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Ethanol extract of lymphanax with gypenoside 17 and ginsenoside Re exerts anti-inflammatory properties by targeting the AKT/NF-κB pathway 含有刺五加甙 17 和人参皂苷 Re 的淋巴皂苷乙醇提取物通过靶向 AKT/NF-κB 通路发挥抗炎作用
IF 6.3 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-08-25 DOI: 10.1016/j.jgr.2024.08.003
Wooram Choi, Hyun Soo Kim, Donghyun Kim, Yong Deog Hong, Hyoung-June Kim, Ji Hye Kim, Jong-Hoon Kim, Jae Youl Cho
Ginseng is processed into several types such as white ginseng, red ginseng, and black ginseng, according to the processing methods such as drying, steaming, and heating. These processing conditions can change the portion of the useful ingredients. Recently, new processing method was established to develop ‘lymphanax’, an aged fresh white ginseng prepared under anaerobic condition. This aging process was revealed to increase the content of gypenoside 17 (Gyp17) as well as ginsenoside Re, known to have anti-inflammatory effects. As the next step, therefore, we aimed to investigate the anti-inflammatory activity of lymphanax using its ethanol extract of lymphanax (Lymphanax-EE). LC-MS/MS identified the ginsenoside content of lymphanax-EE. A nitric oxide (NO) assay revealed the anti-inflammatory activity of lymphanax-EE. Pro-inflammatory gene expression was analyzed by quantitative PCR. Finally, we identified the underlying mechanism for the anti-inflammatory activity of lymphanax-EE through luciferase analysis, Western blotting, and CETSA. The LC-MS/MS analysis revealed lymphanax-EE to contain more protopanaxatriol-type ginsenosides, and Gyp17 than fresh ginseng. Lymphanax-EE (0–200 μg/ml) suppressed NO release and mRNA levels of pro-inflammatory cytokines such as iNOS and COX-2 in LPS-treated RAW264.7 cells. Moreover, lymphanax-EE (200 μg/ml) reduced the activity of NF-κB and phosphorylation of NF-κB signal proteins such as p65, p50, IκBα, and IKKα/β. Finally, lymphanax-EE (200 μg/ml) decreased the phosphorylation of IKKα/β induced by AKT overexpression. Among the components of lymphanax-EE, ginsenoside Re and Gyp17 were found to suppress AKT1 activity. Lymphanax-EE-containing ginsenosides and Gyp17 with anti-inflammatory properties suppressed LPS-induced inflammation by reducing the NF-κB signal.
根据烘干、蒸煮和加热等加工方法,人参被加工成多种类型,如白参、红参和黑参。这些加工条件会改变有用成分的比例。最近,人们建立了新的加工方法,开发出在厌氧条件下制备的陈年新鲜白参 "lymphanax"。研究发现,这种陈化过程增加了人参皂苷 17(Gyp17)和人参皂苷 Re 的含量,而人参皂苷 Re 具有抗炎作用。因此,我们下一步的目标是利用淋巴杉乙醇提取物(Lymphanax-EE)研究淋巴杉的抗炎活性。LC-MS/MS鉴定了Lymphanax-EE中的人参皂苷含量。一氧化氮(NO)测定显示了Lymphanax-EE的抗炎活性。通过定量 PCR 分析了促炎基因的表达。最后,我们通过荧光素酶分析、Western 印迹和 CETSA 确定了 lymphanax-EE 抗炎活性的内在机制。LC-MS/MS分析显示,与新鲜人参相比,淋巴-EE含有更多的原人参三醇型人参皂甙和Gyp17。Lymphanax-EE(0-200 μg/ml)可抑制LPS处理的RAW264.7细胞中NO的释放以及iNOS和COX-2等促炎细胞因子的mRNA水平。此外,lympanax-EE(200 μg/ml)还能降低NF-κB的活性以及NF-κB信号蛋白(如p65、p50、IκBα和IKKα/β)的磷酸化。最后,lympanax-EE(200 μg/ml)降低了AKT过表达诱导的IKKα/β磷酸化。在Lymphanax-EE的成分中,发现人参皂苷Re和Gyp17能抑制AKT1的活性。具有抗炎特性的人参皂苷和Gyp17通过减少NF-κB信号抑制了LPS诱导的炎症。
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引用次数: 0
Enhancement of skin regeneration through activation of TGF-β/SMAD signaling pathway by Panax ginseng meyer non-edible callus-derived extracellular vesicles 三七麦芽非食用茧源性细胞外囊泡通过激活 TGF-β/SMAD 信号通路促进皮肤再生
IF 6.3 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-08-23 DOI: 10.1016/j.jgr.2024.08.002
Ha Young Park, Min Ho Kang, Guewha Lee, Jin Woo Kim
This study aimed to investigate the effects of ginseng non-edible callus-derived extracellular vesicle (GNEV) on skin regeneration, particularly focusing on its impact on proliferation and migration in human dermal fibroblast (HDF). GNEV was isolated from ginseng non-edible callus using sequential filtration and size exclusion chromatography (SEC). The extracellular vesicle was characterized using nanoparticle tracking analysis (NTA). HDF was treated with various concentrations of GNEV, and cell viability, proliferation, and migration were assessed using MTT and scratch wound healing assays. Gene expression related to collagen synthesis () was measured using RT-PCR. Treatment of HDF with GNEV resulted in a significant 2.5-fold increase in cell migration compared to the non-treated group. Furthermore, GNEV demonstrated the upregulation of collagen synthesis genes, specifically , and , by 41.7 %, 59.4 %, 60.2 %, and 21.8 %, respectively. These findings indicated that GNEV activates the signaling pathway, showcasing its potential to induce skin regeneration. In conclusion, GNEV exhibits a notable ability to enhance skin regeneration through its stimulatory effects on cell migration and the upregulation of key collagen synthesis genes. The activation of the signaling pathway further suggests the potential of GNEV as a promising candidate for drug delivery systems in the fields of cosmetics and pharmaceuticals, opening avenues for further research and application in skincare and dermatology.
本研究旨在探讨人参非食用胼胝体衍生的细胞外囊泡(GNEV)对皮肤再生的影响,尤其是对人真皮成纤维细胞(HDF)增殖和迁移的影响。利用顺序过滤和尺寸排阻色谱法(SEC)从人参非食用胼胝体中分离出细胞外囊泡。利用纳米粒子跟踪分析(NTA)对细胞外囊泡进行了表征。用不同浓度的 GNEV 处理 HDF,并用 MTT 和划痕伤口愈合试验评估细胞活力、增殖和迁移。采用 RT-PCR 技术测定了与胶原合成()相关的基因表达。用 GNEV 处理 HDF 后,细胞迁移率比未处理组显著增加了 2.5 倍。此外,GNEV 还能上调胶原合成基因,特别是 、 和 ,上调幅度分别为 41.7%、59.4%、60.2% 和 21.8%。这些发现表明,GNEV 激活了信号通路,展示了其诱导皮肤再生的潜力。总之,GNEV 通过刺激细胞迁移和上调关键胶原合成基因,表现出显著的促进皮肤再生的能力。信号通路的激活进一步表明,GNEV 有潜力成为化妆品和药品领域药物输送系统的候选物质,为护肤品和皮肤病学的进一步研究和应用开辟了道路。
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引用次数: 0
The synergistic effects of Korean Red Ginseng and Cervi Parvum Cornu ameliorating FeCl3-induced arterial thrombosis by downregulating ICAM-1 and VCAM-1 高丽红参和鹿茸通过下调 ICAM-1 和 VCAM-1 改善氯化铁诱导的动脉血栓形成的协同作用
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-06-07 DOI: 10.1016/j.jgr.2024.06.001

In this study, we compared antithrombotic activities of Korean Red Ginseng (KRG) and Cervi Parvum Cornu (CPC) on rats with induced thrombosis. Results indicate that KRG and CPC suppressed the arterial occlusion and the combination of KRG and CPC (KRG + CPC) treatment exhibited a synergistic effect with maximum reduction in thrombosis.

本研究比较了高丽红参(KRG)和鹿茸(CPC)对诱发血栓形成的大鼠的抗血栓活性。结果表明,KRG 和 CPC 可抑制动脉闭塞,而 KRG 和 CPC(KRG + CPC)联合治疗可发挥协同作用,最大程度地减少血栓形成。
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引用次数: 0
The beneficial potential of ginseng for menopause 人参对更年期的潜在益处
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-31 DOI: 10.1016/j.jgr.2024.05.008

Korean Red Ginseng (KRG) has long been used not only as a food supplement but also as a treatment for various diseases. Ginseng originated in South Korea, which later spread to China and Japan, has a wide range of pharmacological activities including immune, endocrine, cardiovascular, and central nervous system effects. KRG is produced by repetitions of steaming and drying of ginseng to extend preservation. During this steaming process, the components of ginseng undergo physio-chemical changes forming a variety of potential active constituents including ginsenoside-Rg3, a unique compound in KRG. Pandemic Coronavirus disease 2019 (COVID-19), has affected both men and women differentially. In particular, women were more vulnerable to COVID-related distress which in turn could aggravate menopause-related disturbances. Complementary and alternative medicinal plants could have aided middle-aged women for several menopause-related symptoms during and post COVID-19 pandemic. This review aimed to explore the beneficial effects of KRG on menopausal symptoms and gynecological cancer.

长期以来,高丽红参(KRG)不仅被用作食品补充剂,还被用来治疗各种疾病。人参起源于韩国,后来传播到中国和日本,具有广泛的药理作用,包括免疫、内分泌、心血管和中枢神经系统作用。KRG 是通过反复蒸煮和干燥人参来延长保存时间的。在蒸制过程中,人参的成分会发生物理化学变化,形成多种潜在的活性成分,包括人参皂苷-Rg3,这是 KRG 中的一种独特化合物。2019 年流行性冠状病毒病(COVID-19)对男性和女性的影响各不相同。特别是,女性更容易受到与 COVID 相关的困扰,这反过来又会加重与更年期相关的困扰。在 COVID-19 大流行期间和之后,补充和替代药用植物可以帮助中年女性缓解一些与更年期有关的症状。本综述旨在探讨 KRG 对更年期症状和妇科癌症的有益影响。
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引用次数: 0
Enhanced immunity effect of Korean Red Ginseng capsule: A randomized, double-blind and placebo-controlled clinical trial 高丽红参胶囊增强免疫力的作用:随机、双盲和安慰剂对照临床试验
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-31 DOI: 10.1016/j.jgr.2024.05.007
<div><h3>Background</h3><p>As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status.</p></div><div><h3>Methods</h3><p>This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration).</p></div><div><h3>Results</h3><p>After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (<em>P</em> < 0.01), (2) CD3 and CD4/CD8 increased significantly after the test (<em>P</em> < 0.05), (3) IgG, IgA, IgM and WBC increased significantly in the mid-term and after the test (<em>P</em> < 0.01); the results of the secondary efficacy indicators: (1) TNF-α decreased significantly in the mid-term (<em>P</em> < 0.05), IFN-γ decreased significantly in the mid-term (<em>P</em> < 0.01), (2) NK increased significantly in the mid-term and after the test (<em>P</em> < 0.05), (3) monocyte increased significantly in the mid-term and after the test (<em>P</em> < 0.01). Inter-group comparison of the test group and the control group, the results of the main efficacy indicators: (1) immune related health scores were higher than that of the control group in the mid-term and after the test (<em>P
免疫作为人体的一种生理功能,可以通过识别自身、排除他物来维护健康。随着经济的发展和社会竞争的日益激烈,亚健康人群逐渐增多,暴露出的最基本问题就是人体免疫力低下。免疫力低下可表现为经常感到疲劳、感冒、精神不振等。要想增强免疫力,食用具有增强免疫力功效的健康食品不失为一种有效的选择。KRG 具有增强免疫力的药理作用。由于对免疫人群的筛查和评估方法不统一,针对亚健康人群的 KRG 免疫力检测相对较少。研究 KRG 对免疫力低下人群的作用,对改善亚健康状态具有重要意义。这是一项为期 180 天的随机、双盲、安慰剂对照临床试验。根据试验方案设计,119 名合格受试者被随机分为服用 KRG 的试验组和安慰剂对照组。受试者需在基线时进行安全性指标(血压和心率、血常规、肝肾功能、尿常规和大便常规)和疗效指标(主要指标和次要指标)检查,在试验中期(服药第90天)进行疗效指标检查,在试验结束后(服药第180天)进行安全性和疗效指标检查。试验后,安慰剂对照组和 KRG 试验组的安全性指标基本在正常范围内,两组的火热度评分无明显差异。通过随访发现,试验组和对照组受试者在试验期间均未出现恶心、胀气、腹泻、腹痛等不良反应和过敏反应。试验组自我比较,主要疗效指标结果:(1)免疫相关健康评分在试验中期和试验后均明显提高(<0.01),(2)CD3和CD4/CD8在试验后明显提高(<0.05),(3)IgG、IgA、IgM和WBC在试验中期和试验后均明显提高(<0.01);次要疗效指标结果:(1)TNF-α中期明显下降(<0.05),IFN-γ中期明显下降(<0.01);(2)NK中期及试验后明显升高(<0.05);(3)单核细胞中期及试验后明显升高(<0.01)。试验组与对照组组间比较,主要疗效指标结果:(1)试验组免疫相关健康评分在试验中期和试验后均高于对照组(< 0.01),(2)试验组 IgA 在试验中期和试验后均高于对照组(< 0.05);次要疗效指标结果:(1)试验组白细胞在中期高于对照组(<0.05);(2)试验组单核细胞在中期和试验后均高于对照组(<0.05),试验组中性粒细胞在中期高于对照组(<0.05)。服用 KRG 对受试者的健康没有不良影响。根据临床试验方案的标准,免疫相关健康评分和主要疗效指标中的 IgA 均为阳性,这表明 KRG 有助于提高人体免疫力。
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引用次数: 0
Effect of ginseng and ginsenosides on attention deficit hyperactivity disorder: A systematic review 人参和人参皂苷对注意力缺陷多动障碍的影响:系统综述
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-28 DOI: 10.1016/j.jgr.2024.05.006

Attention deficit hyperactivity disorder (ADHD) is a rapidly increasing neurodevelopmental disorder but currently available treatments are associated with abuse risk, side effects, and incomplete symptom relief. There is growing interest in exploring complementary options, and ginseng has gained attention for its therapeutic potential. This systematic review aimed to assess current evidence on the efficacy of ginseng and its active components, ginsenosides, for ADHD. Eligible studies were identified through searches of PubMed, Embase, Cochrane Library, and Web of Science, up to June 2023. The inclusion criteria included both human and animal studies that investigated the effects of ginseng or ginsenosides on ADHD. The risk of bias was assessed according to study type. Six human studies and three animal studies met the inclusion criteria. The results suggest that ginseng and ginsenosides may have beneficial effects on ADHD symptoms, particularly inattention, through dopaminergic/norepinephrinergicmodulation and BDNF/TrkB signaling. Ginseng and ginsenosides have promising potential for ADHD treatment. Due to limitations in evidence quality, such as the risk of bias and variability in study designs, larger controlled studies are essential. Integrating ginseng into ADHD management may have valuable implications for individuals seeking well-tolerated alternatives or adjunctive therapies.

注意力缺陷多动障碍(ADHD)是一种快速增长的神经发育障碍,但目前可用的治疗方法存在滥用风险、副作用和症状缓解不彻底等问题。人们对探索辅助治疗方案的兴趣与日俱增,而人参因其治疗潜力而备受关注。本系统综述旨在评估人参及其活性成分人参皂苷对多动症疗效的现有证据。截至 2023 年 6 月,通过检索 PubMed、Embase、Cochrane Library 和 Web of Science,确定了符合条件的研究。纳入标准包括调查人参或人参皂甙对多动症影响的人类和动物研究。根据研究类型对偏倚风险进行了评估。六项人类研究和三项动物研究符合纳入标准。研究结果表明,人参和人参皂苷可能通过多巴胺能/去甲肾上腺素能调节和BDNF/TrkB信号转导对多动症症状,尤其是注意力不集中产生有益影响。人参和人参皂苷具有治疗多动症的潜力。由于证据质量的局限性,如偏倚风险和研究设计的差异性,因此必须进行更大规模的对照研究。将人参纳入多动症治疗可能对寻求耐受性良好的替代疗法或辅助疗法的患者具有重要意义。
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引用次数: 0
Monoclonal antibody-based enzyme-linked immunosorbent assay for quantification of majonoside R2 as an authentication marker for Nngoc Linh and Lai Chau ginsengs 基于单克隆抗体的酶联免疫吸附测定法,用于定量检测作为玉莲和莱州人参鉴别标志的雄花苷 R2
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-23 DOI: 10.1016/j.jgr.2024.05.004

Background

Recent years have witnessed increasing interest in the high amount of ocotillol-type saponin in Panax vietnamensis, particularly in relation to majonoside R2 (MR2). This unique 3%–5% MR2 content impart Ngoc Linh and Lai Chau ginsengs with unique pharmacological activities. However, in the commercial domain, unauthentic species have infiltrated and significantly hindered access to the authentic, efficacious variety. Thus, suitable analytical techniques for distinguishing authentic Vietnamese ginseng species from others is becoming increasingly crucial. Therefore, MR2 is attracting considerable attention as a target requiring effective management measures.

Methods

An enzyme-linked immunosorbent assay (ELISA) was developed by producing monoclonal antibodies against MR2 (mAb 16E11). The method was thoroughly validated, and the potential of the immunoassay was confirmed by high-performance liquid chromatography with ultraviolet spectroscopy. Furthermore, ELISA was applied to the assessment of the MR2 concentrations of various Panax spp., including Korean, American, and Japanese ginsengs.

Results and conclusions

An icELISA using mAb 16E11 exhibited linearity between 3.91 and 250 ng/mL of MR2, with detection and quantification limits of 1.53 and 2.50 46.6 ng/mL, respectively. Based on this study, the developed icELISA using mAb 16E11 could be a valuable tool for analyzing MR2 level to distinguish authentic Ngoc Linh and Lai Chau ginsengs from unauthentic ones. Furthermore, the analysis of the samples demonstrated that Ngoc Linh and Lai Chau ginsengs exhibit a notably higher MR2 value than all other Panax spp. Thus, MR2 might be their ideal marker compound, and various bioactivities of this species should be explored.

背景近年来,人们对越南人参中的大量乌头醇类皂苷,特别是马钱子苷 R2(MR2)越来越感兴趣。3%-5% 的独特 MR2 含量赋予了玉莲和莱州人参独特的药理活性。然而,在商业领域,非正宗人参品种已经渗透进来,严重阻碍了人们获得正宗、有效的人参品种。因此,采用合适的分析技术来区分正宗越南人参品种变得越来越重要。方法通过生产针对 MR2 的单克隆抗体(mAb 16E11),开发了一种酶联免疫吸附测定法(ELISA)。对该方法进行了全面验证,并通过高效液相色谱法和紫外光谱法证实了该免疫测定法的潜力。结果与结论使用 mAb 16E11 的 icELISA 在 3.91 至 250 纳克/毫升的 MR2 之间呈线性关系,检出限和定量限分别为 1.53 和 2.50 - 46.6 纳克/毫升。根据这项研究,使用 mAb 16E11 开发的 icELISA 是分析 MR2 含量的重要工具,可用于区分玉莲和莱州人参的真假。此外,对样品的分析表明,玉莲和莱州人参的 MR2 值明显高于所有其他三七属植物。因此,MR2 可能是其理想的标记化合物,应探索该物种的各种生物活性。
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引用次数: 0
Corrigendum to “Korean red ginseng extract ameliorates melanogenesis in humans and induces anti-photo aging effects in ultraviolet B-irradiated hairless mice” [J Ginseng Res 44 (2020) 496–505] 对高丽红参提取物改善人体黑色素生成和诱导紫外线 B 辐射无毛小鼠抗光老化作用的更正 [《人参研究杂志》44 (2020) 496-505]
IF 6.3 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-23 DOI: 10.1016/j.jgr.2024.05.005
Evelyn Saba , Seung-Hyung Kim , Yuan Yee Lee , Chae-Kyu Park , Jae-Wook Oh , Tae-Hwan Kim , Hyun-Kyoung Kim , Seong-Soo Roh , Man Hee Rhee
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引用次数: 0
Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin 三七皂苷调节 miR-214-3p/NR1I3 影响华法林药效学和药代动力学的机制
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-18 DOI: 10.1016/j.jgr.2024.05.003

Background

With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism.

Methods

The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague–Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3.

Results

PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3′-UTR and significantly downregulated NR1I3 expression.

Conclusion

Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

背景随着膳食补充剂的盛行,中草药与药物的联合使用逐渐增多,同时也带来了药物相互作用的风险。在临床工作中,我们意外地发现三七和华法林这两种活血化瘀的中药联合使用,反而出现了拮抗作用。本研究的目的是评估三七皂苷(PNS)与三七的主要有效成分华法林之间的药物相互作用,并探讨其相互作用机制。采用Elisa检测凝血因子的浓度,HPLC-MS检测大鼠血液中华法林的浓度,免疫印迹检测蛋白质水平,qRT-PCR检测mRNA水平,细胞免疫荧光检测NR1I3的定位,双荧光素酶验证miR-214-3p与NR1I3的结合。结果PNS明显加速了华法林的代谢并降低了其疗效,同时增加了NR1I3和CYP2C9的表达。对 NR1I3 的干扰可缓解同时服用 PNS 引起的华法林代谢加速。此外,我们还发现 PNS 能显著降低 miR-214-3p 的表达,而 miR-214-3p 过表达则会降低 NR1I3 和 CYP2C9 的表达,从而削弱 PNS 对华法林的拮抗作用。结论我们的研究表明,PNS 通过下调 miR-214-3p 导致其靶基因 NR1I3 的表达增加,从而加速华法林的代谢并降低其药效学,这些发现为临床药物应用提供了新的见解,以避免不良反应。
{"title":"Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin","authors":"","doi":"10.1016/j.jgr.2024.05.003","DOIUrl":"10.1016/j.jgr.2024.05.003","url":null,"abstract":"<div><h3>Background</h3><p>With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax <em>notoginseng saponins</em> (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism.</p></div><div><h3>Methods</h3><p>The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague–Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3.</p></div><div><h3>Results</h3><p>PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3′-UTR and significantly downregulated NR1I3 expression.</p></div><div><h3>Conclusion</h3><p>Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 5","pages":"Pages 494-503"},"PeriodicalIF":6.8,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845324000873/pdfft?md5=b55a2f0f2bb8f6ae96158b20db9020e5&pid=1-s2.0-S1226845324000873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141143253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The necessity of eliminating the interference of panaxatriol saponins to maximize the preventive effect of panaxadiol saponins against Parkinson's disease in rats 消除三七皂苷干扰以最大限度发挥三七皂苷对大鼠帕金森病的预防作用的必要性
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-14 DOI: 10.1016/j.jgr.2024.05.002

Background

The effects of individual panaxadiol saponin and panaxatriol saponin on rodent models of Parkinson's disease (PD) have been recognized. However, it is not clear whether purified total ginsenosides as an entirety has effect against PD in rat model. This study compared the protective effects of a purified panaxadiol saponin fraction (PDSF), a purified panaxatriol saponin fraction (PTSF), and their mixtures against the rotenone (ROT)-induced PD in rats.

Methods

Potential effects of PDSF, PTSF, and their mixtures against motor dysfunction and impairments of nigrostriatal dopaminergic neurons (DN), blood-brain barrier (BBB), cerebrovascular endothelial cells (CEC), and glial cells were measured in the models of ROT-induced PD rats and cell damage. Pro-inflammatory NF-kB p65 (p65) activation was localized in DN and other cells in the striatum.

Results

PDSF and PTSF had a dose-dependent effect against motor dysfunction with a larger effective dose range for PDSF. PDSF protected CEC, glial cells, and DN in models of PD rats and cell damage, while PTSF had no such protections. Chronic ROT exposure potently activated p65 in CEC with enhanced pro-inflammatory and decreased anti-inflammatory factors and impaired BBB in the striatum, PDSF almost completely blocked the ROT-induced p65 activation and maintained both anti- and pro-inflammatory factors at normal levels and BBB integrity, but PTSF aggravated the p65 activation with impaired BBB. Furthermore, PTSF nullified all the effects of PDSF when they were co-administrated.

Conclusion

PDSF had significant protective effect against the ROT-induced PD in rats by protecting CEC, glial cells, and DN, likely through inhibiting NF-κB p65 in CEC from triggering neuroinflammation, and also directly protecting glial cells and neurons against ROT-induced toxicity. PDSF has great potential for preventing and treating PD.

背景单个三七皂苷和三七酚皂苷对帕金森病(PD)啮齿动物模型的影响已得到认可。然而,目前尚不清楚纯化的人参皂苷整体是否对大鼠帕金森病模型有作用。本研究比较了纯化的三七皂苷组分(PDSF)、纯化的三七皂苷组分(PTSF)及其混合物对鱼藤酮(ROT)诱导的帕金森病大鼠的保护作用。方法 在ROT诱导的帕金森病大鼠模型和细胞损伤模型中,测量PDSF、PTSF及其混合物对运动功能障碍和黑质纹状体多巴胺能神经元(DN)、血脑屏障(BBB)、脑血管内皮细胞(CEC)和神经胶质细胞损伤的潜在作用。结果PDSF和PTSF对运动功能障碍有剂量依赖性作用,PDSF的有效剂量范围更大。PDSF 能保护脊髓灰质炎大鼠和细胞损伤模型中的 CEC、神经胶质细胞和 DN,而 PTSF 则没有这种保护作用。PDSF几乎完全阻断了ROT诱导的p65活化,并使抗炎和促炎因子维持在正常水平,同时保持了BBB的完整性,但PTSF加剧了p65的活化,并使BBB受损。结论PDSF通过保护CEC、神经胶质细胞和DN,对ROT诱导的大鼠帕金森病具有显著的保护作用,这可能是通过抑制CEC中的NF-κB p65引发神经炎症,并直接保护神经胶质细胞和神经元免受ROT诱导的毒性。PDSF 在预防和治疗帕金森病方面具有巨大潜力。
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引用次数: 0
期刊
Journal of Ginseng Research
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