Non-mitogenic fibroblast growth factor 1 protects against ischemic stroke by regulating microglia/macrophage polarization through Nrf2 and NF-κB pathways.

Microglia are immune cells in the central nervous system (CNS) that participate in response to pathological process after ischemic injury. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is an effective neuroprotective factor that is also known as a metabolic regulator. The present study aimed to investigate the effects and mechanism of the neuroprotective ability of nmFGF1 on microglia in mice after photothrombosis (PT) stroke model, to determine whether it could ameliorate ischemic injury in stroke experiment. We discovered that the intranasal administration of nmFGF1 reduced infarct size and ameliorated neurological deficits in behavioral assessment by regulating the secretion of proinflammatory and anti-inflammatory cytokines. Furthermore, in the in vitro experiments, we found that nmFGF1 regulated the expression levels of proinflammatory and anti-inflammatory cytokines in oxygen-glucose deprivation (OGD) and lipopolysaccharide (LPS) stimulation. Evidence have shown that when nuclear factor erythroid 2-related factor 2 (Nfr2) is activated, it inhibits nuclear factor-kappa B (NF-κB) activation to alleviate inflammation. Interestingly, nmFGF1 treatment in vivo remarkably inhibited NF-κB pathway activation and activated Nrf2 pathway. In addition, nmFGF1 and NF-κB inhibitor (BAY11-7082) inhibited NF-κB pathway in LPS-stimulated BV2 microglia. Moreover, in LPS-stimulated BV2 microglia, the anti-inflammatory effect produced by nmFGF1 was knocked down by Nrf2 siRNA. These results indicate that nmFGF1 promoted functional recovery in experimental stroke by modulating microglia/macrophage-mediated neuroinflammation via Nrf2 and NF-κB signaling pathways, making nmFGF1 a potential agent against ischemic stroke.

rhFGF20 promotes angiogenesis and vascular repair following traumatic brain injury by regulating Wnt/ß-catenin pathway.

The pathology of cerebrovascular disorders takes an important role in traumatic brain injury (TBI) by increasing intracranial pressure. Fibroblast growth factor 20 (FGF20) is a brain-derived neurotrophic factor, that has been shown to play an important role in the survival of dopaminergic neurons and the treatment of Parkinson's disease (PD). However, little is known about the role of FGF20 in the treatment of TBI and its underlying mechanism. The purpose of this study was to evaluate the protective effect of recombinant human FGF20 (rhFGF20) on protecting cerebral blood vessels after TBI. In this study, we indicated that rhFGF20 could reduce brain edema, Evans blue penetration and upregulated the expression of blood-brain barrier (BBB)-related tight junction (TJ) proteins, exerting a protective effect on the BBB in vivo after TBI. In the TBI repair phase, rhFGF20 promoted angiogenesis, neurological and cognitive function recovery. In tumor necrosis factor-α (TNF-α)-induced human brain microvascular endothelial cells (hCMEC/D3), an in vitro BBB disruption model, rhFGF20 reversed the impairment in cell migration and tube formation induced by TNF-α. Moreover, in both the TBI mouse model and the in vitro model, rhFGF20 increased the expression of ß-catenin and GSK3ß, which are the two key regulators in the Wnt/ß-catenin signaling pathway. In addition, the Wnt/ß-catenin inhibitor IWR-1-endo significantly reversed the effects of rhFGF20. These results indicate that rhFGF20 may prevent vascular repair and angiogenesis through the Wnt/ß-catenin pathway.

The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea.

BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human ß-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC50 from 292.0 to 673.9 µg mL- 1. Fourteen samples presented potent inhibitory activity against human BACE1 with EC50 from 236.0 to 881.1 µg mL- 1. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC50 from 2.7 to 14.4 mg mL- 1, 0.9 to 12.7 mg mL- 1, 5.0 to > 25 mg mL- 1, 2.7 to 17.7 mg mL- 1, and 2.4 to 8.7 mg mL- 1, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.