Abstract
Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed β-amyloid-induced paralysis in a caffeine-independent manner. Moreover, GHE's protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.
Highlights
Guarana is the popular name of Paullinia cupana var. sorbilis (Mart.) from which the seeds are widely used
In the Alzheimer’s disease (AD) model, guarana hydroalcoholic extract (GHE) delayed amyloid-β peptide (Aβ)-induced paralysis in a caffeine-independent manner. These results suggest that GHE alleviates polyQ protein aggregation and Aβ-induced toxicity by activating protein degradation and antioxidant defenses, partially through SKN-1 and DAF-16
These results suggest that the protection provided by GHE against Aβ1–42 toxicity is partially dependent on DAF-16 and SKN-1
Summary
Guarana is the popular name of Paullinia cupana var. sorbilis (Mart.) from which the seeds are widely used. The stimulant effect of guarana is associated with high caffeine content, a psychoactive pseudoalkaloid well known for its benefits to human lifespan and aging-associated neuropathologies [4]. Guarana contains other methylxanthines, including theophylline and theobromine, as well as polyphenols, such as catechins and epicatechins [5, 6]. This phytochemical composition has been associated with guarana’s biological activities, which include antioxidant [7,8,9], antimicrobial [6], and chemoprophylactic activities in carcinogenesis [10, 11] and antigenotoxic effects [12]. Guarana extract prepared by extraction with DMSO showed a protective effect in human dopaminergic
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