Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-β1

Abstract

Neuroprotective impact of transforming growth factor β1 (TGF-β1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-β1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-β1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.

7-Isopentenyloxycoumarin: What Is New across the Last Decade

“…This oxyprenylated coumarin, applied at a concentration of 100 μM in every experiment, was able to decrease (80.9%) the LPS-promoted hyperactivation of microglia in the central nervous system, while exhibited only a weak effect on the so called “reactive gliosis”, namely the activation of astrocytes by LPS. Furthermore, 7-isopentenyloxycoumarin showed a marked preventive effect against neuronal death of dopaminergic cells induced by the inflammatory process evoked by the administration of LPS (2.3-fold decrease in respect to controls), confirming what was observed in vitro and in vivo in 2008 and 2009 by Epifano and coworkers [ 12 , 30 , 31 ]. In 2010, Karimi and coworkers investigated the extent of inhibition of 7-isopentenyloxycoumarin on acetylcholinesterase [ 32 ].…”

“…It suggested that the beneficial effects of propolis for human health can be also ascribed to less abundant phytochemicals, like those just mentioned, that could biologically act in synergy with major products typically found in great quantities in propolis like flavonoids and phenolic acids. For example, the reported neuroprotective properties of propolis [ 12 ] could be also ascribed to the presence of 7-isopentenyloxycoumarin, known to exert such effects both in vitro and in vivo [ 13 , 14 ]. The paper by Taddeo and coworkers can also be considered as a great stimulus to continue the search of such secondary metabolites in other bee-derived preparations such ashoney, pollen, royal jelly, and bee wax.…”

The Role of Mitochondria in Brain Cell Protection from Ischaemia by Differently Prepared Propolis Extracts

“…Shimazawa and co-authors investigated the effect of aqueous and ethanolic extracts of Brazilian green propolis in vitro (PC12 cells, 0.4–40 µg/mL) and an aqueous extract in vivo (mice, 30 or 100 mg/kg) and found that propolis significantly inhibited ischaemia-induced neurotoxicity [ 21 ]. Abdel-Rahman and colleagues revealed that in ischaemia/reperfusion-treated groups, propolis (applied at 50 and 100 mg/kg) significantly reduced neurodegeneration and histological alterations in the brain tissues [ 22 ]. Bazmandegan and co-authors investigated the effect of water-extracted brown propolis (100 and 200 mg/kg) against cerebral ischaemia-induced oxidative injury in a mouse model of stroke and demonstrated that treatment resulted in significant restoration of antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activity and a subsequent decrease in the infarct volume compared to the control group.…”

“…Moreover, propolis components protected the cultured neuronal cells RGC 5 and PC12 from oxygen and glucose deprivation-induced damage via modulation of apoptosis and antioxidant activity-related genes [ 21 ]. Furthermore, the neuroprotective effect of propolis was demonstrated in a rat focal cerebral ischaemia model made by middle cerebral artery occlusion; the activity was likely to be mediated through antioxidant effect and upregulation of TGF-b1 [ 22 ]. Despite these promising findings, the mechanism of propolis upon ischaemia-induced brain injuries has not been thoroughly investigated.…”

Punicalin Alleviates OGD/R-Triggered Cell Injury via TGF-β-Mediated Oxidative Stress and Cell Cycle in Neuroblastoma Cells SH-SY5Y

“…Recent shreds of evidence showed that TGF- β could serve as an injury-related cytokine involving brain injury and neurodegenerative diseases. It is reported by Abdel et al that propolis could relieve cerebral injury via the regulation of the TGF- β /Smad pathway [ 8 ]. Another study showed that the TGF- β /Smad pathway involved in the cerebral IRI after isoflurane exposure [ 9 ].…”