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Study on the anti-atherosclerosis mechanisms of Tanyu Tongzhi formula based on network pharmacology, Mendelian randomization, and experimental verification. 基于网络药理学、孟德尔随机化和实验验证的丹俞通脉方抗动脉粥样硬化机制研究
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1080/13880209.2024.2415666
Jin Dai, Xinbin Zhou, Xiaoming Xu, Yuangang Qiu, Shenjie Chen, Wei Mao

Context: Tanyu Tongzhi Formula (TTF) exhibits potential against atherosclerosis; however, its mechanisms remain unclear.

Objective: This study explores the pharmacological mechanisms of TTF in treating atherosclerosis.

Materials and methods: Network pharmacology, molecular docking, mendelian randomization (MR), and liquid chromatography-mass spectrometry (LC-MS) analyses were utilized to reveal potential targets and compounds of TTF against atherosclerosis. After exploring the appropriate concentration of TTF to treat HCAECs using Cell Counting Kit-8 (CCK-8), the HCAECs were divided into three groups: control, oxidized low-density lipoprotein (ox-LDL, 50 μg/mL), and ox-LDL (50 μg/mL) + TTF (1 mg/mL). After 24-h incubation, the efficacy of TTF was verified by CCK-8, Oil red O staining, and ELISA. The expression of key targets was detected by real-time polymerase chain reaction (qPCR) and western blotting.

Results: A total of 137 active compounds and 127 potential TTF targets against atherosclerosis were identified. MR identified ALB, TNF, PPARα, and PPARγ as key targets. Molecular docking indicated that baicalin, naringenin, and curcumin exhibited suitable binding activities to these targets, further confirming by LC-MS analysis. The IC50 of TTF in HCAECs was 18.25 mg/mL. TTF treatment significantly improved atherosclerosis by enhancing cell viability, reducing lipid accumulation, and inhibiting inflammation factors (IL6, IL1B and TNF-α) in ox-LDL-treated HCAECs. Moreover, qPCR or western blotting indicated that TTF could up-regulate PPARα and PPARγ while down-regulate TNF expression.

Discussion and conclusions: Our results revealed active compounds, key pathways, and core targets of TTF against atherosclerosis, providing experimental support for its application in treating of atherosclerosis.

背景:田雨通脉方(TTF)具有抗动脉粥样硬化的作用,但其作用机制尚不清楚:本研究探讨了 TTF 治疗动脉粥样硬化的药理机制:利用网络药理学、分子对接、泯灭随机化(MR)和液相色谱-质谱(LC-MS)分析揭示了 TTF 治疗动脉粥样硬化的潜在靶点和化合物。在利用细胞计数试剂盒-8(CCK-8)探索了处理HCAEC的TTF的适当浓度后,HCAEC被分为三组:对照组、氧化低密度脂蛋白(ox-LDL,50 μg/mL)组和ox-LDL(50 μg/mL)+TTF(1 mg/mL)组。孵育 24 小时后,通过 CCK-8、油红 O 染色和酶联免疫吸附试验验证 TTF 的功效。通过实时聚合酶链式反应(qPCR)和免疫印迹法检测关键靶标的表达:结果:共鉴定出 137 种活性化合物和 127 个潜在的 TTF 靶点,这些化合物和靶点都能对抗动脉粥样硬化。MR确定ALB、TNF、PPARα和PPARγ为关键靶点。分子对接表明,黄芩苷、柚皮苷和姜黄素与这些靶标具有合适的结合活性,LC-MS分析进一步证实了这一点。TTF 在 HCAECs 中的 IC50 值为 18.25 mg/mL。TTF通过提高细胞活力、减少脂质积累和抑制炎症因子(IL6、IL1B和TNF-α),明显改善了经ox-LDL处理的HCAECs的动脉粥样硬化。此外,qPCR或Western印迹表明,TTF能上调PPARα和PPARγ,同时下调TNF的表达:我们的研究结果揭示了TTF抗动脉粥样硬化的活性化合物、关键通路和核心靶点,为其在动脉粥样硬化治疗中的应用提供了实验支持。
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引用次数: 0
Therapeutic efficacy and pharmacological mechanism of Bailing capsule on chronic obstructive pulmonary disease: a meta-analysis and network pharmacology. 百令胶囊对慢性阻塞性肺病的疗效和药理机制:荟萃分析和网络药理学。
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-26 DOI: 10.1080/13880209.2024.2415643
Guanzhou Ma, Yang Jin

Context: Bailing capsule, derived from Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae), has shown potential in the treatment of chronic obstructive pulmonary disease (COPD), a prevalent respiratory disorder.

Objective: This study elucidates the efficacy and mechanism of action of the use of Bailing capsules in the treatment of COPD using meta-analysis and network pharmacology.

Materials and methods: A meta-analysis of randomized controlled trials (RCTs) was performed. The treatment group received Bailing capsules alongside standard therapy, while the control group received standard therapy or in combination with other traditional Chinese medicines. Efficacy outcomes included lung function, exercise tolerance, acute exacerbation risk, and quality of life. Network pharmacology and molecular docking identified key targets of Bailing capsules.

Results: The meta-analysis of 27 RCTs showed significant improvements in the treatment group for forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the 6-min walk test (6MWT). Additionally, there was a marked reduction in acute COPD attacks and an improvement in quality of life. Meanwhile, network pharmacological analysis identified SRC, HIF1A, NFKB1, HDAC2, and PRKACA, as the potential core targets for Bailing capsules in the treatment of COPD.

Discussion and conclusion: Bailing capsules have shown promising results in the treatment of stable COPD. Future studies should focus on large-scale, multicenter RCTs to confirm the long-term benefits and safety of Bailing capsules.

背景:百令胶囊提取自冬虫夏草(Cordyceps sinensis (Berk.) Sacc.)(Clavicipitaceae),在治疗慢性阻塞性肺疾病(COPD)(一种流行的呼吸系统疾病)方面具有潜力:本研究利用荟萃分析和网络药理学阐明了百令胶囊治疗慢性阻塞性肺疾病的疗效和作用机制:对随机对照试验(RCT)进行荟萃分析。治疗组在接受标准疗法的同时服用百令胶囊,对照组则接受标准疗法或与其他中药联合治疗。疗效结果包括肺功能、运动耐量、急性加重风险和生活质量。网络药理学和分子对接确定了百令胶囊的关键靶点:对 27 项研究性临床试验进行的荟萃分析表明,治疗组的 1 秒用力呼气容积(FEV1)、FEV1/FVC 比值和 6 分钟步行测试(6MWT)均有显著改善。此外,慢性阻塞性肺疾病急性发作明显减少,生活质量也有所提高。同时,网络药理学分析发现,SRC、HIF1A、NFKB1、HDAC2和PRKACA是百令胶囊治疗慢性阻塞性肺疾病的潜在核心靶点:百令胶囊在稳定期慢性阻塞性肺疾病的治疗中显示出良好的效果。未来的研究应侧重于大规模、多中心 RCT,以证实百令胶囊的长期疗效和安全性。
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引用次数: 0
Comparative efficacy and safety of Chinese patent medicines as an adjunctive therapy for diabetic peripheral neuropathy: systematic review and network meta-analysis of randomized controlled trials. 中成药作为糖尿病周围神经病变辅助疗法的疗效和安全性比较:随机对照试验的系统综述和网络荟萃分析。
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/13880209.2024.2422084
Qun Wang, Hui Xie, Zihong Wang, Runyun Huang, Min Xu, Yongjun Li, Lingling Shan, Hongyan Zhang, Xianghong Liu, Hongxing Zhang, Yunsheng Xu, Shiguang Sun

Context: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN.

Objective: This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN.

Materials and methods: We conducted searches for randomized controlled trials (RCTs) evaluating CPMs in conjunction with mecobalamin (Mec) or alpha-lipoic acid (αLA) across eight databases up to July 2024. The surface under the cumulative ranking area (SUCRA) was utilized to assess the clinical efficacy rate (CER), the peroneal motor nerve conduction velocity (pMNCV), the peroneal sensory nerve conduction velocity (pSNCV), the median motor nerve conduction velocity (mMNCV), and the median sensory nerve conduction velocity (mSNCV).

Results: The search yielded 128 eligible studies with 31 CPMs with Mec and 39 eligible studies with 17 CPMs with αLA. SUCRA rankings indicated that, when combined with Mec, Mailuoning liquid (lMLN) was the most effective regimen for CER, Honghua injection (iHH) for pMNCV, Maixuekang capsule (cMXK) for pSNCV, Dengzhanxixin injection (iDZXX) for mMNCV, and Tongxinluo capsule (cTXL) for mSNCV. Combined with αLA, Danhong injection (iDH) showed the highest efficacy for CER, pSNCV, and mSNCV, while Xueshuantong injection (iXShT) was the most effective for pMNCV and mMNCV.

Conclusion: This network meta-analysis confirms the efficacy and safety of 37 CPMs combined with Mec or αLA for treating DPN. However, given the potential risk of bias and the very low certainty of the evidence, these recommendations should be adopted with caution.

背景:糖尿病周围神经病变(DPN)是糖尿病最常见的并发症。中成药在临床上被广泛用于治疗糖尿病周围神经病变:本研究旨在总结有关中成药作为 DPN 辅助疗法的危害和益处的最新证据:我们在 8 个数据库中检索了截至 2024 年 7 月评估 CPM 与甲钴胺 (Mec) 或α-硫辛酸 (αLA)联用的随机对照试验 (RCT)。利用累积排名面积下表面(SUCRA)评估临床有效率(CER)、腓运动神经传导速度(pMNCV)、腓感觉神经传导速度(pSNCV)、正中运动神经传导速度(mMNCV)和正中感觉神经传导速度(mSNCV):搜索结果显示,128 项符合条件的研究中有 31 项研究的正中运动神经传导速度为 Mec,39 项符合条件的研究中有 17 项研究的正中感觉神经传导速度为 αLA。SUCRA排名显示,与Mec联合使用时,麦络宁液(lMLN)对CER最有效,红花注射液(iHH)对pMNCV最有效,麦雪康胶囊(cMXK)对pSNCV最有效,灯盏细辛注射液(iDZXX)对mMNCV最有效,通心络胶囊(cTXL)对mSNCV最有效。结合αLA,丹红注射液(iDH)对CER、pSNCV和mSNCV的疗效最高,而学双通注射液(iXShT)对pMNCV和mMNCV的疗效最好:这项网络荟萃分析证实了37种CPM联合Mec或αLA治疗DPN的有效性和安全性。然而,鉴于潜在的偏倚风险和证据的确定性很低,应谨慎采纳这些建议。
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引用次数: 0
Advances in Traditional Chinese Medicine research in diabetic kidney disease treatment. 中医药治疗糖尿病肾病的研究进展。
IF 3.8 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-15 DOI: 10.1080/13880209.2024.2314705
Shiyi Shen, Huiyun Zhong, Xiaoshi Zhou, Guolin Li, Changji Zhang, Yulian Zhu, Yong Yang

Context: Diabetic kidney disease (DKD) is a prominent complication arising from diabetic microangiopathy, and its prevalence and renal impact have placed it as the primary cause of end-stage renal disease. Traditional Chinese Medicine (TCM) has the distinct advantage of multifaceted and multilevel therapeutic attributes that show efficacy in improving clinical symptoms, reducing proteinuria, protecting renal function, and slowing DKD progression. Over recent decades, extensive research has explored the mechanisms of TCM for preventing and managing DKD, with substantial studies that endorse the therapeutic benefits of TCM compounds and single agents in the medical intervention of DKD.

Objective: This review lays the foundation for future evidence-based research efforts and provide a reference point for DKD investigation.

Methods: The relevant literature published in Chinese and English up to 30 June 2023, was sourced from PubMed, Cochrane Library, VIP Database for Chinese Technical Periodicals (VIP), Wanfang Data, CNKI, and China Biology Medicine disc (CBM). The process involved examining and summarizing research on TCM laboratory tests and clinical randomized controlled trials for DKD treatment.

Results and conclusions: The TCM intervention has shown the potential to inhibit the expression of inflammatory cytokines and various growth factors, lower blood glucose levels, and significantly affect insulin resistance, lipid metabolism, and improved renal function. Furthermore, the efficacy of TCM can be optimized by tailoring personalized treatment regimens based on the unique profiles of individual patients. We anticipate further rigorous and comprehensive clinical and foundational investigations into the mechanisms underlying the role of TCM in treating DKD.

背景:糖尿病肾病(DKD)是糖尿病微血管病变引起的突出并发症,其发病率和对肾脏的影响使其成为终末期肾病的主要病因。中医药在改善临床症状、减少蛋白尿、保护肾功能、延缓 DKD 进展等方面具有多方面、多层次的显著疗效。近几十年来,大量研究探索了中医药预防和控制 DKD 的机制,其中大量研究认可了中药复方和单方在 DKD 医疗干预中的疗效:本综述为今后的循证研究工作奠定了基础,并为 DKD 研究提供了一个参考点:方法:从PubMed、Cochrane图书馆、中国科技期刊数据库(VIP)、万方数据、中国知网(CNKI)和中国生物医学文献数据库(CBM)中检索截至2023年6月30日发表的相关中英文文献。研究过程包括对中医实验室检查和临床随机对照试验治疗 DKD 的研究进行检查和总结:中医药干预具有抑制炎症细胞因子和各种生长因子的表达、降低血糖水平、显著影响胰岛素抵抗、脂代谢和改善肾功能的潜力。此外,还可以根据个体患者的独特情况,量身定制个性化的治疗方案,从而优化中医药的疗效。我们期待着对中药治疗 DKD 的作用机制开展进一步严格而全面的临床和基础研究。
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引用次数: 0
Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine. 优化同时定量阿莫替尼和 HAS-719 的灵敏可靠的 UPLC-MS/MS 方法,并将其应用于研究与尼卡地平的相互作用。
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-14 DOI: 10.1080/13880209.2024.2425648
Dongxin Chen, Jie Chen, Yuxin Shen, Xiaohai Chen, Hailun Xia, Ya-Nan Liu, Ren-Ai Xu

Context: Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.

Objective: For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched.

Materials and methods: Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively.

Results: There was favourable linearity in the 0.5-200 ng/mL calibration range for almonertinib and 0.5-100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC(0-∞), AUC(0-t) and Cmax, but had no effect on the metabolism of HAS-719.

Conclusion: According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo.

背景阿莫替尼主要通过CYP3A4代谢,因此可能与多种通过CYP3A4代谢的药物发生相互作用,导致全身暴露量的变化:本实验优化并全面验证了一种准确、简便的超高效液相色谱串联质谱(UPLC-MS/MS)检测方法,用于同时定量检测阿莫替尼及其代谢物HAS-719,并研究了阿莫替尼与尼卡地平在体内和体外的药物相互作用(DDI):采用UPLC-MS/MS和多反应监测(MRM)正离子模式检测分析物,阿莫替尼的离子跃迁为m/z 526.01 → 72.04,HAS-719的离子跃迁为m/z 512.18 → 455.08,IS的离子跃迁为m/z 447.16 → 128.11:阿仑替尼和HAS-719在0.5-200 ng/mL的校准范围和0.5-100 ng/mL的校准范围内线性良好。两种分析物的定量下限(LLOQ)均为 0.5 纳克/毫升。方法学验证所要求的精密度、准确度、稳定性、基质效应和提取回收率均符合FDA指南的要求。随后,UPLC-MS/MS测定法成功用于阿莫替尼和尼卡地平在体内和体外的相互作用。在大鼠肝脏微粒体(RLM)中,尼卡地平对阿莫替尼代谢的半最大抑制浓度(IC50)为1.19 μM,尼卡地平对阿莫替尼代谢的抑制机制为混合抑制。在大鼠药代动力学实验中观察到,尼卡地平能显著改变阿莫替尼的药代动力学特征,包括AUC(0-∞)、AUC(0-t)和Cmax,但对HAS-719的代谢没有影响:结论:研究结果表明,尼卡地平能抑制阿莫替尼的体内外代谢。
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引用次数: 0
Effects of total coumarins from Pileostegia tomentella on exosomal miRNA expression and angiogenesis in colorectal cancer cells. Pileostegia tomentella 中的总香豆素对结直肠癌细胞外泌体 miRNA 表达和血管生成的影响
IF 3.8 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-12 DOI: 10.1080/13880209.2024.2309871
Ying Liu, Dao-Hai Cheng, Zheng-Ying Su, Ji-Hua Lv, Li Wang, Yu-Yin Deng, Li Li

Context: Pileostegia tomentella Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.

Objective: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.

Materials and methods: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.

Results: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.

Discussion and conclusion: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC.

上下文:Pileostegia tomentella Hand.Mazz(Saxifragaceae)总香豆素(TCPT)对结直肠癌(CRC)具有抗肿瘤活性,但作用机制不明。外泌体衍生的 miRNA 介导的肿瘤血管生成显示了内皮细胞功能在 CRC 转移中的重要调节作用:材料与方法:从人 CRC 细胞(HT-29)或用 TCPT(100 μg/mL)处理 24 小时后产生的 HT-29 衍生外泌体,然后通过透射电子显微镜、纳米颗粒追踪分析(NTA)和 Western 印迹进行鉴定。进行了人脐静脉内皮细胞(HUVECs)和外泌体的共培养实验,以检测外泌体在HUVECs中的吸收及其对HUVECs细胞迁移和管腔形成能力的影响。通过测序技术筛选出外泌体中潜在的目标 miRNA。结果表明:外泌体对HUVECs细胞的迁移和管腔形成能力有影响:结果:HT-29衍生的外泌体经过TCPT处理(Exo-TCPT)后,抑制了HUVECs的迁移和管腔形成,降低了血管标志物(FLT-1、VCAM-1和VEGFR-2)在HUVECs中的表达水平。此外,在 Exo-TCPT 中,miR-375-3p 的水平明显上调。拯救实验表明,HUVECs 中 miR-375-3p 的高表达抑制了迁移和管腔形成能力,这与 Exo-TCPT 的效果一致,而应用 miR-375-3p 抑制剂则显示出相反的效果:TCPT在CRC中具有抗血管生成作用,可能是通过上调外泌体miR-375-3p实现的。我们的研究结果将揭示外泌体 miRNA 介导的肿瘤微环境的新靶点,以及 Pileostegia tomentella 在 CRC 中的治疗应用。
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引用次数: 0
Design, synthesis and biological evaluation of novel podophyllotoxin derivatives as tubulin-targeting anticancer agents. 作为微管蛋白靶向抗癌剂的新型荚叶素衍生物的设计、合成和生物学评价。
IF 3.8 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-23 DOI: 10.1080/13880209.2024.2318350
Yujin Guo, Beibei Chen, Jinxiu Guo, Pei Jiang, Jianhua Wang, Wenxue Sun

Context: Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.

Objective: This study synthesizes PPT derivatives to assess their anticancer activities.

Materials and methods: Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound E5 on A549 cell growth were evaluated through molecular docking, in vitro assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and in vivo tests in female BALB/c nude mice treated with E5 (2 and 4 mg/kg). E5 (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.

Results: Among the 16 PPT derivatives tested for cytotoxicity, E5 exhibited potent effects against A549 cells (IC50: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. E5-induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of E5 to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.

Discussion and conclusions: This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with E5 call for extended research and clinical validation, leading to novel and more effective cancer therapies.

背景:用于癌症治疗的鬼臼毒素(PPT)衍生物需要向提高疗效和降低毒性的方向发展:本研究合成了 PPT 衍生物,以评估其抗癌活性:采用 CCK-8 检测法测试了化合物 E1-E16 对四种人类癌细胞株(H446、MCF-7、HeLa、A549)和两种正常细胞株(L02、BEAS-2B)的抗增殖活性。化合物 E5 对 A549 细胞生长的影响是通过分子对接、体外试验(流式细胞仪、伤口愈合、Transwell、菌落形成、Western 印迹)以及用 E5(2 毫克/千克和 4 毫克/千克)处理雌性 BALB/c 裸鼠的体内试验来评估的。与二甲基亚砜对照组相比,E5(4 毫克/千克)能明显减少异种移植肿瘤的生长:结果:在进行细胞毒性测试的 16 种 PPT 衍生物中,E5 对 A549 细胞具有强效作用(IC50:0.35 ± 0.13 µM),在抑制异种移植瘤生长方面超过了参考药物 PPT 和依托泊苷。E5 诱导的细胞周期停滞在 S 期和 G2/M 期,加速了微管蛋白的解聚,触发了细胞凋亡和线粒体去极化,同时调节了细胞凋亡相关蛋白的表达,有效抑制了细胞的迁移和侵袭,表明其具有限制转移的潜力。分子对接显示,E5与秋水仙碱位点的小管蛋白和Akt结合,从而下调PI3K/Akt通路蛋白:这项研究为通过开发和使用 PPT 衍生物推进癌症治疗奠定了基础。与 E5 相关的令人鼓舞的结果要求进行更广泛的研究和临床验证,从而开发出更有效的新型癌症疗法。
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引用次数: 0
Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification. 基于网络药理学、孟德尔随机分析和实验验证的桃红四物汤治疗色素沉着的分子机制。
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-03-31 DOI: 10.1080/13880209.2024.2330609
Jun Chen, Wenyi Ye

Context: Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.

Objective: This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.

Materials and methods: We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.

Results: ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC50) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.

Discussion and conclusion: THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.

背景:色素沉着是一种以黑色素生成过多为特征的常见皮肤病,目前有效的治疗方法有限:本研究探讨桃红四物汤(THSWD)对色素沉着的影响,并阐明其潜在机制:我们采用网络药理学、孟德尔随机化和分子对接等方法来确定桃红四物汤抗色素沉着的中心靶点和机制。细胞计数试剂盒-8(CCK-8)测定法确定了适合 PIG1 细胞的 THSWD 处理浓度。将这些细胞暴露于不同浓度的含 THSWD 血清(2.5%、5%、10%、15%、20%、30%、40% 和 50%),并用 α-MSH (100 nM)处理,以诱导体外色素沉着模型。评估包括黑色素含量、酪氨酸酶活性和 Western 印迹:结果:ALB、IL6 和 MAPK3 成为主要靶点,而槲皮素、芹菜素和木犀草素则是核心活性成分。CCK-8 检测表明,2.5% 至 20% 的浓度适合 PIG1 细胞,50% 的细胞毒性浓度(CC50)为 32.14%。THSWD 可明显降低 α-MSH 诱导的 PIG1 细胞中的黑色素含量和酪氨酸酶活性,同时下调 MC1R 和 MITF 的表达。THSWD 提高了模型细胞中 ALB 和 p-MAPK3/MAPK3 的水平,降低了 IL6 的表达:THSWD通过靶向ALB、IL6和MAPK3缓解色素沉着。这项研究为 THSWD 作为色素沉着的新型治疗方法应用于临床铺平了道路,并提供了新的靶向治疗策略。
{"title":"Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification.","authors":"Jun Chen, Wenyi Ye","doi":"10.1080/13880209.2024.2330609","DOIUrl":"10.1080/13880209.2024.2330609","url":null,"abstract":"<p><strong>Context: </strong>Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.</p><p><strong>Objective: </strong>This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.</p><p><strong>Materials and methods: </strong>We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an <i>in vitro</i> hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.</p><p><strong>Results: </strong>ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC<sub>50</sub>) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.</p><p><strong>Discussion and conclusion: </strong>THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"296-313"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detoxification of paraoxon-ethyl by Lysiphyllum strychnifolium extracts in undifferentiated human neuroblastoma SH-SY5Y cells. 马钱子萃取物在未分化的人神经母细胞瘤 SH-SY5Y 细胞中对乙草胺的解毒作用
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-25 DOI: 10.1080/13880209.2024.2430262
Niramai Ekaratcharoenchai, Thararat Nualsanit, Aungkana Krajarng

Context: Lysiphyllum strychnifolium (Craib) A. Schmitz. (Fabaceae) is a Thai traditional medicine used to remove food and alcohol toxins from the body.

Objective: This study investigates the molecular mechanism of L. strychnifolium extracts against paraoxon-ethyl-induced apoptosis in SH-SY5Y cells.

Materials and methods: The ethanol and water extracts of leaves and stems of L. strychnifolium were prepared at various concentrations (0-100 μg/mL) and co-treated to the cells with 0.375 mM paraoxon-ethyl for 24 and 48 h. Cell viability was performed using the PrestoBlue assay. ROS and caspase activity were detected using 2',7'-dichlorodihydrofluorecein diacetate and caspase-Glo® 3/7, 8, and 9 assay kits. Apoptotic and ER stress-related gene expression were determined by real-time PCR, and nuclear and mitochondrial morphology were observed using Hoechst 33342 and MitoTracker® Deep Red FM staining.

Results: The most effective concentrations of each extract against paraoxon-ethyl-induced cell death were 25 μg/mL of leaf ethanol, 12.5 μg/mL of stem ethanol, 100 μg/mL of leaf water, and 25 μg/mL of stem water extracts. The leaf ethanol extract was the most effective at detoxifying, while stem extracts were highly toxic in high doses. The detoxifying L. strychnifolium extracts against paraoxon-ethyl-induced oxidative stress decreased p53, BiP/GRP78, and CHOP gene expression and minimized caspase 9 and caspase 3, protecting cells from apoptosis. The extracts could also restore mitochondrial membrane potential and reduce the swollen globule mitochondrial shape.

Discussion and conclusion: These findings could potentially protect neuron cells from neurodegenerative issues due to oxidative damage, apoptosis, and other potential consequences.

上下文:Lysiphyllum strychnifolium (Craib) A. Schmitz.(Fabaceae)是一种泰国传统药物,用于清除体内的食物和酒精毒素:本研究探讨了马钱子提取物抗乙基paraoxon诱导的SH-SY5Y细胞凋亡的分子机制:制备不同浓度(0-100 μg/mL)的马钱子叶和茎的乙醇提取物和水提取物,并与 0.375 mM 乙硫克百威共同处理细胞 24 和 48 h。使用 2',7'-二氯二氢荧光素二乙酸酯和 caspase-Glo® 3/7、8 和 9 检测试剂盒检测 ROS 和 caspase 活性。通过实时 PCR 测定凋亡和 ER 应激相关基因的表达,使用 Hoechst 33342 和 MitoTracker® Deep Red FM 染色法观察核和线粒体形态:对乙草胺诱导的细胞死亡最有效的提取物浓度分别为25 μg/mL的叶乙醇提取物、12.5 μg/mL的茎乙醇提取物、100 μg/mL的叶水提取物和25 μg/mL的茎水提取物。叶乙醇提取物的解毒效果最好,而茎提取物在高剂量下毒性很强。马钱子茎叶提取物对乙草胺诱导的氧化应激具有解毒作用,可降低 p53、BiP/GRP78 和 CHOP 基因的表达,并最大限度地减少 caspase 9 和 caspase 3,保护细胞免于凋亡。这些提取物还能恢复线粒体膜电位,缩小线粒体的肿胀球形状:这些发现有可能保护神经元细胞免受氧化损伤、细胞凋亡和其他潜在后果引起的神经退行性问题。
{"title":"Detoxification of paraoxon-ethyl by <i>Lysiphyllum strychnifolium</i> extracts in undifferentiated human neuroblastoma SH-SY5Y cells.","authors":"Niramai Ekaratcharoenchai, Thararat Nualsanit, Aungkana Krajarng","doi":"10.1080/13880209.2024.2430262","DOIUrl":"10.1080/13880209.2024.2430262","url":null,"abstract":"<p><strong>Context: </strong><i>Lysiphyllum strychnifolium</i> (Craib) A. Schmitz. (Fabaceae) is a Thai traditional medicine used to remove food and alcohol toxins from the body.</p><p><strong>Objective: </strong>This study investigates the molecular mechanism of <i>L. strychnifolium</i> extracts against paraoxon-ethyl-induced apoptosis in SH-SY5Y cells.</p><p><strong>Materials and methods: </strong>The ethanol and water extracts of leaves and stems of <i>L. strychnifolium</i> were prepared at various concentrations (0-100 μg/mL) and co-treated to the cells with 0.375 mM paraoxon-ethyl for 24 and 48 h. Cell viability was performed using the PrestoBlue assay. ROS and caspase activity were detected using 2',7'-dichlorodihydrofluorecein diacetate and caspase-Glo® 3/7, 8, and 9 assay kits. Apoptotic and ER stress-related gene expression were determined by real-time PCR, and nuclear and mitochondrial morphology were observed using Hoechst 33342 and MitoTracker® Deep Red FM staining.</p><p><strong>Results: </strong>The most effective concentrations of each extract against paraoxon-ethyl-induced cell death were 25 μg/mL of leaf ethanol, 12.5 μg/mL of stem ethanol, 100 μg/mL of leaf water, and 25 μg/mL of stem water extracts. The leaf ethanol extract was the most effective at detoxifying, while stem extracts were highly toxic in high doses. The detoxifying <i>L. strychnifolium</i> extracts against paraoxon-ethyl-induced oxidative stress decreased <i>p53, BiP/GRP78</i>, and <i>CHOP</i> gene expression and minimized caspase 9 and caspase 3, protecting cells from apoptosis. The extracts could also restore mitochondrial membrane potential and reduce the swollen globule mitochondrial shape.</p><p><strong>Discussion and conclusion: </strong>These findings could potentially protect neuron cells from neurodegenerative issues due to oxidative damage, apoptosis, and other potential consequences.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"882-891"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proanthocyanidin offers protection against diabetic nephropathy: elucidation of its mechanism of action using animal models. 原花青素可预防糖尿病肾病:利用动物模型阐明其作用机制。
IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-06 DOI: 10.1080/13880209.2024.2409772
Dengpiao Xie, Huan Wang, Qing Ji, Jianting Wang

Context: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.

Objective: This study evaluates the efficacy and potential mechanisms of PA in animal models of DN.

Methods: Preclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.

Results: A total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.

Conclusion: These findings suggest that PA alleviates DN by mediating multiple targets and pathways.

背景:糖尿病肾病(DN)是糖尿病的主要并发症,也是接受肾脏替代治疗的患者出现肾病的主要原因。糖尿病肾病会增加糖尿病患者的死亡风险。治疗 DN 的传统方法包括强化控制血糖水平和血压,以及阻断肾素-血管紧张素系统。然而,这种方法对 DN 的治疗效果有限。因此,迫切需要找到新型药物来延缓 DN 的进展。原花青素(PA)已被证明对 DN 具有潜在的益处。然而,其保护机制和功效仍有待阐明:本研究评估了 PA 在 DN 动物模型中的疗效和潜在机制:方法:从中国国家知识基础设施、PubMed、Web of Science、Embase 和 Google Scholar 数据库中检索临床前研究,检索截止日期为 2023 年 8 月。使用关键词("糖尿病肾病"、"肾病、糖尿病"、"糖尿病肾病"、"原花青素"、"花青素聚合物"、"原花青素"、"动物*"、"大鼠 "和 "小鼠")检索数据库。使用 RevMan 5.3 进行统计分析:本次分析共纳入了 22 项研究,涉及 538 只动物。汇总结果表明,PA疗法能显著改善肾功能,降低蛋白尿和血糖水平。PA 的保护机制与抗炎、抗氧化、抗纤维化和抗细胞凋亡作用、抑制内质网应激、缓解线粒体功能障碍和血脂异常有关:这些研究结果表明,PA 可通过介导多个靶点和途径缓解 DN。
{"title":"Proanthocyanidin offers protection against diabetic nephropathy: elucidation of its mechanism of action using animal models.","authors":"Dengpiao Xie, Huan Wang, Qing Ji, Jianting Wang","doi":"10.1080/13880209.2024.2409772","DOIUrl":"10.1080/13880209.2024.2409772","url":null,"abstract":"<p><strong>Context: </strong>Diabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.</p><p><strong>Objective: </strong>This study evaluates the efficacy and potential mechanisms of PA in animal models of DN.</p><p><strong>Methods: </strong>Preclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.</p><p><strong>Results: </strong>A total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.</p><p><strong>Conclusion: </strong>These findings suggest that PA alleviates DN by mediating multiple targets and pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"702-712"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Pharmaceutical Biology
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