Exploring the select efficacy of SaiLuoTong (SLT) on cognition by quantifying plasma constituents and metabolites in people with mild cognitive impairment

Abstract

Mild cognitive impairment (MCI) is a clinical syndrome that carries a high risk of transitioning to dementia, particularly Alzheimer’s disease (AD). Currently, there are no approved treatments for MCI, and with the understanding that there are varying aetiologies, a systematic, multi-target approach is necessary to slow or delay MCI progression to dementia. Compelling evidence has revealed that SaiLuoTong (SLT), a standardised herbal medicine formulation, may alleviate MCI and dementia related symptoms. SLT comprises specific phytoconstituents, Ginkgo biloba (G. biloba), Panax ginseng (P. ginseng), and Crocus sativus (C. sativus), at optimised ratios with demonstrated effects on several mechanistic pathways implicated in the pathophysiology of AD and vascular dementia, offering a promising new direction for the development of novel treatment options for cognitively impaired individuals. The overarching aim of this thesis was to generate correlative data, highlighting the relationship between the concentrations of SLT metabolites and cognitive outcomes obtained from a randomised, double-blinded placebo-controlled 12-week pilot trial testing the efficacy of SLT on cognition in people living with MCI (N = 78). The present study was successful in developing a partially validated LCMS method for the quantification of secondary metabolites from the medicinal herb SLT. It was also able to determine the correlation between the concentrations of these compounds in the blood plasma of individuals with MCI and the cognitive measure outcomes from a 12-week placebo-controlled trial (5). In the SLT group, there was a statistically significant increase in Rb1 concentrations from baseline to midpoint, and from midpoint to endpoint for GB. At endpoint, Rb1 concentrations in the SLT group exceeded those of the placebo group. The correlations between the levels of Rb1 in plasma and the cognitive outcome measure were also significant, where all three tests (Logical Memory Immediate Recall, RCFT Copy Time and Delayed Recall) showed improvements in scores. The improved cognitive outcomes suggest that elevated Rb1 concentrations in the blood plasma of individuals with MCI may improve aspects of executive function and episodic memory retrieval. Whilst there is compelling evidence on the effects of various SLT components on cognition, there is limited evidence on the link between plasma concentrations of these components and cognition in clinical samples. The potential of this type of research is untapped, and its significance is great; allowing us to develop strong relationships between these metabolites and their effects on cognition, allowing future studies to test their synergistic effects, clinical trials can cater their parameters to overcome limitations in study design (storage, extraction, administration time, dose and frequency).

Date of Award	2023
Original language	English