Clinical evaluation of a novel gallotannin-enriched Galla Rhois extract (GRE) on vital cognitive functions in healthy volunteers: A randomized, double-blind, placebo-controlled study

Abstract

Background: Oxidative damage has emerged as one of the significant factors in the onset of neurodegenerative disorders, primarily owing to a) higher usage of oxygen by brain cells and b) higher amounts of lipids in the neuronal membranes. Together, these have resulted in higher susceptibility of brain cells to ROS-induced lipid peroxidation, damage to other cellular macromolecules, including nucleic acids and proteins, and death of neurons by apoptosis, ferroptosis, and necrosis. The design of therapeutics to prevent oxidative damage-induced brain stroke or other irreversible injuries has remained a challenge owing to the continuous production of free radicals at the site of damage. In this respect, plant-derived tannins and tannic acid derivatives have exhibited promising results in scavenging free radicals and inhibiting lipid peroxidation.Objective: This investigation reports the effect of Ghala Rois extract (GRE), a methyl gallate enriched gall formed on the nutgall sumac tree, Rhus javanica L. (Anacardiaceae), on enhancing the cognitive function and overall well-being through a double-blind, placebo-controlled, randomized, parallel-group design study on 80 healthy adult volunteers over a period of six consecutive weeks.Results: Administration of GRE in the dosage of 750 mg/day p.o. (with an equal amount of corn starch as a placebo) after breakfast resulted in significant improvement in cognitive functions as assessed by HappyNeuroPro, a digital therapy tool, and the cognitive tools under Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA) and Adult ADHD Self-Reported Scale (ASRSv1.1). Concomitantly, the GRE-treated subjects also scored significantly higher (p = 0.033) in the roles of Physical and Emotional Problems, Energy/Fatigue, Emotional well-being, and pain as evaluated by linearly independent pairwise comparisons among the estimated marginal means and computed using alpha = 0.05. In the Global Evaluation Questionnaire, over 77% of the treated subjects believed that the product increased their attention span, and helped their memory by 70%, and they also indicated their willingness to buy the commercially available GRE. Evaluation of the complete metabolic profile in the GRE-treated subjects significantly lowered the blood urea nitrogen (BUN) (11.98 mg/dL) as compared to placebo (13.27 mg/dL) (p = 0.011) as well as SGPT/ALT from 28.09 U/L (placebo) to 18.17 U/L (GRE-treated) (p<0.001). However, the vital parameters, including heart rate and systolic/diastolic pressure, were not affected by the consumption of GRE extract.Conclusion: The study demonstrated that GRE could be used as an effective new phytotherapeutic for reversing oxidative damage-induced neuronal degeneration and improving cognitive health in these study individuals.Keywords: Galla Rhois extract (GRE); Rhus javanica L. (family Anacardiaceae); Cognitive functions; ADHD; Executive function; Verbal memory; Safety, Reactive Oxygen Species (ROS)