Journal of Ginseng Research最新文献_第10页

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

Journal of Ginseng Research

Pub Date : 2025-05-01 Epub 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。

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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

Journal of Ginseng Research

Pub Date : 2025-05-01 Epub 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。

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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

Journal of Ginseng Research

Pub Date : 2025-05-01 Epub 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。

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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

Journal of Ginseng Research

Pub Date : 2025-05-01 Epub 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。

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引用次数: 0

Antiviral potential of ginseng: Targeting human pathogenic viruses with compounds derived from ginseng 人参的抗病毒潜力：用人参提取的化合物靶向人类病原病毒

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub Date: 2024-12-10 DOI: 10.1016/j.jgr.2024.12.004

Chen Huo , Jihye Baek , Ki Hyun Kim

The COVID-19 pandemic has highlighted the critical need for effective antiviral therapies, as viral infections remain a leading cause of mortality worldwide. Natural compounds, especially those derived from plants, have been recognized for their therapeutic properties. Ginseng, in particular, has attracted considerable attention for its potential antiviral effects. This review examines the antiviral compounds from ginseng that act against various human pathogenic viruses. We systematically summarize the antiviral activities of ginseng compounds targeting a range of viruses, including human rhinovirus (HRV), influenza virus, human immunodeficiency virus (HIV), hepatitis viruses A, B, and C (HAV, HBV, HCV), herpes simplex virus (HSV), enterovirus 71 (EV71), coxsackievirus, norovirus, and SARS-CoV-2, the virus responsible for COVID-19. This review covers Panax ginseng, P. notoginseng, and P. quinquefolius, discussing their mechanisms of action and therapeutic potential. The analysis incorporates literature from February 2002 through August 2024, providing a comprehensive overview of the existing evidence on the antiviral properties of compounds derived from ginseng. This review aims to underscore the scientific basis for developing ginseng as an antiviral therapeutic agent or nutraceutical.

COVID-19大流行凸显了对有效抗病毒治疗的迫切需要，因为病毒感染仍然是全球死亡的主要原因。天然化合物，特别是从植物中提取的化合物，已被公认具有治疗作用。特别是人参，因其潜在的抗病毒作用而引起了相当大的关注。本文综述了人参中抗多种人类病原病毒的抗病毒化合物。我们系统地总结了人参化合物对一系列病毒的抗病毒活性，包括人类鼻病毒（HRV）、流感病毒、人类免疫缺陷病毒（HIV）、肝炎病毒a、B和C （HAV、HBV、HCV）、单纯疱疹病毒（HSV）、肠病毒71 （EV71）、柯萨奇病毒、诺如病毒和导致COVID-19的SARS-CoV-2。本文综述了人参、三七和西洋参的作用机制和治疗潜力。该分析纳入了2002年2月至2024年8月的文献，全面概述了人参中提取的化合物的抗病毒特性的现有证据。本文综述了人参作为抗病毒药物或营养品开发的科学依据。

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引用次数: 0

Korean Red Ginseng relieves the inflammation and oxidative stress induced by pseudo-typed SARS-CoV-2 高丽红参对假型SARS-CoV-2诱导的炎症和氧化应激有缓解作用

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub Date: 2024-11-23 DOI: 10.1016/j.jgr.2024.11.004

Hyeon Jin Kim , Yena Oh , Sohee Moon , Jieun Oh , Ji Hye Kim , Seung Ho Lee , Sun Hee Hyun , Ji Hye Park , Hun-kun Ko , Jaehyeon Hwang , Han Gyung Kim , Dae-Hyuk Kweon , Jae Youl Cho

Background

Developing antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global goal since the Coronavirus Disease 2019 (COVID-19) pandemic emerged in 2019. Korean Red Ginseng (KRG), recognized for its immunomodulating and antiviral properties, may be effective against SARS-CoV-2. Therefore, we aimed to investigate the efficiency of KRG in a human angiotensin-converting enzyme 2 (hACE2)-expressing mouse model infected with pseudo-typed SARS-CoV-2 (PSV).

Methods

The lung injury score was assessed using H&E staining, and the immune cell population shift in the lung and spleen was observed through flow cytometry. Serum IgM and IgG concentrations were quantified using enzyme-linked immunoassay (ELISA). Pro-inflammatory cytokine levels were measured by cytometric bead assay (CBA) and polymerase chain reaction (PCR). Additionally, the expression of NLR family pyrin domain containing 3 (NLRP3) and inflammation-related transcription factors was detected by immunoblotting. RNA-sequencing and antibody array assays reconfirmed gene expression in inflammation and oxidation.

Results

KRG extract was most effective in treating lung injuries and serum IgM and IgG levels. Also, immune cells, including neutrophils, were regulated in the lungs, and tumor necrosis factor-alpha (TNF-a) levels were reduced. NLRP3 and phosphorylated nuclear factor-κB (NF-kB) and activator protein 1 (AP-1) were downregulated. Heme oxygenase-1 (HO-1) expression was increased, indicating that KRG extract has antioxidant properties. RNA-sequencing and antibody array assays revealed that KRG extract regulates the expression of genes associated with inflammation and oxidative damage.

Conclusions

This study demonstrates that KRG extract may suppress PSV-induced inflammation and oxidative stress, making it a viable antiviral functional food.

自2019年冠状病毒病（COVID-19）大流行出现以来，开发针对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的抗病毒药物一直是全球目标。韩国红参（KRG）具有免疫调节和抗病毒特性，可能对SARS-CoV-2有效。因此，我们旨在研究KRG在表达人血管紧张素转换酶2 （hACE2）的小鼠感染伪型SARS-CoV-2 （PSV）模型中的效率。方法采用H&；E染色法评价大鼠肺损伤评分，流式细胞术观察肺、脾免疫细胞群变化。采用酶联免疫分析法（ELISA）测定血清IgM和IgG浓度。采用细胞计数法（CBA）和聚合酶链反应（PCR）检测促炎细胞因子水平。免疫印迹法检测NLR家族pyrin domain containing 3 （NLRP3）及炎症相关转录因子的表达。rna测序和抗体阵列分析再次证实了基因在炎症和氧化中的表达。结果丹参提取物对肺损伤及血清IgM、IgG水平均有较好的治疗效果。此外，包括中性粒细胞在内的免疫细胞在肺部受到调节，肿瘤坏死因子- α (TNF-a)水平降低。NLRP3、磷酸化核因子-κB （NF-kB）和激活蛋白1 （AP-1）下调。血红素加氧酶-1 （HO-1）表达升高，表明KRG提取物具有抗氧化作用。rna测序和抗体阵列分析显示，KRG提取物调节炎症和氧化损伤相关基因的表达。结论KRG提取物具有抑制psv诱导的炎症和氧化应激的作用，是一种有效的抗病毒功能食品。

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引用次数: 0

Korean Red Ginseng-induced astrocytic HIF-1α: A key regulator of neuroglobin derived from neural stem cell differentiation in physiologic retina and brain 红参诱导的星形细胞HIF-1α：生理性视网膜和脑神经干细胞分化神经红蛋白的关键调节因子

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub Date: 2024-12-31 DOI: 10.1016/j.jgr.2024.12.008

Sunhong Moon , Jinseo Park , Sueun Kim , Minsu Kim , Hui Su Jeon , Hyungsu Kim , Young-Myeong Kim , Ji-Yoon Kim , Yoon Kyung Choi

Background

Neuroglobin (Ngb) and growth-associated protein (GAP) 43 in neurons are associated with axonal regeneration. Korean Red Ginseng Extract (KRGE) enhances glial fibrillary acidic protein (GFAP)-positive astrocytes and hypoxia-inducible factor-1α (HIF-1α) protein activation in normoxic astrocytes. However, crosstalk between neural stem cell (NSC) differentiation and astrocytic HIF-1α in the KRGE-treated normoxic brain and retina remains unclear. We investigated whether KRGE-treated astrocytic HIF-1α can enhance NSC differentiation and increase the mature neurons expressing Ngb and GAP43.

Methods

Mature neuronal markers such as neuronal nuclei (NeuN) or microtubule-associated protein 2 (MAP2) were tested with Ngb in the mouse brain or retinal tissues post-KRGE administration. Direct KRGE treatment of NSCs or astrocytes was evaluated for Ngb levels. The KRGE-treated astrocyte conditioned media (ACM) were transferred to NSCs and HIF-1α levels were reduced using small interfering RNA transfection (si-HIF-1α) in astrocytes. si-HIF-1α-ACM with KRGE was tested for NSC differentiation.

Results

KRGE-administered mice showed significantly enhanced co-expression of Ngb with NeuN in the brain and MAP2 in the retina, along with the NSC marker Nestin, than water-administered mice. The KRGE treatment did not increase Ngb levels in NSCs, but stimulated astrocytes to secrete factors affecting NSCs’ differentiate into mature neurons and astrocytes. The KRGE-treated mouse retinas showed GFAP- and HIF-1α double-positive cells. Co-treatment with si-HIF-1α-transfected KRGE–ACM blocked KRGE–ACM-induced NSC differentiation into astrocytes or Ngb-expressing neurons.

Conclusion

KRGE stimulates astrocytic HIF-1α, which regulates NSC differentiation into mature neurons expressing Ngb, thereby promoting regeneration by enhancing NSC–astrocyte crosstalk in the physiological retina and brain.

神经元中的神经球蛋白（Ngb）和生长相关蛋白（GAP） 43与轴突再生有关。高丽红参提取物（KRGE）增强胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞和缺氧诱导因子-1α (HIF-1α)蛋白的活性。然而，krge处理的正常大脑和视网膜中，神经干细胞（NSC）分化和星形细胞HIF-1α之间的串扰尚不清楚。我们研究了krge处理的星形细胞HIF-1α是否能促进NSC分化，增加Ngb和GAP43的成熟神经元表达。方法用Ngb检测krge给药后小鼠脑或视网膜组织中神经元核（NeuN）或微管相关蛋白2 （MAP2）等成熟神经元标志物。评价KRGE直接治疗NSCs或星形胶质细胞的Ngb水平。将krge处理的星形胶质细胞条件培养基（ACM）转移到NSCs中，通过小干扰RNA转染（si-HIF-1α）降低星形胶质细胞中的HIF-1α水平。si-HIF-1α-ACM结合KRGE进行NSC分化试验。结果与水给药小鼠相比，skrge给药小鼠脑内Ngb与NeuN、视网膜内MAP2及NSC标记物Nestin的共表达显著增强。KRGE处理并未增加Ngb水平，但刺激星形胶质细胞分泌影响NSCs向成熟神经元和星形胶质细胞分化的因子。krge处理的小鼠视网膜显示GFAP-和HIF-1α双阳性细胞。与si- hif -1α-转染的KRGE-ACM共处理可阻断KRGE-ACM诱导的NSC向星形胶质细胞或表达ngb的神经元的分化。结论krge刺激星形胶质细胞HIF-1α，调节NSC向表达Ngb的成熟神经元分化，从而通过增强生理视网膜和脑内NSC -星形胶质细胞串音促进再生。

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引用次数: 0

Ginsenoside Rg1 exerts antidepressant effect by regulating hepatic kynurenine metabolism through promoting the interaction between HNF4α and PGC1α 人参皂苷Rg1通过促进HNF4α和PGC1α的相互作用，调节肝脏犬尿氨酸代谢，发挥抗抑郁作用

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub Date: 2024-12-04 DOI: 10.1016/j.jgr.2024.12.002

Keke Jia , Shuman Pan , Wenyuan Wu , Yiming Sun , Qingyu Zhang

Background

The neuroprotective effect of ginsenoside Rg1 is indeed one of the current research hotspots. However, its limited ability to cross the blood-brain barrier results in low distribution within the brain. Thus, the mechanism through which ginsenoside Rg1 affects the central nervous system needs further examination.

Methods

The LC-MS/MS analysis was used to detect the Kyn level. The expression of kynurenine aminotransferase 2 (KAT2) and kynurenine 3-monooxygenase (KMO) were investigated by qRT-PCR and western blotting analysis. The interaction between the transcription factor hepatocyte nuclear factor-4α (HNF4α) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) was explored by Co-IP assay. The HNF4α binding sites in the KAT2 and KMO genes were analyzed by ChIP. In addition, we specifically knocked down HNF4α in the liver of mice by injecting adeno-associated virus into the tail vein.

Results

Ginsenoside Rg1 upregulated the expression of KAT2 and KMO, thereby increasing the metabolism of Kyn in the liver. Further exploring its mechanism, we discovered that ginsenoside Rg1 increased the expression of KAT2 and KMO by promoting the interaction between the transcription factor HNF4α and PGC1α. Hepatic HNF4α knockdown abolished the antidepressant effects induced by ginsenoside Rg1.

Conclusion

Our findings reveal a novel mechanism in which ginsenoside Rg1 upregulates KAT2 and KMO through the HNF4α/PGC1α pathway, reducing hepatic Kyn levels and subsequently alleviating depression.

人参皂苷Rg1的神经保护作用确实是当前研究的热点之一。然而，它穿过血脑屏障的能力有限，导致其在大脑内的分布很低。因此，人参皂苷Rg1影响中枢神经系统的机制有待进一步研究。方法采用LC-MS/MS法检测Kyn含量。采用qRT-PCR和western blotting检测犬尿氨酸转氨酶2 （KAT2）和犬尿氨酸3-单加氧酶（KMO）的表达。采用Co-IP法探讨转录因子肝细胞核因子-4α (HNF4α)与过氧化物酶体增殖物激活受体-γ共激活因子-1α (PGC1α)之间的相互作用。用ChIP分析KAT2和KMO基因中的HNF4α结合位点。此外，我们通过向小鼠尾静脉注射腺相关病毒特异性地敲除了小鼠肝脏中的HNF4α。结果人参皂苷Rg1上调KAT2和KMO的表达，从而增加肝脏中Kyn的代谢。进一步探索其作用机制，我们发现人参皂苷Rg1通过促进转录因子HNF4α和PGC1α的相互作用而增加KAT2和KMO的表达。肝脏HNF4α敲低可消除人参皂苷Rg1诱导的抗抑郁作用。结论人参皂苷Rg1通过HNF4α/PGC1α通路上调KAT2和KMO，从而降低肝脏Kyn水平，从而缓解抑郁的新机制。

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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

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub 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 , Xin-Yi Zhong , Hua Feng , Xu-Chu Li , Zhi-Hong Zhang , Yao Pan , Ting Luo , Ze-Yuan Deng , 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> < 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> < 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":"2025-03-01","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

Rare ginsenosides transformed from stems and leaves of Panax ginseng reverse obesity by promoting browning of white fat through PKA/CREB pathway via REGγ negative regulation 人参茎叶转化的稀有人参皂苷通过REGγ负调控PKA/CREB通路促进白色脂肪褐化，从而逆转肥胖

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research

Pub Date : 2025-03-01 Epub Date: 2024-11-28 DOI: 10.1016/j.jgr.2024.11.005

Jianbo Chen, Jiyue Sha, Xiaohui Huo, Zhiman Li, Di Qu, Xueqing Li, Meijia Li

Background

White adipose tissue (WAT) browning can promote thermogenesis and could be a promising target for treating obesity. Rare ginsenosides transformed from stems and leaves of Panax ginseng (T-GSSL) exhibit numerous biological activities. However, its potential anti-obesity effects and underlying mechanism remain largely unknown.

Methods

Five amino acids were selected as the catalysts for the transformation of ginsenosides into rare ginsenosides. An obese mouse model was established by feeding mice a high-fat diet (HFD) for 14 weeks. The effects of T-GSSL on obese mice were assessed by measuring body weight, fat mass, energy expenditure (EE), and glucose tolerance. The 3T3-L1 cells were differentiated into mature adipocytes and incubated with T-GSSL. Immunohistochemistry, co-immunoprecipitation (Co-IP), enzyme-linked immunosorbent assays (ELISA), western blotting (WB), real-time polymerase chain reaction (PCR), and other methods were used to investigate the targets and mechanisms of action of T-GSSL.

Results

Ginsenosides in GSSL were hydrolyzed using glutamic acid as a catalyst and 12 rare ginsenosides were produced, with a total conversion rate of 95 %. T-GSSL ameliorated metabolic disorders, lipid ectopic deposition, and obesity, and maintained glucose homeostasis in obese mice. T-GSSL treatment promoted adipose browning and enhanced EE in both HFD mice and 3T3-L1 cells. These effects were decreased in cells treated with a protein kinase A (PKA) antagonist or subjected to PKAcα knockdown, whereas they were increased in REGγ^−/− mice. The inhibition of REGγ alongside the activation of the PKA/CREB pathway elucidates the mechanism through which T-GSSL reverses obesity by promoting the browning of adipose tissue.

Conclusions

T-GSSL attenuates diet-induced obesity by promoting adipose browning through the inhibition of REGγ and subsequent activation of the PKA/CREB pathway.

白色脂肪组织（WAT）褐变可以促进产热，可能是治疗肥胖的一个有希望的靶点。从人参茎叶转化而来的稀有人参皂苷（T-GSSL）具有多种生物活性。然而，其潜在的抗肥胖作用和潜在的机制在很大程度上仍然未知。方法选择5种氨基酸作为催化人参皂苷转化为稀有人参皂苷的催化剂。采用高脂饲料（HFD）饲养14周，建立肥胖小鼠模型。通过测量体重、脂肪量、能量消耗（EE）和葡萄糖耐量来评估T-GSSL对肥胖小鼠的影响。将3T3-L1细胞分化为成熟脂肪细胞，用T-GSSL孵育。采用免疫组织化学、共免疫沉淀法（Co-IP）、酶联免疫吸附法（ELISA）、免疫印迹法（WB）、实时聚合酶链反应（PCR）等方法研究T-GSSL的作用靶点和作用机制。结果以谷氨酸为催化剂水解人参皂苷，制得12种稀有人参皂苷，总转化率达95%。T-GSSL改善了肥胖小鼠的代谢紊乱、脂质异位沉积和肥胖，并维持了葡萄糖稳态。T-GSSL处理促进HFD小鼠和3T3-L1细胞的脂肪褐变和EE增强。在蛋白激酶a （PKA）拮抗剂处理或PKAcα敲低的细胞中，这些作用减弱，而在REGγ−/−小鼠中则增加。REGγ的抑制和PKA/CREB通路的激活阐明了T-GSSL通过促进脂肪组织褐变逆转肥胖的机制。结论st - gssl通过抑制REGγ和随后激活PKA/CREB通路来促进脂肪褐变，从而减轻饮食诱导的肥胖。

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引用次数: 0