Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts from Scutellaria baicalensis and Acacia catechu

Abstract

Dementia and cognitive impairment have become the major concerns worldwide due to a significantly aging population, increasing life span and lack of effective pharmacotherapy. In light of limited pharmaceutical drug choices and the socioeconomic implications of these conditions, the search for safe and effective alternatives from natural sources has gained many attractions within the medical food and dietary supplement industry. Two polyphenol extracts derived from roots of Scutellaria baicalensis and heartwoods of Acacia catechu containing free-B-ring flavonoids and flavans, respectively, were combined into a proprietary blend called UP326. A similar bioflavonoid composition, UP446, has been reported with modulation of pathways related to systemic inflammation. To test the effect of UP326 on memory and learning, a radial arm water maze (RAWM) and contextual fear conditioning (CF) were utilized in aged F344 rats fed with UP326 at doses of 3, 7, and 34 mg/kg for 11 weeks. The 7 and 34 mg/kg dosage groups had significantly fewer errors than aged vehicle control animals and their performance was equivalent to young animal controls. In a separate human clinical trial, test subjects orally given 300 mg of UP326 BID for 30 days showed marked improvement in speed and accuracy of processing complex information in computer tasks and reduced their standard deviation of performance compared to baseline and the placebo group. This data suggest that UP326 may help maintain memory, sustain speed of processing, and reduce the number or memory errors as we age.

Figure 1

HPLC chromatogram and chemical structure of free-B-ring flavonoid (baicalin) and flavan (catechin). The flavonoids were detected using a UV detector at 275 nm and identified based on retention time by comparison with known flavonoid standards.

Figure 2

Radial arm water maze (RAWM) study. After initial training in the RAWM but before administration of UP326, aged rats were able to perform as well as their young cohorts (Figure 2(a)). But after a 3 hr delay was inserted between trials 3 and 4, the aged rats lost all training advantages (Figure 2(b)). After taking UP326 for 2 months, all dose groups showed significant improvement attenuation of age-related memory impairments (Figure 2(c)). 12 rats per group were used for each study.

Figure 3

Effects of UP326 on behavior and memory were also tested using contextual fear conditioning (normal freezing behavior to an electrical shock). Contextual fear testing showed an improvement in normal freezing behavior in aged rats given UP326 approaching that of the young control rats. There was no effect of age or UP326 treatment to freezing to either the auditory cue or novel context. ∗ = p < 0.0001 versus young controls; ^† p < 0.0005 versus aged controls. 12 rats per group were used for each study.

Figure 4

Working memory speed RT median showed improvement from baseline to week 4. Relative to group A placebo, a significant improvement in working memory processing efficiency seen for groups B (UP326) in weeks 2 and 3 of treatment (^∗ p < 0.05).

Figure 5

Working memory speed and reaction time standard deviation showed improvement from baseline to week 4. Relative to group A (placebo), a significant improvement in working memory processing efficiency seen for groups B (UP326) in week 3 of treatment (^∗ p < 0.05).