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Zhongfeng Xingnao prescription alleviates injury of intracerebral hemorrhage via regulating the CaMKII/NF-κB p65/NLRP3/GSDMD signaling axis 中峰心脑方通过调节 CaMKII/NF-κB p65/NLRP3/GSDMD 信号轴减轻脑出血损伤
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-03-13 DOI: 10.1016/j.jtcme.2024.03.005
Jianyuan Yu , Huifen Zhou , Jianwen Guo , Tianhang Chen , Chongyu Shao , Zhiyong Pan , Jiehong Yang , Haitong Wan

Background and aim

The NLRP3 inflammasome can be activated after intracerebral hemorrhage (ICH), triggering an inflammatory response in the brain. Chinese herbal medicine Zhongfeng Xingnao Prescription (ZFXN) is commonly used in China for intracerebral hemorrhage treatment. However, the underlying treatment mechanism of it is unclear. The purpose of our study is to investigate whether ZFXN alleviates injury after intracerebral hemorrhage by blocking the activation of CaMKII/NF-κB p65/NLRP3/GSDMD signaling axis.

Experimental procedure

We evaluated the protective effect of ZFXN in a rat model of collagenase Ⅶ‐induced ICH. The neurological deficit score, cerebral hematoma-injury ratio, pathology, and ultrastructure of tissue surrounding the hematoma were evaluated after 5 days of ZFXN treatment, CaMKII/NF-κB p65/NLRP3/GSDMD signaling axis-related protein expression around the hematoma was assessed by Western blot and immunohistochemistry. Meanwhile, ELISA measured the levels of IL-1β, IL-18, IL-6 and TNF-α in serum.

Results and conclusion

After 5 days of ZFXN treatment, the score of neurological deficit and hematoma damage ratio decreased, and the cell destruction such as edema and vacuole conditions around the hematoma improved. The mechanism investigation results showed that ZFXN down-regulated expressions of CaMKII/NF-κB p65/NLRP3/GSDMD signaling axis-related protein around the hematoma area. In addition, ZFXN could attenuate the inflammatory response by regulating the activation of NLRP3 inflammasome after ICH. For the first time, we found that the efficacy of ZFXN on ICH might be related to the regulation of NLRP3 inflammasome.
背景与目的NLRP3炎性小体可在脑出血(ICH)后被激活,引发脑内炎症反应。中草药中风醒脑方(ZFXN)在中国常用来治疗脑出血。然而,其潜在的治疗机制尚不清楚。我们的研究目的是探讨ZFXN是否通过阻断CaMKII/NF-κB p65/NLRP3/GSDMD信号轴的激活来减轻脑出血后的损伤。实验方法:我们评估了ZFXN对胶原酶Ⅶ诱导的大鼠脑出血模型的保护作用。采用Western blot和免疫组织化学方法检测血肿周围CaMKII/NF-κB p65/NLRP3/GSDMD信号轴相关蛋白的表达,观察ZFXN治疗5 d后大鼠神经功能缺损评分、脑血肿损伤比、病理及血肿周围组织超微结构变化。同时ELISA检测血清中IL-1β、IL-18、IL-6、TNF-α水平。结果与结论ZFXN治疗5 d后,大鼠神经功能缺损评分及血肿损伤率下降,血肿周围水肿、空泡等细胞破坏情况改善。机制研究结果显示,ZFXN下调血肿区周围CaMKII/NF-κB p65/NLRP3/GSDMD信号轴相关蛋白的表达。此外,ZFXN可通过调节脑出血后NLRP3炎性小体的激活来减轻炎症反应。我们首次发现ZFXN对ICH的作用可能与NLRP3炎性小体的调节有关。
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引用次数: 0
Therapeutic efficacy of Punarnavadi mandura against phenylhydrazine-induced hemolytic anemia in rats Punarnavadi mandura 对苯肼引起的大鼠溶血性贫血的疗效
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-04-03 DOI: 10.1016/j.jtcme.2024.03.017
Kayalvizhi Rajendran , David Raj Chellappan , Vigneshwar Ramakrishnan , Uma Maheswari Krishnan

Background & aim

Hemolytic anemia is a blood disorder whose incidence is increasing in the world in recent years especially after the pandemic. Conventional treatments include use of steroids and immunosuppresants that are accompanied by numerous adverse effects. With growing interest in using complex multi-component formulations for multi-targeted therapy, the present study aims to investigate the therapeutic efficacy of a traditional Ayurvedic herbomineral preparation, Punarnavadi Mandura, which has been traditionally used as a supplement in iron-deficiency anemia, against phenylhydrazine-induced hemolytic anemia in rodent models.

Experimental approaches

We employ a combination of in vivo and in silico methods in this work to study the therapeutic potential and to understand the possible molecular targets of this traditional formulation. Conventional drugs prednisolone and ferrous sulphate were used for comparison.

Results and conclusion

The in vivo studies confirm the ability of Punarnavadi Mandura to reverse pathological changes associated with hemolytic anemia at 100 mg/kg and 200 mg/kg concentration. It restored hemoglobin, bilirubin and white blood cell levels to normal and reduced reticulocytes, hemosiderin and Gamna Gandy bodies in the liver, spleen and kidney. In silico studies suggested that the key constituents in Punarnavadi Mandura interact with high affinity to erythropoietic receptor which could contribute to erythropoiesis. The in silico study also predicted that the phytoconstituents of Punarnavadi Mandura could inhibit TNF-α activity which was validated using gene expression studies.
背景,目的溶血性贫血是近年来世界范围内发病率呈上升趋势的一种血液病。传统的治疗方法包括使用类固醇和免疫抑制剂,这伴随着许多不良反应。随着越来越多的人对使用复杂的多组分配方进行多靶向治疗的兴趣,本研究旨在研究传统的阿育吠陀草药制剂Punarnavadi Mandura在啮齿动物模型中对苯肼诱导的溶血性贫血的治疗效果。Punarnavadi Mandura传统上被用作缺铁性贫血的补充剂。实验方法在这项工作中,我们采用体内和计算机相结合的方法来研究这种传统制剂的治疗潜力,并了解这种传统制剂可能的分子靶点。采用常规药物强的松龙和硫酸亚铁进行比较。结果与结论在体内研究证实了100 mg/kg和200 mg/kg浓度的普那那瓦地曼都拉对溶血性贫血相关病理改变的逆转作用。它使血红蛋白、胆红素和白细胞水平恢复正常,并使肝、脾和肾中的网状红细胞、含铁血黄素和甘氏体减少。硅片研究表明,Punarnavadi Mandura的关键成分与促红细胞生成受体具有高亲和力相互作用,可能有助于促红细胞生成。计算机研究还预测了Punarnavadi Mandura的植物成分可以抑制TNF-α活性,并通过基因表达研究验证了这一点。
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引用次数: 0
Protective effects of tiger milk mushroom extract (xLr®) against UVB irradiation in Caenorhabditis elegans via DAF-16 anti-oxidant regulation 虎奶菇提取物(xLr®)通过DAF-16抗氧化调控对秀丽隐杆线虫抗UVB辐射的保护作用
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-11-12 DOI: 10.1016/j.jtcme.2024.11.004
Panthakarn Rangsinth , Rajasekharan Sharika , Chanin Sillapachaiyaporn , Sunita Nilkhet , Kamonwan Chaikhong , Kanika Verma , Anchalee Prasansuklab , Szu-Ting Ng , Chon-Seng Tan , Shin-Yee Fung , Tewin Tencomnao , Siriporn Chuchawankul

Background and aim

A critical causative factor of oxidative stress and inflammation leading to several skin complications is ultraviolet-B (UVB) irradiation. Lignosus rhinocerus (LR), or tiger milk mushroom, is native to Southeast Asia. Cold water extract of an LR cultivar, TM02® (xLr®) is a promising anti-oxidant and anti-inflammatory source. However, the effects of xLr® on UVB-induced photoaging have never been elucidated.

Experimental procedure

This study investigated the protective effects of xLr® and its high, medium, and low molecular weight (HLR, MLR, and LLR, respectively) fractions against UVB irradiation using in vivo Caenorhabditis elegans (C. elegans) model.

Results and conclusion

The investigation revealed a significant lifespan extension of xLr® and its fractions in UVB-irradiated C. elegans, which could be mediated by the regulation of genes associated with anti-oxidant (daf-16 and sod-3) and apoptosis (cep-1, hus-1, ced-13, and egl-1) pathways. xLr® significantly reduced the ROS production in C. elegans and increased the DAF-16 nuclear translocation compared to untreated worms. Additionally, the SOD-3 expression was increased in the xLr®-treated worms. Hence, it suggests that the different components in xLr® work synergistically to protect against UVB irradiation. Our findings may be beneficial for the application of xLr® as a treatment against UVB-induced cellular damage and photoaging.
背景与目的:紫外线b (UVB)照射是引起氧化应激和炎症的一个关键因素,可导致多种皮肤并发症。虎乳菇(Lignosus rhinocerus, LR),或称虎乳菇,原产于东南亚。TM02®(xLr®)是一种很有前途的抗氧化和抗炎来源。然而,xLr®对uvb诱导的光老化的影响尚未被阐明。实验步骤:本研究采用秀丽隐杆线虫(C. elegans)体内模型,研究xLr®及其高、中、低分子量组分(分别为HLR、MLR和LLR)对UVB辐射的保护作用。结果和结论:研究发现xLr®及其组分在uvb照射下的秀丽隐杆线虫中具有显著的延长寿命作用,其作用可能通过调控与抗氧化(daf-16和sod-3)和凋亡(cep-1、hus-1、ce -13和egl-1)通路相关的基因介导。与未处理的线虫相比,xLr®显著降低了线虫体内ROS的产生,增加了DAF-16核易位。此外,在xLr®处理的蠕虫中,SOD-3的表达增加。因此,这表明xLr®中的不同成分协同作用,以防止UVB辐射。我们的发现可能有助于xLr®作为一种治疗uvb诱导的细胞损伤和光老化的方法。
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引用次数: 0
Medicinal plants for the management of post-COVID-19 fatigue: A literature review on the role and mechanisms 药用植物用于治疗 COVID-19 后疲劳:作用和机制文献综述
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-05-23 DOI: 10.1016/j.jtcme.2024.05.006
Yuanyuan Chen, Cheng Zhang, Yibin Feng

Background

COVID-19 infection has a lasting impact on human health, which is known as post-COVID-19 conditions. Fatigue is one of the most commonly reported post-COVID-19 conditions. Management of fatigue in the post-COVID-19 era is necessary and emerging. The use of medicinal plants may provide a strategy for the management of post-COVID-19 fatigue.

Methods

A literature search has been conducted by using PubMed, Embase and Cochrane library databases is performed for studies published up to March 2024. Keywords, such as “post-COVID-19 conditions, persistent COVID-19 symptoms, chronic COVID-19, long-term sequelae, fatigue, post-COVID-19 fatigue, herbal plants, medicinal herbs, traditional Chinese medicine, pharmacological mechanisms, pharmacological actions” are thoroughly searched in Englsih and Chinese. This study reviews the pathophysiology of post-COVID-19 fatigue and potential herbal plants for managing post-COVID-19 fatigue.

Results and conclusion

Representative medicinal plants that have been extensively investigated by previous studies are presented in the study. Three common mechanisms among the most extensively studied for post-COVID-19 fatigue, with each mechanism having medicinal plants as an example. The latest clinical studies concerning the management of post-COVID-19 fatigue using medicinal plants have also been summarized. The study shows the potential for improving post-COVID-19 fatigue by consuming medicinal plants.
covid -19感染对人类健康产生持久影响,这被称为covid -19后状况。疲劳是covid -19后最常见的症状之一。在后covid -19时代,疲劳管理是必要的,也是新兴的。使用药用植物可能为管理covid -19后疲劳提供一种策略。方法利用PubMed、Embase和Cochrane数据库检索截止到2024年3月发表的文献。对“COVID-19后症状、持续性症状、慢性症状、长期后遗症、疲劳、COVID-19后疲劳、草本植物、中草药、中药、药理机制、药理作用”等关键词进行了全面的中英文检索。本研究综述了covid -19后疲劳的病理生理学和治疗covid -19后疲劳的潜在草药。结果与结论本研究中有代表性的药用植物已被前人广泛研究。covid -19后疲劳研究最广泛的三种常见机制,每种机制都以药用植物为例。综述了药用植物治疗新冠肺炎后疲劳的最新临床研究进展。该研究表明,食用药用植物有可能改善covid -19后的疲劳。
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引用次数: 0
Unlocking the mechanistic potential of Thuja occidentalis for managing diabetic neuropathy and nephropathy 挖掘西洋杉治疗糖尿病神经病变和肾病的机制潜力
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-04-24 DOI: 10.1016/j.jtcme.2024.04.009
Diabetes mellitus and its debilitating microvascular complications, including diabetic neuropathy and nephropathy, represent a growing global health burden. Despite advances in conventional therapies, their suboptimal efficacy and adverse effects necessitate exploring complementary and alternative medicine approaches. Thuja occidentalis, a coniferous tree species native to eastern North America, has gained significant attention for its potential therapeutic applications in various disorders, attributed to its rich phytochemical composition. The present comprehensive review evaluates the therapeutic potential of Thuja occidentalis in managing diabetic neuropathy and nephropathy, with a particular emphasis on elucidating the underlying cellular and molecular mechanisms. The review delves into the active constituents of Thuja occidentalis, such as essential oils, flavonoids, tannins, and proanthocyanidin compounds, which have demonstrated antioxidant, anti-inflammatory, and other beneficial properties in preclinical studies. Importantly, the review provides an in-depth analysis of the intricate signaling pathways modulated by Thuja occidentalis, including NF-κB, PI3K-Akt, JAK-STAT, JNK, MAPK/ERK, and Nrf2 cascades. These pathways are intricately linked to oxidative stress, inflammation, and apoptosis processes, which play pivotal roles in the pathogenesis of diabetic neuropathy and nephropathy. Furthermore, the review critically evaluates the evidence-based toxicological data of Thuja occidentalis as a more effective and comprehensive therapeutic strategy in diabetes complications. Therefore, the current review aims to provide a comprehensive understanding of the therapeutic potential of Thuja occidentalis as an adjunctive treatment strategy for diabetic neuropathy and nephropathy while highlighting the need for further research to optimize its clinical translation.
糖尿病及其使人衰弱的微血管并发症,包括糖尿病神经病变和肾病,是全球日益沉重的健康负担。尽管传统疗法取得了进步,但由于其疗效不佳和不良反应,有必要探索补充和替代医学方法。西洋杉(Thuja occidentalis)是一种针叶树种,原产于北美东部,因其丰富的植物化学成分而在各种疾病的潜在治疗应用中获得了极大的关注。本综述评估了西洋杉在控制糖尿病神经病变和肾病方面的治疗潜力,尤其侧重于阐明其潜在的细胞和分子机制。综述深入探讨了侧柏的活性成分,如精油、类黄酮、单宁和原花青素化合物,这些成分在临床前研究中表现出抗氧化、抗炎和其他有益特性。重要的是,这篇综述深入分析了西洋接骨木调节的复杂信号通路,包括 NF-κB、PI3K-Akt、JAK-STAT、JNK、MAPK/ERK 和 Nrf2 级联。这些通路与氧化应激、炎症和细胞凋亡过程密切相关,在糖尿病神经病变和肾病的发病机制中起着关键作用。此外,本综述还对基于证据的毒理学数据进行了批判性评估,认为侧柏叶是一种更有效、更全面的糖尿病并发症治疗策略。因此,本综述旨在全面了解刺五加作为糖尿病神经病变和肾病的辅助治疗策略的治疗潜力,同时强调进一步研究的必要性,以优化其临床转化。
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引用次数: 0
Crocin elicits potent anti-inflammatory and fibrinolytic properties post tendon injury, A new molecule for adhesion therapy 肌腱损伤后,克罗霉素具有强效抗炎和纤维蛋白溶解特性--一种用于粘连治疗的新分子
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-06-09 DOI: 10.1016/j.jtcme.2024.06.001

Background

Post-surgical tendon adhesion formation is a frequent clinical complication with limited treatment options. The aim of this study is to investigate safety and efficacy of orally administration of crocin in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model.

Methods

Structural, mechanical, histological, and biochemical properties of Achilles tendons were analyzed in the presence and absence of crocin. Inflammation and total fibrosis of tendon tissues were graded between groups using macroscopic and histological scoring methods.

Results

Crocin significantly alleviated the severity, length, and density of Achilles tendon adhesions. Moreover, the recruitment of inflammatory cells and inflammation were significantly decreased in post-operative tissue samples of the crocin-treated group, as quantified with Moran scoring system. Histological results showed that crocin elicited a potent anti-fibrotic effect on tendon tissue samples as visualized by decreasing quantity, quality, grading of fibers, and collagen deposition at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histo-pathological changes or damage to heart, kidney, and liver tissues of treated rats.

Conclusion

Our results showed that crocin is a safe effective therapeutic candidate with potent anti-inflammatory and anti-fibrotic properties for adhesion band therapy post tendon surgery.
背景 手术后肌腱粘连是一种常见的临床并发症,但治疗方法有限。本研究旨在探讨在跟腱大鼠模型中口服巴豆苷以减轻术后腱鞘粘连带的安全性和有效性。方法分析巴豆苷存在和不存在时跟腱的结构、机械、组织学和生化特性。采用宏观和组织学评分方法对不同组间肌腱组织的炎症和总纤维化程度进行分级。此外,根据 Moran 评分系统的量化结果,术后跟腱粘连组组织样本中炎症细胞的募集和炎症明显减少。组织学结果表明,使用 Tang 或 Ishiyama 分级系统进行评分时,手术部位纤维的数量、质量、分级和胶原沉积均有所减少,由此可见,巴豆苷对肌腱组织样本具有强效的抗纤维化作用。H&E染色显示,治疗大鼠的心脏、肾脏和肝脏组织未发生组织病理学变化或损伤。 结论我们的研究结果表明,巴豆苷是一种安全有效的候选疗法,具有强大的抗炎和抗纤维化特性,可用于肌腱手术后的粘连带治疗。
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引用次数: 0
Cannabidiol suppresses proliferation and induces cell death, autophagy and senescence in human cholangiocarcinoma cells via the PI3K/AKT/mTOR pathway 大麻二酚通过 PI3K/AKT/mTOR 通路抑制人胆管癌细胞的增殖并诱导细胞死亡、自噬和衰老
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-04-17 DOI: 10.1016/j.jtcme.2024.04.007

Background and aim

Cholangiocarcinoma (CCA) is usually diagnosed at a late stage, leading to treatment failure. Cannabidiol (CBD), exhibits diverse anti-cancer effects in various cancers, offering avenues for improving CCA treatment. This study investigated the effects of CBD on human CCA cells and the underlying mechanisms in vitro and in vivo.

Experimental procedure

The effects of CBD on three CCA cell lines (KKU-213B, KKU-100, KKU-055) were assessed using the SRB assay, clonogenic assay, cell cycle arrest, and 3D holotomography. Morphological changes were examined using transmission electron microscopy, while mitochondrial ROS levels and mitochondrial membrane potential were studied using MitoSOX, JC-1, and DCFH-DA. Cellular senescence induction was evaluated via SA-β-gal staining. Protein associatedwith autophagy and cellular senescence were analyzed using Western blot and/or immunofluorescent assays. A xenograft model demonstrated the anti-tumor activity of CBD and the induction of cellular senescence through immunohistochemistry targeting PCNA, β-gal, and p21.

Results and conclusion

CBD effectively inhibited CCA cell proliferation, suppressed colony formation and induced G0/G1 phase cell cycle arrest. Morphological examination revealed lipid droplets/vesicles in CCA cell lines. CBD induced autophagy by upregulating LC3BII, downregulating p62, and inhibiting the p-PI3K, p-AKT, and p-mTOR pathways. Additionally, CBD disrupted mitochondrial homeostasis by elevating ROS, reducing membrane potential, and induced cellular senescence by increasing the expression of p53 and p21. In-vitro results were confirmed by xenograft models. Overall, CBD suppresses proliferation and induces cell death, autophagy and senescence in CCA cells via the PI3K/AKT/mTOR pathway, which indicates a therapeutic option for CCA treatment.
背景和目的胆管癌(CCA)通常在晚期才被诊断出来,导致治疗失败。大麻二酚(CBD)在多种癌症中表现出不同的抗癌作用,为改善 CCA 的治疗提供了途径。本研究调查了 CBD 对人类 CCA 细胞的影响及其在体外和体内的潜在机制。实验过程 CBD 对三种 CCA 细胞系(KKU-213B、KKU-100 和 KKU-055)的影响通过 SRB 试验、克隆生成试验、细胞周期停滞和三维全图进行评估。透射电子显微镜检查了形态学变化,MitoSOX、JC-1 和 DCFH-DA 研究了线粒体 ROS 水平和线粒体膜电位。细胞衰老诱导通过 SA-β-gal 染色进行评估。通过 Western 印迹和/或免疫荧光检测分析了与自噬和细胞衰老相关的蛋白质。通过针对 PCNA、β-gal 和 p21 的免疫组化,异种移植模型证明了 CBD 的抗肿瘤活性和细胞衰老诱导作用。形态学检查显示,CCA 细胞系中存在脂滴/囊泡。CBD 通过上调 LC3BII、下调 p62 以及抑制 p-PI3K、p-AKT 和 p-mTOR 通路来诱导自噬。此外,CBD 还通过提高 ROS、降低膜电位来破坏线粒体的平衡,并通过增加 p53 和 p21 的表达来诱导细胞衰老。体外实验结果在异种移植模型中得到了证实。总之,CBD 可通过 PI3K/AKT/mTOR 通路抑制 CCA 细胞增殖并诱导细胞死亡、自噬和衰老,为 CCA 治疗提供了一种治疗选择。
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引用次数: 0
Effect of astragalus membranaceus on neurological function in acute aneurysmal subarachnoid hemorrhage patients with high inflammation: A preliminary randomized, double-blind, placebo-controlled clinical trial 黄芪对急性动脉瘤性蛛网膜下腔出血高炎症患者神经功能的影响:一项初步随机、双盲、安慰剂对照临床试验
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-04-11 DOI: 10.1016/j.jtcme.2024.04.002

Background and aim

Astragalus membranaceus (AM) is a traditional Chinese herb. Our previous study revealed that AM can enhance neurological function in patients with acute intracerebral hemorrhage. The aim of this study was to investigated the effects of AM on patients with acute aneurysmal subarachnoid hemorrhage (aSAH).

Experimental procedure

Eighty-eight patients experiencing acute aSAH were randomly allocated to either the treatment group (TG) comprising 44 patients, who received 3 g of AM orally thrice daily for 14 days, or the control group (CG) with 44 patients, who received 3 g of a placebo.

Results

Eighty-three patients (41 in CG and 42 in TG) completed the trial. Stratified analyses revealed serum interleukin-6 (IL-6) median ≥7.28 pg/mL at baseline. The percentage of good GOS scores (GOS 4 or 5) at two weeks (W2) and four weeks (W4) was significantly higher in TG than in CG (W2: 35.3 % vs. 7.7 %, p = 0.042; W4: 62.5 % vs. 30.8 %, p = 0.044). Moreover, a higher percentage of Barthel index scores (>60) was observed in TG than in CG at W2 (35.3 % vs. 7.7 %, p = 0.042) after AM or placebo administration.

Conclusion

Administering AM for 14 days has shown potential in enhancing neurological function four weeks post-aSAH onset, especially in patients with a serum IL-6 level median ≥7.28 pg/mL. Therefore, further research is warranted to explore the anti-inflammatory role of AM. However, this study's limitations include a small sample size and the single-center design, signifying its status as a preliminary investigation.
背景和目的黄芪(AM)是一种传统中草药。我们之前的研究显示,黄芪能增强急性脑出血患者的神经功能。实验过程88名急性蛛网膜下腔出血患者被随机分配到治疗组(TG)和对照组(CG),治疗组有44名患者,每天口服3克AM,共14天;对照组有44名患者,每天口服3克安慰剂。分层分析显示,基线血清白细胞介素-6(IL-6)中位数≥7.28 pg/mL。在两周(W2)和四周(W4)的良好 GOS 评分(GOS 4 或 5 分)中,TG 显著高于 CG(W2:35.3% 对 7.7%,p = 0.042;W4:62.5% 对 30.8%,p = 0.044)。此外,在 W2(35.3 % vs. 7.7 %,p = 0.042)时,观察到 AM 或安慰剂给药后,TG 的 Barthel 指数评分(>60)百分比高于 CG(35.3 % vs. 7.7 %,p = 0.042)。因此,有必要进一步研究 AM 的抗炎作用。然而,这项研究的局限性包括样本量较小和单中心设计,这表明它只是一项初步研究。
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引用次数: 0
Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds 探索大蒜球茎提取物介导的 ROS 在人类三阴性乳腺癌中的抗癌潜力:一种具有治疗活性的化合物来源
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-04-11 DOI: 10.1016/j.jtcme.2024.04.003

Background and aim

Allium sativum L. has been used medicinally and traditionally since antiquity. This study sought to examine the Allium sativum ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using in silico method.

Experimental procedure

Cytotoxicity of ASEE was tested on MCF-7, MDA-MB-231, and Normal Vero cells. The ROS production, apoptosis, MMP, and cell cycle study were conducted utilizing flow cytometer, and western blot was also performed for protein expression analysis. ASEE was phytochemically characterized by the HPLC while AutoDock Vina and iGEMDOCK tools investigated in-silico binding interactions.

Results

The HPLC method identified two active organosulfur chemicals, allicin and alliin, in ASEE. MTT test revealed significant (p < 0.05) inhibition of breast cancer cells proliferation. The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells. TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP. ASEE exposure increased the percentage of cells in the G2/M phase. ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins. Allicin and alliin compounds had strong binding affinity with targeted proteins of breast cancer, and both compounds also showed good pharmacokinetics and druglikeness properties.

Conclusion

ASEE could be useful in the treatment of human triple-negative breast cancer without any safety risks.
背景和目的薤白自古以来就有药用和传统用途。本研究试图利用硅学方法研究薤白乙醇提取物(ASEE)在诱导人类三阴性乳腺癌(TNBC)MDA-MB-231 细胞凋亡方面的作用,以及所发现的成分与细胞死亡标志物之间的分子相互作用。利用流式细胞仪对 ROS 生成、细胞凋亡、MMP 和细胞周期进行了研究,并对蛋白质表达进行了 Western 印迹分析。HPLC 方法鉴定了 ASEE 中的两种活性有机硫化学物质:大蒜素和大蒜素。MTT测试显示,ASEE对乳腺癌细胞的增殖有明显的抑制作用(p < 0.05)。ASEE 对 MDA-MB-231 细胞的抑制作用比对 MCF-7 细胞的抑制作用更明显,但对正常 Vero 细胞没有明显的细胞毒性。经高浓度 ASEE 处理的 TNBC 细胞处于凋亡晚期,ROS 水平升高,MMP 降低。ASEE 暴露增加了处于 G2/M 期的细胞百分比。ASEE 上调了 p53 和 Bax 蛋白,同时下调了 Bcl-2、p-Akt 和 p-p38 蛋白。大蒜素和大蒜素化合物与乳腺癌的靶向蛋白有很强的结合亲和力,这两种化合物还表现出良好的药代动力学和药物亲和性。
{"title":"Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds","authors":"","doi":"10.1016/j.jtcme.2024.04.003","DOIUrl":"10.1016/j.jtcme.2024.04.003","url":null,"abstract":"<div><h3>Background and aim</h3><div><em>Allium sativum</em> L. has been used medicinally and traditionally since antiquity. This study sought to examine the <em>Allium sativum</em> ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using <em>in silico</em> method.</div></div><div><h3>Experimental procedure</h3><div>Cytotoxicity of ASEE was tested on MCF-7, MDA-MB-231, and Normal Vero cells. The ROS production, apoptosis, MMP, and cell cycle study were conducted utilizing flow cytometer, and western blot was also performed for protein expression analysis. ASEE was phytochemi<strong>c</strong>ally characterized by the HPLC while AutoDock Vina and iGEMDOCK tools investigated <em>in-silico</em> binding interactions.</div></div><div><h3>Results</h3><div>The HPLC method identified two active organosulfur chemicals, allicin and alliin, in ASEE. MTT test revealed significant (p &lt; 0.05) inhibition of breast cancer cells proliferation. The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells. TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP. ASEE exposure increased the percentage of cells in the G2/M phase. ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins. Allicin and alliin compounds had strong binding affinity with targeted proteins of breast cancer, and both compounds also showed good pharmacokinetics and druglikeness properties.</div></div><div><h3>Conclusion</h3><div>ASEE could be useful in the treatment of human triple-negative breast cancer without any safety risks.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 6","pages":"Pages 644-655"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140791047","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
Zhilong Huoxue Tongyu capsule protects against atherosclerosis by suppressing EndMT via modulating Hippo/YAP signaling pathway 芝龙藿香通脉胶囊通过调节 Hippo/YAP 信号通路抑制 End MT 防止动脉粥样硬化
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-01 Epub Date: 2024-03-29 DOI: 10.1016/j.jtcme.2024.03.015

Background and aim

Zhilong Huoxue Tongyu Capsule (ZL capsule) has been demonstrated to be an effective and widely-used traditional Chinese medicine (TCM) formula for the treatment of various diseases, especially for atherosclerosis (AS) related cardiovascular and cerebrovascular diseases. Reversal of endothelial-mesenchymal transition (EndMT) plays a crucial role in the cure of AS. But the curative impact of ZL capsule on EndMT remains obscure during the development of AS. The purpose of this study is to explore the effect of ZL capsule on AS and to study the regulation mechanism on EndMT in AS by ZL capsule in vivo and in vitro.

Experimental procedure

An in vivo model of AS was induced in ApoE−/− mice by administrating them with an 8-week period of high-fat diet (HFD). After oral gavage of different doses of ZL capsule and Atorvastatin calcium tablets (ATO) for 4 weeks, the lipid levels, plaque area, lipid deposition, and EndMT were evaluated using standard assays. In order to simulate EndMT in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoprotein (ox-LDL). Western blotting (WB) and immunofluorescence techniques were used to evaluate the intervention effect of ZL capsule on EndMT and Hippo/YAP pathways.

Results and conclusion

ZL capsule demonstrated therapeutic effects on dyslipidemia and EndMT among atherosclerotic mice. To be specific, ZL capusle diminished the total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein (LDL-C) levels, whereas increased that of high-density lipoproteins (HDL-C). Meanwhile, ZL capusle upregulated the expression of endothelial markers (CD31 and VE-cadherin) and reduced that of mesenchymal markers (ɑ-SMA and FSP1), indicating that ZL capusle could inhibit EndMT during the development of AS. Furthermore, molecular docking results indicated that active ingredients including formononetin, calycosin, astragaloside III, astragaloside A in ZL capsule have strong affinity with YAP proteins, and ZL capsule can significantly repress the initiation of Hippo/YAP pathway during AS. In conclusion, ZL capsule effectively attenuated AS progression by exerting inhibitory effects on EndMT through modulation of the Hippo/YAP signaling pathway.
背景和目的芝龙藿香通脉胶囊(ZL胶囊)已被证实是治疗多种疾病,尤其是动脉粥样硬化(AS)相关心脑血管疾病的有效而广泛使用的传统中药配方。内皮-间质转化(EndMT)的逆转在AS的治疗中起着至关重要的作用。但在强直性脊柱炎的发展过程中,ZL 胶囊对 EndMT 的治疗作用仍不明显。本研究的目的是探讨 ZL 胶囊对强直性脊柱炎的影响,并研究 ZL 胶囊在体内和体外对强直性脊柱炎 EndMT 的调节机制。口服不同剂量的ZL胶囊和阿托伐他汀钙片(ATO)4周后,使用标准检测方法评估血脂水平、斑块面积、脂质沉积和内膜增生。为了在体外模拟内切迹,将人脐静脉内皮细胞(HUVECs)置于氧化低密度脂蛋白(ox-LDL)中。结果和结论ZL胶囊对动脉粥样硬化小鼠的血脂异常和内膜增生具有治疗作用。具体而言,ZL 胶囊降低了总胆固醇(TC)、总甘油三酯(TG)和低密度脂蛋白(LDL-C)的水平,而提高了高密度脂蛋白(HDL-C)的水平。同时,ZL 茵陈毛果芸香碱可上调内皮标志物(CD31 和 VE-cadherin)的表达,降低间质标志物(ɑ-SMA 和 FSP1)的表达,表明 ZL 茵陈毛果芸香碱可抑制强直性脊柱炎发病过程中的内膜增生。此外,分子对接结果表明,ZL胶囊中的甲酮素、钙苷、黄芪皂苷Ⅲ、黄芪皂苷A等有效成分与YAP蛋白有很强的亲和力,ZL胶囊能显著抑制强直性脊柱炎发生过程中Hippo/YAP通路的启动。综上所述,ZL胶囊通过调控Hippo/YAP信号通路抑制内生肌生长,从而有效地延缓了AS的进展。
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引用次数: 0
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Journal of Traditional and Complementary Medicine
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