Abstract
The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.
Highlights
Inflammation plays a role in the pathology of neurodegenerative diseases and is dependent on the production of various inflammatory mediators by resident macrophages, such as microglia [1,2]
To determine the effects of bakuchiol on the production of prostaglandin E2 (PGE2) and the inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) after LPS stimulation, BV-2 cells were pretreated with various concentrations of bakuchiol (0, 1.25, 2.5, or 5 μM) for 2 h and stimulated with LPS (1 μg/mL) for an additional 22 h
Bakuchiol significantly decreased the production of IL-6 in a dose-dependent manner, but LPS-stimulated TNF-α production was not affected in BV-2 cells (Figure 1E,F)
Summary
Inflammation plays a role in the pathology of neurodegenerative diseases and is dependent on the production of various inflammatory mediators by resident macrophages, such as microglia [1,2]. MAPKs, such as p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), are involved in the transcriptional regulation of inflammatory factors Overproduction of these inflammatory molecules in microglia causes neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and trauma [5,6]. We have recently reported quantitative analyses of the seven standard components of P. corylifolia, psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol, and examined whether the seven components influenced the production of nitric oxide (NO) in LPS-stimulated BV-2 microglia and had a neuroprotective effect in HT22 hippocampal cells [13]. Based on our previous study, we expanded our investigation of the inhibitory effects of bakuchiol on LPS-stimulated production and expression of inflammatory mediators and cytokines in the BV-2 microglial cell line. We determined the anti-inflammatory effect of bakuchiol in an LPS-injected neuroinflammation mouse model
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