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From source to bedside: Translational studies of centella asiatica for Alzheimer's disease
Author(s) -
Wright Kirsten M.,
Magana Armando Alcazar,
Bollen Melissa,
Caruso Maya,
Gray Nora E.,
Matthews Donald G,
David Jason C.,
Mepham Brigitte,
Stevens Jan F.,
Maier Claudia S.,
Quinn Joseph F.,
Soumyanath Amala
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041268
Subject(s) - centella , bioavailability , pharmacology , traditional medicine , pharmacokinetics , phytochemical , antioxidant , placebo , medicine , cognitive decline , nutraceutical , chemistry , disease , dementia , biochemistry , pathology , alternative medicine
Background Centella asiatica (CA) is a botanical from Eastern medicine reputed to enhance cognition. Preclinical studies on CA and its bioactive components (triterpenoids and caffeoylquinic acids) strongly support its potential as a phytotherapeutic agent for aging, cognitive decline, and Alzheimer’s disease (AD) through influences on antioxidant response, mitochondrial activity, tau phosphorylation, and synaptic density. Translation from preclinical models to humans, and developing an optimized, reproducible product for use in aging and AD clinical trials, present particular challenges for phytotherapeutic agents compared to single chemical entities. Method To perform translational studies, a comprehensive scientific approach was developed including: identifying an optimal dose range for clinical evaluation, analysis and characterization of phytochemical variability, assessment for contamination and adulteration of raw material, formulation and manufacture of a stable botanical intervention and matching placebo, and application to a human pharmacokinetic trial (NCT03929250). Two doses of a custom made CA water extract product (2g and 4g) were administered orally to eight healthy elders (n=4 female, n=4 male) on two separate days. Plasma was collected over 12 hours to determine bioavailability and analyzed using reversed phase liquid chromatography‐tandem mass spectrometry. Result The maximum plasma concentration (C max ) of the bioactive triterpenoids (1‐1.6µM) occurred at two hours (T max ) after oral administration. Conclusion A robust scientific approach is necessary to address the complexity and variability of raw botanicals and botanical extracts for AD. Triterpenoids from CA water extract are orally bioavailable in humans.