al. , 2020).…”

Section: Occurrencesupporting

confidence: 73%

“…It should be stressed that characterization should include quantification of potential bioactives if known, as well as a chemical fingerprint of the extract determined by untargeted analysis (Alcazar Magana et al. , 2020; Kim, Kim, et al. , 2020; Nie et al.…”

Section: Chemistrymentioning

confidence: 99%

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity

et al. 2021

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“…Samples (10 mg) of CAW-iota, the standard rodent diet of our institution (PicoLab Laboratory Rodent Diet 5L0D, LabDiet, St. Louis, MO, USA), or Modified AIN-93M Purified Rodent diet (Dyets Inc, Bethlehem, PA, USA), were suspended in aqueous methanol (70% v / v with 0.1% of formic acid; 10 mL), sonicated (30 min, 25 °C), and centrifuged (14,000× g , 10 min). Supernatants were analyzed using a validated LC-HRMS/MS method [ 6 ]. Individual TT and CQA were quantified using calibration curves constructed with reference compounds.…”

Section: Methodsmentioning

confidence: 99%

Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer’s Disease Model Mice

et al. 2020

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Centella asiatica (CA) is an edible plant and a popular botanical dietary supplement. It is reputed, in Ayurveda, to mitigate age-related cognitive decline. There is a considerable body of preclinical literature supporting CA’s ability to improve learning and memory. This study evaluated the contribution of CA’s triterpenes (TT), widely considered its active compounds, and caffeoylquinic acids (CQA) to the cognitive effects of CA water extract (CAW) in 5XFAD mice, a model of Alzheimer’s disease. 5XFAD mice were fed a control diet alone, or one containing 1% CAW or compound groups (TT, CQA, or TT + CQA) equivalent to their content in 1% CAW. Wild-type (WT) littermates received the control diet. Conditioned fear response (CFR) was evaluated after 4.5 weeks. Female 5XFAD controls showed no deficit in CFR compared to WT females, nor any effects from treatment. In males, CFR of 5XFAD controls was attenuated compared to WT littermates (p = 0.005). 5XFAD males receiving CQA or TT + CQA had significantly improved CFR (p < 0.05) compared to 5XFAD male controls. CFR did not differ between 5XFAD males receiving treatment diets and WT males. These data confirm a role for CQA in CAW’s cognitive effects.

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“…CAW-R61J Fingerprinting. The bioactive centelloids and caffeoylquinic acid compounds in CAW-R61J test material were identified and quantified using the area under the curve of the precursor ion (MS1 quantification) using LC-HRMS at Oregon State University (Corvallis, OR) by comparison against co-chromatographed commercial reference standards as previously described (Alcazar-Magana et al, 2020). In addition toMS1-quantification of known compounds, untargeted LC-HRMS analysis of all the materials was performed.…”

Section: Methodsmentioning

confidence: 99%

Centella asiatica Water Extract Shows Low Potential for Cytochrome P450–Mediated Drug Interactions

Wright

Magaña

Laethem³

et al. 2020

Drug Metab Dispos

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Centella asiatica (CA) shows considerable promise for development as a botanical drug for cognitive decline. Its primary bioactive components include triterpene glycosides asiaticoside and madecassoside and their corresponding aglycones asiatic acid and madecassic acid. Exploration of the bioactivity of CA's caffeoylquinic acids is ongoing. In this study, an aqueous extract of CA (CAW-R61J) was evaluated for drug interaction potential through inhibition or induction of P450 enzymes, as required by the US Food and Drug Administration. CAW-R61J was assessed for induction potential of CYP1A2, CYP2B6, and CYP3A4 using transporter-certified cryopreserved human hepatocytes in sandwich culture. Gene expression of these target P450s was quantified, and enzyme activities were determined to confirm gene expression results. No induction was observed up to 16.7 mg/ml CAW-R61J (equivalent to 1.1 mM asiaticoside, 0.8 mM madecassoside, 0.09 mM asiatic acid, and 0.12 mM madecassic acid). Reversible and time-dependent inhibitory effects of CAW-R61J on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 were evaluated using human liver microsomes. CAW-R61J showed weak reversible inhibition of most of the P450 forms tested, with the strongest being CYP2C9 (IC 50 of 330 mg/ml). CAW-R61J (£1000 mg/ml) was not a time-dependent inhibitor of any of these P450 enzymes. In summary, CAW-R61J had no, or only a weak impact, on P450 induction and inhibition in vitro. The clinical relevance of these results will depend on the in vivo concentration of CAW-R61J components achieved in humans. Plasma triterpene concentrations measured in our recent clinical studies suggest minimal risk of P450-mediated drug interactions by these components. SIGNIFICANCE STATEMENT A preparation of Centella asiatica is currently under clinical development for the prevention or treatment of cognitive decline. The US Food and Drug Administration required an evaluation of its potential for drug interactions mediated through drug-metabolizing enzymes. This in vitro study revealed minimal induction or inhibition of a range of P450 enzymes, including CYP3A4, by the C. asiatica extract, suggesting a low potential for drug interactions modulated by P450 metabolism.

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Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterisation of botanical extracts: application to extracts of Centella asiatica (L.) Urban

Cited by 31 publications

References 68 publications

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity

Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer’s Disease Model Mice

Centella asiatica Water Extract Shows Low Potential for Cytochrome P450–Mediated Drug Interactions

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