Pikuni-Blackfeet traditional medicine: Neuroprotective activities of medicinal plants used to treat Parkinson's disease-related symptoms

Ethnopharmacological relevance: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations. Aim of the study: The aims of this study were to (i) identify medicinal plants used by the Pikuni-Blackfeet tribe to treat individuals with symptoms related to PD or other CNS disorders, and (ii) characterize a subset of the identified plants in terms of antioxidant and neuroprotective activities in cellular models of PD. Materials and methods: Interviews of healers and local people were carried out on the Blackfeet Indian reservation. Plant samples were collected, and water extracts were produced for subsequent analysis. A subset of botanical extracts was tested for the ability to induce activation of the Nrf2-mediated transcriptional response and to protect against neurotoxicity elicited by the PD-related toxins rotenone and paraquat. Results: The ethnopharmacological interviews resulted in the documentation of 26 medicinal plants used to treat various ailments and diseases, including symptoms related to PD. Seven botanical extracts (out of a total of 10 extracts tested) showed activation of Nrf2-mediated transcriptional activity in primary cortical astrocytes. Extracts prepared from Allium sativum cloves, Trifolium pratense flowers, and Amelanchier arborea berries exhibited neuroprotective activity against toxicity elicited by rotenone, whereas only the extracts prepared from Allium sativum and Amelanchier arborea alleviated PQ-induced dopaminergic cell death. Conclusions: Our findings highlight the potential clinical utility of plants used for medicinal purposes over generations by the Pikuni-Blackfeet people, and they shed light on mechanisms by which the plant extracts could slow neurodegeneration in PD.