EFFECT OF BANISTERIOPSIS CAAPI EXTRACT ON THE AMYLOID AGGREGATION OF α-SINUCLEIN: IMPLICATIONS TO PARKINSON'S DISEASE

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized by tremors, imbalance, coordination difficulties, and progressive disability. Histopathologically, PD is distinguished by the presence of Lewy bodies, intracellular aggregates primarily consisting of α-synuclein (aSyn) protein. Currently, there is no cure for PD, and palliative treatments are often associated with numerous side effects and reduced efficacy, underscoring the need for new therapies, including those derived from natural products. This study aims to evaluate the anti-amyloidogenic activity of aqueous extracts from Banisteriopsis caapi (B. caapi), an Amazonian plant used in the ritualistic drink Ayahuasca. The extracts were initially analyzed chemically using High-Performance Liquid Chromatography coupled with Mass Spectrometry (LC-MS/MS), revealing harmine and harmaline as the primary alkaloids, along with other minor glycosides known as banistenosides. The effects of the aqueous extract on aSyn aggregation were then tested. The results showed that B. caapi extract, at concentrations of 0.1-1 mg/mL, significantly inhibited aSyn aggregation in a concentration-dependent manner. Transmission Electron Microscopy (TEM) demonstrated that no amyloid fibrils were present in the samples with the extract, confirming its anti-amyloid effect. The cytotoxicity of the extract was also assessed in human H4 cells using the LIVE/DEAD® kit, indicating that up to 0.5 mg/mL is a viable working range. The extract's effects were evaluated at different time points during aSyn aggregation. Adding 0.25 mg/mL of the extract after 1h, 3h, or 5h of the onset of aggregation inhibited fibril formation, suggesting that some components of the extract might interact with different species during fibril formation, blocking amyloid fibril development. In another model (H4 cells transfected with aSyn plasmid), intracellular aggregation of aSyn was also inhibited by 0.25 mg/mL of the extract without causing cytotoxic effects. These findings suggest that B. caapi extracts have therapeutic potential in inhibiting aSyn aggregation. The next step is to identify the components responsible for this effect, which could open new therapeutic approaches against PD.