Project: Development of a natural neuroprotector derived from the ST-165 bioproduct for stroke Coordinator: Prof. Dr. Walace Gomes Leal – UFOPA/NEUROPROTECT Collaborator: Center for Innovation and Preclinical Testing (CIENP)/Sapiens/Florianópolis Introduction. Stroke is an acute neural disorder that causes death or neurological sequelae, often permanent, in millions of patients in Brazil and worldwide. In Brazil, it is a major public health problem. Recent studies estimate that there was one death from stroke every 7 minutes in 2025. It is expected that 10 million deaths and a similar number of survivors with sequelae will occur by 2050. The ineffectiveness of available therapies for stroke legitimizes the search for alternative neuroprotective agents, for example, those derived from Amazonian biodiversity. Objectives. This project aims to perform efficacy, pharmacokinetic and safety tests necessary for the development of a neuroprotective herbal medicine from the oil of the bioproduct ST-165 for the treatment of stroke. Methods. Photochemical and proof-of-principle studies (establishment of the neuroprotective effect in animals) were previously performed in collaboration with the Center for Innovation and Preclinical Tests (CIENP) in Florianópolis, a laboratory accredited by ANVISA. Ischemic adult rats were treated preventively or therapeutically with 500 mg/kg (orally) of the oil extracted from the seed of the bioproduct ST-165. In the preventive group, the animals were treated for three days before experimental stroke induction (|middle cerebral artery occlusion method). In the therapeutic group, the animals were treated two hours after stroke induction. This treatment continued, once a day, for 7 days. On the eighth day, the animals were perfused and their brains were cut for immunohistochemical procedures to label neurons, astrocytes and microglia. Behavioral tests to assess functional recovery were performed. Results. Phytochemical and chromatographic studies established the chemical composition of the neuroprotectant ST-165. The treated animals showed a conspicuous reduction in the area of cerebral infarction compared to the control animals. There was a reduction in the area of infarction, neuroinflammation and intense neuronal preservation in the ischemic penumbra after treatment with the neuroprotectant ST-165 isolated by hot press. The animals also showed functional recovery, as revealed by the use of specific behavioral tests. Additional studies. In our previous studies, we established proof of principle, in a laboratory accredited by ANVISA, that ST-165 oil protects the brain of rodents after experimental stroke, with low potential for toxicity. However, in order to prepare a report for ANVISA requesting human trials, we need resources to conduct studies on the mechanisms of action of the bioproduct, genotoxicity and safety pharmacology in collaboration with CIENP. Conclusion. The oil from the bioproduct ST-165 is neuroprotective in rodents subjected to experimental stroke with a wide therapeutic window. Additional studies must be conducted, following ANVISA's standards, so that a report can be sent to this agency requesting authorization to conduct clinical trials in humans. This project could present the world with the first natural neuroprotective agent derived from a group from the Amazon. After approval in humans, the neuroprotective phytotherapeutic agent could be incorporated into the Unified Health System (SUS) and benefit millions of people.