Baccharin from Brazilian green propolis induces neurotrophic signaling pathways in PC12 cells: potential for axonal and synaptic regeneration

Autor(es)

do Amaral, Lilian ; Caldas, Gabriel Rocha ; Guinaim dos Santos, Neife Aparecida ; Tame Parreira, Renato Luis ; Bastos, Jairo Kennup ; dos Santos, Antonio Cardozo

• Tipo de documento: Artigo Científico
• Fonte: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 395, n. 6, p. 14-pg., 2022-03-05.

Resumo

Neurodegenerative diseases are characterized by progressive loss of the structure and function of specific neuronal populations, and have been associated with reduced neurotrophic support. Neurotrophins, like NGF (nerve growth factor), are endogenous proteins that induce neuritogenesis and modulate axonal growth, branching, and synapsis; however, their therapeutic application is limited mainly by low stability, short half-life, and inability to cross the blood-brain barrier (BBB). Small neurotrophic molecules that have suitable pharmacokinetics and are able to cross the BBB are potential candidates for neuroprotection. Baccharin is a bioactive small molecule isolated from Brazilian green propolis. In the present study, we investigated the neurotrophic and neuroprotective potential of baccharin in the PC12 cell neuronal model. We used pharmacological inhibitors (K252a, LY294002, and U0126), and ELISA (phospho-trkA, phospho-Akt, and phospho-MEK) to investigate the involvement of trkA receptor, PI3k/Akt pathway, and MAPK/Erk pathway, respectively. Additionally, we evaluated the expression of axonal (GAP-43) and synaptic (synapsin I) proteins by western blot. The results showed that baccharin induces neuritogenesis in NGF-deprived PC12 cells, through activation of trkA receptor and the downstream signaling cascades (PI3K/Akt and MAPK/ERK), which is the same neurotrophic pathway activated by NGF in PC12 cells and neurons. Baccharin also induced the expression of GAP-43 and synapsin I, which mediate axonal and synaptic plasticity, respectively. Additionally, in silico predictions of baccharin showed favorable physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness. Altogether, these findings suggest that baccharin is a promising neurotrophic agent whose therapeutic application in neurodegeneration should be further investigated. (AU)

• Processo FAPESP: 17/04138-8 - Realização de estudos químicos, analíticos, biológicos, farmacológicos e tecnológicos para preenchimento das lacunas no desenvolvimento do setor de própolis brasileiro
• Beneficiário: Jairo Kenupp Bastos
• Modalidade de apoio: Auxílio à Pesquisa - Temático