Pharmacokinetics and metabolomics investigation of an orally modified formula of standardized Centella asiatica extract in healthy volunteers
Open Access
- 25 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-13
- https://doi.org/10.1038/s41598-021-86267-2
Abstract
The formula of a standardized extract of Centella asiatica (ECa 233) was modified to improve its dissolution, with implications for pharmacokinetics and metabolomic profile. This study aimed to understand the resultant changes in disposition kinetics of ECa 233 and alterations to human metabolome after oral administration. This study was a two-sequence of dosages (250 and 500 mg), with an open-label phase I clinical trial. The modified formula was administered in single and multiple doses to twelve healthy Thai volunteers. The major parent compounds, madecassoside and asiaticoside, were rarely absorbed, instead undergoing biotransformation into active metabolites, madecassic acid and asiatic acid with possibility to be eliminated via fecal route. Increasing the dose of ECa 233 resulted in significantly greater plasma levels of those active metabolites, with accumulation of asiatic acid after multiple oral administration for seven days. Examining the impacts of accumulation behavior on metabolomics, the study traced changes in levels pre- and post-dose of five relevant human metabolites. Administration of ECa 233 was found to be significantly associated with an increase of choline, an endogenous metabolite with documented benefits for learning and memory. Therefore, ECa 233 may be useful in mitigating cognitive impairment, through its role in modulating human metabolites.Funding Information
- The 100th Anniversary Chulalongkorn University Fund
- The 90th Anniversary Chulalongkorn University Fund
This publication has 16 references indexed in Scilit:
- Pharmacokinetics of a Standardized Extract of Centella asiatica ECa 233 in RatsPlanta Medica, 2016
- Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host–Microbial InteractionsJournal of Proteome Research, 2016
- Metabolomics of Neurodegenerative DiseasesInternational review of neurobiology, 2015
- In vivo disposition and metabolism of madecassoside, a major bioactive constituent in Centella asiatica (L.) Urb.Journal of Ethnopharmacology, 2013
- 1H NMR metabolomics investigation of an Alzheimer’s disease (AD) mouse model pinpoints important biochemical disturbances in brain and plasmaMetabolomics, 2013
- Centella asiaticaExtract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of ActionInternational Journal of Alzheimer's Disease, 2012
- Sample size estimation in clinical trial.2010
- Pharmacological review on Centella asiatica: A potential herbal cure-allIndian Journal of Pharmaceutical Sciences, 2010
- Screening of Indian medicinal plants for acetylcholinesterase inhibitory activityPhytotherapy Research, 2007
- Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acidJournal of Ethnopharmacology, 1990