Analgesic and anticonvulsant activity of new derivatives of 2-substituted 4-hydroxybutanamides in mice

Earlier in vitro studies of the compounds marked as GT27, GT28, GT29 and BM128 revealed their inhibitory action towards murine γ-aminobutyric acid (GABA) transporters (mGAT1-mGAT4). In the present paper, the pharmacological activity of four γ-hydroxybutyric acid (GHB) amide derivatives was investigated. The following procedures were involved: locomotor activity, hot plate and electroconvulsive threshold tests. The compounds' influence on motor coordination was evaluated in the chimney test, as well. Intraperitoneal (i.p.) administration of the GHB derivatives decreased animals' locomotor activity (ED(50) values ranged between 23.79 and 26.37 mg/kg). At a dose of 25 mg/kg (i.p.) the compounds prolonged the nociceptive reaction time latency in the hot plate assay to various degree and GT28 and GT29 were the most potent ones in this respect. Their analgesic efficacy was particularly pronounced 30 min after their administration [percent of maximal possible effect (%MPE) = 16.93 and 22.72, respectively]. The investigated GHB derivatives, except for GT29 at 100 mg/kg, increased the electroconvulsive threshold by approximately 4-11 mA as compared to the vehicle-treated mice. In the chimney test they impaired the animals' motor coordination to various degree. We suggest further investigations of the compounds to estimate their biological activity.     

三氧化二砷对小鼠过敏性哮喘的治疗作用及机制

目的 :研究三氧化二砷对小鼠过敏性哮喘的治疗作用及对脾T细胞周期和Bcl 2基因表达的影响。方法 :用卵蛋白建立小鼠过敏性哮喘模型 ,收集肺泡灌洗液 (BALF) ,直接计算白细胞总数和分类 ,双缩脲法检测总蛋白含量 ,应用Medlab生物信号采集系统软件检测小鼠肺功能 ,流式细胞术和免疫荧光法检测脾及BALF中T细胞数、T细胞周期和Bcl 2基因表达的变化。结果 :三氧化二砷可使BALF中总蛋白含量下降 ,白细胞总数减少 ,嗜酸细胞和淋巴细胞减少 ,改善哮喘小鼠肺功能 ;使脾及BALF中T细胞数降低 ;在 1.15mg·kg-1的剂量时可诱导脾T细胞凋亡 ,在 4 .6 0mg·kg-1的剂量时抑制其活化增殖 ;可下调脾T细胞Bcl 2基因表达。结论 :三氧化二砷有平喘作用 ,其作用机制可能与其调节T细胞的激活与凋亡 ,下调Bcl 2基因表达有关。     

同病异证H22肝癌小鼠肿瘤组织细胞凋亡通路基因差异表达的特征

目的:观察昆明种H22肝癌小鼠邪毒壅盛证与气虚证肿瘤组织细胞凋亡通路基因表达特征,探讨中医同病异证发生的物质基础。方法:采用小鼠计量化辨证方法,筛选出瘤早期邪毒壅盛证与气虚证同病异证H22肝癌小鼠,采用Affymetrix GeneChip Mouse Exon 1.0 ST Array检测肿瘤组织细胞凋亡通路相关基因表达的特征。结果:依据KEGG数据库细胞凋亡通路,筛选出芯片数据中匹配的33个基因,发现(1)TNF-α和IL-1依赖的细胞凋亡信号通路总体上不利于邪毒壅盛证小鼠肿瘤细胞的凋亡;(2)IL-3依赖的细胞凋亡信号通路总体上反似有利于邪毒壅盛证小鼠肿瘤细胞凋亡;而(3)线粒体介导的细胞凋亡信号通路,邪毒壅盛证小鼠一致表达下调,提示不利于其细胞凋亡。结论:邪毒壅盛肝癌小鼠肿瘤细胞恶性增殖程度高,可能与线粒体介导的细胞凋亡信号通路系列相关基因表达轻度抑制有关。     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

间氯苯哌嗪诱导的小鼠明暗箱焦虑模型 一种新的经济简便抗焦虑药筛选模型

目的　建立经济简便的抗焦虑药模型。方法　用间氯苯哌嗪 (mCPP)诱导产生焦虑 ,观察ddy小鼠和ICR小鼠在明暗箱的行为表现。结果　mCPP在sc 1～ 4mg·kg-1的剂量下即可显著降低ddy小鼠在明箱的活动次数 ,而对暗箱的活动次数影响不显著 ;mCPP在sc 2～ 10mg·kg-1的剂量下对ICR小鼠在明箱的的活动次数影响不明显 ;用地西泮对该模型进行验证 ,发现只用较小的样本量即可得出显著结果。结论　ddy小鼠可取代Wistar大鼠进行mCPP诱导焦虑的明暗箱模型 ,且简便易得 ,经济有效。     

熟地多糖对小鼠免疫功能的影响

目的 :观察熟地多糖 (RGP)对小鼠免疫功能的影响。方法 :小鼠连续给药 7天 ,取全血比色法检测血清溶血素水平 ;小鼠连续给药 10天 ,分别用DNCB致敏、攻击 ,尾静脉注射伊文思蓝溶液 ,取蓝染皮肤检测迟发性超敏反应 ;小鼠连续给药 8天 ,尾静脉注射印度墨汁后 ,立即取血读取OD值。结果 :熟地多糖 1 73g/ (kg·d) ,3 4 6 g/ (kg·d)灌服小鼠 ,可促进小鼠血清循环抗体溶血素的生成 (P <0 0 5 ) ,明显增强小鼠DNCB诱导的DTH反应 (P <0 0 5 ) ,提高小鼠巨噬细胞吞噬指数 (P <0 0 5 ,P <0 0 1) ,而对于吞噬系数无明显影响。结论 :熟地多糖具有提高小鼠免疫功能的作用。     

The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

The bark of Betula platyphylla Sukat. var. japonica Hara (Asian White Birch, AWB) is one of the herbs used in Eastern countries for the treatment of various inflammatory diseases including atopic dermatitis (AD). The present study was performed to examine if and how the bark of AWB inhibits the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PC). With this aim, we examined the skin symptom severity, itching behavior, serum immunoglobulin (Ig) E level and mRNA expression of cytokines at iliac and cervical lymph nodes in the mice. Oral administration of AWB extracts (25, 100 and 250 mg/kg) to the PC-treated mice inhibited the development of AD-like skin lesions as exemplified by a significant decrease in the total skin severity scores, itching behavior and a decrease in hypertrophy and infiltration of inflammatory cells into dermis. The serum IgE level was also significantly reduced by AWB extract. In the RT-PCR results, the expression of interleukin-4 mRNA was reduced by AWB extract, whereas the expression of interferon-gamma mRNA was not changed. These results suggest that AWB inhibits the development of AD-like skin lesions in NC/Nga mice through the suppression of the T-helper 2 cell response.     

Elaeocarpus sylvestris modulates gamma-ray-induced immunosuppression in mice: implications in radioprotection

The study investigated the potential of Elaeocarpus sylvestris var. ellipticus (E.S.), which contains 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), to protect mice from radiation injury by single whole-body irradiation (WBI) in vivo. The results from the present study demonstrate that the E.S. extract significantly improved the rate and duration of survival beyond that of untreated, irradiated control mice. The counts of endogenous colony forming units (CFU) increased in E.S.-treated mice, indicating that E.S. induced the regeneration of hematopoietic cells. E.S. treatment also accelerated the proliferation and recovery of lymphocytes and granulocytes, compared with those levels in untreated, irradiated controls. These results suggest that E.S. extract increases the survival time of mammals exposed to ionizing radiation by intensifying the victims' hematopoietic repair capacities. Therefore, it is concluded that the E.S. extract may be an effective agent of protection from radiation-induced injuries.