Gintonin mitigates experimental autoimmune encephalomyelitis by stabilization of Nrf2 signaling via stimulation of lysophosphatidic acid receptors

Gintonin (GT), a glycolipoprotein fraction isolated from ginseng, exerts neuroprotective effects in models of neurodegenerative diseases such as Alzheimer’s disease. However, the in vivo role of GT in multiple sclerosis (MS) has not been clearly resolved. We investigated the effect of GT in myelin oligodendrocyte glycoprotein (MOG_35-55)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS. GT alleviated behavioral symptoms of EAE associated with reduced demyelination, diminished infiltration and activation of immune cells (microglia and macrophage), and decreased expression of inflammatory mediators in the spinal cord of the EAE group compared to that of the sham group. GT reduced the percentages of CD4⁺/IFN-γ⁺ (Th1) and CD4⁺/IL-17⁺ (Th17) cells but increased the population of CD4⁺/CD25⁺/Foxp3⁺ (Treg) cells in the spinal cord, in agreement with altered mRNA expression of IFN-γ, IL-17, and TGF-ß in the spinal cord in concordance with mitigated blood–brain barrier disruption. The underlying mechanism is related to inhibition of the ERK and p38 mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways and the stabilization of nuclear factor erythroid 2-related factor 2 (Nrf2) via increased expression of lysophosphatidic acid receptor (LPAR) 1–3. Impressively, these beneficial effects of GT were completely neutralized by inhibiting LPARs with Ki16425, a LPAR1/3 antagonist. Our results strongly suggest that GT may be able to alleviate EAE due to its anti-inflammatory and antioxidant activities through LPARs. Therefore, GT is a potential therapeutic option for treating autoimmune disorders including MS.     

膜叶槌果藤水提物镇痛抗炎作用的实验研究

目的：研究膜叶槌果藤水提物镇痛抗炎作用。方法：小鼠分别连续灌胃给予膜叶槌果藤水提物高、中、低剂量（10.88,5.44,2.72 g/kg）7 d,采用扭体法、福尔马林致痛模型、二甲苯致耳肿胀模型及腹腔毛细血管通透性实验,观察其镇痛抗炎作用。结果：膜叶槌果藤水提物可显著抑制冰醋酸引起的小鼠扭体反应次数（P＜0.01）;对福尔马林致小鼠疼痛舔足第Ⅰ,Ⅱ时相累积时间均有显著减少（P＜0.05或P＜0.01）;对二甲苯致小鼠耳肿胀有显著的抑制作用（P＜0.05或P＜0.01）;对冰醋酸引起的毛细血管通透性也有显著的抑制作用（P＜0.01）。结论：膜叶槌果藤水提物具有显著的镇痛抗炎作用。     

新风胶囊对佐剂性关节炎模型大鼠的抗炎作用

目的:研究新风胶囊对佐剂性关节炎(AA)模型大鼠的抗炎作用。方法:取70只SD大鼠随机均分为正常对照组、模型对照(等容生理盐水)组、阳性对照中药[祛风止痛胶囊0.4 g(生药)/kg]组、阳性对照西药(来氟米特片2.1 mg/kg)组和新风胶囊低、中、高剂量[0.8、1.6、3.2 g(生药)/kg]组,依次记为A、B、C、D、E、F、G组,除A组外其余各组大鼠皮内注射弗氏完全佐剂复制AA模型,致炎第12天开始连续ig给药28 d。检测并计算各组大鼠给药前、后足趾肿胀度和关节炎指数,于末次给药24 h后检测各组大鼠血清及关节滑膜组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量并观察踝关节组织病理学形态变化。结果:与A组比较,B组大鼠足趾肿胀度和关节炎指数升高,血清及关节滑膜组织中IL-1β、TNF-α含量增加,差异有统计学意义(P<0.01)。与给药前比较,C、D、E、F、G组大鼠足跖肿胀度和关节炎指数降低,差异有统计学意义(P<0.05)。与B组比较,C、D、E、F、G组大鼠足趾肿胀度和关节炎指数降低,血清及关节滑膜组织中IL-1β、TNF-α含量降低,差异有统计学意义(P<0.01或P<0.05)。B组大鼠踝关节组织出现滑膜增生、炎性细胞浸润;C、D、F、G组大鼠滑膜增生和炎症情况较B组均减轻。结论:新风胶囊对AA模型大鼠具有抗炎作用,其机制可能与促进滑膜细胞凋亡、抑制滑膜增生有关。     

木瓜提取物的抗炎活性研究

目的 研究不同部位木瓜提取物在细胞水平上的抗炎作用及机制.方法 依次用乙酸乙酯、正丁醇萃取已用65％乙醇抽提的木瓜粉末,得到乙酸乙酯、正丁醇及水溶性部位提取物;建立THP-1及L929细胞炎症模型,用MTr法检测3个部位提取物的抗炎活性.利用核转录因子(NF-κB)报告基因系统检测NF-κB的活性,并用半定量PCR检测药物处理后细胞内炎症反应相关基因的表达.结果 与对照组比较,用乙酸乙酯部位处理后的THP-1细胞内Toll样受体及其下游炎症因子的表达水平明显下降,且用该组上清液处理后的L929细胞的活细胞数明显高于其他组.结论 木瓜的乙酸乙酯部位提取物具较好的抗炎效果.     

Studies on the structure-activity relationship of caffeate derivatives as neuroprotective agents

In the present study, novel ester derivatives of CAPE were designed and synthesized as neuroprotective agents. The anti-inflammatory and antioxidant activities of these compounds were evaluated at the cellular level, while the blood-brain barrier (BBB) permeability was predicted by parallel artificial membrane permeability assay (PAMPA). The results revealed that phenolic hydroxyl groups and double bonds in the structure of CAPE had important effects on neuroprotective activities. Accordingly,a preliminary structure-activity relationship was summarized in this paper. In addition, we observed a significant improvement on BBB permeability. These results provided important references for the structural modification and optimization of CAPE in the future.     

Hepatoprotective effect of mulberry water extracts on ethanol-induced liver injury via anti-inflammation and inhibition of lipogenesis in C57BL/6J mice

Many plant extracts and their bioactive substances are well recognized for their potential to exert as chemoprotective agents against common alcoholic liver injury. In this study, the effects of Mulberry water extracts (MWE) treatment in the prevention of alcohol-induced liver injury were investigated in mice. MWE contain many nutrients and bioactive substances, including fifteen types of polyphenols and anthocyanin compounds. The parameters of histopathology, immunohistochemistry, antioxidant defense and proinflammatory mediator demonstrated the inhibitory effect of MWE on alcohol-induced liver injury. Plasma and hepatic content analysis showed that MWE inhibited the levels of liver injury biomarkers (AST, ALT and ALP), triglyceride (TG) and cholesterol (TC). Furthermore, treatment with MWE lessened the expression of lipid synthesis-related proteins, increased the p-AMPK/AMPK ratio and PPAR-α. Fatty acid oxidation and export via microsomal triglyceride transfer protein (MTP) were both activated as well as carnitine palmitoyltransferase-1 (CPT1). These results suggested that MWE prevents alcohol-induced liver injury through the activation of the AMPK and PPAR-α signal. This may be mediated by multiple pathways, including reduced lipid accumulation and lipid synthesis, increased fatty acid transport and fatty acid oxidation responses, decreased oxidative stress and facilitated anti-inflammation.     

鱼龙草颗粒止咳祛痰抗炎作用实验研究

目的 探讨鱼龙草颗粒对小鼠的止咳、祛痰、抗炎作用,阐明鱼龙草颗粒药效学作用机制,为临床使用提供理论依据.方法 将150只小鼠（做3个试验,每个试验50只,每个试验分5组,每组10只）随机分为空白对照组（去离子水,0.2 ml/只）、阳性药物组（磷酸可待因30 mg/kg或盐酸氨溴索0.05 g/kg或阿司匹林0.2 g/kg）和观察组（鱼龙草颗粒）中高剂量组（12.0 g/kg）、中剂量组（6.0 g/kg）、低剂量组（3.0 g/kg）三剂量组,按分组剂量每天上午9：00左右,每只小鼠灌胃给药1次,连续给药5d后进行实验：①小鼠SO2引咳试验：用SO2刺激小鼠呼吸道15 s引起小鼠咳嗽反应,观察3种不同剂量组及磷酸可待因组小鼠咳嗽潜伏期及咳嗽次数;②小鼠气管酚红分泌排泄试验：利用酚红注射后可在小鼠气管分泌排泄机制,腹腔注射2.5％酚红氯化钠注射液30 min,空气栓塞处死小鼠,取出气管,测量3种不同剂量组及盐酸氨溴索组小鼠气管对酚红分泌排泄量;③小鼠二甲苯所致耳廓肿胀试验：利用二甲苯外涂可引起小鼠耳廓炎症反应方法,给予小鼠右耳涂抹二甲苯（100％浓度）,4h后处死小鼠,取下左右耳,对3种不同剂量组及阿司匹林组称重.以上3种试验均设空白对照组并与3种不同剂量组及阳性药物组进行对比观察.结果 ①小鼠SO2引咳试验结果显示：在延长小鼠咳嗽潜伏期方面,高、中剂量组与空白组比较,差异有统计学意义[（60±17）、（58±15）s比（50±18）s] （P ＜0.05）;在减少小鼠咳嗽次数方面,高、中剂量组与空白组比较,差异有统计学意义[（15±5）、（16±9）次/3 min比（35±10）次/3 min] （P ＜0.01）,与低剂量组[（20±7）次/3 min]比较差异有统计学意义（P＜0.05）;磷酸可待因组[咳嗽潜伏期（68±15）s、咳嗽次数（12±6）次/3 min]与空白组比较,差异有统计学意义（P＜0.01）.证明鱼龙草颗粒可延长小鼠咳嗽潜伏期、明显减少咳嗽次数.②空白对照组、鱼龙草颗粒高中低剂量组、盐酸氨溴索组酚红量分别为（1.03±0.37）、（1.59±0.23）、（1.56±0.21）、（1.43±0.26）、（1.55±0.22） mg/L.小鼠气管酚红分泌排泄试验结果显示：高、中剂量组与空白组比较,差异有统计学意义（P＜0.01）;低剂量组与空白组比较,差异有统计学意义（P＜0.05）;盐酸氨溴索组与空白组比较,差异有统计学意义（P＜0.01）.③小鼠结果显示：高、中、低3种剂量组及阿司匹林组4组与空白组比较,差异均有统计学意义[（8.2±2.0）、（10.0±1.1）、（10.9±1.6）、（8.0±1.1）mg比（14.2±1.7）mg]（均P＜0.01）.结论 小鼠的SO2引咳试验、气管酚红分泌排泄试验、二甲苯所致耳廓肿胀试验显示：鱼龙草颗粒对小鼠具有明显的止咳、祛痰、抗炎作用,其临床疗效有待进一步观察.     

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer

Colorectal cancer(CRC),a multifactorial disease,is usually induced and developed through complex mechanisms,including impact of diet and lifestyle,genomic abnormalities,change of signaling pathways,inflammatory response,oxidation stress,dysbiosis,and so on.As natural polyphenolic phytochemicals that exist primarily in tea,tea polyphenols(TPs)have been shown to have many clinical applications,especially as anticancer agents.Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC.TPs can inhibit the growth and metastasis of CRC by exerting the antiinflammatory,anti-oxidative or pro-oxidative,and pro-apoptotic effects,which are achieved by modulations at multiple levels.Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells,including the mitogen-activated protein kinase pathway,phosphatidylinositol-3 kinase/Akt pathway,Wnt/β-catenin pathway,and 67 kDa laminin receptor pathway,to inhibit proliferation and promote cell apoptosis.In addition,novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses.Molecular pathological epidemiology,a novel multidisciplinary investigation,has made great progress on CRC,and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC.This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.     

血脂康胶囊对颈动脉硬化症的抗氧化和抗炎症作用

目的探讨血脂康胶囊对颈动脉硬化症的抗氧化和抗炎症作用。方法将78例颈动脉硬化症患者随机分为两组:血脂康组38例,在常规药物治疗的基础上口服血脂康胶囊600 mg,2次/d,持续12周;对照组40例,常规药物治疗,不服用任何调脂药物及抗氧化剂。分别于治疗前后检测血清总胆固醇(TC)、氧化型低密度脂蛋白(ox-LDL)、高敏C反应蛋白(hs-CRP)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平及血脂系列等。结果血脂康组治疗后TC、ox-LDL、hs-CRP、IL-1β、TNF-α显著下降(P<0.05),且明显低于对照组(P<0.05)。结论血脂康具有一定程度的抗氧化和抑制动脉粥样硬化慢性炎症过程的作用。