alkaloids

生物碱类
  • 文章类型: Journal Article
    猪繁殖与呼吸综合征(PRRS)在世界范围内流行,严重影响养猪业的发展,但疫苗对PRRSV传播的保护作用有限。本研究的目的是鉴定潜在的抗PRRSV药物。我们检查了根据甘草酸与苦参碱的质量比配制的7种化合物的细胞毒性,并计算了它们对PRRSV的体外抑制率。结果表明,7个化合物均对PRRSV具有直接杀伤和治疗作用,并且这些化合物以时间和剂量依赖性方式抑制PRRSV复制。选择具有最强抗PRRSV作用的化合物用于随后的体内实验。将猪分为对照组和药物组进行体内评价。结果表明,用4:1化合物治疗的猪在PRRSV攻击后发病率为100%,在病毒攻击的第8天,死亡率达到75%。这些结果表明该化合物在体内没有实际的抗PRRSV作用,并且实际上可以加速感染猪的死亡。接下来,我们进一步分析了在接种该化合物后表现出半保护作用的猪,以确定该化合物是否可以在体内与疫苗协同作用。结果表明,用所述化合物治疗的猪在PRRSV感染后具有更高的死亡率和更严重的临床反应(p<0.05)。促炎细胞因子(IL-6,IL-8,IL-1β,IFN-γ,和TNF-α)在化合物处理的猪中明显高于阳性对照处理的猪(p<0.05),并且与PRRSV减毒活疫苗没有协同增强(p<0.05)。该化合物增强了炎症反应,促使身体产生过量的炎症细胞因子,造成身体损伤,阻止治疗效果。总之,本研究表明,这些药物的体外有效性并不表明它们在体内有效或可用于开发抗PRRSV药物.我们的发现还表明,确定有效的抗PRRSV药物,需要全面的药物筛选,用于在体外和体内具有固体抗炎作用的化合物。我们的研究可能有助于开发新的抗PRRSV药物。
    Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.
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  • 文章类型: Journal Article
    肝癌和乳腺癌被列为导致高癌症相关死亡率的最常见癌症。由于癌症是一种威胁生命的疾病,影响全球人口,需要开发新的疗法。在可用的治疗选择中包括放射治疗,化疗,手术,和免疫疗法。最先进的现代方法是使用植物衍生的抗癌药物,靶向癌细胞并抑制其增殖。植物衍生的化合物通常被认为比合成药物/传统疗法更安全,可以作为治疗肝癌和乳腺癌的潜在新靶点,彻底改变癌症治疗。生物碱和多酚已被证明通过分子方法充当抗癌剂。它们破坏各种细胞机制,抑制细胞周期蛋白和CDK的产生以阻止细胞周期,并通过上调p53,p21和p38的表达来激活DNA修复机制。在严重的情况下,当无法修复时,它们通过激活caspase-3、8和9并增加Bax/Bcl-2比率来诱导肝癌和乳腺癌细胞的凋亡。它们还使几种信号通路失活,如PI3K/AKT/mTOR,STAT3,NF-kB,嘘,MAPK/ERK,和Wnt/β-catenin途径,控制癌细胞的发展和转移。这篇综述的重点是对癌症中至关重要的特定蛋白质表达的调节,例如在HER2过表达的乳腺癌细胞中;生物碱和多酚已被报道降低HER2以及MMP表达。这项研究回顾了40多种具有针对肝癌和乳腺癌的特定分子靶标的植物性生物碱和多酚。其中,氧化苦参碱,Hirsutine,胡椒碱,Solamargine,和马钱子碱目前正在临床试验中,因为副作用较小,因此有资格作为有效的抗癌剂。由于对抗癌化合物的研究很多,人们迫切需要收集数据,以进入临床试验阶段4,并控制肝癌和乳腺癌的患病率。
    Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.
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  • 文章类型: Journal Article
    酸枣仁(ZSS)是治疗失眠的首选药物。本研究旨在揭示ZSS质量标记的空间分布,并说明该中药的代谢物质量特征。这里,我们进行了基质辅助激光解吸/电离质谱成像(MALDI-MSI)原位检测和成像ZSS中的33种代谢物,包括三种皂苷,六种类黄酮,四种生物碱,八种脂肪酸,和12个氨基酸。代谢物的MALDI图像清楚地显示了ZSS组织不同区域的异质空间分布,比如子叶,胚乳,和胚根。两种皂苷的分布区域,六种类黄酮,ZSS油炸加工后,三种生物碱含量显著增加。根据离子图像,通过正交偏最小二乘判别分析(OPLS-DA)的模式识别方法,对具有不同处理技术的样本进行了明确的区分。同时,将23种具有较高离子强度的主要影响成分鉴定为ZSS的潜在质量标记。在当前研究中获得的结果表明,ZSS的加工改变了其药用成分的含量和分布。MALDI-MSI的分析提供了一种新颖的基于MS的分子成像方法来研究和监测传统药用植物。
    Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.
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  • 文章类型: Journal Article
    微囊化已成为增强生物活性化合物的稳定性和保护性的有希望的策略。在这项工作中,使用15%的麦芽糊精和lasiodiplodan(0.5-1.25%)作为壁膜材料将烤茶微囊化。微胶囊的包封效率进行了表征,吸湿性,水分,水活动,水溶性,溶解性,扫描电子显微镜,FT-IR光谱,热分析,比色法,抗氧化活性,以及酚类化合物和咖啡因的定量。微囊包封率从44.92%到56.39%,通过增加拉索二倍体的浓度,包封效率从66.54变化到70.16。FT-IR揭示了酚酸,黄酮类化合物,和多酚。在样品中观察到微小的颜色变化。热分析表明微胶囊表现出良好的热稳定性,低于250°C没有降解。封装样品显示出高水平的生物活性化合物,表明喷雾干燥微囊化是一种有利的工艺,麦芽糊精,一种低成本的保护剂,当与Lasiodiplodan的特性结合时,可以稳定伴侣提取物的一个很好的选择。
    Microencapsulation has emerged as a promising strategy to enhance the stability and protection of bioactive compounds. In this work, roasted mate tea was microencapsulated using 15 % maltodextrin and lasiodiplodan (0.5-1.25 %) as wall coating materials. The microcapsules were characterized for encapsulation efficiency, hygroscopicity, moisture, water activity, water solubility, dissolubility, scanning electron microscopy, FT-IR spectroscopy, thermal analysis, colorimetry, antioxidant activity, as well as quantification of phenolic compounds and caffeine. Microencapsulation yields ranged from 44.92 to 56.39 %, and the efficiency of encapsulation varied from 66.54 to 70.16 by increasing the lasiodiplodan concentration. FT-IR revealed phenolic acids, flavonoids, and polyphenolics. Minor color variations were observed among the samples. Thermal analysis demonstrated the microencapsulates exhibited good thermal stability with no degradation below 250 °C. Encapsulated samples showed high levels of bioactive compounds, suggesting that microencapsulation by spray-drying was a favorable process, where maltodextrin, a low-cost protective agent, when combined with the properties of lasiodiplodan, can be a good option for stabilizing mate extracts.
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  • 文章类型: Journal Article
    环磷酰胺(CP)是一种广泛应用于化疗的抗肿瘤药物。姜黄素(CUR)和胡椒碱(PP)对神经退行性疾病和神经系统疾病具有保护作用。这项研究旨在测量应用CP的大鼠脑组织中的几个生化参数,以研究联合CUR-PP给药的影响。该研究评估了六组,每组八只大鼠:第1组为对照组;第2组和第3组通过口服管饲法给予200或300mg/kgCUR-PP;第4组仅在第1天接受200mg/kgCP;第5组和第6组接受CP+CUR-PP7天。来自所有参数的数据表明CP引起脑损伤。磷酸化TAU(pTAU),淀粉样β肽1-42(Aβ1-42),谷氨酸(GLU),和γ氨基丁酸(GABA)参数在第4、5和6组中相同。另一方面,8-羟基-2-脱氧鸟苷(8-OHdG),一氧化氮(NO),白细胞介素-6(IL-6),核因子κβ(NF-kβ),丙二醛(MDA),CP+CUR-PP组肿瘤坏死因子-α(TNF-α)水平低于CP组(p<0.05)。然而,超氧化物歧化酶(SOD),过氧化氢酶(CAT),谷胱甘肽过氧化物酶(GPx),与CP组相比,CP+CUR-PP组的还原型谷胱甘肽(GSH)参数更高(p<0.05)。认为Aβ1-42,pTAU中第5组和第6组与第4组的相似性,GLU,和GABA参数阻碍了治疗保护的确定,如果改变应用剂量或研究持续时间,它们可能具有治疗效果.这项研究试图通过测量生化参数和进行组织病理学检查来评估CUR-PP组合对大鼠CP诱导的脑损伤的影响。根据调查结果,在条件与本研究评估的条件相似的情况下,这种CUR-PP组合可被视为替代药物选择.
    Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aβ1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kβ), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aβ1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice.
    METHODS: Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay.
    RESULTS: HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05).
    CONCLUSIONS: C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.
    [摘要] 目的 探讨高迁移率族蛋白B1 (high mobility group box protein B1, HMGB1)-Toll样受体2 (Toll-like receptor 2, TLR2)/TLR4-核因子κB (nuclear factor κB, NF-κB) 通路在微小隐孢子虫感染致肠黏膜损伤中的作用, 以及氧化苦参碱 (oxymatrine, OMT) 对小鼠微小隐孢子虫感染的干预作用。方法 4周龄SPF级BALB/c小鼠40只随机分成4组, 分别为 对照组、感染组、甘草酸 (glycyrrhizin, GA) 组及OMT组。感染组、GA组及OMT组小鼠给予地塞米松免疫抑制1周后, 每 只灌胃1 × 105个微小隐孢子虫卵囊建立微小隐孢子虫肠道感染小鼠模型。模型建立成功后, GA组小鼠连续2周腹腔注 射GA 25.9 mL/(kg·d), OMT组连续2周经口灌胃OMT 50 mg/(kg·d); 对照组正常饮食、饮水。治疗2周后剖杀各组小鼠, 取空肠近端组织。采用苏木精-伊红 (hematoxylin-eosin, HE) 染色观察小鼠肠黏膜病理变化, 测量肠绒毛高度、肠隐窝深 度及两者比值; 采用免疫组织化学染色检测小鼠肠上皮细胞中闭合蛋白 (occludin) 和紧密粘连蛋白1 (zonula occludens protein 1, ZO1) 表达水平, 采用实时荧光定量PCR (quantitative real-time PCR, qPCR) 检测小鼠空肠组织中HMGB1、TLR2、 TLR4、髓样分化因子88 (myeloid differentiation primary response gene 88, MyD88) 、NF-κB p65mRNA相对表达量。结果 HE 染色结果显示, 与对照组比较, 感染组小鼠肠绒毛明显萎缩变短、脱落, 黏膜下层水肿; GA组和OMT组小鼠肠绒毛结构 趋于完整, 排列趋于整齐。各组小鼠肠绒毛高度 (F = 6.207, P = 0.000 5) 、肠隐窝深度 (F = 6.903, P = 0.000 3) 及两者比 值 (F = 37.190, P < 0.000 1) 差异均有统计学意义。感染组小鼠肠绒毛高度 [(321.9 ± 41.1) μm] 显著低于对照组 [(399.5 ± 30.9) μm] (t = 4.178, P < 0.01) 和GA组 [(383.7 ± 42.7) μm] (t = 3.130, P < 0.01), 感染组小鼠肠隐窝深度 [(185.0 ± 35.9) μm] 显著高于对照组 [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) 及GA组 [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05) 。OMT组小 鼠肠绒毛高度 [(375.3 ± 22.9) μm] 显著高于感染组 (t = 3.888, P < 0.01), 与对照组差异无统计学意义 (t = 1.989, P > 0.05); OMT组小鼠肠隐窝深度 [(121.5 ± 27.3) μm] 显著低于感染组 [(185.0 ± 35.9) μm] (t = 4.133, P < 0.01), 与对照组差异无统 计学意义 (t = 0.575, P > 0.05) 。感染组小鼠肠绒毛高度与肠隐窝深度比值 [(1.8 ± 0.2) ] 显著低于对照组 [(3.1 ± 0.3) ] (t = 10.540, P < 0.01) 及GA组 [(2.7 ± 0.3) ] (t = 7.370, P < 0.01); OMT组小鼠肠绒毛高度与肠隐窝深度比值 [(3.1 ± 0.2) ] 显著 高于感染组 (t = 15.020, P < 0.01), 与对照组差异无统计学意义 (t = 0.404, P > 0.05) 。免疫组织化学染色结果显示, 各组 小鼠肠上皮细胞中occludin (F = 28.031, P < 0.000 1) 及ZO1表达水平差异均有统计学意义 (F = 14.122, P <0.0001) 。感染组 小鼠肠上皮细胞中occludin阳性表达率 [(14.3 ± 4.5) %] 低于对照组 [(28.3 ± 0.5) %] (t = 3.810, P < 0.01), GA组 [(30.3 ± 1.3) %] 、OMT组小鼠肠上皮细胞中occludin阳性表达率 [(25.8 ± 1.5) %] 显著高于感染组 (t = 7.620、5.391, P 均< 0.01), 但GA组、OMT组小鼠肠上皮细胞中occludin阳性表达率与对照组差异均无统计学意义 (t = 1.791、2.033, P 均> 0.05) 。 感染组小鼠肠上皮细胞中ZO1阳性表达率 [(14.4 ± 1.8) %] 显著低于对照组 [(24.2 ± 2.8) %] (t = 4.485, P < 0.01), GA组 [(24.1 ± 2.3) %] (t = 5.159, P < 0.01) 、OMT组小鼠肠上皮细胞中ZO1阳性表达率 [(22.5 ± 1.9) %] 显著高于感染组 (t = 4.441, P < 0.05), 但GA组、OMT组小鼠肠上皮细胞中ZO1阳性表达率与对照组差异均无统计学意义 (t = 0.037、0.742, P 均> 0.05) 。qPCR检测结果显示, 各组小鼠空肠组织中HMGB1 (F = 21.980, P < 0.000 1) 、TLR2 (F = 20.630, P < 0.000 1) 、 TLR4 (F = 17.000, P = 0.000 6) 、MyD88 (F = 8.907, P = 0.000 5) 、NF-κB p65 mRNA 表达水平差异均有统计学意义 (F = 8.889, P = 0.000 7) 。感染组小鼠空肠组织中HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] 、NF-κB p65 mRNA 相对表达量 [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] 均 显著高于对照组。与对照组比较, GA组小鼠空肠组织中HMGB1 (0.63 ± 0.01) 、TLR2 (0.42 ± 0.10) 、TLR4 (0.35 ± 0.07) 、 MyD88 (0.70 ± 0.11) 、NF-κB p65 mRNA 相对表达量 (0.75 ± 0.01) 均显著下降 (t = 8.629、5.830、11.500、4.729、6.898, P 均< 0.05) 。与感染组比较, GA组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量均显著降低 (t = 7.052、6.035、4.084、3.165、3.274, P 均< 0.05); OMT 组小鼠空肠组织中HMGB1 (1.14 ± 0.60) 、TLR2 (1.00 ± 0.24) 、TLR4 (1.14 ± 0.07) 、MyD88 (0.96 ± 0.25) 、NF-κB p65 mRNA 相对表达量 (1.12 ± 0.17) 亦显著低于感染组 (t = 7.059、5.320、3.510、 3.466、3.273, P 均< 0.05) 。OMT组与对照组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量 差异均无统计学意义 (t = 0.239、0.518、1.887、0.427、0.641, P均> 0.05) 。结论 微小隐孢子虫感染小鼠后通过上调 HMGB1-TLR2/TLR4-NF-κB 通路表达引起肠道炎症反应、破坏肠黏膜屏障。OMT 可能通过抑制HMGB1-TLR2/TLR4-NF-κB 通路活性抑制小鼠肠道炎症, 并修复肠黏膜屏障。.
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  • 文章类型: Journal Article
    青钱柳(巴塔尔。)叶子,含有一系列生物活性化合物,自古以来就被用作中药同源食品。然而,关于青钱柳(Batal。).第一次,本研究旨在发现和鉴定从青钱柳(Batal。)通过超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-QTOF-MS)进行分析。从青钱柳(Batal。)基于精确质谱的叶子(质量精度,同位素间距和分布)并与文献中报道的碎片光谱进行比较。体外,生物碱通过增加胰岛素抵抗HepG2细胞的葡萄糖消耗和糖原含量来减轻胰岛素抵抗。RNA-seq和western印迹结果显示生物碱可以上调磷脂酰肌醇3-激酶(PI3K)的表达,并增加胰岛素受体蛋白激酶B(AKT)的磷酸化。这项研究不仅阐明了化学成分,而且还揭示了青钱柳(Batal。)叶子,还,它将提供有关开发新药的潜在化合物的化学信息。
    Cyclocarya paliurus (Batal.) leaves, which contain a range of bioactive compounds, have been used as a traditional Chinese medicine homologous food since ancient times. However, there is a paucity of literature on comprehensive studies of alkaloids in the leaves of Cyclocarya paliurus (Batal.). For the first time, this study aimed to discover and identify alkaloids extracted from Cyclocarya paliurus (Batal.) leaves by ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-QTOF-MS). A total of ten alkaloids have been identified from Cyclocarya paliurus (Batal.) leaves based on accurate mass spectra (mass accuracy, isotopic spacing and distribution) and comparison to fragmentation spectra reported in the literature. In vitro, alkaloids alleviated insulin resistance by increasing glucose consumption and glycogen content in insulin resistance HepG2 cells. The RNA-seq and western blotting results showed that alkaloids could upregulate the expression of phosphatidylinositol 3-kinase (PI3K), and increase the phosphorylation of insulin receptor protein kinase B (AKT). This study not only clarified the chemical constituents and revealed that diverse alkaloids also presented from Cyclocarya paliurus (Batal.) leaves, also, it will provide chemical information on potential compounds for developing new drugs.
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  • 文章类型: Journal Article
    党参属(Campanulaceae)的物种具有悠久的应用历史,因其可食用和治疗特性而备受赞誉。对党参跨越植物学的学术调查,植物化学,质量保证,药效学,和毒性,揭示了丰富而全面的知识体系。这项研究综合了来自SciFinder等备受尊敬的科学数据库的信息,PubMed,中国国家知识基础设施,和中草药经典,为党参研究创建了一个完整的科学概念和理论框架。在这篇文章中,植物化学成分包括糖类,聚乙炔,多烯,黄酮类化合物,生物碱,木脂素,萜类化合物,并对有机酸进行了总结。迄今为止,已经从党参中分离和鉴定了350多种单体化合物,最近的研究主要集中在多糖上,芳香衍生物,木脂素,和聚乙炔。党参在各个系统中表现出广泛的药理活性,包括免疫,血,心血管,中枢神经,和消化系统,无明显毒性或不良反应报告。现有的研究,专注于各种提取物和活性部分,而不识别特定的活性分子,使对作用机制的理解复杂化。迫切需要推进对其化学成分和药理作用的研究,以充分阐明其药效学性质及其物质组成的基础。这些努力对于合理发展至关重要,利用率,以及该草药的临床应用。
    Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into Codonopsis span botany, phytochemistry, quality assurance, pharmacodynamics, and toxicity, revealing a rich and comprehensive body of knowledge. This study synthesizes information from esteemed scientific databases like SciFinder, PubMed, China National Knowledge Infrastructure, and Chinese herbal classics to create a thorough scientific conceptual and theoretical framework for Codonopsis research. In this article, the phytochemical composition includes saccharides, polyacetylenes, polyenes, flavonoids, alkaloids, lignans, terpenoids, and organic acids was summarized. To date, over 350 monomeric compounds have been isolated and identified from Codonopsis, with recent studies primarily focusing on polysaccharides, aromatic derivatives, lignans, and polyacetylenes. Codonopsis exhibits broad pharmacological activities across various systems, including immune, blood, cardiovascular, central nervous, and digestive systems, with no significant toxicity or adverse effects reported. The existing research, focusing on various extracts and active parts without identifying specific active molecules, complicates the understanding of the mechanisms of action. There is an urgent need to advance research on the chemical composition and pharmacological effects to fully elucidate its pharmacodynamic properties and the basis of its material composition. Such efforts are crucial for the rational development, utilization, and clinical application of this herb.
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  • 文章类型: Letter
    我们饶有兴趣地阅读了Kulesza等人的文章。关于大麻二酚是否真的有效治疗下背部疼痛的问题的叙述性综述[1]。在使用合适的搜索词并应用纳入和排除标准进行文献检索后,作者在分析中纳入了10项研究[1]。其中一篇文章是社论,四篇论文是评论[1]。已发现大麻二酚在治疗下腰痛方面无效,需要进一步的研究来回答感兴趣的问题。审查令人印象深刻,但是有几点需要讨论。
    We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]. After a literature search using suitable search terms and application of inclusion and exclusion criteria, the authors included 10 studies in the analysis [1]. One of the articles included was an editorial and four papers were reviews [1]. Cannabidiol has been found to be ineffective in treating lower back pain and further studies are needed to answer the question of interest. The review is impressive, but several points require discussion.
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  • 文章类型: Journal Article
    金莲花(TCB)是毛茸茸科的多年生植物,具有药用和食用价值。它分布广泛,在各个地区普遍使用,包括亚洲,欧洲,和北美。TCB的主要化学成分包括生物碱,黄酮类化合物,酚酸,和挥发油化合物。TCB以其抗炎作用而闻名,清热,解毒,和改善视力的特性。其干花常用作治疗上呼吸道感染的中药,慢性扁桃体炎,咽炎,流感,还有支气管炎.现代药理学已经证明了抗癌,抗炎,抗高血压药,和TCB的抗氧化作用。本研究全面概述了TCB的各个方面,包括草药文本研究,植物学,植物化学,药理学,传统用途,临床应用,和质量控制,旨在为TCB的科学应用以及现代研究与传统药用的整合提供新思路。
    Trollius chinensis Bunge (TCB) is a perennial plant of the Ranunculaceae family with medicinal and edible values. It is widely distributed and commonly used in various regions, including Asia, Europe, and North America. The main chemical components of TCB include alkaloids, flavonoids, phenolic acids, and volatile oil compounds. TCB is renowned for its anti-inflammatory, heat-clearing, detoxifying, and eyesight-improving properties. Its dried flowers are commonly used as a traditional Chinese medicine indicated for the treatment of upper respiratory tract infections, chronic tonsillitis, pharyngitis, influenza, and bronchitis. Modern pharmacology has demonstrated the anti-cancer, anti-inflammatory, antihypertensive, and antioxidant effects of TCB. This study presents a comprehensive overview of various aspects of TCB, including herbal textual research, botany, phytochemistry, pharmacology, traditional uses, clinical application, and quality control, aiming to provide new ideas on the scientific application of TCB as well as the integration of modern research with traditional medicinal uses.
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