RESUMO
Propolis, a compound produced by honeybees, has long been used in food and beverages to improve health and prevent diseases. We previously reported that the ethanol extracts of Brazilian green propolis and its constituents artepillin C, kaempferide, and kaempferol mitigate oxidative stress-induced cell death via oxytosis/ferroptosis. Here, we investigated the potential of Brazilian green propolis and its constituents to protect against endoplasmic reticulum stress in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis, artepillin C, and kaempferol attenuated tunicamycin-induced unfolded protein response and cell death. Interestingly, artepillin C inhibited both tunicamycin-induced protein aggregation in HT22 cells and the spontaneous protein aggregation of mutant canine superoxide dismutase 1 (E40K-SOD1-EGFP) in Neuro2a cells. These findings indicate that in addition to oxidative stress, the ethanol extracts of Brazilian green propolis help prevent endoplasmic reticulum stress-related neuronal cell death, which is proposedly involved in several neurodegenerative diseases. Moreover, artepillin C, a major constituent of Brazilian green propolis, may exhibit chemical chaperone-like properties.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fenilpropionatos/farmacologia , Própole/química , Própole/farmacologia , Substâncias Protetoras/farmacologia , Agregados Proteicos/efeitos dos fármacos , Animais , Brasil , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/farmacologia , Ácidos Cumáricos/farmacologia , Etanol/química , Fator de Iniciação 2 em Eucariotos/metabolismo , Flavonoides/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Quempferóis/farmacologia , Proteínas de Membrana/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Tricotecenos/farmacologia , Tunicamicina/toxicidade , eIF-2 Quinase/metabolismoRESUMO
Propolis is a sticky dark-colored substance produced by honey bees and comprises resin, balsam, wax, essential and aromatic oils, pollen, and several other substances; it is used in food and beverages to improve health and prevent diseases. We studied the neuroprotective effects of extracts of Brazilian green propolis in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis had a more potent preventive effect on oxidative stress-induced cell death, oxytosis/ferroptosis, in HT22â¯cells than water extracts of Brazilian green propolis, whereas it did not protect against anticancer drug-induced apoptotic cell death. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. The flavonoid derivatives kaempferide and kaempferol are antioxidants with radical-scavenging abilities that additionally induce antioxidant response element-mediated transcriptional activity, suggesting that upregulation of endogenous antioxidant defense protects against oxidative stress. In contrast, artepillin C attenuated reactive oxygen species production; however, it did not induce antioxidant response element activation. These findings indicate that the ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases.