首页 > 最新文献

Journal of Ginseng Research最新文献

英文 中文
Ginsenoside Re promotes osteogenic differentiation via BMP2/p38 pathway in vivo and in vitro 人参皂苷Re在体内外通过BMP2/p38通路促进成骨分化
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-12 DOI: 10.1016/j.jgr.2025.03.003
Yunjia Wang , Gengming Zhang , Linhua Deng , Hongqi Zhang , Emmanuel Alonge , Zhongjing Jiang

Background

Ginsenosides have been used in traditional Chinese medicine to treat fractures. Ginsenoside Re, a key component of P. ginseng, however, the molecular mechanisms underlying these effects remain inadequately understood. This study aims to investigate the effects of Ginsenoside Re on bone formation in fractures and to explore the underlying molecular mechanisms involved.

Methods

Cell proliferation and osteogenic differentiation were evaluated using the Cell Counting Kit-8 (CCK-8) assay and alkaline phosphatase (ALP) staining, respectively. Quantitative PCR (qPCR) and western blotting were employed to quantify mRNA and protein expression levels. To assess bone formation in vivo, a zebrafish caudal fin regeneration model was utilized, with calcein staining applied to visualize mineralized tissue. Additionally, a bone morphogenetic protein 2a (bmp2a) knockout zebrafish model was generated using the CRISPR-Cas9 system to further investigate the molecular mechanisms underlying ginsenoside Re-mediated bone formation.

Results

Ginsenoside Re promotes normal development and survival in zebrafish. In a zebrafish model, ginsenoside Re enhances bone regeneration, accompanied by upregulated expression of osteogenic markers. Following a 10-day treatment with 20 μM ginsenoside Re, mRNA sequencing (mRNA-Seq) analysis identified bmp2a as a critical regulator of bone formation. In vitro, ginsenoside Re stimulates osteogenic differentiation in MC3T3-E1 cells, elevating both mRNA and protein levels of bone morphogenetic protein 2 (BMP2). Co-treatment with noggin or SB203580 reverses ginsenoside Re-induced osteogenesis: noggin suppresses BMP2 expression and p38 phosphorylation, whereas SB203580 specifically inhibits p38 activity. In a bmp2a knockout zebrafish model, the pro-osteogenic effects of ginsenoside Re are completely abolished. Similarly, in wild-type zebrafish, both noggin and SB203580 attenuate the bone-promoting effects of ginsenoside Re. Noggin reduces the expression of bmp2a and p38a, while SB203580 specifically targets p38a.

Conclusions

In conclusion, our findings demonstrate, for the first time, that ginsenoside Re at an optimal concentration of 20 μM enhances bone formation by modulating the osteogenic system. Mechanistically, we reveal that this pro-osteogenic effect is mediated through the BMP2/p38 signaling pathway.
背景:人参皂苷在中药中用于治疗骨折。人参皂苷Re是人参的关键成分,然而,这些作用的分子机制尚不清楚。本研究旨在探讨人参皂苷Re对骨折骨形成的影响,并探讨其潜在的分子机制。方法分别采用细胞计数试剂盒-8 (CCK-8)法和碱性磷酸酶(ALP)染色法检测各组细胞增殖和成骨分化。采用定量PCR (qPCR)和western blotting检测各组mRNA和蛋白的表达水平。为了评估体内骨形成,我们利用斑马鱼尾鳍再生模型,钙黄蛋白染色显示矿化组织。此外,利用CRISPR-Cas9系统构建骨形态发生蛋白2a (bone morphogenetic protein 2a, bmp2a)敲除斑马鱼模型,进一步研究人参皂苷re介导骨形成的分子机制。结果人参皂苷Re能促进斑马鱼的正常发育和存活。在斑马鱼模型中,人参皂苷Re增强骨再生,并伴有成骨标志物的上调表达。用20 μM人参皂苷Re治疗10天后,mRNA测序(mRNA- seq)分析发现bmp2a是骨形成的关键调节因子。在体外,人参皂苷Re刺激MC3T3-E1细胞成骨分化,提高骨形态发生蛋白2 (bone morphogenetic protein 2, BMP2) mRNA和蛋白水平。与noggin或SB203580共同治疗逆转人参皂苷再诱导的成骨:noggin抑制BMP2表达和p38磷酸化,而SB203580特异性抑制p38活性。在bmp2a基因敲除的斑马鱼模型中,人参皂苷Re的促成骨作用被完全消除。同样,在野生型斑马鱼中,noggin和SB203580都减弱了人参皂苷Re的促骨作用。noggin降低了bmp2a和p38a的表达,而SB203580特异性靶向p38a。结论本研究首次证实,在最佳浓度为20 μM时,人参皂苷Re通过调节成骨系统促进骨形成。在机制上,我们揭示了这种促成骨作用是通过BMP2/p38信号通路介导的。
{"title":"Ginsenoside Re promotes osteogenic differentiation via BMP2/p38 pathway in vivo and in vitro","authors":"Yunjia Wang ,&nbsp;Gengming Zhang ,&nbsp;Linhua Deng ,&nbsp;Hongqi Zhang ,&nbsp;Emmanuel Alonge ,&nbsp;Zhongjing Jiang","doi":"10.1016/j.jgr.2025.03.003","DOIUrl":"10.1016/j.jgr.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenosides have been used in traditional Chinese medicine to treat fractures. Ginsenoside Re, a key component of P. ginseng, however, the molecular mechanisms underlying these effects remain inadequately understood. This study aims to investigate the effects of Ginsenoside Re on bone formation in fractures and to explore the underlying molecular mechanisms involved.</div></div><div><h3>Methods</h3><div>Cell proliferation and osteogenic differentiation were evaluated using the Cell Counting Kit-8 (CCK-8) assay and alkaline phosphatase (ALP) staining, respectively. Quantitative PCR (qPCR) and western blotting were employed to quantify mRNA and protein expression levels. To assess bone formation <em>in vivo</em>, a zebrafish caudal fin regeneration model was utilized, with calcein staining applied to visualize mineralized tissue. Additionally, a bone morphogenetic protein 2a (<em>bmp2a</em>) knockout zebrafish model was generated using the CRISPR-Cas9 system to further investigate the molecular mechanisms underlying ginsenoside Re-mediated bone formation.</div></div><div><h3>Results</h3><div>Ginsenoside Re promotes normal development and survival in zebrafish. In a zebrafish model, ginsenoside Re enhances bone regeneration, accompanied by upregulated expression of osteogenic markers. Following a 10-day treatment with 20 μM ginsenoside Re, mRNA sequencing (mRNA-Seq) analysis identified <em>bmp2a</em> as a critical regulator of bone formation. <em>In vitro</em>, ginsenoside Re stimulates osteogenic differentiation in MC3T3-E1 cells, elevating both mRNA and protein levels of bone morphogenetic protein 2 (BMP2). Co-treatment with noggin or SB203580 reverses ginsenoside Re-induced osteogenesis: noggin suppresses BMP2 expression and p38 phosphorylation, whereas SB203580 specifically inhibits p38 activity. In a <em>bmp2a</em> knockout zebrafish model, the pro-osteogenic effects of ginsenoside Re are completely abolished. Similarly, in wild-type zebrafish, both noggin and SB203580 attenuate the bone-promoting effects of ginsenoside Re. Noggin reduces the expression of <em>bmp2a</em> and <em>p38a</em>, while SB203580 specifically targets <em>p38a</em>.</div></div><div><h3>Conclusions</h3><div>In conclusion, our findings demonstrate, for the first time, that ginsenoside Re at an optimal concentration of 20 μM enhances bone formation by modulating the osteogenic system. Mechanistically, we reveal that this pro-osteogenic effect is mediated through the BMP2/p38 signaling pathway.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 4","pages":"Pages 395-405"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307035","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
Can Panax ginseng help protect the body from the harmful effects of airborne particulate matter? 人参能保护身体免受空气中颗粒物的有害影响吗?
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-04 DOI: 10.1016/j.jgr.2025.03.001
Tae Woo Kwon , Yujeong Ha , Hyo-Sung Jo , Won Myoung Lee , Seung-Yeol Nah , Hyun Jeong Yang , Ik-Hyun Cho
Recent studies have shown that exposure to airborne particulate matter (PM) adversely affects human health through various mechanisms, including oxidative stress, inflammatory response, apoptosis, autophagy, ferroptosis, and endoplasmic reticulum stress. Natural products have a wide range of physiological and pharmacological activities but with less toxicity than synthetic drugs; in recent years, natural products have become increasingly popular in the field of food and drug development. Panax (P.) ginseng is one of the more well-known natural products, and there have recently been increasing reports indicating that P. ginseng may alleviate toxicity caused by exposure to PM. In the current review, we summarize the positive potential role that P. ginseng-derived substances (total extract, saponin fraction, non-saponin fraction, their ingredients, etc.) have on PM-induced adverse reactions, and we also discuss their potential utility in food and drug development for prevention and treatment. Despite some promising findings, current research may be limited by a lack of comprehensive clinical studies and standardized methodologies. Future research should prioritize the investigation of P. ginseng's clinical efficacy and the development of advanced formulations to maximize its protective potential against PM-induced health risks.
最近的研究表明,暴露于空气中的颗粒物(PM)通过多种机制对人体健康产生不利影响,包括氧化应激、炎症反应、细胞凋亡、自噬、铁下垂和内质网应激。天然产物具有广泛的生理和药理活性,但毒性低于合成药物;近年来,天然产物在食品和药物开发领域越来越受欢迎。人参是比较知名的天然产物之一,最近有越来越多的报道表明,人参可以减轻暴露于PM引起的毒性。本文综述了人参衍生物质(总提取物、皂苷部分、非皂苷部分及其成分等)在pm诱导不良反应中的潜在积极作用,并讨论了其在食品和药物开发中的潜在应用,以预防和治疗pm诱导的不良反应。尽管有一些有希望的发现,目前的研究可能受到缺乏全面的临床研究和标准化方法的限制。未来的研究应优先研究人参的临床疗效和开发先进的配方,以最大限度地发挥其对pm诱导的健康风险的保护潜力。
{"title":"Can Panax ginseng help protect the body from the harmful effects of airborne particulate matter?","authors":"Tae Woo Kwon ,&nbsp;Yujeong Ha ,&nbsp;Hyo-Sung Jo ,&nbsp;Won Myoung Lee ,&nbsp;Seung-Yeol Nah ,&nbsp;Hyun Jeong Yang ,&nbsp;Ik-Hyun Cho","doi":"10.1016/j.jgr.2025.03.001","DOIUrl":"10.1016/j.jgr.2025.03.001","url":null,"abstract":"<div><div>Recent studies have shown that exposure to airborne particulate matter (PM) adversely affects human health through various mechanisms, including oxidative stress, inflammatory response, apoptosis, autophagy, ferroptosis, and endoplasmic reticulum stress. Natural products have a wide range of physiological and pharmacological activities but with less toxicity than synthetic drugs; in recent years, natural products have become increasingly popular in the field of food and drug development. <em>Panax (P.) ginseng</em> is one of the more well-known natural products, and there have recently been increasing reports indicating that <em>P. ginseng</em> may alleviate toxicity caused by exposure to PM. In the current review, we summarize the positive potential role that <em>P. ginseng</em>-derived substances (total extract, saponin fraction, non-saponin fraction, their ingredients, etc.) have on PM-induced adverse reactions, and we also discuss their potential utility in food and drug development for prevention and treatment. Despite some promising findings, current research may be limited by a lack of comprehensive clinical studies and standardized methodologies. Future research should prioritize the investigation of <em>P. ginseng</em>'s clinical efficacy and the development of advanced formulations to maximize its protective potential against PM-induced health risks.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 4","pages":"Pages 331-341"},"PeriodicalIF":6.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307304","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
Korean black ginseng extract alleviates Alzheimer's disease-related cognitive impairment by activating the Nrf2/HO-1 pathway and suppressing the p38 MAPK/NF-κB/STAT3 pathways and NLRP3 inflammasome via TLR2 and TLR4 modulation 黑参提取物通过TLR2和TLR4调节激活Nrf2/HO-1通路,抑制p38 MAPK/NF-κB/STAT3通路和NLRP3炎性体,减轻阿尔茨海默病相关认知功能障碍
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-02-24 DOI: 10.1016/j.jgr.2025.02.002
Yujeong Ha , Hyo-Sung Jo , Tae Woo Kwon , Seung Ho Jeon , Sang-Kwan Moon , Ji Hoon Jung , Min Soo Kim , Seung-Yeol Nah , Jong Kil Lee , Ik-Hyun Cho

Background

Korean black ginseng, a specially processed ginseng through repeat steaming and drying, has various pharmacological effects. However, its role in cognitive impairment remains unclear.

Purpose and methods

This study examined whether Korean black ginseng extract (BGE; 50 and 100 mg/kg, orally, 18 weeks) may mitigate cognitive impairment in a 5xFAD mouse model of Alzheimer's disease (AD).

Results

BGE significantly improved cognitive performance in 5xFAD mice, associated with reduced Aβ accumulation in the frontal cortex and hippocampus. BGE suppressed microglial and astrocytic activation, alongside the downregulation of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and enzymes (cyclooxygenase-2 and inducible nitric oxide synthase). These changes coincided with the inhibition of key inflammatory signaling pathways, such as p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB)/p65, signal transducer and activator of transcription (STAT) 3, and NOD-like receptor protein 3 (NLRP3) inflammasome. Furthermore, BGE reduced the generation of reactive oxygen species and enhanced the nuclear-E2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway in the brains linked to the downregulation of toll-like receptors (TLR)-2 and TLR-4 in the brain.

Conclusion

Taken together, BGE could improve AD-related cognitive decline and neurodegeneration by simultaneously regulating anti-inflammatory pathways (p38 MAPK/NF-κB/STAT3 and NLRP3 inflammasome) and an antioxidant pathway (Nrf2/HO-1) via modulation of TLR2/4.
韩国黑参是一种经过反复蒸干加工而成的人参,具有多种药理作用。然而,它在认知障碍中的作用仍不清楚。目的与方法研究高丽黑参提取物(BGE;50和100 mg/kg,口服,18周)可能减轻5xFAD阿尔茨海默病(AD)小鼠模型的认知障碍。结果bge显著改善5xFAD小鼠的认知能力,减少额叶皮质和海马中Aβ的积累。BGE抑制小胶质细胞和星形胶质细胞的激活,同时下调促炎细胞因子(白细胞介素-6和肿瘤坏死因子-α)和酶(环氧合酶-2和诱导型一氧化氮合酶)。这些变化与关键的炎症信号通路,如p38丝裂原活化蛋白激酶(MAPK)、核因子κB (NF-κB)/p65、信号传导和转录激活因子(STAT) 3、nod样受体蛋白3 (NLRP3)炎症小体的抑制一致。此外,BGE减少了活性氧的产生,增强了大脑中与toll样受体(TLR)-2和TLR-4下调相关的核e2相关因子2 (Nrf2)-血红素加氧酶1 (HO-1)信号通路。结论BGE可通过调节TLR2/4同时调节抗炎途径(p38 MAPK/NF-κB/STAT3和NLRP3炎性体)和抗氧化途径(Nrf2/HO-1),改善ad相关认知能力下降和神经退行性变。
{"title":"Korean black ginseng extract alleviates Alzheimer's disease-related cognitive impairment by activating the Nrf2/HO-1 pathway and suppressing the p38 MAPK/NF-κB/STAT3 pathways and NLRP3 inflammasome via TLR2 and TLR4 modulation","authors":"Yujeong Ha ,&nbsp;Hyo-Sung Jo ,&nbsp;Tae Woo Kwon ,&nbsp;Seung Ho Jeon ,&nbsp;Sang-Kwan Moon ,&nbsp;Ji Hoon Jung ,&nbsp;Min Soo Kim ,&nbsp;Seung-Yeol Nah ,&nbsp;Jong Kil Lee ,&nbsp;Ik-Hyun Cho","doi":"10.1016/j.jgr.2025.02.002","DOIUrl":"10.1016/j.jgr.2025.02.002","url":null,"abstract":"<div><h3>Background</h3><div>Korean black ginseng, a specially processed ginseng through repeat steaming and drying, has various pharmacological effects. However, its role <em>i</em><em>n</em> cognitive impairment remains unclear.</div></div><div><h3>Purpose and methods</h3><div>This study examined whether Korean black ginseng extract (BGE; 50 and 100 mg/kg, orally, 18 weeks) may mitigate cognitive impairment in a 5xFAD mouse model of Alzheimer's disease (AD).</div></div><div><h3>Results</h3><div>BGE significantly improved cognitive performance in 5xFAD mice, associated with reduced Aβ accumulation in the frontal cortex and hippocampus. BGE suppressed microglial and astrocytic activation, alongside the downregulation of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and enzymes (cyclooxygenase-2 and inducible nitric oxide synthase). These changes coincided with the inhibition of key inflammatory signaling pathways, such as p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB)/p65, signal transducer and activator of transcription (STAT) 3, and NOD-like receptor protein 3 (NLRP3) inflammasome. Furthermore, BGE reduced the generation of reactive oxygen species and enhanced the nuclear-E2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway in the brains linked to the downregulation of toll-like receptors (TLR)-2 and TLR-4 in the brain.</div></div><div><h3>Conclusion</h3><div>Taken together, BGE could improve AD-related cognitive decline and neurodegeneration by simultaneously regulating anti-inflammatory pathways (p38 MAPK/NF-κB/STAT3 and NLRP3 inflammasome) and an antioxidant pathway (Nrf2/HO-1) via modulation of TLR2/4.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 294-305"},"PeriodicalIF":6.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870184","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
Roles and mechanisms of ginsenoside Rg1 in coronary artery disease: Progress and perspectives 人参皂苷Rg1在冠状动脉疾病中的作用及机制研究进展
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-02-18 DOI: 10.1016/j.jgr.2025.02.003
Lixiao Zhang , Pengfei Chen , Lin Xu , Ming Guo
Coronary artery disease (CAD) is a leading cause of morbidity and mortality globally, necessitating innovative therapeutic strategies. Panax ginseng Meyer, esteemed in traditional Chinese medicine as the “King of Herbs,” has garnered scientific attention for its cardiovascular benefits. Among its bioactive components, ginsenoside Rg1 stands out as a potent therapeutic candidate. This review consolidates current research on Rg1's multifaceted mechanisms in CAD management, including its roles in enhancing endothelial function, inhibiting smooth muscle cell proliferation, modulating inflammation, regulating lipid metabolism, preventing thrombosis, and promoting angiogenesis. Furthermore, Rg1 exhibits cardioprotective properties by mitigating ischemic myocardial injury, reducing myocardial hypertrophy, and preventing fibrosis. Despite promising preclinical findings, the clinical translation of Rg1 is hindered by challenges such as poor bioavailability, potential drug interactions, and limited clinical trial data. This review underscores the need for rigorous clinical studies to validate Rg1's efficacy and safety, paving the way for its incorporation into CAD therapeutic regimens.
冠状动脉疾病(CAD)是全球发病率和死亡率的主要原因,需要创新的治疗策略。在中医中被尊为“草药之王”的人参因其对心血管的益处而受到科学界的关注。在其生物活性成分中,人参皂苷Rg1作为一种有效的治疗候选物脱颖而出。本文综述了目前关于Rg1在CAD管理中的多层面机制的研究,包括其在增强内皮功能、抑制平滑肌细胞增殖、调节炎症、调节脂质代谢、预防血栓形成和促进血管生成方面的作用。此外,Rg1通过减轻缺血性心肌损伤、减轻心肌肥厚和预防纤维化表现出心脏保护作用。尽管临床前研究结果很有希望,但Rg1的临床转化受到诸如生物利用度差、潜在药物相互作用和临床试验数据有限等挑战的阻碍。这篇综述强调需要严格的临床研究来验证Rg1的有效性和安全性,为将其纳入CAD治疗方案铺平道路。
{"title":"Roles and mechanisms of ginsenoside Rg1 in coronary artery disease: Progress and perspectives","authors":"Lixiao Zhang ,&nbsp;Pengfei Chen ,&nbsp;Lin Xu ,&nbsp;Ming Guo","doi":"10.1016/j.jgr.2025.02.003","DOIUrl":"10.1016/j.jgr.2025.02.003","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is a leading cause of morbidity and mortality globally, necessitating innovative therapeutic strategies. Panax ginseng Meyer, esteemed in traditional Chinese medicine as the “King of Herbs,” has garnered scientific attention for its cardiovascular benefits. Among its bioactive components, ginsenoside Rg1 stands out as a potent therapeutic candidate. This review consolidates current research on Rg1's multifaceted mechanisms in CAD management, including its roles in enhancing endothelial function, inhibiting smooth muscle cell proliferation, modulating inflammation, regulating lipid metabolism, preventing thrombosis, and promoting angiogenesis. Furthermore, Rg1 exhibits cardioprotective properties by mitigating ischemic myocardial injury, reducing myocardial hypertrophy, and preventing fibrosis. Despite promising preclinical findings, the clinical translation of Rg1 is hindered by challenges such as poor bioavailability, potential drug interactions, and limited clinical trial data. This review underscores the need for rigorous clinical studies to validate Rg1's efficacy and safety, paving the way for its incorporation into CAD therapeutic regimens.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 225-236"},"PeriodicalIF":6.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870505","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 Rg2, a principal effective ingredient of Panax ginseng, attenuates DSS-induced ulcerative colitis through NF-κB/NLRP3 pathway 人参皂苷Rg2是人参的主要有效成分,通过NF-κB/NLRP3途径减轻dss诱导的溃疡性结肠炎
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-02-10 DOI: 10.1016/j.jgr.2025.02.001
Ji Zhang , Jing Xie , Zhiqiang Niu , Long You , Yanan Liu , Rui Guo , Guigui Yang , Ziliang He , Ting Shen , Honggang Wang , Qi Yan , Weicheng Hu

Background

Ginsenoside Rg2 (G-Rg2), a major active compound of Panax ginseng, exhibits a wide range of pharmacological properties, including anticancer, antioxidant and neuroprotective effects. However, the mechanisms by which G-Rg2 mitigates ulcerative colitis (UC) have not been clearly elucidated.

Aims

In the present study, we aimed to elucidate the underlying mechanisms by which G-Rg2 mitigated UC.

Methods

In this study, we investigated the efficacy of G-Rg2 in ameliorating dextran sulfate sodium (DSS)-induced UC and its potential mechanisms using a DSS-induced UC mouse model and Lipopolysaccharides (LPS)/nigericin (Nig)-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation on immortalized bone marrow-derived macrophages (iBMDMs).

Results

Oral administration of G-Rg2 at doses of 10 and 20 mg/kg significantly mitigated weight loss, normalized food and water intake, and improved colon histopathology in DSS-induced UC mice. G-Rg2 also restored mRNA expression levels of occludin, claudin-3, zona occluden (ZO)-1 and mucin 2, thereby enhancing intestinal barrier integrity. G-Rg2 significantly suppressed the nuclear translocation of p65, the subunit of nuclear factor kappa-B (NF-κB), as well as downregulated NLRP3, cleaved IL-1β and caspase1 p20 expression induced by LPS/Nig in iBMDMs.

Conclusion

G-Rg2 effectively reduced colon inflammation in DSS-induced UC mice and diminishes inflammatory responses under LPS/Nig conditions by regulating NF-κB/NLRP3 pathway, thereby inhibiting NLRP3 inflammasome activation, which may serve as a potent therapeutic agent for UC.
人参皂苷Rg2 (G-Rg2)是人参的一种主要活性化合物,具有抗癌、抗氧化和神经保护等多种药理作用。然而,G-Rg2减轻溃疡性结肠炎(UC)的机制尚未明确阐明。目的在本研究中,我们旨在阐明G-Rg2减轻UC的潜在机制。方法在本研究中,我们通过DSS诱导的UC小鼠模型和脂多糖(LPS)/奈及利菌素(Nig)诱导的NOD-、LRR-和pyrin结构域蛋白3 (NLRP3)炎性体对永生化骨髓源性巨噬细胞(iBMDMs)的激活,研究G-Rg2对DSS诱导UC的改善作用及其潜在机制。结果10和20 mg/kg剂量的G-Rg2可显著减轻dss诱导UC小鼠的体重,使食物和水的摄入正常化,并改善结肠组织病理学。G-Rg2还能恢复occludin、claudin-3、occluden (ZO)-1和mucin 2 mRNA的表达水平,从而增强肠屏障的完整性。G-Rg2显著抑制核因子κ b (NF-κB)亚基p65的核易位,下调LPS/Nig诱导的iBMDMs中NLRP3、裂解IL-1β和caspase1 p20的表达。结论- rg2通过调节NF-κB/NLRP3通路,抑制NLRP3炎性小体的激活,可有效减轻dss诱导UC小鼠的结肠炎症,降低LPS/Nig条件下的炎症反应,可能是UC的有效治疗药物。
{"title":"Ginsenoside Rg2, a principal effective ingredient of Panax ginseng, attenuates DSS-induced ulcerative colitis through NF-κB/NLRP3 pathway","authors":"Ji Zhang ,&nbsp;Jing Xie ,&nbsp;Zhiqiang Niu ,&nbsp;Long You ,&nbsp;Yanan Liu ,&nbsp;Rui Guo ,&nbsp;Guigui Yang ,&nbsp;Ziliang He ,&nbsp;Ting Shen ,&nbsp;Honggang Wang ,&nbsp;Qi Yan ,&nbsp;Weicheng Hu","doi":"10.1016/j.jgr.2025.02.001","DOIUrl":"10.1016/j.jgr.2025.02.001","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenoside Rg2 (G-Rg2), a major active compound of <em>Panax ginseng</em>, exhibits a wide range of pharmacological properties, including anticancer, antioxidant and neuroprotective effects. However, the mechanisms by which G-Rg2 mitigates ulcerative colitis (UC) have not been clearly elucidated.</div></div><div><h3>Aims</h3><div>In the present study, we aimed to elucidate the underlying mechanisms by which G-Rg2 mitigated UC.</div></div><div><h3>Methods</h3><div>In this study, we investigated the efficacy of G-Rg2 in ameliorating dextran sulfate sodium (DSS)-induced UC and its potential mechanisms using a DSS-induced UC mouse model and Lipopolysaccharides (LPS)/nigericin (Nig)-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation on immortalized bone marrow-derived macrophages (iBMDMs).</div></div><div><h3>Results</h3><div>Oral administration of G-Rg2 at doses of 10 and 20 mg/kg significantly mitigated weight loss, normalized food and water intake, and improved colon histopathology in DSS-induced UC mice. G-Rg2 also restored mRNA expression levels of occludin, claudin-3, zona occluden (ZO)-1 and mucin 2, thereby enhancing intestinal barrier integrity. G-Rg2 significantly suppressed the nuclear translocation of p65, the subunit of nuclear factor kappa-B (NF-κB), as well as downregulated NLRP3, cleaved IL-1β and caspase1 p20 expression induced by LPS/Nig in iBMDMs.</div></div><div><h3>Conclusion</h3><div>G-Rg2 effectively reduced colon inflammation in DSS-induced UC mice and diminishes inflammatory responses under LPS/Nig conditions by regulating NF-κB/NLRP3 pathway, thereby inhibiting NLRP3 inflammasome activation, which may serve as a potent therapeutic agent for UC.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 282-293"},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870183","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
Effects of red ginseng extract and red ginseng dietary fiber on the maintenance of intestinal immune and functional homeostasis in diet-induced obese mice 红参提取物和红参膳食纤维对饮食性肥胖小鼠肠道免疫和功能平衡维持的影响
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-30 DOI: 10.1016/j.jgr.2025.01.006
Seung-Hwan Seo , Do-Won Ham , Ji-Eun Lee , Seung-Min Jong , Sang-Kyu Kim , Seung-Ho Lee , Hye-Young Yu , Eun-Hee Shin

Background

Obesity is an important risk factor of intestinal inflammatory disease. This study aimed to evaluate the effects of Red ginseng extract powder (RGEP) and Red ginseng dietary fiber (RGDF) on the maintenance of immune and functional homeostasis in recovering obesity-induced impairment of intestinal immunity.

Methods

Diet-induced obesity in C57BL/6 male mice was achieved by feeding them a 60 % high-fat diet for six weeks. The diet-induced obese (DIO) mice were administered RGEP (205, 410, or 820 mg/kg), fructooligosaccharide (FOS, 820 mg/kg), or RGDF (410, 820, or 1640 mg/kg) once daily for 4–8 weeks. The effects of RGEP or RGDF administration were evaluated via stool trait and gastrointestinal (GI) motility, inflammatory biomarkers and cytokines in mesenteric lymph nodes and intestine, mucosal protective genes, bacterial toxicity, and histopathological features of the intestines.

Results

RGEP or RGDF administration to the DIO mice reduced mucosal barrier damaging factor (α1-antitrypsin), inflammatory cytokine levels, factors related to inflammatory responses (C-reactive protein (CRP), iNOS, NF-κB, MPO, and Calprotectin), and levels of urinary indican and intestinal β-glucuronidase. Conversely, RGEP or RGDF administration increased intestinal motility, levels of short-chain fatty acids (SCFAs) and β-defensin-2, and mucus barrier functional factor (MUC2) expression. Histopathological features of the small intestine recovered to normal levels after RGEP or RGDF administration.

Conclusion

Our results demonstrated that RGEP and RGDF were effective for maintaining intestinal immune and functional homeostasis by recovering impaired immune and barrier function in DIO mice.
背景:肥胖是肠道炎症性疾病的重要危险因素。本研究旨在探讨红参提取物粉(RGEP)和红参膳食纤维(RGDF)在恢复肥胖引起的肠道免疫损伤中维持免疫和功能稳态的作用。方法C57BL/6雄性小鼠连续6周以60%高脂饮食诱导肥胖。饮食诱导肥胖(DIO)小鼠每天1次给予RGEP(205、410或820 mg/kg)、低聚果糖(FOS, 820 mg/kg)或RGDF(410、820或1640 mg/kg),持续4-8周。RGEP或RGDF的作用通过粪便特征和胃肠道(GI)运动、肠系膜淋巴结和肠道中的炎症生物标志物和细胞因子、粘膜保护基因、细菌毒性和肠道组织病理学特征来评估。结果rgep或RGDF可降低DIO小鼠黏膜屏障损伤因子(α - 1-抗胰蛋白酶)、炎症细胞因子、炎症反应相关因子(c -反应蛋白(CRP)、iNOS、NF-κB、MPO和钙保护蛋白)、尿氮和肠道β-葡萄糖醛酸酶水平。相反,RGEP或RGDF可增加肠道蠕动、短链脂肪酸(SCFAs)和β-防御素-2水平以及粘液屏障功能因子(MUC2)的表达。RGEP或RGDF给药后小肠组织病理学特征恢复到正常水平。结论RGEP和RGDF通过恢复DIO小鼠受损的免疫和屏障功能,可有效维持肠道免疫和功能稳态。
{"title":"Effects of red ginseng extract and red ginseng dietary fiber on the maintenance of intestinal immune and functional homeostasis in diet-induced obese mice","authors":"Seung-Hwan Seo ,&nbsp;Do-Won Ham ,&nbsp;Ji-Eun Lee ,&nbsp;Seung-Min Jong ,&nbsp;Sang-Kyu Kim ,&nbsp;Seung-Ho Lee ,&nbsp;Hye-Young Yu ,&nbsp;Eun-Hee Shin","doi":"10.1016/j.jgr.2025.01.006","DOIUrl":"10.1016/j.jgr.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Obesity is an important risk factor of intestinal inflammatory disease. This study aimed to evaluate the effects of Red ginseng extract powder (RGEP) and Red ginseng dietary fiber (RGDF) on the maintenance of immune and functional homeostasis in recovering obesity-induced impairment of intestinal immunity.</div></div><div><h3>Methods</h3><div>Diet-induced obesity in C57BL/6 male mice was achieved by feeding them a 60 % high-fat diet for six weeks. The diet-induced obese (DIO) mice were administered RGEP (205, 410, or 820 mg/kg), fructooligosaccharide (FOS, 820 mg/kg), or RGDF (410, 820, or 1640 mg/kg) once daily for 4–8 weeks. The effects of RGEP or RGDF administration were evaluated via stool trait and gastrointestinal (GI) motility, inflammatory biomarkers and cytokines in mesenteric lymph nodes and intestine, mucosal protective genes, bacterial toxicity, and histopathological features of the intestines.</div></div><div><h3>Results</h3><div>RGEP or RGDF administration to the DIO mice reduced mucosal barrier damaging factor (α1-antitrypsin), inflammatory cytokine levels, factors related to inflammatory responses (C-reactive protein (CRP), iNOS, NF-κB, MPO, and Calprotectin), and levels of urinary indican and intestinal β-glucuronidase. Conversely, RGEP or RGDF administration increased intestinal motility, levels of short-chain fatty acids (SCFAs) and β-defensin-2, and mucus barrier functional factor (MUC2) expression. Histopathological features of the small intestine recovered to normal levels after RGEP or RGDF administration.</div></div><div><h3>Conclusion</h3><div>Our results demonstrated that RGEP and RGDF were effective for maintaining intestinal immune and functional homeostasis by recovering impaired immune and barrier function in DIO mice.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 271-281"},"PeriodicalIF":6.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870182","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 alleviates radiation-induced acute lung vascular endothelium injury by reducing mitochondrial apoptosis via Sirt1 人参皂苷Rg5通过Sirt1减少线粒体凋亡,减轻辐射引起的急性肺血管内皮损伤
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-27 DOI: 10.1016/j.jgr.2025.01.004
Churong Li , Biao Zhao , Jing Xiong , Linjie Li , Dalong Pang , Keith Unger , Mira Jung , Jiahua Lyu , Hao Kuang , Long Liang , Tao Li , Long Chen , Hansong Bai

Background

Ginsenoside Rg5 possesses potent anti-oxidative, anti-inflammatory, and cytoprotective properties. This study explored the protective effects of ginsenoside Rg5 on radiation-induced pulmonary microvascular endothelial cells (PMECs) injury and the associated molecular mechanisms.

Materials and methods

C57BL/6 mice were used for in vivo studies and primary human PMECs (PPMECs) were utilized as in vitro models. Mice with or without ginsenoside Rg5 pretreatment were irradiated by varying doses. Lung tissues were analyzed for histopathological changes and the expression of endothelial markers. In vitro, PPMECs were irradiated with or without ginsenoside Rg5 pretreatment and analyzed for apoptosis, oxidative stress, mitochondrial function, and endothelial barrier integrity.

Results

Ginsenoside Rg5 pretreatment attenuated radiation-induced acute lung damage, preserved endothelial cell junction integrity, and maintained endothelial barrier function in vivo. In vitro, ginsenoside Rg5 significantly reduced IR-induced oxidative stress, apoptosis, and mitochondrial dysfunction in PPMECs. Ginsenoside Rg5 suppressed radiation-induced Mfn2 acetylation and proteasomal degradation via Sirt1-mediated deacetylation, thereby preserving mitochondrial dynamics and integrity. The protective effects of ginsenoside Rg5 on the integrity of mitochondrial and endothelial tight junction proteins and barrier function were also Sirt1-dependent.

Conclusions

Ginsenoside Rg5 exerts a protective effect against radiation-induced endothelial injury by modulating mitochondrial dynamics and function, as well as maintaining endothelial barrier integrity, in a Sirt1-dependent manner.
人参皂苷Rg5具有有效的抗氧化、抗炎和细胞保护作用。本研究探讨人参皂苷Rg5对辐射致肺微血管内皮细胞(PMECs)损伤的保护作用及其分子机制。材料与方法体内实验采用sc57bl /6小鼠,体外实验采用原代人PMECs (PPMECs)模型。用人参皂苷Rg5预处理或不预处理的小鼠进行不同剂量的辐照。分析肺组织病理变化及内皮标志物的表达。在体外,分别在人参皂苷Rg5预处理或不预处理的情况下照射ppmes,并分析其凋亡、氧化应激、线粒体功能和内皮屏障完整性。结果人参皂苷Rg5预处理在体内可减轻放射性急性肺损伤,保持内皮细胞连接完整性,维持内皮屏障功能。在体外,人参皂苷Rg5显著降低ir诱导的PPMECs氧化应激、细胞凋亡和线粒体功能障碍。人参皂苷Rg5通过sirt1介导的去乙酰化抑制辐射诱导的Mfn2乙酰化和蛋白酶体降解,从而保持线粒体动力学和完整性。人参皂苷Rg5对线粒体和内皮紧密连接蛋白完整性和屏障功能的保护作用也依赖于sirt1。结论人参皂苷Rg5通过调节线粒体动力学和功能,维持内皮屏障的完整性,以sirt1依赖的方式对辐射诱导的内皮损伤具有保护作用。
{"title":"Ginsenoside Rg5 alleviates radiation-induced acute lung vascular endothelium injury by reducing mitochondrial apoptosis via Sirt1","authors":"Churong Li ,&nbsp;Biao Zhao ,&nbsp;Jing Xiong ,&nbsp;Linjie Li ,&nbsp;Dalong Pang ,&nbsp;Keith Unger ,&nbsp;Mira Jung ,&nbsp;Jiahua Lyu ,&nbsp;Hao Kuang ,&nbsp;Long Liang ,&nbsp;Tao Li ,&nbsp;Long Chen ,&nbsp;Hansong Bai","doi":"10.1016/j.jgr.2025.01.004","DOIUrl":"10.1016/j.jgr.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenoside Rg5 possesses potent anti-oxidative, anti-inflammatory, and cytoprotective properties. This study explored the protective effects of ginsenoside Rg5 on radiation-induced pulmonary microvascular endothelial cells (PMECs) injury and the associated molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>C57BL/6 mice were used for <em>in vivo</em> studies and primary human PMECs (PPMECs) were utilized as <em>in vitro</em> models. Mice with or without ginsenoside Rg5 pretreatment were irradiated by varying doses. Lung tissues were analyzed for histopathological changes and the expression of endothelial markers. <em>In vitro</em>, PPMECs were irradiated with or without ginsenoside Rg5 pretreatment and analyzed for apoptosis, oxidative stress, mitochondrial function, and endothelial barrier integrity.</div></div><div><h3>Results</h3><div>Ginsenoside Rg5 pretreatment attenuated radiation-induced acute lung damage, preserved endothelial cell junction integrity, and maintained endothelial barrier function <em>in vivo</em>. <em>In vitro</em>, ginsenoside Rg5 significantly reduced IR-induced oxidative stress, apoptosis, and mitochondrial dysfunction in PPMECs. Ginsenoside Rg5 suppressed radiation-induced Mfn2 acetylation and proteasomal degradation via Sirt1-mediated deacetylation, thereby preserving mitochondrial dynamics and integrity. The protective effects of ginsenoside Rg5 on the integrity of mitochondrial and endothelial tight junction proteins and barrier function were also Sirt1-dependent.</div></div><div><h3>Conclusions</h3><div>Ginsenoside Rg5 exerts a protective effect against radiation-induced endothelial injury by modulating mitochondrial dynamics and function, as well as maintaining endothelial barrier integrity, in a Sirt1-dependent manner.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 260-270"},"PeriodicalIF":6.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870508","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
Corrigendum to “Ginsenoside-Re-rich ethanol extract of Panax ginseng berry enhances healthspan extension via mitostasis and NAD metabolism” [J Ginseng Res Volume 49, Issue 1, January 2025, Pages 92–102] “富含人参皂苷的乙醇提取物通过有丝分裂和NAD代谢提高健康寿命”的勘误[J人参研究,vol . 49, Issue 1, January 2025, Pages 92-102]
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-24 DOI: 10.1016/j.jgr.2025.01.005
Minjeong Kim , Su Hwan Kim , Juewon Kim , Eun-Ju Jin , Shibo Wei , Yunju Jo , Chang-Myung Oh , Ki-Tae Ha , Jong-Hwa Roh , Wan-Gi Kim , Donghyun Cho , Young Jin Choi , Su Myung Jung , Dongryeol Ryu
{"title":"Corrigendum to “Ginsenoside-Re-rich ethanol extract of Panax ginseng berry enhances healthspan extension via mitostasis and NAD metabolism” [J Ginseng Res Volume 49, Issue 1, January 2025, Pages 92–102]","authors":"Minjeong Kim ,&nbsp;Su Hwan Kim ,&nbsp;Juewon Kim ,&nbsp;Eun-Ju Jin ,&nbsp;Shibo Wei ,&nbsp;Yunju Jo ,&nbsp;Chang-Myung Oh ,&nbsp;Ki-Tae Ha ,&nbsp;Jong-Hwa Roh ,&nbsp;Wan-Gi Kim ,&nbsp;Donghyun Cho ,&nbsp;Young Jin Choi ,&nbsp;Su Myung Jung ,&nbsp;Dongryeol Ryu","doi":"10.1016/j.jgr.2025.01.005","DOIUrl":"10.1016/j.jgr.2025.01.005","url":null,"abstract":"","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 2","pages":"Page 224"},"PeriodicalIF":6.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445793","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
Gintonin enhances epithelial barrier function by activating NRF2 pathway in radiation-induced intestinal injury Gintonin通过激活NRF2通路增强辐射诱导肠道损伤的上皮屏障功能
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-19 DOI: 10.1016/j.jgr.2025.01.003
Hyosun Jang , Hyewon Kim , Su-Hyun Oh , Yeonghoon Son , Rami Lee , Seung-Yeol Nah , Hae-June Lee

Background

Because the intestine is a radio-sensitive organ in the body, and radiation-induced intestinal injury is a major clinical problem associated with radiotherapy or radiological accidents. Dysfunction of the epithelial barrier leads to bacterial translocation to other organs, resulting in severe inflammation. Recent findings suggest that gintonin (GT) suppresses oxidative stress and inflammation in neuroinflammatory diseases.

Purpose

This study objected to elucidate the mitigating effects of GT on radiation-induced intestinal injury.

Methods

The therapeutic effects of GT were assessed in a mouse model of radiation-induced intestinal injury using histological, immunohistochemical, and real-time PCR. Additionally, the direct effects of GT and NF-E2-related factor 2 (NRF2) activators on radiation-induced epithelial damage were assessed using Caco-2 cell monolayers.

Results

GT treatment reversed radiation-induced body weight loss, attenuated intestinal damage, and inhibited inflammatory response by reducing inflammatory cell infiltration and cytokine expression in the intestines of mice. Additionally, GT treatment activated NRF2 and ameliorated intestinal barrier damage. In vitro experiments showed that GT treatment affected epithelial permeability and intercellular junction expression in Caco-2 cell monolayers under irradiated conditions. Moreover, treatment with NRF2 activator improved epithelial permeability, improved the expression of intercellular junctions in irradiated epithelial cells, and attenuated radiation-induced intestinal injury in a mouse model.

Conclusion

GT maintains epithelial integrity by activating NRF2-mediated antioxidant activity in radiation-induced intestinal epithelial damage of mice. Overall, these results suggest that GT could be a novel therapeutic agent for radiation-induced intestinal damage.
由于肠道是人体对辐射敏感的器官,辐射引起的肠道损伤是与放射治疗或放射事故相关的主要临床问题。上皮屏障功能障碍导致细菌转移到其他器官,导致严重的炎症。最近的研究表明,gintonin (GT)可以抑制神经炎症性疾病的氧化应激和炎症。目的探讨GT对放射性肠损伤的缓解作用。方法采用组织学、免疫组织化学、实时荧光定量PCR等方法,观察GT对小鼠辐射性肠损伤模型的治疗作用。此外,使用Caco-2细胞单层评估了GT和nf - e2相关因子2 (NRF2)激活剂对辐射诱导的上皮损伤的直接影响。结果gt治疗逆转了辐射引起的小鼠体重下降,减轻了肠道损伤,并通过降低肠道炎症细胞浸润和细胞因子表达来抑制炎症反应。此外,GT治疗激活了NRF2并改善了肠屏障损伤。体外实验表明,在辐照条件下,GT处理影响了Caco-2单层细胞的上皮通透性和细胞间连接表达。此外,在小鼠模型中,NRF2激活剂可以改善上皮细胞的通透性,提高辐照上皮细胞细胞间连接的表达,并减轻辐射诱导的肠道损伤。结论在辐射诱导的小鼠肠上皮损伤中,t通过激活nrf2介导的抗氧化活性来维持上皮的完整性。综上所述,这些结果表明GT可能是一种新的治疗放射性肠损伤的药物。
{"title":"Gintonin enhances epithelial barrier function by activating NRF2 pathway in radiation-induced intestinal injury","authors":"Hyosun Jang ,&nbsp;Hyewon Kim ,&nbsp;Su-Hyun Oh ,&nbsp;Yeonghoon Son ,&nbsp;Rami Lee ,&nbsp;Seung-Yeol Nah ,&nbsp;Hae-June Lee","doi":"10.1016/j.jgr.2025.01.003","DOIUrl":"10.1016/j.jgr.2025.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Because the intestine is a radio-sensitive organ in the body, and radiation-induced intestinal injury is a major clinical problem associated with radiotherapy or radiological accidents. Dysfunction of the epithelial barrier leads to bacterial translocation to other organs, resulting in severe inflammation. Recent findings suggest that gintonin (GT) suppresses oxidative stress and inflammation in neuroinflammatory diseases.</div></div><div><h3>Purpose</h3><div>This study objected to elucidate the mitigating effects of GT on radiation-induced intestinal injury.</div></div><div><h3>Methods</h3><div>The therapeutic effects of GT were assessed in a mouse model of radiation-induced intestinal injury using histological, immunohistochemical, and real-time PCR. Additionally, the direct effects of GT and NF-E2-related factor 2 (NRF2) activators on radiation-induced epithelial damage were assessed using Caco-2 cell monolayers.</div></div><div><h3>Results</h3><div>GT treatment reversed radiation-induced body weight loss, attenuated intestinal damage, and inhibited inflammatory response by reducing inflammatory cell infiltration and cytokine expression in the intestines of mice. Additionally, GT treatment activated NRF2 and ameliorated intestinal barrier damage. In vitro experiments showed that GT treatment affected epithelial permeability and intercellular junction expression in Caco-2 cell monolayers under irradiated conditions. Moreover, treatment with NRF2 activator improved epithelial permeability, improved the expression of intercellular junctions in irradiated epithelial cells, and attenuated radiation-induced intestinal injury in a mouse model.</div></div><div><h3>Conclusion</h3><div>GT maintains epithelial integrity by activating NRF2-mediated antioxidant activity in radiation-induced intestinal epithelial damage of mice. Overall, these results suggest that GT could be a novel therapeutic agent for radiation-induced intestinal damage.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 3","pages":"Pages 248-259"},"PeriodicalIF":6.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870507","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 molecular mechanism of ginsenoside Rh2 and its octyl ester derivative on anti-angiogenesis in cancer treatment: The battle between PI3K and ROS 人参皂苷Rh2及其辛酯衍生物在癌症治疗中抗血管生成的分子机制:PI3K和ROS之间的斗争
IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-11 DOI: 10.1016/j.jgr.2025.01.002
Qi-Rui Hu , Xin-Yi Zhong , Hua Feng , Xu-Chu Li , Zhi-Hong Zhang , Yao Pan , Ting Luo , Ze-Yuan Deng , Fang Chen

Background

The cancer treatments that target tumor associated angiogenesis (TAA) induced by vascular endothelial growth factor A (VEGFA) have become valued. Ginsenoside Rh2 has been proved to inhibit TAA through VEGFA. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited better inhibitory effects than Rh2 on liver cancer in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on TAA.

Purpose

To explore the inhibitory effects of Rh2 and Rh2-O on TAA and to investigate the underlying mechanisms.

Method

The inhibitory effects of Rh2 and Rh2-O on TAA were evaluated by conditioned medium, co-culture, and tumor-bearing mice. The network pharmacology was used to explore the possible targets, which were subsequently verified by specific agonists or inhibitors.

Results

Rh2 and Rh2-O could efficiently inhibit TAA in a dose-dependent manner (P < 0.05). Moreover, the enhancement on phosphorylation of PI3K and STAT3 could reverse the inhibitory effects of Rh2 and Rh2-O on TAA while N-acetylcysteine could improve the effects (P < 0.05).

Conclusion

Rh2 and Rh2-O could inhibit TAA via inhibiting the VEGFA, which was mediated by PI3K/STAT3 and PI3K/HIF-1α pathway. Meanwhile the generation of ROS could be a foe for Rh2 and Rh2-O to inhibit TAA.
背景以血管内皮生长因子A (VEGFA)诱导的肿瘤相关血管生成(TAA)为靶点的肿瘤治疗越来越受到重视。人参皂苷Rh2已被证明通过VEGFA抑制TAA。然而,潜在的机制仍不清楚。此外,在我们前期的研究中,Rh2的辛酯衍生物(Rh2- o)对肝癌的抑制作用优于Rh2,这表明Rh2- o也可能对TAA有抑制作用。目的探讨Rh2和Rh2- o对TAA的抑制作用及其机制。方法通过条件培养基、共培养和荷瘤小鼠实验,评价Rh2和Rh2- o对TAA的抑制作用。网络药理学用于探索可能的靶点,随后由特异性激动剂或抑制剂验证。结果rh2和Rh2-O能有效抑制TAA,且呈剂量依赖性(P <;0.05)。此外,增强PI3K和STAT3的磷酸化可以逆转Rh2和Rh2- o对TAA的抑制作用,而n -乙酰半胱氨酸可以改善这种抑制作用(P <;0.05)。结论rh2和Rh2-O通过PI3K/STAT3和PI3K/HIF-1α途径抑制VEGFA抑制TAA。同时,ROS的生成可能是Rh2和Rh2- o抑制TAA的敌人。
{"title":"The molecular mechanism of ginsenoside Rh2 and its octyl ester derivative on anti-angiogenesis in cancer treatment: The battle between PI3K and ROS","authors":"Qi-Rui Hu ,&nbsp;Xin-Yi Zhong ,&nbsp;Hua Feng ,&nbsp;Xu-Chu Li ,&nbsp;Zhi-Hong Zhang ,&nbsp;Yao Pan ,&nbsp;Ting Luo ,&nbsp;Ze-Yuan Deng ,&nbsp;Fang Chen","doi":"10.1016/j.jgr.2025.01.002","DOIUrl":"10.1016/j.jgr.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>The cancer treatments that target tumor associated angiogenesis (TAA) induced by vascular endothelial growth factor A (VEGFA) have become valued. Ginsenoside Rh2 has been proved to inhibit TAA through VEGFA. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited better inhibitory effects than Rh2 on liver cancer in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on TAA.</div></div><div><h3>Purpose</h3><div>To explore the inhibitory effects of Rh2 and Rh2-O on TAA and to investigate the underlying mechanisms.</div></div><div><h3>Method</h3><div>The inhibitory effects of Rh2 and Rh2-O on TAA were evaluated by conditioned medium, co-culture, and tumor-bearing mice. The network pharmacology was used to explore the possible targets, which were subsequently verified by specific agonists or inhibitors.</div></div><div><h3>Results</h3><div>Rh2 and Rh2-O could efficiently inhibit TAA in a dose-dependent manner (<em>P</em> &lt; 0.05). Moreover, the enhancement on phosphorylation of PI3K and STAT3 could reverse the inhibitory effects of Rh2 and Rh2-O on TAA while N-acetylcysteine could improve the effects (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Rh2 and Rh2-O could inhibit TAA via inhibiting the VEGFA, which was mediated by PI3K/STAT3 and PI3K/HIF-1α pathway. Meanwhile the generation of ROS could be a foe for Rh2 and Rh2-O to inhibit TAA.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 2","pages":"Pages 208-222"},"PeriodicalIF":6.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445790","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
期刊
Journal of Ginseng Research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1