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Applications of nanomaterials with enzyme-like activity for the detection of phytochemicals and hazardous substances in plant samples. 具有类酶活性的纳米材料在植物样品中植物化学物质和有害物质检测中的应用。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-08 DOI: 10.1186/s13020-024-01014-9
Lei Xu, Mao-Ling Luo, Jing-Jing Dai, Huan Zhu, Peng Li, Dan Wang, Feng-Qing Yang

Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed.

草药、蔬菜、水果和谷物等植物与人类生活息息相关。开发有效的检测方法以确保其安全性并量化其活性成分具有重要意义。最近,具有类似酶活性的纳米材料(称为纳米酶)在各种检测方法中得到了广泛开发,包括比色法、荧光法、化学发光法和电化学分析法。本综述介绍了基于纳米酶分析植物样品中植物化学物质和有害物质的最新进展,包括一些活性成分、有机磷农药、重金属离子和霉菌毒素。此外,还讨论了目前在实际样品分析中存在的不足和面临的挑战。
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引用次数: 0
Puerarin: a hepatoprotective drug from bench to bedside. 葛根素:从实验室到临床的保肝药物
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-08 DOI: 10.1186/s13020-024-01011-y
Yi-Xiang He, Meng-Nan Liu, Hao Wu, Qi Lan, Hao Liu, Maryam Mazhar, Jin-Yi Xue, Xin Zhou, Hui Chen, Zhi Li

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

葛根是一种历史悠久的食药两用植物,在中国被广泛使用。葛根素是从葛根中提取的主要成分,具有多种药理特性。近年来,葛根素因其显著的保肝作用而受到越来越多的关注,如代谢功能障碍相关性脂肪肝、酒精相关性肝病和肝癌等。本文探讨了葛根素通过炎症因子、氧化应激、脂质代谢、细胞凋亡和自噬等多种机制对各种肝病的药理作用。由于葛根素的溶解度有限,药代动力学研究显示其生物利用度较低。然而,将葛根素与新型给药系统结合可提高其生物利用度。同时,葛根素具有毒性低、安全性高的特点,为其进一步应用奠定了坚实的基础。此外,本文还讨论了葛根素的临床试验,突出了其独特的优势。鉴于其卓越的药理作用,葛根素有望成为治疗各种肝病的潜在药物。
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引用次数: 0
Development of a new paradigm model for deciphering action mechanism of Danhong injection using a combination of isothermal shift assay and database interrogation. 结合等温移位测定法和数据库查询法,建立破译丹红注射液作用机制的新范式模型。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-05 DOI: 10.1186/s13020-024-01017-6
Tianxiang Wang, Changmei Yang, Yuxiang Tang, Ke Wen, Yuxin Ma, Yuling Chen, Zhiqiang Li, Yujiao Zhao, Songbiao Zhu, Xianbin Meng, Sijing Du, Zelong Miao, Wei Wei, Haiteng Deng

Background: Identification of active components of traditional Chinese Medicine (TCM) and their respective targets is important for understanding the mechanisms underlying TCM efficacy. However, there are still no effective technical methods to achieve this.

Methods: Herein, we have established a method for rapidly identifying targets of a specific TCM and interrogating the targets with their corresponding active components based on Isothermal Shift Assay (iTSA) and database interrogation.

Results: We optimized iTSA workflow and identified 110 targets for Danhong injection (DHI) which is used as an effective remedy for cardiovascular and cerebrovascular diseases. Moreover, we identified the targets of the nine major ingredients found in DHI. Database interrogation found that the potential targets for DHI, in which we verified that ADK as the target for salvianolic acid A and ALDH1B1 as the target for protocatechualdehyde in DHI, respectively.

Conclusion: Overall, we established a novel paradigm model for the identification of targets and their respective ingredients in DHI, which facilitates the discovery of drug candidates and targets for improving disease management and contributes to revealing the underlying mechanisms of TCM and fostering TCM development and modernization.

背景:鉴定传统中药(TCM)的活性成分及其各自的靶点对于了解传统中药的疗效机制非常重要。方法:在此,我们建立了一种基于等温移位分析(iTSA)和数据库查询的方法,用于快速鉴定特定中药的靶点,并查询靶点与其相应的活性成分:结果:我们优化了iTSA工作流程,确定了丹红注射液(DHI)的110个靶点,丹红注射液是治疗心脑血管疾病的有效药物。此外,我们还鉴定了丹红注射液中九种主要成分的靶标。通过数据库查询发现了丹参注射液的潜在靶点,其中我们验证了丹参注射液中的丹酚酸 A 的靶点是 ADK,原儿茶醛的靶点是 ALDH1B1:总之,我们建立了一个新的范式模型,用于识别 DHI 中的靶点及其各自的成分,这有助于发现候选药物和靶点,改善疾病管理,并有助于揭示中医药的内在机制,促进中医药的发展和现代化。
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引用次数: 0
Proteomic analysis and experimental validation reveal the blood-brain barrier protective of Huanshaodan in the treatment of SAMP8 mouse model of Alzheimer's disease. 蛋白质组分析和实验验证揭示了黄少丹在治疗 SAMP8 阿尔茨海默病小鼠模型中的血脑屏障保护作用。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-05 DOI: 10.1186/s13020-024-01016-7
Yunfang Su, Ningning Liu, Pan Wang, Congcong Shang, Ruiqin Sun, Jinlian Ma, Zhonghua Li, Huifen Ma, Yiran Sun, Zijuan Zhang, Junying Song, Zhishen Xie, Jiangyan Xu, Zhenqiang Zhang

Background: Huanshaodan (HSD) is a Chinese Herbal Compound which has a definite clinical effect on Alzheimer's disease (AD), however, the underlying mechanism remains unclear. The aim of this study is to preliminarily reveal the mechanism of HSD in the treatment of AD model of SAMP8 mice.

Methods: Chemical composition of HSD and its drug-containing serum were identified by Q-Orbitrap high resolution liquid mass spectrometry. Six-month-old SAMP8 mice were treated with HSD and Donepezil hydrochloride by gavage for 2 months, and Wogonin for 28 days. Behavioral test was performed to test the learning and memory ability of mice. Immunofluorescence (IF) or Western-blot methods were used to detect the levels of pSer404-tau and β-amyloid (Aβ) in the brain of mice. Hematoxylin-eosin (H&E) staining and Transmission electron microscopy (TEM) assay was applied to observe the pathological changes of neurons. Proteomic technology was carried out to analyze and identify the protein network of HSD interventions in AD. Then the pathological process of the revealed AD-related differential proteins was investigated by IF, Q-PCR, Western-blot, Fluorescence in situ hybridization (FISH) and 16S rRNA sequencing methods.

Results: The results showed that HSD and Wogonin, one of the components in its drug-containing serum, can effectively improve the cognitive impairments of SAMP8 mice, protect hippocampal neurons and synapses, and reduce the expression of pSer404-tau and Aβ. HSD and Wogonin reduced the levels of fibrinogen β chain (FGB) and γ chain (FGG), the potential therapeutic targets revealed by proteomics analysis, reduced the colocalization of FGB and FGG with Aβ, ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), increased level of and myelin basic protein (MBP). Meanwhile, HSD and Wogonin increased ZO-1 and Occludin levels, improved brain microvascular injury, and reduced levels of bacteria/bacterial DNA and lipopolysaccharide (LPS) in the brain of mice. In addition, 16S rRNA sequencing indicated that HSD regulated the structure of intestinal microbiota of mice.

Conclusion: The effects of HSD on AD may be achieved by inhibiting the levels of fibrinogen and the interactions on glia cells in the brain, and by modulating the structure of intestinal microbiota and improving the blood-brain barrier function.

背景:黄少丹(HSD)是一种中药复方制剂,对阿尔茨海默病(AD)有确切的临床疗效,但其作用机制尚不清楚。本研究旨在初步揭示 HSD 治疗 SAMP8 小鼠 AD 模型的机制:方法:采用 Q-Orbitrap 高分辨率液质联用仪鉴定 HSD 及其含药血清的化学成分。用 HSD 和盐酸多奈哌齐灌胃治疗 6 个月大的 SAMP8 小鼠 2 个月,Wogonin 治疗 28 天。对小鼠的学习和记忆能力进行行为测试。采用免疫荧光(IF)或Western-blot方法检测小鼠大脑中pSer404-tau和β-淀粉样蛋白(Aβ)的水平。采用血红素-伊红(H&E)染色和透射电子显微镜(TEM)检测来观察神经元的病理变化。蛋白质组学技术分析并鉴定了HSD干预AD的蛋白质网络。结果表明,HSD和Western-blot技术对AD神经元的病理改变有显著的抑制作用,而Western-blot技术对AD神经元的病理改变无显著的抑制作用:结果表明:HSD及其含药血清中的一种成分Wogonin能有效改善SAMP8小鼠的认知障碍,保护海马神经元和突触,降低pSer404-tau和Aβ的表达。HSD和Wogonin降低了蛋白质组学分析所揭示的潜在治疗靶点纤维蛋白原β链(FGB)和γ链(FGG)的水平,减少了FGB和FGG与Aβ、离子化钙结合适配分子1(Iba-1)、胶质纤维酸性蛋白(GFAP)的共定位,提高了髓鞘碱性蛋白(MBP)的水平。同时,HSD 和 Wogonin 能提高 ZO-1 和 Occludin 的水平,改善脑微血管损伤,降低小鼠脑内细菌/细菌 DNA 和脂多糖(LPS)的水平。此外,16S rRNA 测序表明,HSD 可调节小鼠肠道微生物群的结构:结论:HSD对AD的作用可能是通过抑制脑内纤维蛋白原的水平和与胶质细胞的相互作用,以及通过调节肠道微生物群的结构和改善血脑屏障功能来实现的。
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引用次数: 0
Uncovering the role of traditional Chinese medicine in immune-metabolic balance of gastritis from the perspective of Cold and Hot: Jin Hong Tablets as a case study. 从寒热温凉的角度揭示中药在胃炎免疫代谢平衡中的作用:以金红片为例。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-04 DOI: 10.1186/s13020-024-00998-8
Boyang Wang, Lihao Xiao, Pan Chen, Tingyu Zhang, Peng Zhang, Liang Cao, Ziyi Zhou, Haibo Cheng, Tong Zhang, Shao Li

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs.

慢性胃炎(CG)是一种常见的胃黏膜慢性炎症性病变。在中医胃炎的诊断中,CG 可分为寒证和热证。然而,CG 中寒证/热证的分子特征以及寒证/热证中药在治疗 CG 方剂中的作用机制仍不清楚。本研究收集了 35 例寒热证 CG 患者和 3 例 scRNA-seq CG 样本的转录组学数据。此外,我们还收集了 25 个用于 CG 的方剂以及这些方剂中记录的 89 味中药。我们结合转录组学数据集和机器学习算法进行综合分析,发现寒热证CG的生物标志物。然后,对所收集的方剂和寒热性药材的靶标谱进行预测,以发现它们针对寒热性郑州肺癌的特征和生物标志物。这些生物标志物表明,热证可能具有过度炎症和代谢旺盛的特点,而寒证则在免疫调节和能量代谢方面表现出抑制的趋势。热性中药的生物标志物和特定途径倾向于调节免疫反应和能量代谢,而寒性中药的生物标志物和特定途径更有可能参与抗炎作用。最后,以金红片为例,根据公开的转录组学数据集以及转录组学和酶联免疫吸附检测验证了这一发现。瘦素和 IL-6 等生物标志物以及免疫细胞的比例在干预后都发生了显著变化。这些发现可能反映了寒热ZHENG以及寒热药材的机制,并在宏观和微观之间架起了一座桥梁。
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引用次数: 0
Acupuncture may play a key role in anti-depression through various mechanisms in depression. 针灸可通过各种机制在抗抑郁方面发挥关键作用。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-04 DOI: 10.1186/s13020-024-00990-2
Peng Li, Jiangna Zhao, Xiuxiang Wei, Longfei Luo, Yuzhou Chu, Tao Zhang, Anning Zhu, Juntao Yan

Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.

抑郁症已成为一个重大的全球健康问题,对个人产生了深远的影响,其高发率和相关的自杀率就证明了这一点。考虑到抑郁症的普遍性,缺乏最佳的治疗方法仍然是一个挑战。针灸在治疗产后抑郁、中风后抑郁和青少年抑郁等各种抑郁症方面的疗效已获得大量临床和实验验证。本文试图阐明针灸在当代抑郁症治疗中的独特属性和内在机制。研究表明,针灸在抑郁症动物模型中发挥了多种生理效应,包括对大脑、血清和脑肠轴的调节。这些效应可归因于多种机制,包括抗炎和抗氧化作用、促进神经元可塑性、神经保护、神经营养作用、神经递质调节、内分泌和免疫功能调节以及细胞信号通路调节。目前,针灸的治疗机制涉及多靶点、多途径和双向调节。因此,针灸是一种前景广阔的替代医学模式,具有广阔的研究前景,值得全面深入研究和推广。
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引用次数: 0
Correction: Electroacupuncture negatively regulates the Nesfatin-1/ERK/CREB pathway to alleviate HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma. 更正:电针可负向调节 Nesfatin-1/ERK/CREB 通路,从而缓解手术创伤导致的 HPA 轴亢进和焦虑样行为。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-29 DOI: 10.1186/s13020-024-00999-7
Jiayuan Zheng, Yu Wang, Chi Zhang, Anjing Zhang, Yuxiang Zhou, Yunhua Xu, Jin Yu, Zhanzhuang Tian
{"title":"Correction: Electroacupuncture negatively regulates the Nesfatin-1/ERK/CREB pathway to alleviate HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma.","authors":"Jiayuan Zheng, Yu Wang, Chi Zhang, Anjing Zhang, Yuxiang Zhou, Yunhua Xu, Jin Yu, Zhanzhuang Tian","doi":"10.1186/s13020-024-00999-7","DOIUrl":"https://doi.org/10.1186/s13020-024-00999-7","url":null,"abstract":"","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"133"},"PeriodicalIF":5.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342732","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
Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon. 揭示马兜铃酸与肝癌的相关性:时空异质性现象
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-28 DOI: 10.1186/s13020-024-01003-y
Chengxian Li, Xinyu Li, Ming Niu, Dake Xiao, Ye Luo, Yinkang Wang, Zhi-E Fang, Xiaoyan Zhan, Xu Zhao, Mingxia Fang, Jiabo Wang, Xiaohe Xiao, Zhaofang Bai

Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.

马兜铃酸是马兜铃科植物中的一类天然化合物,具有相似的结构骨架和化学特性。接触马兜铃酸是导致严重肾病和泌尿系统癌症的风险因素。然而,马兜铃酸对肝脏的致癌性尚不清楚,而肝脏是马兜铃酸代谢的主要场所。虽然已在肝脏中检测到马兜铃酸诱导突变的特征指纹,而且已知马兜铃酸具有肝毒性,但马兜铃酸是否会直接导致肝癌仍有待验证。本综述总结了马兜铃酸在实验动物中长期致癌性研究的结果。我们认为,这些植物化学物质致癌性的时空异质性可以解释为什么从未在成年个体中发现马兜铃酸导致肝癌的直接证据。我们还总结了已报道的减轻马兜铃酸所致肝毒性的方法,以更好地应对相关的全球安全问题,并为今后的研究提供了方向和建议。
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引用次数: 0
Metabolomics integrated with network pharmacology of blood-entry constituents reveals the bioactive component of Xuefu Zhuyu decoction and its angiogenic effects in treating traumatic brain injury. 代谢组学与入血成分网络药理学的结合揭示了学府煎剂的生物活性成分及其在治疗脑外伤中的血管生成作用。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-26 DOI: 10.1186/s13020-024-01001-0
Teng Li, Lianglin Zhang, Menghan Cheng, En Hu, Qiuju Yan, Yao Wu, Weikang Luo, Hong Su, Zhe Yu, Xin Guo, Quan Chen, Fei Zheng, Haigang Li, Wei Zhang, Tao Tang, Jiekun Luo, Yang Wang

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated.

Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI.

Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments.

Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002.

Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

背景:薛福竹煎剂(XFZYD)已被广泛用于治疗创伤性脑损伤(TBI)。然而,其生物活性成分及其内在机制尚未阐明:本研究旨在调查 XFYZD 在血液中吸收的生物活性成分及其治疗创伤性脑损伤的机制:本研究采用综合策略,分三步研究 XFZYD 的物质基础和药理机制。第一步包括:(1)对XFZYD进行代谢组学分析,以获得其主要功能和靶点;(2)从数据库中筛选XFZYD的入血成分和靶点;(3)通过代谢组学和网络药理学的综合分析,获得针对关键功能的潜在成分。第二步是在体外筛选有效成分的药理作用。第三步,在体内验证顶级活性化合物的作用,并通过蛋白质拮抗剂实验探索其机制:代谢组学分析表明,XFZYD主要通过影响血管功能来治疗创伤性脑损伤小鼠。我们通过网络药理学筛选出了 62 种 XFZYD 的入血成分。然后,我们重点研究了 39 种与血管基因相关的 XFZYD 反应代谢产物。在天然产物库中,我们验证了羟基红花黄色素 A(HSYA)、香兰素、藁本内酯、芍药苷等物质对内皮细胞增殖的促进作用明显优于对照组。其中,HSYA 的疗效更优。进一步的动物实验表明,通过 mNSS 和足部过失试验,HSYA 可减轻创伤性脑损伤小鼠的神经功能障碍;通过 HE、nissl 和 TUNEL 染色,HSYA 可减少神经元损伤。HSYA 增加了脑微血管的密度,提高了血管生成标志蛋白 VEGFA 和 CD34 的表达,并显著激活了 PI3K/Akt/mTOR 信号通路。在 PI3K 拮抗剂 LY294002 的干预下,血管生成效应消失:结论:该研究采用一种新颖的策略,将吸收到血液中的成分的网络药理学与代谢组学相结合,筛选出 HSYA 是 XFZYD 的顶级生物活性成分之一,它能在创伤后通过激活 PI3K/Akt/mTOR 信号通路刺激血管生成。
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引用次数: 0
Qin-Yu-Qing-Chang decoction reshapes colonic metabolism by activating PPAR-γ signaling to inhibit facultative anaerobes against DSS-induced colitis. 秦艽清肠汤通过激活PPAR-γ信号重塑结肠新陈代谢,从而抑制变性厌氧菌,对抗DSS诱导的结肠炎。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-26 DOI: 10.1186/s13020-024-01006-9
Feng Xu, Jingyi Hu, Yanan Li, Cheng Cheng, Ryan Au, Yiheng Tong, Yuguang Wu, Yuan Cui, Yulai Fang, Hongxin Chen, Lei Zhu, Hong Shen

Background: Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted.

Methods: The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts.

Results: Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist.

Conclusions: In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes.

背景:秦艽清长煎(QYQC)是一种来自中国的中药配方,被广泛用于治疗溃疡性结肠炎(UC),对结肠功能具有潜在的益处。然而,QYQC 的基本分子机制在很大程度上仍处于未知状态:方法:利用超高效液相色谱-质谱/质谱分析法测定了逍遥丸的主要成分,并在硫酸钠葡聚糖诱导的小鼠结肠炎模型中评估了逍遥丸的功效。对结肠炎症反应和粘膜屏障功能进行了全面评估。应用 RNA 测序、分子对接、结肠能量代谢和 16S rRNA 测序分析,揭示了 QYQC 治疗 UC 的复杂机制。检测过氧化物酶体增殖激活受体-γ(PPAR-γ)在细胞核和细胞质中的信号转导。此外,还战略性地使用了 PPAR-γ 拮抗剂来确认 QYQC 的功能目标:结果:利用超高效液相色谱-质谱/质谱联用技术,系统地鉴定了组成 QYQC 的九种中药的主要成分。结果:利用超高效液相色谱-质谱(UHPLC-MS/MS)系统鉴定了九味中药的主要成分。此外,QYQC 还能减轻炎症反应,改善粘膜屏障功能。此外,QYQC 还能通过触发 PPAR-γ 信号传导和增加 PPAR-γ 进入细胞核的比例来增强线粒体柠檬酸循环(TCA 循环)。这阻止了兼性厌氧菌,尤其是致病性大肠杆菌(肠杆菌科大肠杆菌)的无限制扩张,从而改善了结肠炎。分子对接结果表明,QYQC 的代表性化学成分,包括黄芩苷、芍药苷、木耳苷和白茅苷与 PPAR-γ 结合良好。在 PPAR-γ 拮抗剂存在的情况下,QYQC 对结肠炎的影响会减弱:总之,QYQC 通过激活 PPAR-γ 信号传导和增加进入细胞核的 PPAR-γ 的比例来改善 UC,从而增强肠上皮细胞的能量代谢,从而防止兼性厌氧菌的失控增殖。
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Chinese Medicine
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