Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

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BackgroundDouchi (fermented Glycine max Merr.) is produced from fermented soybeans, which is widely used in traditional herbal medicine. In this study, we investigated whether Douchi attenuates protein kinase C (PKC) and interleukin (IL)-4 response and cutaneous inflammation in Atopic dermatitis (AD)-like NC/Nga mice.MethodsTo induce AD-like skin lesions, D. farinae antigen was applied to the dorsal skin of 3-week-old NC/Nga mice. After inducing AD, Douchi extract was administered 20 mg/kg daily for 3 weeks to the Douchi-treated mice group. We identified the changes of skin barrier and Th2 differentiation through PKC and IL-4 by immunohistochemistry.ResultsDouchi treatment of NC/Nga mice significantly reduced clinical scores (p < 0.01) and histological features. The levels of PKC and IL-4 were significantly reduced in the Douchi-treated group (p < 0.01). The reduction of IL-4 and PKC led to decrease of inflammatory factors such as substance P, inducible nitric oxide synthase (iNOS) and Matrix metallopeptidase 9 (MMP-9) (all p < 0.01). Douchi also down-regulated Th1 markers (IL-12, TNF-α) as well as Th2 markers (IL-4, p-IκB) (p < 0.01).ConclusionDouchi alleviates AD-like skin lesions through suppressing of PKC and IL-4. These results also lead to diminish levels of substance P, iNOS and MMP-9 in skin lesions. Therefore, Douchi may have potential applications for the prevention and treatment of AD.

BACKGROUND/OBJECTIVESOne of the mechanisms considered to be prevalent in the development of Alzheimer's disease (AD) is hyper-stimulation of microglia. Black chokeberry (Aronia melanocapa L.) is widely used to treat diabetes and atherosclerosis, and is known to exert anti-oxidant and anti-inflammatory effects; however, its neuroprotective effects have not been elucidated thus far.MATERIALS/METHODSWe undertook to assess the anti-inflammatory effect of the ethanolic extract of black chokeberry friut (BCE) in BV2 cells, and evaluate its neuroprotective effect in the lipopolysaccharide (LPS)-induced mouse model of AD.RESULTSFollowing stimulation of BV2 cells by LPS, exposure to BCE significantly reduced the generation of nitric oxide as well as mRNA levels of numerous inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). In addition, AD was induced in a mouse model by intraperitoneal injection of LPS (250 µg/kg), subsequent to which we investigated the neuroprotective effects of BCE (50 mg/kg) on brain damage. We observed that BCE significantly reduced tissue damage in the hippocampus by downregulating iNOS, COX-2, and TNF-α levels. We further identified the quinic acids in BCE using liquid chromatography-mass spectrometry (LCMS). Furthermore, we confirmed the neuroprotective effect of BCE and quinic acid on amyloid beta-induced cell death in rat hippocampal primary neurons.CONCLUSIONSOur findings suggest that black chokeberry has protective effects against the development of AD.