Secondary Topic: Research Methodology
Tertiary Topic: Basic Science
A MULTIDISCIPLINARY APPROACH TO THE DEVELOPMENT OF A RATIONAL PHYTOTHERAPEUTIC FROM CENTELLA ASIATICA
Kirsten Wright, ND, MS; Nora Gray, PhD; Maya Caruso, BS; Donald G Matthews, PhD; Charles Murchison, MS, , Portland, OR, United States; Armando Alcazar Magana, PhD, Oregon State University, Corvallis, OR, United States; Jonathan Zweig, BS; Jennifer Zhu, BA; Christopher Harris, BS, , Portland, OR, United States; Parnian Lak, PhD, Oregon State University, Corvallis, OR, United States; Doris Kretzschmar, PhD; Margeux Hunter, BA, , Portland, OR, United States; Jan F Stevens, PhD; Claudia S Maier, PhD, Oregon State University, Corvallis, OR, United States; Joseph Quinn, MD, Oregon Health and Science University and Portland VA Medical Center , Portland, OR, United States; Amala Soumyanath, PhD, , Portland, OR, United States
Late Breaker: No
Alzheimer’s Disease (AD) is a debilitating form of dementia with a high global burden and need for effective treatments. Centella asiatica (CA) is a botanical from Eastern medicine reputed to enhance cognition. Previous studies on CA and its bioactive components in preclinical models strongly support its potential as a phytotherapeutic for cognitive decline and AD. The development of effective and reproducible phytotherapeutics warrants a plethora of specialized skills due to the complexity and variability of botanical extracts. We will present our approach to the development of a rational phytotherapeutic from CA for future examination in clinical trials of AD.
Our team is comprised of a multidisciplinary group of pharmacognosists, chemists, neuroscientists, clinicians and statisticians to perform preclinical and translational work on CA. This work encompasses phytochemical analysis and profiling, fingerprinting of extracts, bioassay-guided fractionation, in vitro and in vivo testing of mechanism(s) of action including metabolomics analysis, and development of methods to analyze CA-derived compounds in biological matrices. Translational studies include the development of a standardized formulation for human consumption and bioavailability assessments.
Aqueous CA extracts improve cognitive function in mouse and Drosophila models of aging and AD. This may be due to influences on the antioxidant response, mitochondrial activity, tau phosphorylation and synaptic density. Sensitive liquid chromatography coupled to mass spectrometry (LC-MS) methods have been developed to fingerprint CA extracts and measure biologically active compounds (triterpenes and caffeoylquinic acids) in biological matrices. These bioactives have been found to be bioavailable in rodents allowing for the use of interspecies scaling in determining doses for future translational studies in humans.
A multidisciplinary approach is essential to the development of rational phytotherapeutics. Our methodology is an example of a robust scientific approach to developing a phytotherapeutic for examination in AD.