Perilla frutescens Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation.

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether Perilla frutescens leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.

Rubus fruticosus leaf extract inhibits vascular dementia-induced memory impairment and neuronal loss by attenuating neuroinflammation.

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

Radioembolization With Yttrium-90 Resin Microspheres in Hepatocellular Carcinoma: A Multicenter Prospective Study.

OBJECTIVES: The aim of this prospective study was to reveal the efficacy and safety of Yttrium-90 (Y) radioembolization in Korean patients with hepatocellular carcinoma (HCC). METHODS: A total of 40 HCC patients were prospectively recruited from 7 centers. The response to treatment was assessed on the basis of the modified Response Evaluation Criteria in Solid Tumors criteria. The time to progression and overall survival were also evaluated, and the assessment of safety was done according to National Cancer Institute Common Terminology Criteria, Version 3.0. RESULTS: Forty-two treatments of Y radioembolization were carried out. Median follow-up was 29 months. At 3 months, the complete response, partial response (PR), and stable disease were seen in 4 (10.0%), 19 (47.5%), and 15 (37.5%) patients, respectively. The response rate was 57.5% (23/40), and disease control rate was 95% (38/40) at 3 months. The response rate at 6 months was 63.9% (23/36), and disease control rate was 83.3% (30/36). The median time to progression was 18 months. During follow-up, 10 HCC-related deaths occurred and the 3-year survival rate was 75%. In 19 patients with Barcelona Clinic Liver Cancer-B stage, the 3-year survival rate was 50%. The tumor number (>5) was the only significant predictor associated with survival. The most common adverse event was abdominal pain of mild to moderate degree, and all the complications were manageable. Twenty-six (65%) patients underwent other treatments such as transarterial chemoembolization because of local progression or remnant viable lesion. CONCLUSIONS: Y radioembolization might be a safe and effective treatment modality in intermediate-stage to advanced-stage HCC.