Auraptene Acts as an Anti-Inflammatory Agent in the Mouse Brain

Abstract

Abstract:The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and neuronal cell death in the hippocampus, possibly through its anti-inflammatory effects in the brain. We suggested that these effects were at least partly mediated by the suppression of inflammatory mediators derived from astrocytes. The present study showed that (1) AUR, as a pretreatment for five days before and another three days after ischemic surgery, suppressed microglial activation, cyclooxygenase (COX)-2 expression in astrocytes, and COX-2 mRNA expression in the hippocampus; (2) AUR suppressed the lipopolysaccharide-induced expression of COX-2 mRNA and the mRNA of pro-inflammatory cytokines in cultured astrocytes; (3) AUR was still detectable in the brain 60 min after its intraperitoneal administration. These results support our previous suggestion that AUR directly exerts anti-inflammatory effects on the brain.

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

“…It has been reported that three flavonoids (naringin, neoponcirin and poncirin) and three coumarins (umbelliferone, imperatorin and auraptene) isolated from the 70% ethanolic extract of Ponciri fructus have various pharmacological actions including antioxidant [27], anxiolytic-like [28], anticancer [29], and anti-inflammatory effects [30][31][32]. Therefore, we propose that PFE can have antiproliferative and antioxidant effects based on the various pharmacological activities of the chemical-chemical interactions on the development and progression of lesions in a TP-induced model of BPH.…”

Auraptene and Other Prenyloxyphenylpropanoids Suppress Microglial Activation and Dopaminergic Neuronal Cell Death in a Lipopolysaccharide-Induced Model of Parkinson’s Disease

“…Neuroinflammation, in particular microglial activation, has recently been attracting a great deal of attention as the key player in PD because activated microglia have been observed to enclose the lost dopaminergic neurons in the brains of PD patients and PD animal models [12,13]. When taken together with our findings that AUR suppressed the activation of microglia in ischemic brains [9,10] and inflammatory brains [11], we were prompted to investigate the effects of AUR on the brains of LPS-induced PD model mice. In the present study, we observed that AUR suppressed microglial activation and subsequent dopaminergic neuronal cell death in the SN of the brains of LPS-induced PD model mice, as expected.…”

“…Nevertheless, Okuyama et al recently reported the ability of AUR to penetrate the brain [10]. The permeability of 7-IP and GOFA through the blood-brain-barrier (BBB) will be examined in future studies.…”

“…Immunoreactivity was developed and visualized by DAB substrate (SK-4100; Vector Laboratories, Burlingame, CA, USA). Regarding the quantification of IBA1-positive signals, ImageJ software (NIH, Bethesda, MD, USA) was used as previously described [10], and TH and GAD67-positive signals were manually counted.…”

“…Epifano and co-workers showed that AUR exerted in vitro neuroprotective effects against N -methyl- d -aspartate (NMDA)-induced excitotoxicity in a mixed cortical cell culture [7] and in vivo neuroprotective activity in a maximal electroshock-induced seizure mouse model [8]. Furthermore, Okuyama and co-workers recently reported that AUR exerts anti-inflammatory effects not only in peripheral tissues, but also in the brain because it suppressed inflammatory responses in the ischemic brain [9,10] and ameliorated lipopolysaccharide (LPS)-induced inflammation in the mouse brain [11]. In the present study, we focused on the suppressive effects of AUR on the activation of microglia in the brain because recent studies reported that the pathogenesis of Parkinson’s disease (PD) is closely associated with inflammation [12], mainly activated microglia [13].…”