Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation ofthe adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulationof immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. Wepreviously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibitingmonocyte chemoattractant protein-1 (MCP-1) expression in the progression phase to high-fat diet (HFD)-induced obesity.In the current study, we evaluated the effects of naringenin on neutrophil infiltration into adipose tissue, because neutrophilsalso infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adiposetissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-inducedexpression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expressionin 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did notaffect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration andactivation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppressesneutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.九州保健福祉大学201

Characterization of anti-herpes simplex virus type 1 activity of an alkaloid FK 3000 from Stephania cepharantha

A morphinane alkaloid FK 3000 (6,7-di-O-acetylsinococuline) from the root tubers of Stephania cepharantha showed antiviral activity against acyclovir (ACV)- and phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1), influenza virus, measles virus, and poliovirus. The anti-HSV action of FK 3000 was assessed in comparison with that of PAA that inhibits the activity of HSV DNA polymerase and HSV DNA synthesis. FK 3000 inhibited the growth of thymidine kinase-deficient and ACV and PAA-resistant HSV-1 strains, as well as wild type HSV strains in Vero cells. This compound, as well as PAA, interfered with the synthesis of late viral proteins but not early viral proteins. The analysis of HSV DNA synthesis by slot blot hybridization showed that FK 3000 inhibited the viral DNA synthesis in a dose-dependent manner. However, the viral RNA was partially synthesized in the presence of FK 3000 (even at a dose that HSV DNA synthesis was inhibited) and PAA, indicating that FK 3000, as well as PAA, allowed early viral RNA synthesis but not viral DNA synthesis. Since partially purified HSV DNA polymerase activity was not inhibited by FK 3000, this compound was suggested to inhibit HSV DNA synthesis by a mechanism different from that of PAA. Stephania cepharantha(タマザキツヅラフジ)から得たモルフィン骨格を有するアルカロイドFK3000はacyclovirやphosphonoacetic acid(PAA)抵抗性を有するHSV-1, influenza virs, measles virus, poho virsに対しても抗ウイルス作用を有していた。この抗HSV作用をHSV DNA polymeraseを阻害することによりHSV DNA合成を阻害することが知られているPAAとの比較から検討した。HSVに感染したVero細胞においてFK3000は,PAAと同様に後期ウイルス蛋白の合成を阻害したが初期ウイルス蛋白には影響しなかった。Slot blot hybridization法でHSV DNA合成を調べると,FK3000は濃度依存的にウイルスDNA合成を阻害することが判明した。しかし,ウイルスRNA合成はHSV DNA合成が阻害される濃度でもFK3000およびPAAによって部分的にのみ阻害された。このことはPAAと同様にFK3000はウイルスDNA合成は阻害するが初期ウイルスRNAの合成は許容することを示している。FK3000は粗精製したHSV-DNA polymerase活性を阻害しないことから,PAAと異なった機構でHSV DNA合成を阻害していることが示唆された

Inhibitory activities of Thai medicinal plants against herpes simplex type 1, poliovirus type 1, and measles virus

Forty-eight ethanol- and 43 water-extracts of 49 traditional Thai medicines were evaluated for antiviral activities by a plaque reduction assay. For preliminary characterization of the mode of their antiviral action, poliovirus type 1, measles virus and herpes simplex virus type 1 (HSV-1) that are different in nucleic acid component and enveloped structure were used in this study. Fifty-two, 28 and 29 extracts exhibited inhibitory activities against poliovirus, measles virus and HSV-1, respectively. Of 29 extracts with anti-HSV-1 activities, the inhibitory activities of Rhinacanthus nasutus (leaf), Terminalia citrina (fruit) and Thevetia peruviana (leaf) were observed in both ethanol and water extracts. The ethanol extracts of Derris scandens (leaf) and Plumbago indica (leaf) and the water extract of Capsicum frutescens (fruit) were active against only HSV-1, suggesting the mechanism of their antiviral action likely unique to HSV-1 but neither poliovirus nor measles virus. Contrarily, 26 extracts displayed inhibitory activities against poliovirus and/or measles virus. These findings suggest that the 29 extracts from traditional Thai medicines are potential candidates for anti-HSV agents. 49種のタイ伝統薬物から作製した48のエタノールエキス,43の水エキスに対する抗ウイルス活性をプラーク減少法で検索した。本研究では,核酸やエンベロープ構造の異なるポリオウイルス1型,麻疹ウイルス,単純ヘルペスウイルス1型に対して検討を行なった。その結果ポリオウイルス1型に対しては52種,麻疹ウイルスには28種,単純ヘルペスウイルス1型には29種のエキスが阻害活性を示した。単純ヘルペス1型に有効であった29種の中では,Rhinacanthus nasutus(葉),Terminalia citrina(果実),Thevetia peruviana(葉)はエタノール,水の両エキスで阻害作用を示した。Derris scandens(葉),Plumbago indica(葉)およびCapsicum frutescens(果実)のエタノールエキスは単純ヘルペスウイルス1型にのみ活性があった。このことはポリオウイルスや麻疹ウイルスには無効で,単純ヘルペス1型のみに特異的に有効であることを示唆している。一方,26種のエキスはポリオウイルスあるいは麻疹ウイルス,また両方に有効であった。これらの結果はタイ伝統薬物からの29のエキスが抗ヘルペス剤として有力な候補となることを示している

Hyperthermia enhances photodynamic therapy by regulation of HCP1 and ABCG2 expressions via high level ROS generation

Photodynamic therapy (PDT) is a cancer treatment that make use of the cancer-specific accumulation of porphyrins. We have reported that mitochondrial reactive oxygen species (mitROS) upregulate uptake transporter of porphyrins, heme carrier protein-1 (HCP-1). The accumulation of cancer-specific porphyrins was increased by mitROS production, thereby the cancer-specific PDT cytotoxicity was enhanced. Thus we investigated whether mitROS production by hyperthermia can enhanced the cytotoxicity of PDT or not. In this study, 1 h of hyperthermia at 42 °C increased the mitROS production, and both the accumulation of cancer-specific porphyrins and the PDT cytotoxicity increased. Moreover, the authors treated cells with N-acetyl-L-cysteine (NAC) to examine the effect of mitROS. NAC inhibited the increasing ROS production after hyperthermia to restrain the post-treatment increase of cancer-specific porphyrins accumulation. Moreover, the increase of ROS production in cancer cells after hyperthermia upregulated HCP-1 expression and downregulated ABCG2 expression. These regulation were inhibited by NAC. These results suggest that hyperthermia treatment increased mitROS production, which involved HpD accumulation and enhanced PDT effects in cancer cells. The mechanism of this phenomenon was most likely to be due to both the upregulation of HCP-1 and the downregulation of ABCG2 by mitROS

Effect of inactivated Streptococcus pneumoniae as non-pathogenic particles on the severity of pneumonia caused by respiratory syncytial virus infection in mice

The severity of pneumonia in respiratory syncytial virus (RSV) infection is strongly related to hostimmune response and external factors such as bacteria and environmental chemicals. Weinvestigated the effect of inactivated Streptococcus pneumoniae (ISP) as non-pathogenic particleson the severity of pneumonia in RSV-infected mice. Mice were intranasally exposed to ISP beforeRSV infection. On day 5 post-infection, we examined the lung tissues, virus titer, and infiltratedcells in the lungs. The ISP did not cause significant histopathological effects on lungs of RSVinfectedmice and reduced virus titer in the lungs. It reduced the ratio of lymphocyte infiltrationinto the lungs and consequently the ratio of macrophage increased. In addition, we found that ISPincreased RANTES level in bronchoalveolar lavage fluid from RSV-infected mice on day 1 postinfection,but reduced type I interferon levels. Thus, ISP did not exacerbate pneumonia in RSVinfection; rather, it might mildly reduce the severity. We characterize and discuss the inherentactivity of ISP as non-pathogenic particles inducing the role of RANTES on the pneumonia in RSVinfection.九州保健福祉大学201

Efficacy of Brazilian Propolis against Herpes Simplex Virus Type 1 Infection in Mice and Their Modes of Antiherpetic Efficacies

Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected mice three times daily on days 0 to 6 after infection to evaluate their efficacies against HSV-1 infection and significantly limited development of herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to inactivated HSV-1 antigen in infected mice. Oral AF-08-administration significantly augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice, while direct exposure of splenocytes of infected mice to AF-06 significantly elevated IFN-γ production in vitro. Thus, AF-08 might have components that are active in vivo even after oral administration and those of AF-06 might be active only in vitro. Because DTH is a major host defense for intradermal HSV-1 infection, augmentation of DTH response by AF-06 or 08, directly or indirectly, respectively, may contribute to their efficacies against HSV-1 infection. In addition, AF-06 and 07 possibly contain anti-HSV-1 components contributing to their efficacies. Such biological activities of Brazilian propolis may be useful to analyze its pharmacological actions

The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey

Objective To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Background: The beta 3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression. Methods: The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MOD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls. Results: No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027). Conclusions: We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.ArticlePROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. 38(2):341-344 (2012)journal articl