Triptolide

雷公藤甲素
  • 文章类型: Journal Article
    由于其最低的环境风险和其他道德考虑,植物来源的消毒剂用于控制啮齿动物种群。然而,植物来源的杀菌剂的效果不是立竿见影的,它们对啮齿动物控制的功效是有争议的,这对杀菌剂的研究和应用产生了负面影响。这里,对现有文献进行了荟萃分析,以评估两种植物来源的杀菌剂的效果,雷公藤甲素和curcumol,啮齿动物种群。使用随机效应和固定效应模型,我们计算了加权平均差(WMD)和相对危险度(RR)及其相应的95%置信区间(95%CIs).在施用植物来源的消毒剂后,啮齿动物种群密度呈下降趋势。啮齿动物的三个结果相关指标,即,捕获率(RR=0.31,95%CI[0.20,0.47]),妊娠率(RR=0.49,95%CI[0.40,0.61]),和精子存活率(WMD=-17.53,95%CI[-28.96,-6.06]),显著下降,如卵巢明显减少所示,子宫,和睾丸器官系数。然而,干预后有效啮齿动物洞的数量没有显著变化,表明所研究的灭菌剂没有直接根除啮齿动物种群。本研究为阐明植物源杀菌剂对啮齿动物种群的抑制机制和合理使用这些杀菌剂提供了理论依据。
    Owing to their low minimal environmental risk and other ethical considerations, plant-derived sterilants are used to control rodent populations. However, the effects of plant-derived sterilants are not immediate, and their efficacy on rodent control is controversial, which negatively affects sterilant research and application. Here, a meta-analysis of the available literature was conducted to evaluate the effects of two plant-derived sterilants, triptolide and curcumol, on rodent populations. Using a random-effects and a fixed-effects model, we calculated the weighted mean difference (WMD) and relative risk (RR) and their corresponding 95% confidence intervals (95% CIs). After the application of plant-derived sterilants, the rodent population density tended to decrease. Three outcome-related measures in rodents, i.e., capture rate (RR = 0.31, 95% CI [0.20, 0.47]), pregnancy rate (RR = 0.49, 95% CI [0.40, 0.61]), and sperm survival rate (WMD = -17.53, 95% CI [-28.96, -6.06]), significantly decreased, as shown by a significant reduction of ovarian, uterine, and testicular organ coefficients. However, the number of effective rodent holes did not change significantly after the interventions, indicating that the studied sterilants did not directly eradicate the rodent populations. This study provides a theoretical basis for elucidating the inhibitory mechanisms of plant-derived sterilants on rodent populations and for the rational use of these sterilants.
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  • 文章类型: Journal Article
    民族药理学相关性:雷公藤甲素(TP),雷公藤的主要生物活性成分(TWHF),具有解决TWHF在临床上治疗糖尿病肾病(DKD)的缺点的潜力。研究目的:我们进行了一项荟萃分析,以评估TP治疗DKD的疗效,并为TP的进一步临床应用提供坚实的证据。材料与方法:八个数据库(CNKI,VIP,CBM,万方,PubMed,WebofScience,EMBASE,和Cochrane图书馆)以电子方式搜索合格的研究,直到2020年10月17日。我们选择了使用TP与肾素-血管紧张素系统抑制剂或非功能性液体的动物实验研究,以按照纳入和排除标准治疗DKD。两名研究人员从纳入的研究中独立提取数据,并使用实验室动物实验系统评价中心的偏倚风险工具评估偏倚风险。固定效应荟萃分析,亚组分析,使用RevMan5.3软件进行meta回归。印版注册号:INPLASY2020100042。结果:共纳入26项研究。Meta分析显示TP显著降低白蛋白尿(14项研究;标准化均差SMD:-1.44[-1.65,-1.23],I2=87%),尿白蛋白/尿肌酐比值(UACR)(8项研究;SMD:-5.03[-5.74,-4.33],I2=84%),总蛋白尿(4项研究;SMD:-3.12[-3.75,-2.49],I2=0%),血清肌酐(18项研究;SMD:-0.30[-0.49,-0.12],I2=76%),和血尿素氮(12项研究;SMD:-0.40[-0.60,-0.20],I2值=55%)在DKD动物中,与车辆控制相比。然而,关于TP与肾素-血管紧张素系统(RAS)抑制剂在DKD治疗中的比较,在改善白蛋白尿方面没有显着差异(3项研究;SMD:-0.35[-0.72,0.02],I2=41%),血清肌酐(3项研究;SMD:-0.07[-0.62,0.48],I2=10%),和血尿素氮(2项研究;SMD:-0.35[-0.97,0.28],I2=0%)。值得注意的是,TP在降低UACR方面表现出更高的能力(2项研究;SMD:-0.66[-1.31,-0.01],I2=0%)和总蛋白尿(2项研究;SMD:-1.18[-1.86,-2049],I2=0%)。Meta回归表明TP降低DKD白蛋白尿的疗效与应用剂量相关。此外,在诊断为DKD后,未检测到TP和RAS抑制剂之间的白蛋白尿减弱的发表偏倚。系统审查注册:https://clinicaltrials.gov/,标识符INPLASY2020100042。
    Ethnopharmacological Relevance: Triptolide (TP), the primary biologically active ingredient of Tripterygium wilfordii Hook F (TWHF), possesses the potential to solve the shortcomings of TWHF in treating diabetic kidney disease (DKD) in the clinic. Aim of the Study: We conducted a meta-analysis to evaluate the efficacy of TP in treating DKD and offer solid evidence for further clinical applications of TP. Materials and Methods: Eight databases (CNKI, VIP, CBM, WanFang, PubMed, Web of Science, EMBASE, and Cochrane library) were electronically searched for eligible studies until October 17, 2020. We selected animal experimental studies using TP versus renin-angiotensin system inhibitors or nonfunctional liquids to treat DKD by following the inclusion and exclusion criteria. Two researchers independently extracted data from the included studies and assessed the risk of bias with the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias tool. Fixed-effects meta-analyses, subgroup analyses, and meta-regression were conducted using RevMan 5.3 software. Inplasy registration number: INPLASY2020100042. Results: Twenty-six studies were included. Meta-analysis showed that TP significantly reduced albuminuria (14 studies; standardized mean difference SMD: -1.44 [-1.65, -1.23], I2 = 87%), urine albumin/urine creatinine ratio (UACR) (8 studies; SMD: -5.03 [-5.74, -4.33], I2 = 84%), total proteinuria (4 studies; SMD: -3.12 [-3.75, -2.49], I2 = 0%), serum creatinine (18 studies; SMD: -0.30 [-0.49, -0.12], I2 = 76%), and blood urea nitrogen (12 studies; SMD: -0.40 [-0.60, -0.20], I2 value = 55%) in DKD animals, compared to the vehicle control. However, on comparing TP to the renin-angiotensin system (RAS) inhibitors in DKD treatment, there was no marked difference in ameliorating albuminuria (3 studies; SMD: -0.35 [-0.72, 0.02], I2 = 41%), serum creatinine (3 studies; SMD: -0.07 [-0.62, 0.48], I2 = 10%), and blood urea nitrogen (2 studies; SMD: -0.35 [-0.97, 0.28], I2 = 0%). Of note, TP exhibited higher capacities in reducing UACR (2 studies; SMD: -0.66 [-1.31, -0.01], I2 = 0%) and total proteinuria (2 studies; SMD: -1.18 [-1.86, -2049], I2 = 0%). Meta-regression implicated that the efficacy of TP in reducing DKD albuminuria was associated with applied dosages. In addition, publication bias has not been detected on attenuating albuminuria between TP and RAS inhibitors after the diagnosis of DKD. Systematic Review Registration: https://clinicaltrials.gov/, identifier INPLASY2020100042.
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  • 文章类型: Journal Article
    Tripterygium wilfordii Hook. f. (TWHF) is a traditional Chinese herbal medicine and widely used to treat diabetic kidney disease in China. Emerging evidences have revealed its ability to attenuate diabetic nephropathy (DN). Tripterygium wilfordii polyglycosides (TWPs), triptolide (TP), and celastrol are predominantly active compounds isolated from TWHF. The effects and molecular mechanisms of TWHF and its active compounds have been investigated in recent years. Currently, it is becoming clearer that the effects of TWHF and its active compounds involve in anti-inflammation, anti-oxidative stress, anti-fibrosis, regulating autophagy, apoptosis, and protecting podocytes effect. This review presents an overview of the current findings related to the effects and mechanisms of TWHF and its active compounds in therapies of DN, thus providing a systematic understanding of the mechanisms and therapeutic targets by which TWHF and its active compounds affect cells and tissues in vitro and in vivo.
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  • 文章类型: Journal Article
    雷公藤甲素是从中草药雷公藤中分离出的主要生物活性成分。具有多种药理特性。微RNA(miRNA/miRs)是短的非编码RNA,其在转录后调节基因表达。miRNA涉及几个细胞内过程,因此,它们的失调有助于各种疾病的发病机理。因此,miRNA作为疾病的生物标志物和治疗靶点具有巨大潜力,与药物治疗有关。以前的研究报道,特定的miRNA是靶向的,暴露于雷公藤甲素后,它们的表达水平会发生变化。因此,miRNA正在成为雷公藤内酯醇药理活性中的关键介质。本文综述了目前关于miRNA作为靶分子在雷公藤甲素药理活性中的研究进展。包括抗肿瘤,抗炎,免疫抑制,肾保护,心脏保护,抗血管生成活性和多器官毒性作用。此外,讨论了所涉及的多种信号通路,以全面了解雷公藤甲素在靶miRNAs调控中的潜在分子机制。
    Triptolide is the main bioactive constituent isolated from the Chinese herb Tripterygium wilfordii Hook F., which possesses a variety of pharmacological properties. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miRNAs are implicated in several intracellular processes, whereby their dysregulation contributes to pathogenesis of various diseases. Thus, miRNAs have great potential as biomarkers and therapeutic targets for diseases, and are implicated in drug treatment. Previous studies have reported that specific miRNAs are targeted, and their expression levels can be altered following exposure to triptolide. Thus, miRNAs are emerging as crucial mediators in the pharmacological activities of triptolide. The present review summarizes current literature on miRNAs as target molecules in the pharmacological activities of triptolide, including antitumor, anti-inflammatory, immunosuppressive, renal protective, cardioprotective, antiangiogenesis activities and multiorgan toxicity effects. In addition, the diverse signaling pathways involved are discussed to provide a comprehensive understanding of the underlying molecular mechanisms of triptolide in the regulation of target miRNAs.
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  • 文章类型: Journal Article
    雷公藤甲素和雷公藤甲素,从雷公藤(也称为雷神藤)中分离出的化合物,对类风湿性关节炎(RA)有效。雷公藤红素靶向涉及NF‑κB的许多信号通路,内质网Ca2-ATP酶,骨髓分化因子2,Toll样受体4,促炎趋化因子,DNA损伤,细胞周期阻滞和细胞凋亡。雷公藤甲素,抑制NF‑κB,NF‑κB受体激活剂(RANK)/RANK配体/骨保护素信号通路,环氧合酶-2,基质金属蛋白酶和细胞因子。本综述审查了雷公藤甲素和雷公藤甲素的化学和生物利用度,以及它们治疗RA的分子靶点。临床研究表明,雷公藤具有几种有希望的生物活性,但其多靶点毒性限制了其应用。因此,需要控制雷公藤的剂量和结构修饰以降低毒性。在这次审查中,讨论了这些有前途的天然产物的未来研究方向。
    Celastrol and triptolide, chemical compounds isolated from Tripterygium wilfordii hook (also known as thunder god vine), are effective against rheumatoid arthritis (RA). Celastrol targets numerous signaling pathways involving NF‑κB, endoplasmic reticulum Ca2+‑ATPase, myeloid differentiation factor 2, toll‑like receptor 4, pro‑inflammatory chemokines, DNA damage, cell cycle arrest and apoptosis. Triptolide, inhibits NF‑κB, the receptor activator of NF‑κB (RANK)/RANK ligand/osteoprotegerin signaling pathway, cyclooxygenase‑2, matrix metalloproteases and cytokines. The present review examined the chemistry and bioavailability of celastrol and triptolide, and their molecular targets in treating RA. Clinical studies have demonstrated that T. wilfordii has several promising bioactivities, but its multi‑target toxicity has restricted its application. Thus, dosage control and structural modification of T. wilfordii are required to reduce the toxicity. In this review, future directions for research into these promising natural products are discussed.
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  • 文章类型: Journal Article
    Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of studies have been published emphasizing the value of triptolide in the treatment of diverse inflammatory disorders. Here, we systematically review the mechanism of action and the therapeutic properties of triptolide in various inflammatory diseases according to different systematic organs, including lupus nephritis, inflammatory bowel disease, asthma, and rheumatoid arthritis with pubmed and Embase. Based on this review, potential research strategies might contribute to the clinical application of triptolide in the future.
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  • 文章类型: Journal Article
    Triptolide is a complex triepoxide diterpene natural product that has attracted considerable interest in the organic chemistry and medicinal chemistry societies due to its intriguing structural features and multiple promising biological activities. In this review, progress in the total syntheses of triptolide are systematically summarized. We hope to gain a better understanding of the field and provide constructive suggestions for future studies of triptolide.
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  • 文章类型: Journal Article
    Objective: Triptolide (TL), a natural product isolated from Tripterygium wilfordii Hook F (TwHF), shows potent anticancer effects in vitro and in vivo. We aimed to summary the biochemical mechanisms through which TL has been shown to induce apoptosis, autophagy and inhibit angiogenesis in pancreatic cancer (PC). Methods: We undertook a systematic review of preclinical evidence. We searched electronic databases. The potential mechanisms and the underlying signaling pathways have been accumulated as well. Results: We screened 116 abstracts for eligibility and included 17 preclinical studies in the analysis. Details of the animals and cell lines were provided in 16 studies (94.1%). Six studies (75.0%) randomly assigned animals to treatment or control groups and only 1 study (12.5%) reported on blinding. The majority of the TL\'s research field has focused on its pro-apoptotic effects through downregulation of inhibitory pathways and upregulation of apoptotic pathways. The studies have shown that TL is effective both in vitro and in vivo against PC cells. Conclusion: This study provides a systematic summary of TL\'s anti-pancreatic cancer profile and the underlying mechanisms of with special emphasis on the apoptosis, autophagy, angiogenesis and related molecular pathways. Improved study quality in terms of treatment allocation methods reporting, randomization and blinding will accelerate needed progress toward trials.
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    文章类型: Journal Article
    OBJECTIVE: Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. However, the processes through which triptolide exerts immunosuppression and anti-inflammation are not understood well. In this review, we discuss the autoimmune disorders and inflammatory conditions that are currently treated with triptolide. Triptolide also possesses anti-tumorigenic effects. We discuss the toxicity of various triptolide derivatives and offer suggestions to improve its safety. This study also examines the clinical trials that have investigated the efficacy of triptolide. Our aim is to examine the mechanisms that are responsible for the immunosuppressive, anti-inflammatory, and anti-cancer effects of triptolide.
    METHODS: The present review provides a comprehensive summary of the literature with respect to the immunosuppressive, anti-inflammatory, and anti-cancer properties of triptolide.
    RESULTS: Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects.
    CONCLUSIONS: Triptolide can be used alone or in combination with existing therapeutic modalities as novel treatments for autoimmune disorders, cancers, and for immunosuppression.
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