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Compound K-enriched Korean red ginseng prevents lung cancer progression by targeting cancer cells and fibroblasts 高丽参通过靶向癌细胞和成纤维细胞,阻止肺癌的发展
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-04-04 DOI: 10.1016/j.jgr.2025.03.010
Jung Ho Hwang , Se Yong Park , Ju-Hee Kang , Hyun Jin Jung , Jiwon Park , Han-Joo Maeng , Min-Koo Choi , Ha Suk Song , Im-Sook Song , Seung Hyun Oh

Background

Despite the efficacy of anticancer drugs, patients frequently experience relapse, metastasis, and resistance. A promising therapeutic approach not only targets cancer cell growth but also modulates cancer-associated fibroblasts, which support malignancies. Compound K (CK), a metabolite derived from red ginseng, has demonstrated anticancer properties. Recently, we developed a CK-enriched red ginseng extract (CKP) and explored its potential to suppress lung cancer by inhibiting cancer cell proliferation and inactivating fibroblasts.

Methods

To evaluate the in vitro efficacy of CKP in inhibiting lung cancer cell proliferation, MTT and colony formation assays were performed. The apoptotic effects of CKP on lung cancer cells were assessed using Western blot and flow cytometry. Furthermore, the ability of CKP to inhibit TGF β1-induced migration of cancer cells was investigated through Western blot, RT-PCR, and a wound healing assay. Additionally, the impact of CKP on lung fibroblast inactivation was examined via Western blot and RT-PCR analysis. For in vivo experiments, a xenograft model was utilized, incorporating a combination of lung cancer cells and lung fibroblasts in xenografts.

Results

CKP significantly reduced the proliferation and invasiveness of TGF-β1-stimulated A549 cells, demonstrating its potential to inactivate lung fibroblasts. Additionally, CKP inhibited the secretion of cytokines, such as interleukin-6, interleukin-8, and TGF-β1, by activated fibroblasts. In vivo, CKP markedly inhibited tumor growth in the xenograft model.

Conclusion

In conclusion, CKP effectively induced apoptosis in lung cancer cells, suppressed metastasis, and inactivated fibroblasts, thereby preventing cancer invasion and reducing extracellular matrix production, highlighting its potential as a novel anticancer agent.
背景尽管抗癌药物有效,但患者经常出现复发、转移和耐药。一种有希望的治疗方法不仅针对癌细胞生长,而且还调节支持恶性肿瘤的癌症相关成纤维细胞。化合物K (CK)是红参的代谢物,具有抗癌作用。最近,我们开发了一种富含ck的红参提取物(CKP),并通过抑制癌细胞增殖和使成纤维细胞失活来探索其抑制肺癌的潜力。方法采用MTT法和集落形成法评价CKP体外抑制肺癌细胞增殖的效果。采用Western blot和流式细胞术观察CKP对肺癌细胞的凋亡作用。此外,通过Western blot、RT-PCR和伤口愈合实验研究了CKP抑制TGF β1诱导的癌细胞迁移的能力。此外,通过Western blot和RT-PCR分析检测CKP对肺成纤维细胞失活的影响。在体内实验中,采用异种移植物模型,将肺癌细胞和肺成纤维细胞结合在异种移植物中。结果sckp显著降低TGF-β1刺激的A549细胞的增殖和侵袭性,表明其具有灭活肺成纤维细胞的潜力。此外,CKP抑制活化成纤维细胞分泌白细胞介素-6、白细胞介素-8、TGF-β1等细胞因子。在体内,CKP显著抑制异种移植模型的肿瘤生长。结论CKP可有效诱导肺癌细胞凋亡,抑制转移,使成纤维细胞失活,从而阻止肿瘤侵袭,减少细胞外基质的产生,是一种新型抗癌药物。
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引用次数: 0
Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease 人参:阿尔茨海默病中淀粉样蛋白、tau病理学和认知功能的调节剂
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-04-02 DOI: 10.1016/j.jgr.2025.03.011
Jaeuk Hwang , Musung Keum , Young Min Choe , Guk-Hee Suh , Hye Ji Choi , Boung Chul Lee , Shin Gyeom Kim , Hyun Soo Kim , Dahyun Yi , Jee Wook Kim
Alzheimer's disease (AD), the leading cause of dementia, is characterized by the presence of beta-amyloid (Aβ) plaques, tau hyperphosphorylation, and cognitive decline. Despite advancements in Aβ-targeting therapies, the multifaceted nature of AD underscores the need for complementary treatments. Panax ginseng, renowned for its cognitive-enhancing properties, has demonstrated potential in addressing AD pathology. This review systematically explores the therapeutic potential of P. ginseng and its bioactive ginsenosides, focusing on their effects on Aβ, tau proteins, and cognitive function. We summarize the findings from preclinical and clinical studies, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation. Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models. Clinical studies further suggest its cognitive benefits in mild cognitive impairment, subjective memory impairment, and as adjunctive therapy in AD, with particularly pronounced effects in individuals lacking apolipoprotein ε4 allele. This review provides a comprehensive overview of the potential of P. ginseng as both a therapeutic and preventive agent for AD, highlighting the scientific basis for further exploration of P. ginseng-derived compounds to optimize their efficacy and clinical application.
阿尔茨海默病(AD)是痴呆症的主要原因,其特征是存在β -淀粉样蛋白(Aβ)斑块,tau过度磷酸化和认知能力下降。尽管a β靶向治疗取得了进展,但阿尔茨海默病的多面性强调了补充治疗的必要性。人参以其增强认知能力的特性而闻名,已证明在解决AD病理方面具有潜力。本文系统地探讨了人参及其生物活性皂苷的治疗潜力,重点介绍了它们对Aβ、tau蛋白和认知功能的影响。我们总结了临床前和临床研究的结果,强调了神经保护机制,如抑制Aβ产生,增强Aβ清除和抑制tau过度磷酸化。研究表明,人参及其生物活性人参皂苷具有改善AD模型认知功能的潜力。临床研究进一步表明,它对轻度认知障碍、主观记忆障碍和AD的辅助治疗具有认知益处,对缺乏载脂蛋白ε4等位基因的个体效果尤其显著。本文综述了人参作为阿尔茨海默病的治疗和预防药物的潜力,强调了进一步探索人参衍生化合物以优化其疗效和临床应用的科学基础。
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引用次数: 0
Identification of AIF1 as a protein target of notoginsenosides in brain tissue of mice with intracerebral hemorrhage based on hapten immunoaffinity fishing technique 基于半抗原免疫亲和捕捞技术的脑出血小鼠脑组织中三七皂苷蛋白靶点AIF1的鉴定
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-04-02 DOI: 10.1016/j.jgr.2025.04.001
Feiyan Chen , Wei Qin , Qianlin Li , Chu Li , Cuihua Chen , Lin Chen , Qi Yao , Zhu Zhu , Yunan Zhao

Background

Intracerebral hemorrhage (ICH) is a deadly stroke with high mortality or disability. Although recent research has demonstrated the efficacy of Panax notoginseng in ICH therapy, it is unclear which proteins may be targeted to achieve these advantages.

Methods

First, we generated polyclonal antibodies against notoginsenosides by immunizing rats with a ginsenoside Rh1-mcKLH conjugate. Second, the potential target proteins of notoginsenosides in brain tissue of ICH mice were identified using LC-MS-based hapten immunoaffinity fishing (HIAF). Third, the disease target databases and these proteins intersected. Fourth, biolayer interferometry (BLI), molecular docking, and site-directed mutagenesis were performed to validate allograft inflammatory factor 1 (AIF1) as a protein target of notoginsenosides. Last, bioinformatics analysis was performed to examine AIF1's biological characteristics.

Results

A potential protein target of notoginsenosides, AIF1, was found by intersecting the identified protein targets with the disease target databases via LC-MS-based HIAF. BLI analysis revealed that Compound K (CK) and AIF1 had the highest direct interaction, with an average shift value of 0.1091 nm. Subsequently, site-directed mutagenesis, molecular docking, and BLI kinetic analysis demonstrated that CK specifically bound to AIF1 with an affinity value of 4.33 ± 0.17E-6 M, with a significant reliance on residues L122 and E125. Bioinformatics analysis showed that AIF1 and its directly interacting proteins were associated with microglial activation.

Conclusion

Our study proposed a new technology for screening natural small molecule protein targets, and successfully identified AIF1 as a protein target of notoginsenosides, providing a chemical and biological basis for further research into targeting AIF1 to treat ICH.
脑出血(ICH)是一种死亡率和致残率高的致死性中风。虽然最近的研究已经证明了三七在脑出血治疗中的功效,但尚不清楚哪些蛋白质可能是实现这些优势的目标。方法首先用三七皂苷Rh1-mcKLH偶联物免疫大鼠,制备三七皂苷多克隆抗体。其次,采用LC-MS-based半抗原免疫亲和钓鱼(HIAF)技术对脑出血小鼠脑组织中三七皂苷的潜在靶蛋白进行鉴定。第三,疾病靶点数据库和这些蛋白质交叉。第四,通过生物层干涉法(BLI)、分子对接和定点诱变验证异体移植物炎症因子1 (AIF1)是三七皂苷的蛋白靶点。最后进行生物信息学分析,对AIF1的生物学特性进行检测。结果通过LC-MS-based HIAF将鉴定的蛋白靶点与疾病靶点数据库交叉,发现了三七皂苷的一个潜在蛋白靶点AIF1。BLI分析表明,化合物K (CK)与AIF1的直接相互作用最强,平均位移值为0.1091 nm。随后,通过定点诱变、分子对接和BLI动力学分析表明,CK特异性结合AIF1,亲和值为4.33±0.17E-6 M,显著依赖于残基L122和E125。生物信息学分析表明,AIF1及其直接相互作用蛋白与小胶质细胞活化有关。结论本研究提出了一种筛选天然小分子蛋白靶点的新技术,成功鉴定出AIF1为三七皂苷蛋白靶点,为进一步研究AIF1靶向治疗脑出血提供了化学生物学基础。
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引用次数: 0
Comprehensive understanding and underlying molecular mechanisms of the adaptogenic effects of Panax ginseng 人参适应作用的全面认识及其分子机制
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-04-02 DOI: 10.1016/j.jgr.2025.03.013
Natasha Christabella Sutopo , Nurinanda Prisky Qomaladewi , Hye Won Lee , Myeong Soo Lee , Ji Hye Kim , Jae Youl Cho
Panax ginseng Meyer, a traditional herbal remedy with a long history, has been widely used worldwide. Phytochemical studies have shown that its physiological activity is due to a variety of active compounds, and extensive research has demonstrated the adaptogenic potential of ginseng in various physiological and pathological contexts. However, the molecular mechanisms supporting its adaptogenic effects remain inadequately elucidated, leading to undervaluation of its adaptogenic properties. This review uses a comprehensive literature analysis to examine five major health benefits attributed to ginseng extracts or derivatives: anti-inflammatory, antioxidant, anti-fatigue, cardiovascular protection, and cognitive enhancement. Moreover, it categorizes the biomarkers identified in each efficacy study and analyzes their interaction networks using KEGG pathway information. In that way, four key biomarkers pivotal to the adaptogenic attributes of P. ginseng are identified: superoxide dismutase, tumor necrosis factor, nuclear factor erythroid 2-related factor 2, and caspase-1. These biomarkers play an integral role in the manifestation of P. ginseng's five major effects, contributing significantly to its adaptogenic efficacy. This novel approach to understanding adaptogenic mechanisms is intended to offer innovative insights into the pharmacological effects of P. ginseng and its derivatives.
人参是一种历史悠久的传统草药,在世界范围内得到了广泛的应用。植物化学研究表明,人参的生理活性是由多种活性化合物引起的,广泛的研究表明人参在各种生理和病理环境下具有适应原潜力。然而,支持其适应作用的分子机制仍未充分阐明,导致其适应特性被低估。这篇综述使用了全面的文献分析来研究人参提取物或衍生物的五种主要健康益处:抗炎、抗氧化、抗疲劳、心血管保护和增强认知。此外,它还对每项功效研究中发现的生物标志物进行了分类,并使用KEGG途径信息分析了它们的相互作用网络。通过这种方式,确定了人参适应基因属性的四个关键生物标志物:超氧化物歧化酶、肿瘤坏死因子、核因子红系2相关因子2和caspase-1。这些生物标志物在人参五大作用的表现中起着不可或缺的作用,对人参的适应效应起着重要作用。这种理解适应机制的新方法旨在为人参及其衍生物的药理作用提供创新的见解。
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引用次数: 0
Ginsenoside Rh2 alleviates inflammatory response and enhances motor function recovery in spinal cord injury mice via the ROS/MAPK14 signaling pathway 人参皂苷Rh2通过ROS/MAPK14信号通路减轻脊髓损伤小鼠炎症反应,促进运动功能恢复
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-28 DOI: 10.1016/j.jgr.2025.03.008
Yanlan Wu , Fangming Song , Xiuwei Tan , Jin Huang , Junliang Lu , Baihui Yang , Fang Fang , Xiaoxia Ye , Laoyi Geer , Fengxin Li , Qian Wei , Xuefeng Lu , Jiake Xu , Jie Jiang , Yiji Su

Background

Inhibiting inflammation in nervous system is a vital part of treating for spinal cord injury (SCI). Compounds originating from plants can decrease the damage in the spinal cord for recovering the function of nerve and interrupting the inflammatory reaction. 20(S)-Ginsenoside Rh2 (G-Rh2) from Panax ginseng is an anti-inflammatory property inhibiting the expression of MAPK14 protein by enabling the MAPK pathway. Therefore, this research explored the anti-inflammatory effects of G-Rh2 on SCI using cellular and animal models.

Methods

To explore G-Rh2's anti-inflammatory potential in SCI, we employed bioinformatics analysis to anticipate target proteins and signaling pathways associated with G-Rh2 and SCI. We utilized BV2 microglia cells to model inflammation induced by lipopolysaccharide (LPS), and a modified Allen's technique in a mouse SCI model. Our investigation utilized a range of methodologies including quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-Linked Immunosorbent Assay (ELISA), Immunofluorescence (IF) and Western Blot (WB).

Results

Bioinformatics analysis and molecular docking identified MAPK14 as a key target of G-Rh2. In BV2 cells experiments, G-Rh2 reduced the expression and generation of inflammatory factors, reactive oxygen species (ROS), and transcription factors involved in the MAPK signaling pathway. G-Rh2 showed a decrease in inflammatory reaction and improvements in motor function in the mouse model using the modified Allen's approach for SCI.

Conclusion

G-Rh2 mitigates inflammatory responses and enhances motor function recovery in mice with SCI via the ROS/MAPK14 signaling pathway.
背景抑制神经系统炎症是脊髓损伤治疗的重要组成部分。植物源性化合物可减轻脊髓损伤,恢复神经功能,阻断炎症反应。人参中的20(S)-人参皂苷Rh2 (G-Rh2)具有抗炎特性,通过激活MAPK通路抑制MAPK14蛋白的表达。因此,本研究通过细胞和动物模型探讨G-Rh2对脊髓损伤的抗炎作用。方法为了探索G-Rh2在脊髓损伤中的抗炎作用,我们采用生物信息学分析方法预测G-Rh2与脊髓损伤相关的靶蛋白和信号通路。我们利用BV2小胶质细胞模拟脂多糖(LPS)诱导的炎症,并在小鼠脊髓损伤模型中采用改良的Allen’s技术。我们的研究使用了一系列方法,包括定量实时聚合酶链反应(qRT-PCR)、酶联免疫吸附试验(ELISA)、免疫荧光(IF)和Western Blot (WB)。结果生物信息学分析和分子对接鉴定MAPK14为G-Rh2的关键靶点。在BV2细胞实验中,G-Rh2降低炎症因子、活性氧(ROS)和MAPK信号通路相关转录因子的表达和生成。G-Rh2在使用改良Allen入路治疗脊髓损伤的小鼠模型中显示炎症反应减少和运动功能改善。结论- rh2通过ROS/MAPK14信号通路减轻脊髓损伤小鼠的炎症反应,促进运动功能恢复。
{"title":"Ginsenoside Rh2 alleviates inflammatory response and enhances motor function recovery in spinal cord injury mice via the ROS/MAPK14 signaling pathway","authors":"Yanlan Wu ,&nbsp;Fangming Song ,&nbsp;Xiuwei Tan ,&nbsp;Jin Huang ,&nbsp;Junliang Lu ,&nbsp;Baihui Yang ,&nbsp;Fang Fang ,&nbsp;Xiaoxia Ye ,&nbsp;Laoyi Geer ,&nbsp;Fengxin Li ,&nbsp;Qian Wei ,&nbsp;Xuefeng Lu ,&nbsp;Jiake Xu ,&nbsp;Jie Jiang ,&nbsp;Yiji Su","doi":"10.1016/j.jgr.2025.03.008","DOIUrl":"10.1016/j.jgr.2025.03.008","url":null,"abstract":"<div><h3>Background</h3><div>Inhibiting inflammation in nervous system is a vital part of treating for spinal cord injury (SCI). Compounds originating from plants can decrease the damage in the spinal cord for recovering the function of nerve and interrupting the inflammatory reaction. 20(S)-Ginsenoside Rh2 (G-Rh2) from Panax ginseng is an anti-inflammatory property inhibiting the expression of MAPK14 protein by enabling the MAPK pathway. Therefore, this research explored the anti-inflammatory effects of G-Rh2 on SCI using cellular and animal models.</div></div><div><h3>Methods</h3><div>To explore G-Rh2's anti-inflammatory potential in SCI, we employed bioinformatics analysis to anticipate target proteins and signaling pathways associated with G-Rh2 and SCI. We utilized BV2 microglia cells to model inflammation induced by lipopolysaccharide (LPS), and a modified Allen's technique in a mouse SCI model. Our investigation utilized a range of methodologies including quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-Linked Immunosorbent Assay (ELISA), Immunofluorescence (IF) and Western Blot (WB).</div></div><div><h3>Results</h3><div>Bioinformatics analysis and molecular docking identified MAPK14 as a key target of G-Rh2. In BV2 cells experiments, G-Rh2 reduced the expression and generation of inflammatory factors, reactive oxygen species (ROS), and transcription factors involved in the MAPK signaling pathway. G-Rh2 showed a decrease in inflammatory reaction and improvements in motor function in the mouse model using the modified Allen's approach for SCI.</div></div><div><h3>Conclusion</h3><div>G-Rh2 mitigates inflammatory responses and enhances motor function recovery in mice with SCI via the ROS/MAPK14 signaling pathway.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 4","pages":"Pages 415-425"},"PeriodicalIF":6.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ginsenoside Rg5 modulates the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating inflammation, apoptosis and pyroptosis in hyperuricemia nephropathy 人参皂苷Rg5通过抑制NOX1调节TLR4和BCL-2通路,从而减轻高尿酸血症肾病的炎症、凋亡和焦亡
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-25 DOI: 10.1016/j.jgr.2025.03.009
Yu-Xin Zhang , Hui Wan , Guan-Yue Shan , Jun-Ya Cheng , Zhi-Cheng Gao , Yi-Ying Liu , Wen-Na Shi , Zi-Jun Sun , Hai-Jun Li

Background

Hyperuricemia nephropathy (HN) is a form of renal injury caused by hyperuricemia, which can progress to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Ginsenoside Rg5, a major bioactive compound isolated from Panax ginseng, is recognized for its notable effects, including anti-inflammatory, antioxidant, and anticancer activities.

Method

The toxic doses of MSU crystals and Rg5-induced HK-2 cell damage were assessed using the CCK-8 assay and quantifying oxidative stress markers (MDA, GSH, SOD). Intracellular stress was evaluated with JC-1 and DCFH-DA probes. Bioinformatics analysis identified NOX1, TLR4, and Bcl-2 as potential targets. The protein expression associated with stress, inflammation, pyroptosis, and apoptosis in HK-2 cells was evaluated through a combination of Western blotting, ELISA, flow cytometry, immunofluorescence, and overexpression methods. An HN mice model was established through administration of YE and adenine, and the effects of Rg5 were evaluated. The in vivo mechanisms were further verified.

Results

Rg5 reduced serum uric acid, BUN, ADH, and creatinine levels in MSU crystals-stimulated HK-2 cells and hyperuricemic mice, alleviating renal damage. Rg5 inhibited NOX1 and suppressed the TLR4 pathway, reducing oxidative stress, inflammation, pyroptosis, and apoptosis. NOX1 overexpression reversed the effects of Rg5, while TLR4 overexpression had no effect. Rg5's efficacy was similar to NOX1 inhibitor ML171.

Conclusion

These results indicate that Rg5 can modulate the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating oxidative stress, inflammation, pyroptosis, and apoptosis in HN, highlighting its potential as a therapeutic approach for controlling HN.
背景:高尿酸血症肾病(HN)是一种由高尿酸血症引起的肾损伤,可发展为慢性肾病(CKD)和终末期肾病(ESRD)。人参皂苷Rg5是一种从人参中分离出来的主要生物活性化合物,具有显著的抗炎、抗氧化和抗癌作用。方法采用CCK-8法,定量测定氧化应激标志物(MDA、GSH、SOD),观察MSU晶体的毒性剂量及rg5诱导的HK-2细胞损伤。采用JC-1和DCFH-DA探针检测细胞内应激。生物信息学分析确定NOX1、TLR4和Bcl-2为潜在靶点。通过Western blotting、ELISA、流式细胞术、免疫荧光和过表达等方法评估HK-2细胞中与应激、炎症、焦亡和凋亡相关的蛋白表达。通过给药YE和腺嘌呤建立HN小鼠模型,评价Rg5的作用。进一步验证了其体内机制。结果rg5可降低MSU晶体刺激的HK-2细胞和高尿酸血症小鼠血清尿酸、BUN、ADH和肌酐水平,减轻肾损害。Rg5抑制NOX1,抑制TLR4通路,减少氧化应激、炎症、焦亡和细胞凋亡。NOX1过表达逆转了Rg5的作用,而TLR4过表达无影响。Rg5的疗效与NOX1抑制剂ML171相似。结论Rg5可通过抑制NOX1调控TLR4和BCL-2通路,从而减轻HN的氧化应激、炎症、焦亡和凋亡,具有治疗HN的潜力。
{"title":"Ginsenoside Rg5 modulates the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating inflammation, apoptosis and pyroptosis in hyperuricemia nephropathy","authors":"Yu-Xin Zhang ,&nbsp;Hui Wan ,&nbsp;Guan-Yue Shan ,&nbsp;Jun-Ya Cheng ,&nbsp;Zhi-Cheng Gao ,&nbsp;Yi-Ying Liu ,&nbsp;Wen-Na Shi ,&nbsp;Zi-Jun Sun ,&nbsp;Hai-Jun Li","doi":"10.1016/j.jgr.2025.03.009","DOIUrl":"10.1016/j.jgr.2025.03.009","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia nephropathy (HN) is a form of renal injury caused by hyperuricemia, which can progress to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Ginsenoside Rg5, a major bioactive compound isolated from Panax ginseng, is recognized for its notable effects, including anti-inflammatory, antioxidant, and anticancer activities.</div></div><div><h3>Method</h3><div>The toxic doses of MSU crystals and Rg5-induced HK-2 cell damage were assessed using the CCK-8 assay and quantifying oxidative stress markers (MDA, GSH, SOD). Intracellular stress was evaluated with JC-1 and DCFH-DA probes. Bioinformatics analysis identified NOX1, TLR4, and Bcl-2 as potential targets. The protein expression associated with stress, inflammation, pyroptosis, and apoptosis in HK-2 cells was evaluated through a combination of Western blotting, ELISA, flow cytometry, immunofluorescence, and overexpression methods. An HN mice model was established through administration of YE and adenine, and the effects of Rg5 were evaluated. The in vivo mechanisms were further verified.</div></div><div><h3>Results</h3><div>Rg5 reduced serum uric acid, BUN, ADH, and creatinine levels in MSU crystals-stimulated HK-2 cells and hyperuricemic mice, alleviating renal damage. Rg5 inhibited NOX1 and suppressed the TLR4 pathway, reducing oxidative stress, inflammation, pyroptosis, and apoptosis. NOX1 overexpression reversed the effects of Rg5, while TLR4 overexpression had no effect. Rg5's efficacy was similar to NOX1 inhibitor ML171.</div></div><div><h3>Conclusion</h3><div>These results indicate that Rg5 can modulate the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating oxidative stress, inflammation, pyroptosis, and apoptosis in HN, highlighting its potential as a therapeutic approach for controlling HN.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 4","pages":"Pages 426-437"},"PeriodicalIF":6.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ginsenoside Rb2 demonstrates potent antiviral activity against Zika virus infection 人参皂苷Rb2对寨卡病毒感染具有有效的抗病毒活性
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-22 DOI: 10.1016/j.jgr.2025.03.007
Tong Wu , Ting Wang , Hanlin Chen , Zhongyuan Tan , Yuanjiu Miao , Ning Chen , Zhenhua Zheng

Background

Zika virus (ZIKV) infection can result in severe neurological complications, yet no approved antiviral treatments are currently available. Ginseng, a medicinal herb extensively utilized in Asian traditional medicine, has demonstrated efficacy against various diseases, which has sparked interest in exploring its potential antiviral properties for the treatment of ZIKV.

Methods

We evaluated the antiviral effects of ginsenoside Rb2 (G-Rb2) in human neuronal cell lines (SK-N-SH and CCF-STTG) and in a lethal ZIKV-infected mouse model. The antiviral efficacy was assessed using bioluminescence imaging with a NanoLuc luciferase reporter ZIKV. In vitro assays were conducted to determine the direct impact of G-Rb2 on ZIKV, while surface plasmon resonance (SPR) was employed to analyze its interaction with ZIKV envelope proteins and viral particles.

Results

G-Rb2 (200 μM) significantly inhibited ZIKV infection in vitro and protected mice from ZIKV-induced mortality. Bioluminescence imaging validated its antiviral efficacy. In vitro studies demonstrated that incubation with G-Rb2 reduced viral infectivity, and SPR analysis confirmed direct binding between G-Rb2 and ZIKV components.

Conclusion

G-Rb2 effectively inhibits ZIKV infection both in vitro and in vivo, presumably through direct interaction with viral particles. Given the accessibility of ginseng and its established processing methods, G-Rb2 emerges as a promising candidate for the treatment of ZIKV in humans. Further research is warranted to elucidate its mechanisms of action and evaluate its clinical potential.
寨卡病毒(ZIKV)感染可导致严重的神经系统并发症,但目前尚无获批的抗病毒治疗方法。人参是亚洲传统医学中广泛使用的一种草药,已被证明对多种疾病有疗效,这引起了人们对探索其治疗寨卡病毒的潜在抗病毒特性的兴趣。方法观察人参皂苷Rb2 (G-Rb2)对人神经元细胞株SK-N-SH和CCF-STTG以及zikv致死性感染小鼠模型的抗病毒作用。采用NanoLuc荧光素酶报告基因ZIKV的生物发光成像技术评估抗病毒效果。G-Rb2对寨卡病毒的直接作用通过体外实验确定,表面等离子体共振(SPR)技术分析了G-Rb2与寨卡病毒包膜蛋白和病毒颗粒的相互作用。结果g - rb2 (200 μM)能显著抑制寨卡病毒感染,保护小鼠免于死亡。生物发光成像证实了其抗病毒效果。体外研究表明,与G-Rb2孵育可降低病毒的传染性,SPR分析证实G-Rb2与寨卡病毒组分直接结合。结论ong - rb2在体外和体内均能有效抑制寨卡病毒感染,可能与病毒颗粒直接相互作用。鉴于人参的可及性及其已建立的加工方法,G-Rb2成为治疗人类寨卡病毒的有希望的候选药物。需要进一步的研究来阐明其作用机制并评估其临床潜力。
{"title":"Ginsenoside Rb2 demonstrates potent antiviral activity against Zika virus infection","authors":"Tong Wu ,&nbsp;Ting Wang ,&nbsp;Hanlin Chen ,&nbsp;Zhongyuan Tan ,&nbsp;Yuanjiu Miao ,&nbsp;Ning Chen ,&nbsp;Zhenhua Zheng","doi":"10.1016/j.jgr.2025.03.007","DOIUrl":"10.1016/j.jgr.2025.03.007","url":null,"abstract":"<div><h3>Background</h3><div>Zika virus (ZIKV) infection can result in severe neurological complications, yet no approved antiviral treatments are currently available. Ginseng, a medicinal herb extensively utilized in Asian traditional medicine, has demonstrated efficacy against various diseases, which has sparked interest in exploring its potential antiviral properties for the treatment of ZIKV.</div></div><div><h3>Methods</h3><div>We evaluated the antiviral effects of ginsenoside Rb2 (G-Rb2) in human neuronal cell lines (SK-N-SH and CCF-STTG) and in a lethal ZIKV-infected mouse model. The antiviral efficacy was assessed using bioluminescence imaging with a NanoLuc luciferase reporter ZIKV. <em>In vitro</em> assays were conducted to determine the direct impact of G-Rb2 on ZIKV, while surface plasmon resonance (SPR) was employed to analyze its interaction with ZIKV envelope proteins and viral particles.</div></div><div><h3>Results</h3><div>G-Rb2 (200 μM) significantly inhibited ZIKV infection <em>in vitro</em> and protected mice from ZIKV-induced mortality. Bioluminescence imaging validated its antiviral efficacy. <em>In vitro</em> studies demonstrated that incubation with G-Rb2 reduced viral infectivity, and SPR analysis confirmed direct binding between G-Rb2 and ZIKV components.</div></div><div><h3>Conclusion</h3><div>G-Rb2 effectively inhibits ZIKV infection both <em>in vitro</em> and <em>in vivo</em>, presumably through direct interaction with viral particles. Given the accessibility of ginseng and its established processing methods, G-Rb2 emerges as a promising candidate for the treatment of ZIKV in humans. Further research is warranted to elucidate its mechanisms of action and evaluate its clinical potential.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 4","pages":"Pages 406-414"},"PeriodicalIF":6.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Compound K suppresses epidermal aging induced by IL-17A treatment and UVB irradiation 化合物K对IL-17A和UVB照射诱导的表皮衰老具有抑制作用
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-21 DOI: 10.1016/j.jgr.2025.03.004
A Young Kim, Ji-Yong Jung, Donghyun Kim, Jeong Hun Cho, Yong Deog Hong, Hyoung-June Kim, Si-Young Cho
We evaluated the anti-accelerated epidermal skin aging effects of compound K (CK) on keratinocytes using IL-17A and ultraviolet B. CK restored epidermal functions and reduced the induction of pro-inflammatory cytokines by inhibiting NF-κB and p38 MAPK activation. CK plays a significant role in controlling accelerated epidermal skin aging.
我们利用IL-17A和紫外线b来评估复方K (CK)对角质形成细胞的抗表皮加速老化作用。CK通过抑制NF-κB和p38 MAPK的激活来恢复表皮功能,减少促炎细胞因子的诱导。CK对表皮加速老化有显著的调控作用。
{"title":"Compound K suppresses epidermal aging induced by IL-17A treatment and UVB irradiation","authors":"A Young Kim,&nbsp;Ji-Yong Jung,&nbsp;Donghyun Kim,&nbsp;Jeong Hun Cho,&nbsp;Yong Deog Hong,&nbsp;Hyoung-June Kim,&nbsp;Si-Young Cho","doi":"10.1016/j.jgr.2025.03.004","DOIUrl":"10.1016/j.jgr.2025.03.004","url":null,"abstract":"<div><div>We evaluated the anti-accelerated epidermal skin aging effects of compound K (CK) on keratinocytes using IL-17A and ultraviolet B. CK restored epidermal functions and reduced the induction of pro-inflammatory cytokines by inhibiting NF-κB and p38 MAPK activation. CK plays a significant role in controlling accelerated epidermal skin aging.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 326-330"},"PeriodicalIF":6.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The antitumor effects and apoptotic mechanism of 20(S)-Protopanaxadiol in acute myeloid leukemia 20(S)-原嘌呤二醇对急性髓细胞白血病的抗肿瘤作用及凋亡机制
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-20 DOI: 10.1016/j.jgr.2025.03.006
Ye Zhang , Saisai Ma , Yichen Xu , Shuaida Wu , Shuangshuang Wu , Minmin Liu , Yingjie Guo , Yang Zhan

Background

Panax ginseng Meyer is a well-known herb in traditional Chinese medicine, with ginsenosides being its primary bioactive components. Among these, 20(S)-protopanaxadiol (20(S)-PPD) has demonstrated anti-tumor effects in various cancers. However, its role in acute myeloid leukemia (AML) remains unclear.

Methods

MTT assays were conducted to assess the impact of 20(S)-PPD on AML cell proliferation, while flow cytometry was used to analyze its effects on apoptosis. Western blotting and network pharmacology analyses were employed to explore the signaling pathways and protein expression levels modulated by 20(S)-PPD in AML. c-Myc mRNA levels in AML cells were quantified using RT-PCR.

Results

20(S)-PPD effectively inhibits proliferation and induces apoptosis in AML cells, both in vitro and in patient samples. It achieves this by inhibiting the PI3K/AKT/mTOR pathway and activating the PERK/ATF4/CHOP pathway. Additionally, 20(S)-PPD reduces c-Myc protein and mRNA levels, primarily by decreasing c-Myc mRNA stability. Moreover, combining 20(S)-PPD with ABT-199 significantly enhances pro-apoptotic effects and markedly reduces c-Myc protein and mRNA levels in both AML and cytarabine-resistant (AraC-R) AML cells. This combination therapy holds promise for overcoming resistance and improving treatment outcomes in AML.

Conclusion

This study demonstrates the potent antitumor activity of 20(S)-PPD in AML and elucidates its underlying mechanisms. Notably, 20(S)-PPD exhibits significant antitumor effects against AML cells, both as a single agent and in combination with ABT-199, where it displays pronounced synergy. These results suggest a promising new therapeutic strategy for AML treatment.
人参是一种著名的传统中药,人参皂苷是其主要的生物活性成分。其中,20(S)-protopanaxadiol (20(S)-PPD)在多种癌症中显示出抗肿瘤作用。然而,其在急性髓性白血病(AML)中的作用尚不清楚。方法采用smtt法观察20(S)-PPD对AML细胞增殖的影响,流式细胞术观察其对细胞凋亡的影响。采用Western blotting和网络药理学分析,探讨20(S)-PPD在AML中调控的信号通路和蛋白表达水平。结果20(S)-PPD在体外和患者样本中均能有效抑制AML细胞增殖并诱导细胞凋亡。它通过抑制PI3K/AKT/mTOR通路和激活PERK/ATF4/CHOP通路来实现这一目标。此外,20(S)-PPD降低c-Myc蛋白和mRNA水平,主要是通过降低c-Myc mRNA的稳定性。此外,20(S)-PPD联合ABT-199可显著增强AML和阿糖胞苷耐药(AraC-R) AML细胞的促凋亡作用,并显著降低c-Myc蛋白和mRNA水平。这种联合治疗有望克服耐药性并改善AML的治疗结果。结论本研究证实20(S)-PPD在AML中具有较强的抗肿瘤活性,并阐明其作用机制。值得注意的是,无论是单独使用还是与ABT-199联合使用,20(S)-PPD对AML细胞都表现出显著的抗肿瘤作用,并表现出明显的协同作用。这些结果为AML治疗提供了一个有希望的新治疗策略。
{"title":"The antitumor effects and apoptotic mechanism of 20(S)-Protopanaxadiol in acute myeloid leukemia","authors":"Ye Zhang ,&nbsp;Saisai Ma ,&nbsp;Yichen Xu ,&nbsp;Shuaida Wu ,&nbsp;Shuangshuang Wu ,&nbsp;Minmin Liu ,&nbsp;Yingjie Guo ,&nbsp;Yang Zhan","doi":"10.1016/j.jgr.2025.03.006","DOIUrl":"10.1016/j.jgr.2025.03.006","url":null,"abstract":"<div><h3>Background</h3><div>Panax ginseng Meyer is a well-known herb in traditional Chinese medicine, with ginsenosides being its primary bioactive components. Among these, 20(S)-protopanaxadiol (20(S)-PPD) has demonstrated anti-tumor effects in various cancers. However, its role in acute myeloid leukemia (AML) remains unclear.</div></div><div><h3>Methods</h3><div>MTT assays were conducted to assess the impact of 20(S)-PPD on AML cell proliferation, while flow cytometry was used to analyze its effects on apoptosis. Western blotting and network pharmacology analyses were employed to explore the signaling pathways and protein expression levels modulated by 20(S)-PPD in AML. c-Myc mRNA levels in AML cells were quantified using RT-PCR.</div></div><div><h3>Results</h3><div>20(S)-PPD effectively inhibits proliferation and induces apoptosis in AML cells, both in vitro and in patient samples. It achieves this by inhibiting the PI3K/AKT/mTOR pathway and activating the PERK/ATF4/CHOP pathway. Additionally, 20(S)-PPD reduces c-Myc protein and mRNA levels, primarily by decreasing c-Myc mRNA stability. Moreover, combining 20(S)-PPD with ABT-199 significantly enhances pro-apoptotic effects and markedly reduces c-Myc protein and mRNA levels in both AML and cytarabine-resistant (AraC-R) AML cells. This combination therapy holds promise for overcoming resistance and improving treatment outcomes in AML.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potent antitumor activity of 20(S)-PPD in AML and elucidates its underlying mechanisms. Notably, 20(S)-PPD exhibits significant antitumor effects against AML cells, both as a single agent and in combination with ABT-199, where it displays pronounced synergy. These results suggest a promising new therapeutic strategy for AML treatment.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 306-314"},"PeriodicalIF":6.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current clinical trends in developing strategies for dementia disorders and the role of Korean Red Ginseng 目前的临床趋势,发展战略的痴呆症和韩国红参的作用
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-20 DOI: 10.1016/j.jgr.2025.03.005
Manho Kim
Recently, the development of the FDA approved monoclonal antibodies (mAbs) targeting amyloid proteins, such as aducanumab, lecanemab, and donanemab, etc. Although these are in initial stage, developing mAbs is believed to proposed as next stage of AD therapeutics. However, their high cost makes them impractical as main stream of dementia treatments, and efficacies might not overcome the current AchEI (Acetyl choline Esterase Inhibitors). AchEI compliance issues are caused by side effects, such as nausea or vomiting due to Ach's adverse event. There are several categories of medicines, nootropics, functional foods that enhance cognition. These usually have used together or sometimes independently. In addition to conventional anti-AD medication, however, efficacy re-evaluation in Korea to assess which may for the physicians to prohibit further prescription.
These situations, too-high-cost of advanced new drugs, compliance issues of current medications and re-evaluation of nootropics are facing the ultra-expanding dementia population in South Korea. Korean Red Ginseng has been recognized for cognitive enhancement properties. Additionally, pleiotropic phenomena of KRG, not only cognition but also overall human health systems, warranting further underling medical evidence. These efficacies and multi-effectiveness can be a high potential candidate for the current trends in developing strategies for dementia disorders.
最近,FDA批准了针对淀粉样蛋白的单克隆抗体(mab)的开发,如aducanumab, lecanemab和donanemab等。尽管这些尚处于初始阶段,但开发单克隆抗体被认为是阿尔茨海默病治疗的下一阶段。然而,它们的高成本使其成为痴呆症治疗的主流不切实际,而且其疗效可能无法克服目前的乙酰胆碱酯酶抑制剂(Acetyl choline Esterase Inhibitors)。乙酰胆碱合成酶的依从性问题是由副作用引起的,如乙酰胆碱的不良事件引起的恶心或呕吐。有几类药物,益智药,功能性食品可以增强认知能力。这些通常一起使用,有时单独使用。然而,除了常规的抗ad药物外,在韩国重新评估其疗效后,可能会禁止医生进一步开具处方。这些情况、先进新药成本过高、现有药物的依从性问题以及益智药的重新评估都是韩国急剧扩大的痴呆症人口所面临的问题。韩国红参被认为具有增强认知能力的特性。此外,KRG的多效性现象,不仅是认知,而且是整个人类健康系统,需要进一步的医学证据。这些功效和多效性可以成为当前发展痴呆症策略趋势的高潜力候选物。
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Journal of Ginseng Research
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