Ilex paraguariensis extract provides increased resistance against oxidative stress and protection against Amyloid beta-induced toxicity compared to caffeine in Caenorhabditis elegans

ABSTRACT

Ilex paraguariensis is a plant from South America, used to prepare a tea-like beverage rich in caffeine and polyphenols with antioxidant proprieties. Caffeine consumption is associated with a lower risk of age-associated neuropathologies, besides several extracts that have antioxidant proprieties are known to be neuroprotective, and oxidative stress strongly correlates with Aβ-toxicity. This study aims to investigate the neuroprotective effects of the Ilex paraguariensis hydroalcoholic extract (IPHE) and to evaluate if caffeine agent present in IPHE exerts neuroprotective effects in an amyloid beta-peptide (Aβ)-induced toxicity in Caenorhabditis elegans. The wild-type and CL2006 worms were treated with IPHE (2 and 4 mg/mL) or caffeine (200 and 400 μM) since larval stage 1 (L1) until they achieved the required age for each assay. IPHE and caffeine increased the lifespan and appeared to act directly by reactive oxygen species (ROS) scavenger in both wild-type and CL2006 worms, also conferred resistance against oxidative stress in wild-type animals. Furthermore, both treatments delayed Aβ-induced paralysis and decreased AChE activity in CL2006. The protective effect of IPHE against Aβ-induced paralysis was found to be dependent on heat shock factor hsf-1 and FOXO-family transcription factor daf-16, which are respectively involved in aging-related processes and chaperone synthesis, while that of caffeine was dependent only on daf-16. Mechanistically, IPHE and caffeine decreased the levels of Aβ mRNA in the CL2006 worms; however, only IPHE induced expression of the heat shock chaperonin hsp-16.2, involved in protein homeostasis. The results were overall better when treated with IPHE than with caffeine.

GRAPHICAL ABSTRACT

KEYWORDS:

• Neurodegenerative diseases
• Alzheimer’s disease
• proteostasis
• reactive oxygen species
• amyloid beta
• natural extract
• Aβ-toxicity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are thankful to Programa de Apoio a Núcleos Emergentes (PRONEM/FAPERGS) [16/2551-0000248-7] for providing financial assistance. R.P.O. received CNPq fellowship. F.A.A.S. received PROEX/CAPES [23038.005848/2018-31] and CNPq fellowship. L.P.A received PNPD/CAPES fellowship. M.L.M.; T.L.S.; D.C.Z.; F.B.O.B.; and L.M.C received fellowships from CAPES, respectively numbers: 88882.182147/2018-01; 88882.182186/2018-01; 88882.182122/2018-01; 88887.210042/2018-00; and 88882.182175/2018-01. A.F. received fellowship from PIBIC/UFSM/CNPq. The authors are also thankful to the Caenorhabditis Genetics Stock Center for providing all strains, CGC is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

Notes on contributors

Marina Lopes Machado

Marina Lopes Machado is a Master and PhD Student in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Leticia Priscilla Arantes

Leticia Priscilla Arantes is a Master and PhD in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Tássia Limana da Silveira

Tássia Limana da Silveira is a Master and PhD Student in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Daniele Coradini Zamberlan

Daniele Coradini Zamberlan is a Master and PhD in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Larissa Marafiga Cordeiro

Larissa Marafiga Cordeiro is a Master and PhD Student in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Fabiane Baptista Bicca Obetine

Fabiane Baptista Bicca Obetine is a Master Student in Biological Sciences at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Aline Franzen da Silva

Aline Franzen da Silva is a Pharmacy student at Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.

Ivana Beatrice Mânica da Cruz

Ivana Beatrice Ma^nica da Cruz is a Master and PhD in Genetics and Molecular Biology at the Federal University of Rio Grande do Sul. Associate professor at Federal University of Santa Maria.

Felix Alexandre Antunes Soares

Felix Alexandre Antunes Soares is a Master and PhD in Biological Sciences at Federal University of Rio Grande do Sul. Adjunct professor at the Federal University of Santa Maria.

Riva de Paula Oliveira

Riva de Paula Oliveira is a PhD in Biochemistry and Immunology, Federal University of Minas Gerais. Adjunvt Professor at Federal University of Rio Grande do Norte.