Potential therapeutic action and mechanisms of action of adaptogenic plants in neurodegenerative diseases

• Grant number: 22/12675-1
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Fulvio Rieli Mendes
• Grantee: Fulvio Rieli Mendes
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: Cory Harris ; Daniel Carneiro Carrettiero ; João Henrique Ghilardi Lago ; Maria Camila Almeida
• Associated scholarship(s): 24/09127-8 - Behavioral and biochemical evaluation of the effects of Ilex paraguariensis on the embryolarval stage of zebrafish under neuroinflammation induced by lipopolysaccharide., BP.MS; 24/09209-4 - EFFECTS OF KETAMINE TREATMENT IN AN LPS-INDUCED NEUROINFLAMATION MODEL AND EVALUATION OF ANTIOXIDANT AND ANTI-INFLAMMATORY PROTECTION PATHWAYS MODULATED BY NRF2, BP.DR

Abstract

Alzheimer's (AD) and Parkinson's (PD) diseases are some of the most debilitating neurodegenerative pathologies. Sadly, the current pharmacotherapy consists of drugs with limited potential administered to restore relevant neurotransmitter systems, such as acetylcholinesterase inhibitors blocking the enzyme responsible for the metabolizing acetylcholine in AD and L-dopa and other agents that increase dopamine synthesis in PD. Oxidative stress and neuroinflammation are important contributing factors to the etiopathology of these diseases, so any substances capable of synergistically modulating both the inflammatory and the oxidative stress pathways are considered the most promising prophylactic-therapeutic agents. This project aims to initially determine the antioxidant properties, the action on the acetylcholinesterase, monoamine oxidase, and tyrosinase enzymes of the selected plant extracts popularly known to improve memory and symptoms of aging: guarana (Paullinia cupana), muira puama (Ptychopetalum olacoides), catuaba (Trichilia catigua), mate (Ilex paraguariensis), nó-de-cachorro (Heteropterys tomentosa) and Brazilian ginseng (Pfaffia glomerata). The three extracts that produce the most significant biological effects in the initial tests will be further evaluated in cytoprotection studies against stressors, i.e., oxidative stress and lipopolysaccharides (LPS). The putative cytoprotective mechanisms will be investigated for the extract with the best activity, using Western blotting, ELISA, and flow cytometry techniques. Furthermore, mice will be subjected to the standardized neuroinflammation model induced by systemic LPS administration, followed, over time, by a battery of memory test assessments. Finally, the brains of these mice will be processed to determine the degree to which the most effective plant extract increases the antioxidant markers and modulates the metabolizing enzyme activities beneficially, resulting in an overall decrease of the histologically-stained neuroinflammation markers. (AU)