mechanisms of action

行动机制
  • 文章类型: Journal Article
    四氢大麻酚(THCV)是一种植物大麻素,在北美大麻市场上越来越受欢迎。据报道,在几项独立的临床前研究中,THCV可以降低血糖并作为食欲抑制剂。这为它赢得了“减肥杂草”的流行绰号,“尽管对这些影响的人类研究很少。此外,THCV通常被错误地归类为四氢大麻酚(THC)的令人陶醉的类似物,这在消费者和监管机构之间造成了混乱。在这篇文章中,我们检查了临床前和临床上关于THCV的已知情况,并强调行动机制,为了阐明THCV和THC之间的科学差异。THCV,虽然在结构上与THC相似,在文献中目前报道的剂量下具有不同的药理活性和生理作用。我们强调了进一步THCV研究的机会领域,以确定独特健康的全部和适当潜力,健康,和该化合物的治疗应用。
    Tetrahydrocannabivarin (THCV) is a phytocannabinoid that is becoming popular across the North American cannabis market. THCV has been reported to reduce blood sugar and act as an appetite suppressant in several independent pre-clinical studies, which has earned it the popular nickname of \"diet weed,\" despite few human studies of these effects. Additionally, THCV is usually and incorrectly categorized as an intoxicating analogue of tetrahydrocannabinol (THC), which causes confusion among both consumers and regulators. In this article, we examine what is known pre-clinically and clinically about THCV, as well as highlight mechanisms of action, in order to clarify the scientific differences between THCV and THC. THCV, although structurally similar to THC, has distinct pharmacological activity and physiological effects at the doses currently reported in the literature. We highlight areas of opportunity for further THCV research in order to determine the full and appropriate potential for unique health, wellness, and therapeutic applications of this compound.
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  • 文章类型: Journal Article
    炎症是一种复杂的生物反应,在各种病理状况中起着关键作用,包括炎症性疾病。寻找有效的治疗剂导致研究人员探索天然产物,因为它们具有不同的化学组成和潜在的治疗益处。这篇综述全面审查了天然产物作为炎症性疾病潜在治疗剂的研究现状。本文讨论了各种天然化合物的抗炎特性,他们的行动机制,以及它们在治疗炎症性疾病方面的潜在应用。此外,配方和交付系统,也强调了这一领域的挑战和未来前景。
    Inflammation is a complex biological response that plays a pivotal role in various pathological conditions, including inflammatory diseases. The search for effective therapeutic agents has led researchers to explore natural products due to their diverse chemical composition and potential therapeutic benefits. This review comprehensively examines the current state of research on natural products as potential therapeutic agents for inflammatory diseases. The article discusses the antiinflammatory properties of various natural compounds, their mechanisms of action, and their potential applications in managing inflammatory disorders. Additionally, formulation and delivery systems, challenges and future prospects in this field are also highlighted.
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  • 文章类型: Journal Article
    全球范围内,乳腺癌(BC)在恶性疾病中患病率最高。BC也是女性死亡的主要原因。值得注意的是,BC发病率一直以每年约2.2%的增长率持续增加。持续BC是世界范围内的主要公共卫生问题。因此,应该紧急开发新的化疗药物来对抗这种致命的疾病。香豆素具有有趣的结构和机理变化,在几种形式的BC中表现出有希望的活性,包括具有多重耐药性的BCs。特别是,由香豆素和一种或多种抗BC药效团组成的香豆素杂种可以同时靶向BC细胞中的不同生物组分。因此,香豆素杂种是有用的支架,可以帮助提高香豆素的抗BC功效,减少副作用,改善药代动力学,尽量减少药物-药物相互作用,规避耐药性。这次审查,其中对2020年至今发表的文章进行了评估,突出显示对乳腺癌具有治疗作用的香豆素杂种的景观。这些发现可以帮助对新型抗乳腺癌疗法的进一步研究。
    Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.
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  • 文章类型: Journal Article
    背景:植物病原体每年造成大量作物损失,对全球粮食安全构成严重威胁。杀菌剂通常用于控制它们,但是农药抗性的快速发展使许多无效,因此,寻找新型高效的绿色农药来预防和控制植物病害已成为农作物种植的重中之重。
    结果:生物测定研究的结果表明,大多数目标化合物在体外表现出一定的抗菌活性。特别是,化合物X7对水稻黄单胞菌pv具有较高的抑制活性。稻米(Xoo),EC50值为27.47μgmL-1,超过了噻唑锌(41.55μgmL-1)和噻二唑铜(53.39μgmL-1)等常规对照剂。对分子对接的进一步研究表明,X7与2FBW具有很强的结合亲和力。通过扫描电子显微镜观察到的形态变化表明,在X7处理下,Xoo的表面出现皱纹和破裂,通过无标记蛋白质组分析总共2662个蛋白质。三个实验阐明了X7诱导Xoo生理和生化特性发生重大变化的机制,进而影响细菌的繁殖和生长。
    结论:这项工作代表了关键的进步,为防治植物病原体的研究和开发提供了重要的参考。©2024化学工业学会。
    BACKGROUND: Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting.
    RESULTS: The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro. In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 27.47 μg mL-1, surpassing conventional control agents such as thiazole zinc (41.55 μg mL-1) and thiodiazole copper (53.39 μg mL-1). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo, which in turn affected the reproduction and growth of bacteria.
    CONCLUSIONS: This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    水稻细菌性叶枯病和水稻细菌性条斑对世界范围内的水稻生产造成了巨大的危害。为了发现一种有效的新型抗菌剂,首次设计并合成了一系列含有1,3,4-恶二唑和酰胺部分的新型反式白藜芦醇(RSV)衍生物。它们中的大多数对米黄单胞菌和米黄单胞菌均表现出优异的抗菌活性。尤其是,化合物J12抑菌效果最好,半数最大有效浓度为4.2和5.0mg/L,分别,优于RSV(63.7和75.4mg/L),双甲噻唑(79.5和89.6mg/L),和噻二唑铜(105.4和112.8mg/L)。此外,化合物J12对水稻细菌性条纹和水稻细菌性叶枯病具有良好的防治效果,保护活性为46.2%和42.1%,治疗活性为44.5%和41.7%,分别。初步机制表明,化合物J12不仅能显著降低生物膜的形成,胞外多糖生产,和胞外酶的合成,但也破坏细菌细胞表面的形态,从而降低细菌的致病性。此外,化合物J12可以增加防御相关酶的活性,并影响多种致病相关基因的表达,包括植物-病原体相互作用,MAPK信号通路,和苯丙素生物合成,这可以提高水稻对水稻细菌性条纹感染的防御能力。目前的工作表明,RSV衍生物可以用作开发抗菌剂的有希望的候选物。
    Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.
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  • 文章类型: Journal Article
    大蒜(AlliumsativumL.)是一种广泛丰富的香料,以其香气和辛辣的味道而闻名。它含有几种生物活性化合物,为人类提供广泛的健康益处,包括那些与营养有关的,生理学,和医学。因此,大蒜被认为是最有效的疾病预防饮食之一。许多体外和体内研究报道了含硫化合物,大蒜素和ajoene,因为它们有效的抗癌,抗糖尿病,抗炎,抗氧化剂,抗菌,免疫增强,和心脏保护特性。作为生物活性化合物的丰富天然来源,包括多糖,皂苷,单宁,芳樟醇,香叶醇,phellandrene,β-phellandrene,ajoene,Alliin,S-烯丙基-巯基半胱氨酸,和β-phellandrene,大蒜具有许多治疗性应用,可能在针对各种人类疾病的药物开发中发挥作用。在当前的审查中,讨论了大蒜及其主要生物活性成分及其生物学功能和作用机制,以及它们在疾病预防和治疗中的作用。
    Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, β-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and β-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
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  • 文章类型: Journal Article
    背景:为了发现更有效的农业抗菌剂,制备了一系列包含哌嗪接头和N-乙酰基部分的新喹唑啉衍生物,并评估了它们的抗菌和抗真菌活性。
    结果:所有目标化合物均通过1H和13CNMR以及高分辨率质谱(HRMS)进行表征,结合4-三氟甲氧基取代基的最有效的化合物E19的化学结构通过单晶X射线衍射测量清楚地证实。生物测定结果表明,某些化合物在体外对米黄单胞菌pv细菌具有明显的抑制作用。oryzicola(Xoc)。例如,化合物E19对该病原体的EC50(50%活性的有效浓度)值为7.1μg/mL,比商业杀菌剂噻二唑铜和双甲噻唑(EC50=110.2和72.4μg/mL,分别)。随后,机理研究表明,化合物E19可能通过改变细胞形态发挥其抗菌功效,增加细菌细胞质膜的通透性,抑制细菌胞外多糖和胞外酶活性(淀粉酶和纤维素酶)的产生,并阻止Xoc的游泳运动。此外,蛋白质组学分析表明,化合物E19可以通过下调相关差异蛋白的表达来减少细菌鞭毛的生物合成并降低鞭毛运动。
    结论:化合物E19显示出作为用于控制Xoc的候选杀菌剂的进一步开发的良好潜力。©2024化学工业学会。
    BACKGROUND: To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N-acetyl moiety were prepared and assessed for their antibacterial and antifungal activities.
    RESULTS: All the target compounds were characterized by 1H and 13C NMR as well as high-resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4-trifluoromethoxy substituent was clearly confirmed via single crystal X-ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15- and 10-fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC50 = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down-regulating the expression of the related differential proteins.
    CONCLUSIONS: Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    肝癌在全球癌症相关死亡原因中排名第三,构成了重大的公共卫生挑战。然而,目前的治疗方法不足,促使人们对小说的需求不断增长,安全,和有效的治疗方法。天然产物(NPs)由于其多样化的生物活性而成为药物开发中的有希望的候选物。低毒性,和最小的副作用。本文首先对肝癌的现有治疗方法和药物进行综述。然后总结了来自各种来源的NP对肝癌的治疗效果。最后,我们分析了NPs治疗肝癌的潜在机制,包括抑制血管生成,迁移,和侵袭;细胞周期的调节;诱导凋亡,自噬,焦亡,和铁凋亡;对肿瘤代谢的影响;免疫调节;肠道功能的调节;以及关键信号通路的调节。本系统综述旨在全面概述NPs在肝癌治疗中的研究。为药物和功能食品的进一步开发和应用奠定了基础。
    Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
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  • 文章类型: Journal Article
    外来体已成为细胞间通讯和细胞与其环境之间的各种生理过程的关键介质。这些纳米大小的囊泡已被广泛研究并证实在动物系统中表现出多功能性。特别是,它们参与细胞间信号传导,影响疾病进展,并表现出生物活性。然而,植物来源外泌体(PDEs),尤其是治疗性PDEs,在过去的几十年中,受到的关注相对有限。最近的研究表明,PDEs除了参与细胞间的通讯外,还参与信号分子的转运。因为它们在细胞微环境中充当功能分子。这一特点突出了PDE在广泛的应用中的巨大潜力,包括抗氧化,抗炎,肿瘤细胞消除,免疫调节,和组织再生。此外,PDE作为有效的药物载体有着巨大的希望,增强治疗剂的稳定性和生物利用度,并因此能够靶向递送至特定细胞或组织。因此,PDE可以作为药物递送和治疗各种疾病的有效工具。这篇全面的综述概述了治疗性PDEs的最新研究,专注于他们的提取,隔离,表征方法,生物活动,和应用前景。综述了药用植物外泌体样纳米囊泡的研究进展,特别强调中医,并强调了它们在疾病治疗和纳米颗粒递送中的重要性。主要目标是加速这些纳米囊泡的临床翻译,同时为创新药物的研究和开发提供新的方法和方法。
    Exosomes have emerged as critical mediators of intercellular communication and various physiological processes between cells and their environment. These nano-sized vesicles have been extensively investigated and confirmed to exhibit multifunctionality in animal systems. In particular, they participate in intercellular signaling, influence disease progression, and exhibit biological activity. However, Plant-Derived Exosomes (PDEs), especially therapeutic PDEs, have received relatively limited attention in the past few decades. Recent studies have demonstrated that PDEs are involved in signaling molecule transport in addition to intercellular communication, as they serve as functional molecules in the cellular microenvironment. This characteristic highlights the immense potential of PDEs for a wide array of applications, including antioxidation, anti-inflammation, tumour cell elimination, immune modulation, and tissue regeneration. In addition, PDEs hold substantial promise as efficient drug carriers, enhancing the stability and bioavailability of therapeutic agents and consequently enabling targeted delivery to specific cells or tissues. Therefore, PDEs may serve as effective tools for drug delivery and the treatment of various diseases. This comprehensive review provides an overview of recent studies on therapeutic PDEs, focusing on their extraction, isolation, characterization methods, biological activities, and application prospects. It summarises the research progress of exosome-like nanovesicles derived from medicinal plants, with a specific emphasis on traditional Chinese medicine, and highlights their importance in disease treatment and nanoparticle delivery. The main objective is to accelerate the clinical translation of these nanovesicles while providing novel approaches and methodologies for the research and development of innovative drugs.
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  • 文章类型: Journal Article
    阅读(RAx)和将化学品分类是毒理学中众所周知的概念。最近,ECHA提出了一种用于危险识别的支链羧酸(BCA)的分组方法,其中包括60多种支链饱和羧酸。分组仅基于结构考虑。由于两个成员的发展影响,ECHA假定“所有短碳链酸。..很可能是生殖和发育毒物。“这项工作分析了BCA的可用数据。通过消除BCA的金属和有机盐,可以显着减少该组中化合物的数量,未知或可变组成的化合物,和复杂的反应产物或生物材料(UVCB化合物)。对于所产生的减少数量的化合物,类似的物理化学数据和预期的类似生物转化支持分组。然而,对该组化合物的不良反应分析和机理信息表明,BCA,作为一个班级,不会对大鼠造成发育影响。相反,发育毒性仅限于具有共同作用模式(组蛋白脱乙酰酶抑制)的特定结构的选定BCA。因此,提议的分组范围不合理,更详细的分析表明,仅结构相似性不足以将支链羧酸分组以产生发育毒性。
    Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that \"all short carbon chain acids … are likely reproductive and developmental toxicants\". This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.
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