Guarana Extract Protects Against Neuronal Death in Huntington’s Animal Model, Study Reports

Extract from a South American fruit called guarana was found to reduce neuronal death and accumulation of protein aggregates in a roundworm model of Huntington’s disease, a study reports.

The study, “Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways,” was published in Oxidative Medicine and Cellular Longevity.

Due to its antioxidant and stimulant properties, guarana is a key ingredient in several sports and energy drinks. Research on guarana’s biological roles have also demonstrated the fruit’s ability to regulate the immune system, as well as its weight loss, anti-mutation, and anti-cancer effects.

Guarana’s stimulant effect is associated with a high caffeine content, a psychoactive agent known for its benefits related to human lifespan and aging-associated neuropathologies.

Preclinical studies on the effects of guarana extract or its powdered seeds on neurodegenerative diseases have shown it can provide protection against the effects of Parkinson’s disease; prevent protein aggregation and reduce brain cell death in Alzheimer’s disease; and reduce the accumulation of proteins aggregates in a roundworm model of Huntington’s disease.

Despite previous evidence of guarana’s protective effects in these diseases, little is known about the biological mechanisms underlying the plant’s “shield function.”

In this study, Brazilian researchers investigated the protective effects of guarana hydroalcoholic extract (GHE) in roundworm (known as Caenorhabditis elegans) models of Huntington’s and Alzheimer’s disease.

GHE is a solid extract obtained from guarana seeds by extracting their soluble properties with alcohol and water, followed by evaporation of the solution.

Huntington’s roundworms were given 10 mg/mL or 50 mg/mL of GHE with their regular food, i.e., bacteria called Escherichia Coli. Effects of a six-day GHE treatment in 70 Huntington’s worms were assessed.

In healthy control worms, GHE treatment significantly increased the animals’ lifespan — by one day with a lower concentration, and by two days with a higher concentration — along with tolerance to heat stress.

GHE treatment significantly improved the survival rate of brain cells in Huntington’s worms treated with GHE at both concentrations.

The presence of toxic and insoluble protein aggregates is a common feature of more than 20 neurodegenerative conditions. In Huntington’s disease, characterized by glutamine (CAG) repetitions on the huntingtin (Htn) protein gene, the cleavage of Htn results in the formation of small protein aggregates, called polyQ oligomers.

To determine whether GHE’s effect on neurons was related to a reduction of protein accumulation within cells, the researchers counted the number of protein aggregates in the muscle tissue of 20 adult Huntington’s worms treated with 10 mg/mL or 50 mg/mL of GHE  for three days.

GHE treatment at both concentrations caused a significant reduction in protein aggregates in muscle tissue. Specifically, Huntington’s worms treated with 10 mg/mL had approximately 70 protein aggregates while those treated with 50 mg/mL had about 65, compared with 79 observed in the control group.

GHE treatment also increased the expression of genes associated with stress resistance and longevity. These genes are activated by two transcription factors, a type of molecular “switch,” called DAF-16 and SKN-1.

“… the protection provided by GHE … is partially dependent on DAF-16 and SKN-1. Since both transcription factors are key regulators of many important biological processes, including lifespan, stress responses, and proteostasis, we reasoned that GHE treatment might protect worms against polyQ … toxicity by increasing antioxidant capacity and proteostasis,” the authors wrote.

“This study demonstrated the GHE-induced protection of C. elegans in AD and HD models, by the activation of antioxidant and protein degradation pathways,” they added. “Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.”