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Identifying Dose Components of Manual Acupuncture to Determine the Dose-Response Relationship of Acupuncture Treatment: A Systematic Review. 识别手针剂量成分以确定针灸治疗的剂量-反应关系:一项系统综述。
Pub Date : 2022-03-16 DOI: 10.1142/S0192415X22500264
Da-Eun Yoon, In-Seon Lee, Younbyoung Chae
The dose-response relationship is a hallmark of pharmacological studies. However, this relationship has not been fully established in acupuncture research. This systematic review aims to provide the characteristics of the dose-response relationship in acupuncture research. We further summarized the differences in acupuncture effects according to dose components. Dose components of acupuncture were categorized into three groups: number of needles, stimulation intensity, and total number/frequency of treatments. The PubMed database was used to identify studies examining the effects of different doses of acupuncture from the establishment of the database to August 13, 2020. Dose components and responses were extracted from each study, and the results of low- and high-dose conditions were compared. Fourteen studies were included in this study. Of the included studies, 37.5% showed statistically significant enhanced responses to acupuncture treatment under high-dose conditions compared to low-dose conditions. Significant differences between high- and low-dose conditions were observed most frequently in studies that used various stimulation intensities (four out of six studies), followed in order by studies that used various numbers of needles (two out of seven studies), and those that used various numbers or frequencies of treatment (none of the three studies). Responses were categorized into symptom changes, physiological changes, experimentally induced pain/stimuli perception, and needling sensation. Stimulation intensity, which is considered one of the most important needling components, might indeed have a great impact on clinical responses to acupuncture.
剂量-反应关系是药理学研究的一个标志。然而,这种关系在针灸研究中尚未得到充分证实。本系统综述旨在提供针灸研究中剂量-反应关系的特点。我们进一步总结了不同剂量成分针刺效果的差异。针刺剂量成分分为针数、刺激强度和总次数/次数三组。PubMed数据库用于确定从数据库建立到2020年8月13日期间检查不同剂量针灸效果的研究。从每项研究中提取剂量成分和反应,并比较低剂量和高剂量条件下的结果。本研究共纳入14项研究。在纳入的研究中,37.5%的研究显示,与低剂量条件相比,高剂量条件下针灸治疗的疗效有统计学显著增强。高剂量和低剂量条件之间的显著差异在使用各种刺激强度的研究中最为常见(六项研究中有四项),其次是使用不同数量的针头的研究(七项研究中有两项),以及使用不同数量或频率的治疗(三项研究中没有一项)。反应分为症状变化、生理变化、实验诱导的疼痛/刺激感知和针刺感觉。刺激强度被认为是最重要的针刺成分之一,可能确实对针灸的临床反应有很大的影响。
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引用次数: 7
Hydroxysafflor Yellow A Alleviates Ischemic Stroke in Rats via HIF-1[Formula: see text], BNIP3, and Notch1-Mediated Inhibition of Autophagy. 羟基红花黄A通过HIF-1、BNIP3和notch1介导的自噬抑制减轻大鼠缺血性脑卒中。
Pub Date : 2022-03-16 DOI: 10.1142/S0192415X22500331
Yuliang Zhang, Yi Liu, Q. Cui, Zitong Fu, Haoyu Yu, Ao-lei Liu, Jingjing Liu, Xiude Qin, Shaoqin Ge, Guoshan Zhang
Stroke has become a major cause of death and disability worldwide. The cellular recycling pathway autophagy has been implicated in ischemia-induced neuronal changes, but whether autophagy plays a beneficial or detrimental role is controversial. Hydroxysafflor Yellow A (HSYA), a popular herbal medicine, is an extract of Carthamus tinctorius and is used to treat ischemic stroke (IS) in China. HSYA has been shown to prevent cardiovascular and cerebral ischemia/reperfusion injury in animal models. However, the specific active ingredients and molecular mechanisms of HSYA in IS remain unclear. Here, we investigated the effect of HSYA treatment on autophagy in a rat model of IS. IS was induced in rats by middle cerebral artery occlusion. Rats were treated once daily for 3 days with saline, HYSA, or the neuroprotective agent Edaravone. Neurobehavioral testing was performed on days 1, 2, and 3 post-surgery. Brains were removed on day 3 post-surgery for histological evaluation of infarct area, morphology, and for qRT-PCR and western blot analysis of the expression of the autophagy factor LC3 and the signaling molecules HIF-1[Formula: see text], BNIP3, and Notch1. Molecular docking studies were performed in silico to predict potential interactions between HSYA and LC3, HIF-1[Formula: see text], BNIP3, and Notch1 proteins. The result showed that HSYA treatment markedly alleviated IS-induced neurobehavioral deficits and reduced brain infarct area and tissue damage. HSYA also significantly reduced hippocampal expression levels of LC3, HIF-1[Formula: see text], BNIP3, and Notch1. The beneficial effect of HSYA was generally superior to that of Edaravone. Molecular modeling suggested that HSYA may bind strongly to HIF-1[Formula: see text], BNIP3, and Notch1 but weakly to LC3. In conclusion, HSYA inhibits post-IS autophagy induction in the brain, possibly by suppressing HIF-1[Formula: see text], BNIP3 and Notch1. HSYA may have utility as a post-IS neuroprotective agent.
中风已成为世界范围内死亡和残疾的主要原因。细胞再循环途径自噬与缺血诱导的神经元变化有关,但自噬是否起有益或有害的作用尚存争议。羟基红花黄A (HSYA)是一种流行的草药,是红花(Carthamus tinctorius)的提取物,在中国用于治疗缺血性中风(is)。在动物模型中,HSYA已被证明可以预防心血管和脑缺血再灌注损伤。然而,HSYA在IS中的具体活性成分和分子机制尚不清楚。在此,我们研究了HSYA处理对大鼠IS模型自噬的影响。大鼠大脑中动脉闭塞诱导IS。用生理盐水、HYSA或神经保护剂依达拉奉治疗大鼠,每天1次,连用3天。术后第1、2、3天进行神经行为测试。术后第3天取脑,对梗死面积、形态学进行组织学评估,并对自噬因子LC3、信号分子HIF-1(公式见文)、BNIP3、Notch1的表达进行qRT-PCR和western blot分析。通过计算机进行分子对接研究,预测HSYA与LC3、HIF-1、BNIP3和Notch1蛋白之间的潜在相互作用。结果表明,HSYA治疗可明显减轻is诱导的神经行为缺陷,减少脑梗死面积和组织损伤。HSYA还显著降低了海马LC3、HIF-1、BNIP3和Notch1的表达水平。HSYA的有益效果普遍优于依达拉奉。分子模拟表明,HSYA可能与HIF-1、BNIP3和Notch1结合强烈,但与LC3结合较弱。综上所述,HSYA抑制脑is后自噬诱导,可能是通过抑制HIF-1[公式:见文]、BNIP3和Notch1。HSYA可能作为is后神经保护剂具有实用价值。
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引用次数: 8
Effects of Capsaicin on the Hypoglycemic Regulation of Metformin and Gut Microbiota Profiles in Type 2 Diabetic Rats. 辣椒素对2型糖尿病大鼠二甲双胍和肠道微生物群的降糖调节作用。
Pub Date : 2022-03-16 DOI: 10.1142/S0192415X22500355
Zhiqiang Kang, Jingui Hu, Manyun Chen, Yu Mao, Lili Xie, Nianyu Yang, Tao Liu, Wei Zhang, Weihua Huang
Dietary capsaicin (CAP), the main irritant component in pepper, can reduce the incidence of diabetes, while metformin (MET) is a first-line oral hypoglycemic drug. The purpose of this study was to investigate whether CAP on the hypoglycemic effect of MET is pertinent to gut microbiota. The glucose and insulin tolerance of diabetic rats were monitored. The glycolipid metabolism was analyzed by detecting blood biochemical parameters. Liver pathological changes were observed by Hematoxylin eosin (HE) staining. The inflammatory cytokines and intestinal tight junction proteins were detected by RT-qPCR and Western blot. 16S rRNA sequencing was employed to analyze gut microbiota profiles. The results showed that CAP and MET co-treatment could significantly reduce fasting blood glucose, improve glucose tolerance, lessen liver injury and inflammatory infiltration, down-regulate inflammatory cytokines and up-regulate intestinal tight junction proteins in diabetic rats by comparing it with MET monotherapy. Moreover, CAP and MET co-treatment altered gut microbiota profiles by regulating microbials' abundances such as Akkermansia. In conclusion, CAP showed the significant hypoglycemic effect of MET and remodulated gut microbiota profiles in diabetic rats.
辣椒中的主要刺激成分辣椒素(CAP)可以降低糖尿病的发病率,而二甲双胍(MET)是一线口服降糖药物。本研究的目的是研究CAP对MET降血糖作用的影响是否与肠道微生物群有关。监测糖尿病大鼠的葡萄糖和胰岛素耐受性。通过检测血液生化参数分析糖脂代谢。苏木精-伊红(HE)染色观察肝脏病理变化。采用RT-qPCR和Western印迹法检测炎性细胞因子和肠紧密连接蛋白。16S rRNA测序用于分析肠道微生物群图谱。结果表明,CAP和MET联合治疗可显著降低糖尿病大鼠的空腹血糖,改善糖耐量,减轻肝损伤和炎症浸润,下调炎性细胞因子,上调肠道紧密连接蛋白。此外,CAP和MET联合治疗通过调节微生物的丰度(如阿克曼菌)改变了肠道微生物群。总之,CAP显示了MET的显著降血糖作用,并对糖尿病大鼠的肠道微生物群进行了调节。
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引用次数: 2
Cordyceps Improves Obesity and its Related Inflammation via Modulation of Enterococcus cecorum Abundance and Bile Acid Metabolism. 冬虫夏草通过调节盲肠球菌丰度和胆汁酸代谢改善肥胖及其相关炎症。
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500343
Guo-Dong Wu, An Pan, Xu Zhang, Yuan-Yuan Cai, Qi Wang, Feng-Qing Huang, Raphael N. Alolga, Jing Li, Lian-Wen Qi, Qun Liu
Dysbiotic gut microbiota has been identified as a primary mediator of inherent inflammation that underlies the pathogenesis of obesity. Cordyceps comprises the larval body and the stroma of Cordyceps sinensis (BerK.) Sacc. parasiting on Hepialidae larvae of moths (H. pialusoberthur) with potent metabolic regulation functions. The underlying anti-obesity mechanisms, however, remain largely unknown. Here, we demonstrate that the water extract of Cordyceps attenuates glucose and lipid metabolism disorders and its associated inflammation in high-fat diet (HFD)-fed mice. 16S rRNA gene sequencing and microbiomic analysis showed that Cordyceps reduced the amounts of Enterococcus cecorum, a bile-salt hydrolase-producing microbe to regulate the metabolism of bile acids in the gut. Importantly, E. cecorum transplantation or liver-specific knockdown of farnesoid X receptor (FXR), a bile acid receptor, diminished the protective effect of Cordyceps against HFD-induced obesity. Together, our results shed light on the mechanisms that underlie the glucose- and lipid-lowering effects of Cordyceps and suggest that targeting intestinal E. cecorum or hepatic FXR are potential anti-obesity and anti-inflammation therapeutic avenues.
肠道微生物群失调已被确定为肥胖发病机制的内在炎症的主要介质。虫草由冬虫夏草幼虫体和基质组成。寄生在具有强大代谢调节功能的蛾类(H.pialusoberthur)的Hepilidae幼虫上。然而,潜在的抗肥胖机制在很大程度上仍然未知。在这里,我们证明了冬虫夏草的水提取物可以减轻高脂肪饮食(HFD)喂养的小鼠的葡萄糖和脂质代谢紊乱及其相关炎症。16S rRNA基因测序和微生物组学分析表明,虫草减少了盲肠肠球菌的数量,盲肠肠球菌是一种产生胆汁盐水解酶的微生物,可调节肠道中胆汁酸的代谢。重要的是,盲肠大肠杆菌移植或肝脏特异性敲除法尼素X受体(一种胆汁酸受体),降低了虫草对HFD诱导的肥胖的保护作用。总之,我们的研究结果揭示了虫草降血糖和降脂作用的机制,并表明靶向肠道盲肠或肝脏FXR是潜在的抗肥胖和抗炎治疗途径。
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引用次数: 6
Therapeutic Effect and Mechanism of Acupuncture in Autoimmune Diseases. 针刺治疗自身免疫性疾病的疗效及机制
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500252
Jing Wang, Fangyi Zhu, Wei Huang, Zhengyi Chen, Ping Zhao, Yanting Lei, Yumei Liu, Xi-jun Liu, Bo Sun, Hulun Li
Autoimmune diseases (AIDs) are conditions arising from abnormal immune reactions to autoantigens, which can be defined as the loss of immune tolerance to autoantigens, causing the production of autoantibodies and subsequent inflammation and tissue injury. The etiology of AIDs remains elusive, which may involve both genetic and environmental factors, such as diet, drugs, and infections. Despite rapid progress in the treatment of autoimmune diseases over the past few decades, there is still no approach that can cure AIDs. As an alternative approach, traditional Chinese medicine (TCM) such as acupuncture has been used in an attempt to treat AIDs including multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), and the results have proven to be quite promising, despite the fact that its mechanism is still not fully understood. In this review, the present knowledge regarding mechanisms of acupuncture in the treatment of AIDs has been summarized, and deeper insights will be provided in order to better understand how acupuncture may regulate immune responses during AIDs.
自身免疫性疾病(AIDs)是由对自身抗原的异常免疫反应引起的疾病,可以定义为对自身抗原失去免疫耐受性,导致自身抗体的产生和随后的炎症和组织损伤。艾滋病的病因仍然难以捉摸,这可能涉及遗传和环境因素,如饮食、药物和感染。尽管在过去的几十年里,自身免疫性疾病的治疗取得了迅速的进展,但仍然没有办法治愈艾滋病。作为一种替代方法,针灸等传统中医(TCM)已被用于治疗艾滋病,包括多发性硬化症(MS)、类风湿性关节炎(RA)和炎症性肠病(IBD),尽管其机制尚未完全了解,但结果已被证明是相当有希望的。本文就针刺治疗艾滋病的机制进行综述,以期对针刺如何调节艾滋病患者的免疫反应提供更深入的认识。
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引用次数: 4
The Changing Global Landscape in the Development of Artemisinin-Based Treatments: A Clinical Trial Perspective. 青蒿素类药物开发过程中不断变化的全球格局:临床试验视角。
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500306
Xiang-Jun Kong, Kun-Meng Liu, Hua-Li Zuo, Hsien-Da Huang, Yuanjia Hu
Artemisinin and its derivatives (ARTs), due to their potent antimalarial activities, are widely used as frontline antimalarials across the world. Although the large-scale deployment of ARTs has significantly contributed to a substantial decline in malaria deaths, the global malaria burden is still high. New antimalarial treatments need to be developed to manage the growing artemisinin resistance. Understanding the status of ART development is crucial for developing strategies for new alternatives and identifying opportunities to develop ART-based treatments. This study sampled ART clinical trials from the past two decades to gain an overview of the global ART-development landscape. A total of 768 trials were collected to analyze the disease focuses, activity trends, development status, geographic distribution, and combination treatment profiles of ART trials. The findings highlighted the constant focus of ARTs on malaria, the evolving combination research focus, the distinctions between ART development preferences across global regions, the urgent demands for treatments for artemisinin-resistant malaria, and the unavoidable need to consider ART combinations in the development of new antimalarials.
青蒿素及其衍生物由于其强大的抗疟活性,在世界各地被广泛用作一线抗疟药物。尽管大规模部署ART大大降低了疟疾死亡人数,但全球疟疾负担仍然很高。需要开发新的抗疟治疗方法来控制日益增长的青蒿素耐药性。了解抗逆转录病毒疗法的发展状况对于制定新的替代方案的战略和确定开发基于抗逆转录病毒治疗的机会至关重要。这项研究对过去二十年的抗逆转录病毒治疗临床试验进行了抽样,以了解全球抗逆转录病毒疗法的发展前景。共收集了768项试验,以分析ART试验的疾病焦点、活动趋势、发展状况、地理分布和联合治疗概况。研究结果强调了抗逆转录病毒疗法对疟疾的持续关注,不断发展的组合研究重点,全球各地区抗逆转录病毒治疗开发偏好之间的差异,对青蒿素耐药性疟疾治疗的迫切需求,以及在开发新的抗疟药时不可避免地需要考虑抗逆转录病毒药物组合。
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引用次数: 0
Ameliorative Effects of Malonyl Ginsenoside from Panax ginseng on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice. 人参丙二醇人参皂苷通过IRS1/PI3K/Akt和AMPK信号通路改善2型糖尿病小鼠糖脂代谢和胰岛素抵抗的作用
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500367
D. Wang, Jia-mei Wang, Fuhong Zhang, F. Lei, Xin Wen, Jia Song, Guang-zhi Sun, Zhi Liu
Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.
我们之前的研究表明,人参丙二醇人参皂苷(PG-MGR)在治疗T2DM中起着至关重要的作用。然而,其潜在机制尚不清楚。在本研究中,我们研究了PG-MGR对高脂肪饮食(HFD)和链脲佐菌素诱导的糖尿病小鼠的抗糖尿病作用机制,并确定了PG-MGR的主要作用成分。结果表明,HPLC-ESI-MS/MS法在PG-MGR中鉴定出16种丙二醇人参皂苷。PG-MGR治疗显著降低空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平,改善胰岛素抵抗和葡萄糖耐量。同时,PG-MGR通过降低天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)的表达改善肝损伤。此外,Western blot分析显示,PG-MGR处理后,肝脏和骨骼肌中p-PI3K/PI3K、p-AKT/AKT、p-AMPK/AMPK、p-ACC/ACC和GLUT4蛋白表达水平显著上调,p-IRS-1/IRS-1、Fas和SREBP-1c蛋白表达水平显著降低。这些发现表明PG-MGR通过激活IRS-1/PI3K/AKT和AMPK信号通路,具有改善糖脂代谢和胰岛素抵抗的潜力。
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引用次数: 5
Traditional Uses, Phytochemistry, Pharmacology, Quality Control, Industrial Application, Pharmacokinetics and Network Pharmacology of Pogostemon cablin: A Comprehensive Review. 广藿香的传统用途、植物化学、药理学、质量控制、工业应用、药代动力学和网络药理学综述。
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500288
Fangfang Xu, Wan-ping Cai, Ting Ma, Huimei Zeng, Xiaolan Kuang, Wei-Ying Chen, Bo Liu
Pogostemonis Herba (PH) is the dried aerial parts of Pogostemon cablin (Blanco) Benth, which is mainly distributed and used in Asian countries. PH is an aromatic damp-resolving drug in traditional Chinese medicine (TCM), which is usually used for the treatment of vomiting, chest tension, tiredness, abdominal pain, diarrhea, and headache. In this review, the summary of chemical constituents in the aerial parts, biological activities, history of uses, quality control methods, industrial applications, pharmacokinetics and network pharmacology are reported. By collating the chemical constituents of various parts of PH, a total of 174 components were identified, including 66 terpenes, 6 pyrones, 40 flavonoids, 21 phenylpropanoids, 9 steroids, 4 polysaccharides and 28 others. Pharmacological research has found that PH possesses multi-pharmacological activities, including regulating the gastrointestinal tract, inhibition of pathogenic microorganisms, and anti-inflammation, which provide more scientific interpretation for the clinical usage of PH. In addition, the shortcomings of the current research on PH and the recommendation of future studies on PH are analyzed. We hope this review can provide some insight for further research and applications of PH in future.
广藿香(Pogostemonis Herba,PH)是广藿香的干燥地上部分,主要分布和使用于亚洲国家。PH在中医中是一种芳香的解湿药物,通常用于治疗呕吐、胸闷、疲倦、腹痛、腹泻和头痛。本文综述了地上部分的化学成分、生物活性、使用历史、质量控制方法、工业应用、药代动力学和网络药理学。通过对PH各部位化学成分的整理,共鉴定出174种成分,其中萜烯66种,吡喃酮6种,黄酮类40种,苯丙烷类21种,甾体9种,多糖4种,其他28种。药理学研究发现,PH具有调节胃肠道、抑制病原微生物和抗炎等多种药理活性,为PH的临床应用提供了更科学的解释。此外,还分析了目前PH研究的不足和未来PH研究的建议。我们希望这篇综述能为PH的进一步研究和应用提供一些见解。
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引用次数: 8
Integrative Analysis of the Gut Microbiota and Metabolome in Obese Mice with Electroacupuncture by 16S rRNA Gene Sequencing and HPLC-MS-based Metabolic Profiling. 基于16S rRNA基因测序和hplc - ms代谢谱的电针治疗肥胖小鼠肠道微生物群和代谢组综合分析
Pub Date : 2022-03-10 DOI: 10.1142/S0192415X22500276
Yuan-Cheng Si, Chenchen Ren, Er-Wei Zhang, Zhao-xia Kang, Xiaowei Mo, Qing-qing Li, Bo Chen
Acupuncture has been used to treat numerous diseases such as obesity in China for thousands of years. Several mechanisms of acupuncture on obesity have been surveyed based on metabolomics, but the effects of acupuncture on the alterations in the gut flora are still unclear. In this study, an integrated approach based on 16S rRNA gene sequencing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) metabolic profiling was conducted to investigate the effects of acupuncture on high-fat-diet-induced obesity through the regulation of the relative abundances of gut microbiota and their relationships with biomarker candidates. A total of 10 significantly altered bacterial genera and 11 metabolites were recognized, which recovered to normal levels after electroacupuncture treatment. The relative abundances of the bacterial families Muribaculaceae,Lachnospiraceae,Desulfovibrionaceae,Helicobacteraceae, Prevotellaceae,Ruminococcaceae,Rikenellaceae,Deferribacteraceae,Bacteroidaceae andTannerellaceaewere remarkedly changed among the three groups. Potential biomarkers, including LysoPC(0:0/16:0) ([Formula: see text]1),PC(0:0/18:0) ([Formula: see text]2),Cholic acid([Formula: see text]3),LysoPC(16:0) ([Formula: see text]4), 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid([Formula: see text]5), 5beta-Cyprinolsulfate([Formula: see text]6),PC(18:0/0:0) ([Formula: see text]7), 1-Nitro-5-hydroxy-6-glutathionyl-5,6-dihydronaphthalene([Formula: see text]8),Glycocholic acid([Formula: see text]9),[Formula: see text]-Arginine([Formula: see text]10) andGulonic acid([Formula: see text]11), were involved in several metabolic pathways, such as the glycerophospholipid metabolism and primary bile acid biosynthesis. Interestingly, there was a strong correlation between the perturbed gut flora in Bilophila and Bifidobacterium and the altered intestinal metabolite of 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid and Cholanoic acid and [Formula: see text]-Arginine. This finding suggested that the effects of electroacupuncture might change the proportions of Bilophila and Bifidobacterium by regulating the constituents of the functional metabolite of 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid and Cholanoic acid and [Formula: see text]-Arginine. These results indicated that the effects of electroacupuncture focused on custom metabolic pathways as well as depend on the changes in the gut microbiota in obesity. These findings suggest that the 16S rRNA gene sequencing and HPLC-MS-based metabolomics approach can be applied to comprehensively assess the effects of traditional Chinese medicines.
几千年来,针灸在中国一直被用来治疗肥胖等多种疾病。基于代谢组学研究了针灸治疗肥胖的几种机制,但针灸对肠道菌群改变的影响尚不清楚。本研究采用基于16S rRNA基因测序结合高效液相色谱-质谱(HPLC-MS)代谢谱的综合方法,通过调节肠道微生物群的相对丰度及其与生物标志物候选物的关系,研究针灸对高脂肪饮食诱导的肥胖的影响。共鉴定出10个显著改变的细菌属和11个代谢物,经电针治疗后恢复到正常水平。三组间Muribaculaceae、Lachnospiraceae、Desulfovibrionaceae、Helicobacteraceae、Prevotellaceae、Ruminococcaceae、Rikenellaceae、Deferribacteraceae、Bacteroidaceae和tannerellaceae细菌科的相对丰度发生了显著变化。潜在的生物标记物,包括LysoPC(0:0/16:0)([公式:看到文本]1),PC(0:0/18:0)((公式:看到文本)2),胆酸((公式:看到文本)3),LysoPC(16:0)((公式:看到文本)4),3(公式:看到文本),6(公式:看到文本),7(公式:看到文本)-Trihydroxy-5[公式:看到文本]-cholanoic酸([公式:看到文本]5),5 beta-cyprinolsulfate([公式:看到文本]6),PC(18:0/0:0)([公式:看到文本]7),1-Nitro-5-hydroxy-6-glutathionyl-5, 6-dihydronaphthalene([公式:看到文本]8),Glycocholic酸([公式:9),[公式:见文本]-精氨酸([公式:见文本]10)和古醛酸([公式:见文本]11),参与几个代谢途径,如甘油磷脂代谢和初级胆汁酸生物合成。有趣的是,嗜杆菌和双歧杆菌肠道菌群的紊乱与肠道代谢物3[公式:见文]、6[公式:见文]、7[公式:见文]-三羟基-5[公式:见文]-胆酸和胆酸与[公式:见文]-精氨酸的改变有很强的相关性。这一发现表明,电针的作用可能通过调节3[公式:见文],6[公式:见文],7[公式:见文]-三羟基-5[公式:见文]-胆酸和胆酸和[公式:见文]-精氨酸的功能代谢物成分而改变嗜双歧杆菌和双歧杆菌的比例。这些结果表明,电针的作用主要集中在自定义代谢途径上,并依赖于肥胖患者肠道微生物群的变化。这些发现表明,16S rRNA基因测序和基于hplc - ms的代谢组学方法可用于综合评估中药的作用。
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引用次数: 5
Exploring the Potential Pharmacological Mechanism of Hesperidin and Glucosyl Hesperidin against COVID-19 Based on Bioinformatics Analyses and Antiviral Assays. 基于生物信息学分析和抗病毒试验探讨橙皮苷和葡萄糖基橙皮苷抗COVID-19的潜在药理机制
Pub Date : 2022-03-02 DOI: 10.1142/S0192415X22500148
Yun Huang, Wei Zhou, Jing Sun, Guoliang Ou, N. Zhong, Zhigang Liu
The development of anti-COVID-19 drugs has become the top priority since the outbreak of the epidemic, and Traditional Chinese medicine plays an important role in reducing mortality. Here, hesperidin and its glycosylation product, glucosyl hesperidin were selected to determine their antiviral activity against SARS-CoV-2 due to their structural specificity as reported. To be specific, their binding ability with ACE2, M, S, RBD and N proteins were verified with both in silico and wet lab methods, i.e., molecular docking and binding affinity tests, including biolayer interferometry assay (BLI) and isothermal titration calorimetry assay (ITC). Moreover, systematic pharmacological analysis was conducted to reveal their pharmacological mechanism in treating COVID-19. Finally, their antiviral activity against SARS-CoV-2 was determined in vitro in a biosafety level 3 (BSL3) laboratory. The results demonstrated their outstanding binding affinity with ACE2, M, S and RBD proteins, while showed barely unobserved binding with N protein, indicating their key roles in influencing the invasion and early replication phase of SARS-CoV-2. In addition, both hesperidin and glucosyl hesperidin were shown to have a great impact on immune, inflammation and virus infection induced by COVID-19 according to the systematic pharmacological analysis. Moreover, the IC50s of hesperidin and glucosyl hesperidin against SARS-CoV-2 were further determined (51.5 [Formula: see text]M and 5.5 mM, respectively) with cell-based in vitro assay, suggesting their great anti-SARS-CoV-2 activity. All in all, present research was the first to verify the binding ability of hesperidin and glucosyl hesperidin with SARS-CoV-2 proteins with both in silico and wet-lab methods and proposed the possibility of applying hesperidin and glucosyl hesperidin to treat COVID-19.
自疫情爆发以来,抗新冠肺炎药物的开发成为当务之急,中医药在降低死亡率方面发挥着重要作用。本研究选择橙皮苷及其糖基化产物葡萄糖基橙皮苷,根据其结构特异性测定其对SARS-CoV-2的抗病毒活性。具体而言,通过硅和湿实验室方法,即分子对接和结合亲和力测试,包括生物层干涉法(BLI)和等温滴定量热法(ITC),验证了它们与ACE2、M、S、RBD和N蛋白的结合能力。并进行系统药理分析,揭示其治疗新冠肺炎的药理机制。最后,在生物安全三级(BSL3)实验室体外测定了它们对SARS-CoV-2的抗病毒活性。结果表明,它们与ACE2、M、S和RBD蛋白具有良好的结合亲和力,而与N蛋白的结合几乎没有观察到,表明它们在影响SARS-CoV-2的侵袭和早期复制阶段发挥了关键作用。此外,系统药理分析表明,橙皮苷和葡萄糖基橙皮苷对COVID-19诱导的免疫、炎症和病毒感染均有很大的影响。体外细胞法测定橙皮苷和葡萄糖基橙皮苷抗SARS-CoV-2的ic50(分别为51.5 M和5.5 mM),表明其具有较强的抗SARS-CoV-2活性。总而言之,本研究首次通过硅法和湿法验证了橙皮苷和葡萄糖基橙皮苷与SARS-CoV-2蛋白的结合能力,并提出了橙皮苷和葡萄糖基橙皮苷应用于治疗COVID-19的可能性。
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引用次数: 8
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The American journal of Chinese medicine
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