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Comprehensive profiling of Lingzhihuang capsule by liquid chromatography coupled with mass spectrometry-based molecular networking and target prediction 灵栀黄胶囊的液相色谱-质谱联用分子网络及靶标预测分析
Pub Date : 2022-02-22 DOI: 10.1097/HM9.0000000000000012
Mengliang Huang, Sijia Yu, Qing Shao, Hao Liu, Yingchao Wang, Hongzhang Chen, Yansheng Huang, Yi Wang
Abstract Objective: Lingzhihuang capsule (LZHC) is a natural product that consists of 10 commonly used medicinal plants, and it is used in traditional Chinese medicine to promote people's overall health. Previously, LZHC was successfully used as adjuvant therapy for treating patients with cancer. However, the chemical constituents of LZHC and their potential biological functions remain unclear. The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets. Methods: The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry combined with mass spectrometry-based molecular networking. The targets were predicted using SwissTargetPrediction software, and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software. Results: We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking, including triterpene (the main structural type) and other clusters (ie, flavonoids and organic acids). Our results suggested that multiple pivotal targets were regulated by LZHC, including tumor necrosis factor, nitric oxide synthase 2, glucocorticoid receptor, estrogen receptor, 3-oxo-5-alpha-steroid 4-dehydrogenase 2, prostaglandin e2 receptor ep4 subtype, estrogen receptor beta, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, mitogen-activated protein kinase 3, and rac-alpha serine, which are related to signal transduction, positive regulation of transcription from RNA polymerase II promoters, oxidation-reduction processes, inflammatory responses, and other biological processes. Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC, such as cancer-related proteoglycans, the PI3K-Akt-signaling pathway, and the cAMP-signaling pathway. Conclusions: Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation, anti-aging, and tumor suppression. Graphical abstract: http://links.lww.com/AHM/A12
【摘要】目的:灵芝黄胶囊(LZHC)是由10种常用药用植物组成的天然产物,在中药中具有促进人体整体健康的作用。此前,LZHC被成功地用作治疗癌症患者的辅助疗法。然而,LZHC的化学成分及其潜在的生物学功能尚不清楚。本研究的目的是研究其主要生物活性成分,并预测其药理作用靶点。方法:采用超高效液相色谱-飞行时间质谱联用质谱分子网络技术对其成分进行推定鉴定。使用SwissTargetPrediction软件预测目标,并使用Database for Annotation, Visualization, and Integrated Discovery对相关基因本体和京都百科全书的基因和基因组路径进行分析。利用Cytoscape 3.8.0软件构建基于质谱的分子网络和化合物靶点通路网络。结果:通过质谱网络鉴定出了94个化合物,包括三萜(主要结构类型)和其他簇(黄酮类化合物和有机酸类化合物)。我们的研究结果表明,LZHC调控多个关键靶点,包括肿瘤坏死因子、一氧化氮合酶2、糖皮质激素受体、雌激素受体、3-氧-5- α -类固醇4-脱氢酶2、前列腺素e2受体ep4亚型、雌激素受体β、磷脂酰肌醇4,5-二磷酸3-激酶催化亚基α异构体、丝裂原活化蛋白激酶3和rac- α丝氨酸,这些靶点与信号转导有关。RNA聚合酶II启动子、氧化还原过程、炎症反应和其他生物过程的转录正调控。这些靶点的功能注释表明LZHC可能调控多种信号通路,如癌症相关蛋白聚糖、pi3k - akt信号通路和camp信号通路。结论:揭示了枸杞的化学成分,为枸杞具有免疫调节、抗衰老、抑制肿瘤等作用提供了科学依据。图形摘要:http://links.lww.com/AHM/A12
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引用次数: 17
Granulation process analysis technologies and potential applications in traditional Chinese medicine 造粒过程分析技术及其在中药中的潜在应用
Pub Date : 2022-02-22 DOI: 10.1097/HM9.0000000000000015
Tongcan Cui, Yizhe Hou, Huimin Feng, S. Wu, Wen-long Li, Zheng Li
Abstract Pharmaceutical production is changing from batch production to continuous production, during which granulation is one of the most important unit operations. The quality of mass-produced products is traditionally guaranteed by conducting off-line testing, which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes (CQAs) of the pharmaceutical granulation technology. Since the U.S. Food and Drug Administration proposed process analytical technology (PAT) in 2004, many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination. In this article, we review the recent research and application of two PAT modes in the granulation process, namely, single CQA and multi-CQA PAT, with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process. Furthermore, the potential applications in traditional Chinese Medicine are discussed.
医药生产正在由批量生产向连续生产转变,其中制粒是最重要的单元操作之一。批量生产产品的质量传统上是通过离线检测来保证的,无法满足连续生产对药品造粒工艺关键工艺参数和关键质量属性(cqa)实时监控的需求。自2004年美国食品和药物管理局提出过程分析技术(PAT)以来,已经开发了许多PAT工具来监测造粒过程,并提供有关造粒操作条件和终点确定的信息。本文综述了单CQA和多CQA两种PAT模式在造粒过程中的研究与应用,旨在为全面提高制药造粒过程的技术水平提供参考。并对其在中药领域的应用前景进行了展望。
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引用次数: 0
An inspiration to the studies on mechanisms of acupuncture and moxibustion action derived from 2021 Nobel Prize in Physiology or Medicine 2021年诺贝尔生理学或医学奖对针灸作用机制研究的启发
Pub Date : 2022-01-20 DOI: 10.1097/HM9.0000000000000023
Yi Guo, Yong-ming Li, Tianle Xu, M. Zhu, Zhifang Xu, Baomin Dou, Yanwei Li, Zhihan Chen
Abstract The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or Medicine. Specifically, Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel, evaluating the structure of the Piezo channel and its physiological and pathological functions, and proposed a possible role for the Piezo channel in acupuncture mechanical stimulation. Professor Michael Xi Zhu introduced the discovery of the transient receptor potential (TRP) family, reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family, and that information regarding associations between the meridian and lymphatic systems may have important research and medical value. In addition, Professor Tianle Xu reviewed the history of ion channel research, particularly the physiological and pharmacological effects of non-classical ion channels (eg, the acid sensing ion channel family) and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture actions. Professor Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational research. Finally, Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical stimulation. Therefore, we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medicine is in helping interpret how acupuncture and moxibustion adjust homeostasis (ie, by activating mechanical and thermal sensation), which is conducive to validating and promoting the clinical efficacy of acupuncture modalities.
受2021年诺贝尔生理学或医学奖的启发,《针灸与草药》编委会最近召开了一次学术研讨会,重点研究针灸疗效和艾灸作用的机制。具体而言,肖柏龙教授介绍了机械激活压电离子通道的诺贝尔奖研究成果,评价了压电通道的结构及其生理病理功能,并提出了压电通道在针刺机械刺激中的可能作用。此外,许天乐教授回顾了离子通道的研究历史,特别是非经典离子通道(如酸感离子通道家族)的生理和药理作用,并指出针刺德气手法的表征和神经回路对阐明针刺作用机制具有重要意义。李永明教授同样提出,2021年的诺贝尔奖可能为揭示针灸的组织学基础,分析针灸临床转化从基础研究到转化研究的主要科学问题打开了大门。最后,郭毅教授总结了近30年来针灸诱导穴位微环境的研究进展,并提出了针灸可能通过物理和机械刺激激活穴位离子通道受体,从而启动物化耦合网络的假说。因此,我们得出结论,2021年诺贝尔生理学或医学奖的主要成就是帮助解释针灸如何调节体内平衡(即通过激活机械和热感觉),这有利于验证和促进针灸方式的临床疗效。
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引用次数: 8
Development and evaluation of Panax notoginseng saponins contained in an in situ pH-triggered gelling system for sustained ocular posterior segment drug delivery 用于眼后段持续给药的原位ph触发胶凝系统中三七皂苷的开发与评价
Pub Date : 2021-12-01 DOI: 10.1097/HM9.0000000000000020
Peng Lu, Renxing Wang, Y. Xing, Yanquan Gao, Qingqing Zhang, Bin Xing, Ying Zhang, Chang-hai Yu, Xinfu Cai, Q. Shang, D. Kebebe, Jiaxin Pi, Zhidong Liu
Supplemental Digital Content is available in the text Abstract Objective: This study aimed to lay the foundation for the research on Panax notoginseng saponins (PNS) in pH-sensitive in situ gel and the development and improvement of related preparations. Methods: We used Carbopol®940, a commonly used pH-sensitive polymer, and the thickener hydroxypropyl methylcellulose (HPMC E4M) as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS. In addition, formula optimization was performed by assessing gelling capability with the results of in vitro release studies. In vitro (corneal permeation, rheological, and stability) and in vivo (ocular irritation and preliminary pharmacokinetics in the vitreous) studies were also performed. Results: The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug, making it an ideal ocular delivery system for improving posterior ocular bioavailability. Conclusions: This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations. It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.
摘要目的:本研究旨在为ph敏感原位凝胶中三七皂苷(PNS)的研究及相关制剂的开发与完善奠定基础。方法:以常用的ph敏感聚合物Carbopol®940和增稠剂羟丙基甲基纤维素(HPMC E4M)为眼用凝胶基质,制备眼用PNS原位凝胶。此外,通过体外释放研究结果评估凝胶性能,对配方进行优化。体外(角膜渗透、流变学和稳定性)和体内(眼刺激和玻璃体中的初步药代动力学)研究也进行了。结果:含PNS的原位胶凝系统具有药物缓释作用,是一种理想的提高眼后生物利用度的眼部给药系统。结论:本研究为原位ph触发凝胶中PNS的研究以及相关制剂的开发和完善奠定了基础。它将中医与当代原位胶凝法相结合,为糖尿病视网膜病变等后眼疾病的治疗提供了新的方向。
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引用次数: 3
The rationale behind the four major anti-coronavirus principles of Chinese herbal based on systems medicine. 基于系统医学的中草药四大抗冠状病毒原理背后的原理。
Pub Date : 2021-12-01 Epub Date: 2022-01-14 DOI: 10.1097/HM9.0000000000000019
Guanyuan Jin, Louis Lei Jin, Bonnie Xia Jin

As the novel coronavirus disease 2019 (COVID-19) and its multi variants continue to rage into the second year of a global pandemic, many success stories of applying Chinese herbal medicine (CHM) to COVID-19 patients continue to emerge from China and other parts of the world. Herewith, the authors summarized those experiences from a systems medicine perspective and categorize the four major treatment principles: (1) focusing on eliminating toxins in the early stage of the disease, (2) tonifying the body against deficiency throughout the entire disease course, (3) treating affected lung and intestine simultaneously based on visceral interactions, and (4) and cooling the blood and removing blood stasis at the later stage. The rationale behind these principles is shown via a scientific interpretation. This is not only helpful in reducing the complexity of promoting the CHM applications to enhance anti-pandemic efficacy but also to ramp up the process of integrating traditional Chinese medicine with modern medical practices.

随着2019年新型冠状病毒疾病(新冠肺炎)及其多变种继续肆虐至全球大流行的第二年,中国和世界其他地区继续涌现出许多将中草药应用于新冠肺炎患者的成功案例。在此,作者从系统医学的角度总结了这些经验,并将四大治疗原则分类:(1)注重在疾病早期排除毒素,(2)在整个病程中补虚,(3)基于内脏相互作用同时治疗受影响的肺和肠,(4)后期凉血化瘀。这些原则背后的原理是通过科学的解释来说明的。这不仅有助于降低推广中药应用以提高抗疫疗效的复杂性,而且有助于加快中医药与现代医学实践相结合的进程。
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引用次数: 0
Outcome measures in clinical trials of traditional Chinese medicine for stable angina pectoris 中药治疗稳定型心绞痛临床试验的疗效评价
Pub Date : 2021-12-01 DOI: 10.1097/HM9.0000000000000014
D. Xing, Mingjun Zhu, Chunxiang Liu, Hui Wang
Abstract Objective: This work aimed to present a descriptive analysis of the outcome measures used in clinical trials of traditional Chinese medicine (TCM) for patients with stable angina pectoris, and to provide baseline data for the development of core outcome sets (COSs) for relevant clinical trials. Methods: Medical databases were searched to identify randomized trials of the effects of TCM for the treatment of stable angina pectoris. Outcome measures of each trial were extracted. Descriptive statistics were used to analyze the baseline characteristics of outcomes in clinical trials of TCM. Results: 94 randomized trials (with 9,111 participants) involving 79 different outcomes were identified. The mean number of outcomes was 5 (1–21 per trial). The 5 most commonly reported outcomes were efficacy rate of electrocardiogram, efficacy rate of angina pectoris, efficacy rate of TCM syndrome, fasting lipid indices, and withdrawal rate of nitroglycerin. Several challenges were identified: (1) significant heterogeneity of outcomes and differences in the technique and timing of the measurement of the same outcome; (2) transformation of continuous data into categorical data and presented as such in >90% of trials; (3) few trials on the outcomes associated with the advantages and characteristics of TCM; and (4) selective reporting of outcomes. Conclusions: The outcomes used are excessively heterogenous, and the choice of some outcomes (timing and techniques) for measurement is confusing or inappropriate. Hence, developing and implementing a COS is necessary for greater consistency.
摘要目的:对稳定型心绞痛患者中医临床试验的结局指标进行描述性分析,为制定相关临床试验的核心结局集(COSs)提供基线数据。方法:检索医学数据库,确定中药治疗稳定型心绞痛的随机试验。提取每个试验的结局指标。采用描述性统计分析中医临床试验结果的基线特征。结果:94项随机试验(9111名参与者)涉及79种不同的结果。平均结局数为5个(每个试验1-21个)。最常报道的5项指标为心电图有效率、心绞痛有效率、中医证候有效率、空腹血脂指标、硝酸甘油停药率。我们发现了几个挑战:(1)结果的显著异质性以及测量相同结果的技术和时间的差异;(2)将连续数据转换为分类数据,并在>90%的试验中以分类数据的形式呈现;(3)与中医优势和特点相关的结局试验较少;(4)选择性报告结果。结论:使用的结果过于异质性,一些测量结果(时间和技术)的选择令人困惑或不适当。因此,开发和实现COS对于提高一致性是必要的。
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引用次数: 11
Trigger points and sensitized acupoints: same book, different covers? 触发点和致敏穴位:同一本书,不同封面?
Pub Date : 2021-12-01 DOI: 10.1097/hm9.0000000000000018
Mingsheng Sun, Mingxiao Yang, Jing Rong, Xingsha Ma, Hui Zheng, Dingjun Cai, Ling Zhao, F. Liang
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引用次数: 1
Acupuncture – a national heritage of China to the world: international clinical research advances from the past decade 针灸——中国走向世界的民族遗产:近十年来国际临床研究进展
Pub Date : 2021-12-01 DOI: 10.1097/hm9.0000000000000017
Baoyan Liu, Bo Chen, Yi Guo, Lixin Tian
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引用次数: 21
The inhibitory effect of lotus leaf extract on hyperuricemia and its potential mechanism 荷叶提取物对高尿酸血症的抑制作用及其可能机制
Pub Date : 2021-11-08 DOI: 10.1097/HM9.0000000000000001
Yating An, Jia Hao, Jian Li, Wei He, Lei Wang, Yi Zhang
Abstract Objective: Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis. Based on its good clinical evidence and anti-hypertensive effectiveness, this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract (LL) and lotus leaf total alkaloids fraction (LA). Methods: The xanthine oxidase (XOD) inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD. The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate (PO)-induced rat model by determining mRNA expression for renal urate transporters. Results: At a concentration of 40 μg/mL, LL and LA suppressed XOD enzymatic activity by 37.35% ± 9.50% and 47.73% ± 8.32%, respectively. Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats. Both LL and LA administration could inhibit XOD mRNA and protein expression, activate renal organic anion transporter 1/3 mRNA expression, and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1. Conclusions: Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA. Our results suggest that they act on two targets: decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver, and regulating the mRNA expression of renal urate transporters in the kidneys.
摘要目的:荷叶是一种传统的中草药,几个世纪以来一直被成功地用于消肿利尿。基于其良好的临床证据和降压效果,本研究旨在探讨荷叶粗提物(LL)和荷叶总生物碱部位(LA)抑制高尿酸血症作用的潜在机制。方法:通过测定肝脏黄嘌呤氧化酶mRNA和蛋白的表达水平,分析LL和LA对黄嘌呤氧化酶(XOD)的体外抑制作用。在氧酸钾(PO)诱导的大鼠体内模型中,通过测定肾尿酸转运蛋白mRNA的表达,分析荷叶对高尿酸血症的抑制作用。结果:在40 μg/mL浓度下,LL和LA对XOD酶活性的抑制作用分别为37.35%±9.50%和47.73%±8.32%。l和LA均能显著降低po诱导的高尿酸血症大鼠血清和肝脏尿酸浓度。两种给药方式均能抑制XOD mRNA和蛋白表达,激活肾有机阴离子转运蛋白1/3 mRNA表达,并通过降低肾GLUT9和肾尿酸转运蛋白1抑制肾尿酸重吸收。结论:深入了解了LL和LA抑制高尿酸血症作用的机制。我们的研究结果表明,它们作用于两个目标:通过抑制肝脏中XOD的mRNA和蛋白表达来减少尿酸的产生,以及调节肾脏中肾尿酸转运蛋白的mRNA表达。
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引用次数: 2
Carbon quantum dot preparation and application to detecting active ingredients in traditional Chinese medicine 碳量子点的制备及其在中药有效成分检测中的应用
Pub Date : 2021-11-08 DOI: 10.1097/hm9.0000000000000002
Bo Liu, Shangxin Guo, Xiaohui Fan, Xingchu Gong
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引用次数: 2
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Acupuncture and herbal medicine
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