Pub Date : 2026-03-01Epub Date: 2025-12-13DOI: 10.1016/j.jgr.2025.12.004
XueYing Wang , Yi Yang , TianYu Zheng , ChengZhi Wang , SiYu Qu , HongMei Luo , Chi Xu , YanLing Li
Background
Menopause involves both physical and psychological changes, notably vasomotor and mood symptoms. Menopausal symptoms adversely affect women's quality of life and work. This study evaluates the effects of red ginseng beverage (RGB) on menopausal symptoms in Chinese women.
Methods
This 90-day, randomized, double-blind, placebo-controlled trial involved 112 eligible women assigned to either an RGB or placebo group. Primary outcomes were the Kupperman Index. Secondary outcomes included vasomotor markers, psychological assessments, lipid profiles, exercise-induced fatigue test indicators and safety indicators. Safety assessments included fire-heat symptom scale, female hormone levels, endometrial thickness, breast ultrasound, and standard laboratory tests. All outcomes were assessed at baseline and upon study completion.
Results
RGB group primary outcomes compared to placebo: (1) the Kupperman Index (KI) scores were significantly improved after test (p < 0.001), (2) the levels of serum nitric oxide (NO) increased significantly (p < 0.01), the content of and endothelin-1 (ET-1) decreased significantly (p < 0.01); the results of the secondary outcomes in RGB group: (1) Beck Depression Inventory (BDI) and Athens Insomnia Scale (AIS) scores decreased significantly (p < 0.001), (2) Total cholesterol and low-density lipoprotein cholesterol decreased significantly (p < 0.05), (3) Creatine kinase and blood lactate decreased significantly (p < 0.05), subjective physical strength rating scale scores decreased significantly (p < 0.01). No intergroup differences were observed in hormonal levels, endometrial thickness, urinalysis, hematology, or biochemistry. RGB administration showed no significant effect on fire-heat symptom scores.
Conclusion
These findings demonstrate RGB's efficacy and safety for menopausal symptom management.
{"title":"Effect of red ginseng beverage on menopausal symptoms in Chinese women: A randomized, double-blind, placebo-controlled clinical trial","authors":"XueYing Wang , Yi Yang , TianYu Zheng , ChengZhi Wang , SiYu Qu , HongMei Luo , Chi Xu , YanLing Li","doi":"10.1016/j.jgr.2025.12.004","DOIUrl":"10.1016/j.jgr.2025.12.004","url":null,"abstract":"<div><h3>Background</h3><div>Menopause involves both physical and psychological changes, notably vasomotor and mood symptoms. Menopausal symptoms adversely affect women's quality of life and work. This study evaluates the effects of red ginseng beverage (RGB) on menopausal symptoms in Chinese women.</div></div><div><h3>Methods</h3><div>This 90-day, randomized, double-blind, placebo-controlled trial involved 112 eligible women assigned to either an RGB or placebo group. Primary outcomes were the Kupperman Index. Secondary outcomes included vasomotor markers, psychological assessments, lipid profiles, exercise-induced fatigue test indicators and safety indicators. Safety assessments included fire-heat symptom scale, female hormone levels, endometrial thickness, breast ultrasound, and standard laboratory tests. All outcomes were assessed at baseline and upon study completion.</div></div><div><h3>Results</h3><div>RGB group primary outcomes compared to placebo: (1) the <em>Kupperman Index</em> (KI) scores were significantly improved after test (<em>p</em> < 0.001), (2) the levels of serum nitric oxide (NO) increased significantly (<em>p</em> < 0.01), the content of and endothelin-1 (ET-1) decreased significantly (<em>p</em> < 0.01); the results of the secondary outcomes in RGB group: (1) <em>Beck Depression Inventory</em> (BDI) and <em>Athens Insomnia Scale</em> (AIS) scores decreased significantly (<em>p</em> < 0.001), (2) Total cholesterol and low-density lipoprotein cholesterol decreased significantly (<em>p</em> < 0.05), (3) Creatine kinase and blood lactate decreased significantly (<em>p</em> < 0.05), subjective physical strength rating scale scores decreased significantly (<em>p</em> < 0.01). No intergroup differences were observed in hormonal levels, endometrial thickness, urinalysis, hematology, or biochemistry. RGB administration showed no significant effect on <em>fire-heat symptom scores</em>.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate RGB's efficacy and safety for menopausal symptom management.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 2","pages":"Article 100931"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365456","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}
Pub Date : 2026-03-01Epub Date: 2025-12-04DOI: 10.1016/j.jgr.2025.11.012
Zhihui Wang , Junyu Mou , Wen Han , Siyuan Liu , Min Wang , Guibo Sun
Background
Atherosclerosis (AS) is a major cause of severe cardiovascular disease and stroke. Ginsenoside Re (Re) has been shown to significantly alleviate AS in mice. Our study demonstrates for the first time that Re can reduce endothelial cell (EC) glycolysis, although the specific mechanism remains unclear.
Methods
The effects of Re on lipid levels, aortic wall thickness, inflammation, and aortic fibrosis in AS mice were assessed by measuring serum lipids, carotid artery intima-media thickness, Hematoxylin-Eosin, Masson, and Oil Red O staining, and enzyme-linked immunosorbent assay. The effects of Re on EC proliferation and migration were examined using CCK-8 and wound healing assays in a human umbilical vein endothelial cell model stimulated with oxidized low-density lipoprotein. Furthermore, immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to investigate the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways in vivo and in vitro.
Results
Re demonstrated strong anti-AS activity, evidenced by improved blood lipid profiles, reduced inflammatory factors, and decreased levels of glycolysis-related products and enzymes. In vivo, Re protected against AS by inhibiting glycolysis. In vitro, Re suppressed EC migration through inhibition of the glycolysis-related PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways.
Conclusion
Re may benefit AS mice by inhibiting EC glycolysis and migration through suppression of the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways. This work broadens the theoretical basis for the therapeutic use of Re in AS.
{"title":"Ginsenoside Re regulates PFKFB3-mediated glycolysis to inhibit endothelial cell migration to ameliorate atherosclerosis","authors":"Zhihui Wang , Junyu Mou , Wen Han , Siyuan Liu , Min Wang , Guibo Sun","doi":"10.1016/j.jgr.2025.11.012","DOIUrl":"10.1016/j.jgr.2025.11.012","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a major cause of severe cardiovascular disease and stroke. Ginsenoside Re (Re) has been shown to significantly alleviate AS in mice. Our study demonstrates for the first time that Re can reduce endothelial cell (EC) glycolysis, although the specific mechanism remains unclear.</div></div><div><h3>Methods</h3><div>The effects of Re on lipid levels, aortic wall thickness, inflammation, and aortic fibrosis in AS mice were assessed by measuring serum lipids, carotid artery intima-media thickness, Hematoxylin-Eosin, Masson, and Oil Red O staining, and enzyme-linked immunosorbent assay. The effects of Re on EC proliferation and migration were examined using CCK-8 and wound healing assays in a human umbilical vein endothelial cell model stimulated with oxidized low-density lipoprotein. Furthermore, immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to investigate the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways in vivo and in vitro.</div></div><div><h3>Results</h3><div>Re demonstrated strong anti-AS activity, evidenced by improved blood lipid profiles, reduced inflammatory factors, and decreased levels of glycolysis-related products and enzymes. In vivo, Re protected against AS by inhibiting glycolysis. In vitro, Re suppressed EC migration through inhibition of the glycolysis-related PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways.</div></div><div><h3>Conclusion</h3><div>Re may benefit AS mice by inhibiting EC glycolysis and migration through suppression of the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways. This work broadens the theoretical basis for the therapeutic use of Re in AS.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 2","pages":"Article 100924"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365476","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}
Pub Date : 2026-03-01Epub Date: 2025-06-05DOI: 10.1016/j.jgr.2025.05.006
Kai Tang , Congcong Huang , Zhengjie Huang, Zhilei Lin, Zhen Wang, Ninghua Tan
Background
Injury of retinal ganglion cells (RGCs) is one of the earliest signs of diabetic retinopathy (DR), preceding retinal microvascular abnormalities. Driven by metabolic and biochemical cascades, diabetes-dependent senescence in the retinal neural cells is responsible for neurodegeneration and subsequent permanent visual loss. This study investigated the involvement of ginsenoside Rg1 (Rg1) in neuropathy associated with DR to identify a possible therapeutic target.
Methods
The anti-aging and synaptogenesis effects, and neuroprotective mechanism of Rg1 were investigated in high glucose-induced RGCs and STZ-induced DR mice.
Results
Rg1 effectively reduced the β-galactosidase activity, promoted the neurite outgrowth, and reversed the expression of senescence and synaptic development-related proteins. Mechanistically, the compromised mitochondrial biogenesis induced by hyperglycaemia manifested as a critical driver of functional and structural impairments in RGCs. Meanwhile, Rg1 interacts with VDR to potentiate transcription of PGC-1α via the VDR/cAMP/PKA/CREB pathway. Activation of PGC-1α by Rg1 revitalized hyperglycaemia-hampered mitochondrial biogenesis, and resultantly alleviated senescence and neurite outgrowth inhibition of RGCs both in vitro and in vivo models.
Conclusion
Rg1 ameliorates neuropathy of DR by activating VDR non-genomic pathway and facilitating mitochondrial biogenesis. These results suggest a therapeutic approach for mitigating neurodegeneration in early DR, and provide insights into the potential clinical application of VDR agonism with Rg1 in regulating mitochondrial quality control.
{"title":"Ginsenoside Rg1 ameliorates the senescence and neurite injury of retinal ganglion cells in DR via targeting VDR and promoting mitochondrial biogenesis","authors":"Kai Tang , Congcong Huang , Zhengjie Huang, Zhilei Lin, Zhen Wang, Ninghua Tan","doi":"10.1016/j.jgr.2025.05.006","DOIUrl":"10.1016/j.jgr.2025.05.006","url":null,"abstract":"<div><h3>Background</h3><div>Injury of retinal ganglion cells (RGCs) is one of the earliest signs of diabetic retinopathy (DR), preceding retinal microvascular abnormalities. Driven by metabolic and biochemical cascades, diabetes-dependent senescence in the retinal neural cells is responsible for neurodegeneration and subsequent permanent visual loss. This study investigated the involvement of ginsenoside Rg1 (Rg1) in neuropathy associated with DR to identify a possible therapeutic target.</div></div><div><h3>Methods</h3><div>The anti-aging and synaptogenesis effects, and neuroprotective mechanism of Rg1 were investigated in high glucose-induced RGCs and STZ-induced DR mice.</div></div><div><h3>Results</h3><div>Rg1 effectively reduced the β-galactosidase activity, promoted the neurite outgrowth, and reversed the expression of senescence and synaptic development-related proteins. Mechanistically, the compromised mitochondrial biogenesis induced by hyperglycaemia manifested as a critical driver of functional and structural impairments in RGCs. Meanwhile, Rg1 interacts with VDR to potentiate transcription of PGC-1α via the VDR/cAMP/PKA/CREB pathway. Activation of PGC-1α by Rg1 revitalized hyperglycaemia-hampered mitochondrial biogenesis, and resultantly alleviated senescence and neurite outgrowth inhibition of RGCs both <em>in vitro</em> and <em>in vivo</em> models.</div></div><div><h3>Conclusion</h3><div>Rg1 ameliorates neuropathy of DR by activating VDR non-genomic pathway and facilitating mitochondrial biogenesis. These results suggest a therapeutic approach for mitigating neurodegeneration in early DR, and provide insights into the potential clinical application of VDR agonism with Rg1 in regulating mitochondrial quality control.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 2","pages":"Article 100878"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365485","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}
Pub Date : 2026-03-01Epub Date: 2025-10-06DOI: 10.1016/j.jgr.2025.10.001
Jun Xu , Meng Geng , Fang Tong , Yumeng Wang , Linhui Qin , Wenbo Zhao , Sijie Li , Xunming Ji , Changhong Ren
Background
Chronic cerebral hypoperfusion (CCH) is a major risk factor for vascular cognitive impairment (VCI). Angiogenesis plays a critical role in recovery from cerebrovascular disease. Panaxadiol (PD), a key active component of ginseng, exhibits neuroprotective effects; however, its role in promoting angiogenesis post-CCH remains unclear.
Methods
A bilateral common carotid artery stenosis (BCAS) model was used to investigate the effects of PD (50 mg/kg, 30 days) on cerebral blood flow (CBF), cognitive function, and angiogenesis in mice. Cognitive tests included the Morris water maze (MWM), novel object recognition (NOR), and Y-maze. Vascular changes were assessed using laser speckle imaging and immunofluorescence. The effects of PD on endothelial cell (EC) functions were evaluated in vitro using bEnd.3 cells. Potential mechanisms were examined through protein chip analysis, protein-protein interaction (PPI) network analysis, molecular docking techniques, and in vitro experimental validation.
Results
PD increased CBF and alleviated cognitive impairment in BCAS mice. It enhanced neovascularization in the hippocampus and promoted ECs proliferation, migration, and tube formation in vitro. Mechanistically, PD activated the vascular endothelial growth factor A (VEGF-A)/p38 mitogen-activated protein kinase (p38 MAPK) pathway while inhibited steroid receptor coactivator (Src) phosphorylation.
Conclusion
PD ameliorates BCAS-induced cognitive deficits by promoting angiogenesis through the VEGF-A/p38 MAPK/Src signaling pathway, highlighting its potential as a therapeutic agent for CCH and VCI.
{"title":"Panaxadiol promotes angiogenesis against chronic cerebral hypoperfusion injury through the VEGF-A/p38 MAPK/Src signaling pathway","authors":"Jun Xu , Meng Geng , Fang Tong , Yumeng Wang , Linhui Qin , Wenbo Zhao , Sijie Li , Xunming Ji , Changhong Ren","doi":"10.1016/j.jgr.2025.10.001","DOIUrl":"10.1016/j.jgr.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Chronic cerebral hypoperfusion (CCH) is a major risk factor for vascular cognitive impairment (VCI). Angiogenesis plays a critical role in recovery from cerebrovascular disease. Panaxadiol (PD), a key active component of ginseng, exhibits neuroprotective effects; however, its role in promoting angiogenesis post-CCH remains unclear.</div></div><div><h3>Methods</h3><div>A bilateral common carotid artery stenosis (BCAS) model was used to investigate the effects of PD (50 mg/kg, 30 days) on cerebral blood flow (CBF), cognitive function, and angiogenesis in mice. Cognitive tests included the Morris water maze (MWM), novel object recognition (NOR), and Y-maze. Vascular changes were assessed using laser speckle imaging and immunofluorescence. The effects of PD on endothelial cell (EC) functions were evaluated <em>in vitro</em> using bEnd.3 cells. Potential mechanisms were examined through protein chip analysis, protein-protein interaction (PPI) network analysis, molecular docking techniques, and <em>in vitro</em> experimental validation.</div></div><div><h3>Results</h3><div>PD increased CBF and alleviated cognitive impairment in BCAS mice. It enhanced neovascularization in the hippocampus and promoted ECs proliferation, migration, and tube formation <em>in vitro</em>. Mechanistically, PD activated the vascular endothelial growth factor A (VEGF-A)/p38 mitogen-activated protein kinase (p38 MAPK) pathway while inhibited steroid receptor coactivator (Src) phosphorylation.</div></div><div><h3>Conclusion</h3><div>PD ameliorates BCAS-induced cognitive deficits by promoting angiogenesis through the VEGF-A/p38 MAPK/Src signaling pathway, highlighting its potential as a therapeutic agent for CCH and VCI.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 2","pages":"Article 100904"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365548","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}
Pub Date : 2026-01-01Epub Date: 2025-10-09DOI: 10.1016/j.jgr.2025.10.002
Rahmi Lee , McKennon J. Wiles , Ellison R. Black , Seung Hyun Roh , Evelina Bouckova , Madison H. Wustrau , Joshua C. Flowers , Paige E. Vetter , Jaehoon Lee , Byung-Cheol Han , Seonil Kim
Background
Stress affects brain functions, which leads to the development of mental disorders. There is increasing focus on the role of nutritional, herbal and nutraceutical compounds on mental and cognitive functioning. Interestingly, studies suggest that American ginseng (Panax quinquefolius L.) extracts (G1899) improve cognition.
Methods
We examined whether G1899 showed protective effects on stress-induced behavioral changes in animals. 200 mg/kg G1899 was orally administered daily for 4 weeks to 2-3-month-old female and male mice before inducing stress. To induce acute stress in animals, we intraperitoneally injected a low dose of lipopolysaccharides (LPS) (10 μg/kg), and saline was used as a control. We also used chronic restraint stress (CRS) as a chronic stress model in mice. After LPS injection or CRS, multiple behavioral assays were carried out – a sucrose preference test, an open filed test, reciprocal social interaction, contextual fear conditioning, and a tail suspension test – to determine whether acute or chronic stress affected animals' behaviors and whether G1899 had protective effects against stress-induced behavioral dysfunction.
Results
We found that both LPS injection and CRS induced stress-related behavioral dysfunction, including depression-like behavior, anhedonia, social dysfunction, and fear memory impairments in mice. However, G1899 was sufficient to reverse stress-induced behavioral abnormalities in animals. Our data further suggested that G1899 reduced the activity of hippocampal neurons by suppressing glutamatergic activity.
Conclusion
G1899 supplements can be protective against both acute and chronic stress in mice by suppressing neuronal and synaptic activity.
{"title":"American ginseng (Panax quinquefolius L.) extracts (G1899) reverse stress-induced behavioral abnormalities in mice","authors":"Rahmi Lee , McKennon J. Wiles , Ellison R. Black , Seung Hyun Roh , Evelina Bouckova , Madison H. Wustrau , Joshua C. Flowers , Paige E. Vetter , Jaehoon Lee , Byung-Cheol Han , Seonil Kim","doi":"10.1016/j.jgr.2025.10.002","DOIUrl":"10.1016/j.jgr.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Stress affects brain functions, which leads to the development of mental disorders. There is increasing focus on the role of nutritional, herbal and nutraceutical compounds on mental and cognitive functioning. Interestingly, studies suggest that American ginseng (<em>Panax quinquefolius</em> L.) extracts (G1899) improve cognition.</div></div><div><h3>Methods</h3><div>We examined whether G1899 showed protective effects on stress-induced behavioral changes in animals. 200 mg/kg G1899 was orally administered daily for 4 weeks to 2-3-month-old female and male mice before inducing stress. To induce acute stress in animals, we intraperitoneally injected a low dose of lipopolysaccharides (LPS) (10 μg/kg), and saline was used as a control. We also used chronic restraint stress (CRS) as a chronic stress model in mice. After LPS injection or CRS, multiple behavioral assays were carried out – a sucrose preference test, an open filed test, reciprocal social interaction, contextual fear conditioning, and a tail suspension test – to determine whether acute or chronic stress affected animals' behaviors and whether G1899 had protective effects against stress-induced behavioral dysfunction.</div></div><div><h3>Results</h3><div>We found that both LPS injection and CRS induced stress-related behavioral dysfunction, including depression-like behavior, anhedonia, social dysfunction, and fear memory impairments in mice. However, G1899 was sufficient to reverse stress-induced behavioral abnormalities in animals. Our data further suggested that G1899 reduced the activity of hippocampal neurons by suppressing glutamatergic activity.</div></div><div><h3>Conclusion</h3><div>G1899 supplements can be protective against both acute and chronic stress in mice by suppressing neuronal and synaptic activity.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100905"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877049","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}
Pub Date : 2026-01-01Epub Date: 2025-11-28DOI: 10.1016/j.jgr.2025.11.009
Do Su Lim , Sung Ho Ahn , Wonjun Cho , Hyeon Ji Gwon , Jun Hwi Ko , Min Kyung Pyo , A.M. Abd El-Aty , Soon Auck Hong , Jong Wook Shin , Ji Hoon Jeong , Tae Woo Jung
Aim
The current study aimed to investigate the effects of the ginsenoside Rg5 (Rg5) on aging-induced apoptosis and ferroptosis in tenocytes and explore its mechanism of action.
Methods
The expression of various proteins related to this study was assessed via Western blotting. Cell viability and caspase 3 activity assays were conducted. Cellular iron content and oxidative stress markers in tenocytes were evaluated via commercial assay kits. siRNA transfection and inhibitors were used to explore the mechanism involved. In in vivo studies, H&E staining was performed to analyze the histopathology of the tendon tissue of mice.
Results
Rg5 treatment attenuated apoptosis, ferroptosis, ER stress, and oxidative stress in D-galactose-treated tenocytes. Moreover, it mitigated ECM degradation and enhanced cell migration in tenocytes in the presence of D-galactose. Rg5 treatment dose-dependently increased SIRT6 expression and the levels of autophagy markers, such as those associated with LC3 conversion and p62 degradation. siRNA-mediated suppression of SIRT6 or 3-MA, an autophagy inhibitor, reduced the effects of Rg5 on D-galactose-treated tenocytes. Rg5 administration improved tissue damage as well as ER stress and ferroptosis markers in the Achilles tendons of mouse models established by local injection of D-galactose and collagenase type I. In addition to the in vitro results, it promoted SIRT6 expression and p62 degradation in in vivo studies.
Conclusion
These results suggest that Rg5 attenuates ER stress and oxidative stress through the SIRT6/autophagy axis, thereby mitigating ferroptosis and apoptosis in aging-conditioned tenocytes. The present study sheds light on a novel therapeutic strategy for aging-mediated tendinopathy involving the use of Rg5.
{"title":"Ginsenoside Rg5 mitigates tenocyte death via SIRT6/autophagy-dependent signaling in an aging model","authors":"Do Su Lim , Sung Ho Ahn , Wonjun Cho , Hyeon Ji Gwon , Jun Hwi Ko , Min Kyung Pyo , A.M. Abd El-Aty , Soon Auck Hong , Jong Wook Shin , Ji Hoon Jeong , Tae Woo Jung","doi":"10.1016/j.jgr.2025.11.009","DOIUrl":"10.1016/j.jgr.2025.11.009","url":null,"abstract":"<div><h3>Aim</h3><div>The current study aimed to investigate the effects of the ginsenoside Rg5 (Rg5) on aging-induced apoptosis and ferroptosis in tenocytes and explore its mechanism of action.</div></div><div><h3>Methods</h3><div>The expression of various proteins related to this study was assessed <em>via</em> Western blotting. Cell viability and caspase 3 activity assays were conducted. Cellular iron content and oxidative stress markers in tenocytes were evaluated <em>via</em> commercial assay kits. siRNA transfection and inhibitors were used to explore the mechanism involved. In <em>in vivo</em> studies, H&E staining was performed to analyze the histopathology of the tendon tissue of mice.</div></div><div><h3>Results</h3><div>Rg5 treatment attenuated apoptosis, ferroptosis, ER stress, and oxidative stress in D-galactose-treated tenocytes. Moreover, it mitigated ECM degradation and enhanced cell migration in tenocytes in the presence of D-galactose. Rg5 treatment dose-dependently increased SIRT6 expression and the levels of autophagy markers, such as those associated with LC3 conversion and p62 degradation. siRNA-mediated suppression of SIRT6 or 3-MA, an autophagy inhibitor, reduced the effects of Rg5 on D-galactose-treated tenocytes. Rg5 administration improved tissue damage as well as ER stress and ferroptosis markers in the Achilles tendons of mouse models established by local injection of D-galactose and collagenase type I. In addition to the <em>in vitro</em> results, it promoted SIRT6 expression and p62 degradation in <em>in vivo</em> studies.</div></div><div><h3>Conclusion</h3><div>These results suggest that Rg5 attenuates ER stress and oxidative stress through the SIRT6/autophagy axis, thereby mitigating ferroptosis and apoptosis in aging-conditioned tenocytes. The present study sheds light on a novel therapeutic strategy for aging-mediated tendinopathy involving the use of Rg5.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100921"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877038","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}
Pub Date : 2026-01-01Epub Date: 2025-10-27DOI: 10.1016/j.jgr.2025.10.005
Chuan Li , Yuhao Zhou , Yuxi Nie , Jingran Fu , Jia Zeng , Shike Zhang , Liang Han , Zhuojia Li , Hongcan Yang , Shujue Li , Beixin Yu , Xiaoling Ying , Wenqi Wu
Background
Kidney stone disease (KSD), notably characterized by heightened oxidative stress and cell death within renal tubular epithelial cells due to high oxalate. Ginsenoside Ro (Ro), a scarce oleanane-type saponin isolated from Panax ginseng Mey. and Achyranthes bidentata Bl., has garnered attention for the anti-tumor, anti-oxidant, and anti-inflammatory properties. This study aims to investigate the protective effects and mechanisms of Ro on crystal-induced renal injury in vivo and in vitro.
Materials and methods
In vitro, we assessed renal injury, renal crystal deposition, and inflammatory infiltration in a glyoxylic acid (Gly)-induced stone formation mouse model, with administration of Ro. The protective effects of Ro on proximal tubular epithelial cell line HK-2 damaged by hyperoxaluria were assessed via MTS assay and live/dead cell staining in vivo. Additionally, we examined reactive oxygen species (ROS) levels and crystal adhesion-related proteins. Subsequently, we identified ZnT1 as the target of Ro through RNA-seq, immunohistochemical (IHC) staining, Western blotting (WB), molecular docking, molecular dynamics simulations, bio‐layer interferometry (BLI) and cellular thermal shift assay (CETSA). Further, we constructed HK-2 cells over-expressing and knocking out of ZnT1 to evaluated cellular damage and crystal adhesion effects. Finally, the role of Ro in high oxalate-induced cuproptosis in HK-2 was examined via cuproptosis-related events, including DLAT oligomerization, cuproptosis-associated proteins FDX1 and HSP70, mitochondrial ROS levels, JC-1 staining, and GSH levels.
Results
Ro effectively mitigated renal injury induced by Gly in mice. Moreover, it notably ameliorated renal crystal deposition and infiltration of F4/80-positive macrophages observed in Gly mice. Additionally, in vitro studies demonstrated that Ro alleviated oxidative damage and crystal adhesion induced by high oxalate in HK-2 cells. Mechanistically, Ro significantly suppressed ZnT1 expression, and notably, over-expression of ZnT1 reversed the inhibitory of Ro on NaOx-induced proliferation suppression, crystal adhesion, and augmented ROS generation in HK-2 cells. Additionally, NaOx elevated cuproptosis in HK-2 cells, and this elevation was blocked by ZnT1 over-expression, which in turn was reversed by TTM, a cuproptosis inhibitor.
Conclusion
This study provided evidence that Ro mitigated cuproptosis HK-2 cells induced by high oxalate through inhibiting ZnT1, thus effectively suppressing oxidative stress and crystal deposition triggered by high oxalate.
{"title":"Ginsenoside Ro alleviated cuproptosis induced by high oxalate via inhibiting zinc transporter ZnT1 in renal tubular epithelial cells","authors":"Chuan Li , Yuhao Zhou , Yuxi Nie , Jingran Fu , Jia Zeng , Shike Zhang , Liang Han , Zhuojia Li , Hongcan Yang , Shujue Li , Beixin Yu , Xiaoling Ying , Wenqi Wu","doi":"10.1016/j.jgr.2025.10.005","DOIUrl":"10.1016/j.jgr.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Kidney stone disease (KSD), notably characterized by heightened oxidative stress and cell death within renal tubular epithelial cells due to high oxalate. Ginsenoside Ro (Ro), a scarce oleanane-type saponin isolated from <em>Panax ginseng</em> Mey. and <em>Achyranthes bidentata</em> Bl., has garnered attention for the anti-tumor, anti-oxidant, and anti-inflammatory properties. This study aims to investigate the protective effects and mechanisms of Ro on crystal-induced renal injury <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Materials and methods</h3><div><em>In vitro</em>, we assessed renal injury, renal crystal deposition, and inflammatory infiltration in a glyoxylic acid (Gly)-induced stone formation mouse model, with administration of Ro. The protective effects of Ro on proximal tubular epithelial cell line HK-2 damaged by hyperoxaluria were assessed via MTS assay and live/dead cell staining <em>in vivo</em>. Additionally, we examined reactive oxygen species (ROS) levels and crystal adhesion-related proteins. Subsequently, we identified ZnT1 as the target of Ro through RNA-seq, immunohistochemical (IHC) staining, Western blotting (WB), molecular docking, molecular dynamics simulations, bio‐layer interferometry (BLI) and cellular thermal shift assay (CETSA). Further, we constructed HK-2 cells over-expressing and knocking out of ZnT1 to evaluated cellular damage and crystal adhesion effects. Finally, the role of Ro in high oxalate-induced cuproptosis in HK-2 was examined via cuproptosis-related events, including DLAT oligomerization, cuproptosis-associated proteins FDX1 and HSP70, mitochondrial ROS levels, JC-1 staining, and GSH levels.</div></div><div><h3>Results</h3><div>Ro effectively mitigated renal injury induced by Gly in mice. Moreover, it notably ameliorated renal crystal deposition and infiltration of F4/80-positive macrophages observed in Gly mice. Additionally, <em>in vitro</em> studies demonstrated that Ro alleviated oxidative damage and crystal adhesion induced by high oxalate in HK-2 cells. Mechanistically, Ro significantly suppressed ZnT1 expression, and notably, over-expression of ZnT1 reversed the inhibitory of Ro on NaOx-induced proliferation suppression, crystal adhesion, and augmented ROS generation in HK-2 cells. Additionally, NaOx elevated cuproptosis in HK-2 cells, and this elevation was blocked by ZnT1 over-expression, which in turn was reversed by TTM, a cuproptosis inhibitor.</div></div><div><h3>Conclusion</h3><div>This study provided evidence that Ro mitigated cuproptosis HK-2 cells induced by high oxalate through inhibiting ZnT1, thus effectively suppressing oxidative stress and crystal deposition triggered by high oxalate.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100908"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877057","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}
Pub Date : 2026-01-01Epub Date: 2025-10-10DOI: 10.1016/j.jgr.2025.10.003
Linlin Gao , Fushuang Zheng , Zhiling Fu , Wei Wang
Background
Sepsis-induced acute lung injury (ALI) is a life-threatening condition with high mortality and limited effective treatments. Aging of alveolar type II (AT2) epithelial cells and mitochondrial dysfunction are key contributors to ALI pathogenesis. Ginsenoside Rb1, a major bioactive component of ginseng, has shown potential in modulating cellular senescence and mitochondrial health. This study aimed to evaluate the therapeutic efficacy of Rb1-loaded lung tissue-derived decellularized extracellular matrix hydrogel (dECM-gel) in alleviating sepsis-induced ALI.
Methods and results
Rb1-loaded dECM-gel was formulated and characterized for its rheological properties. In vitro, primary AT2 cells were treated with lipopolysaccharide (LPS) to mimic ALI conditions. The impact of Rb1-loaded dECM-gel on cellular senescence, mitochondrial function, and oxidative stress was assessed using β-galactosidase staining, JC-1 dye for mitochondrial membrane potential, ATP quantification assays, and transmission electron microscopy. Results demonstrated that Rb1-loaded dECM-gel significantly reduced AT2 cell senescence, improved mitochondrial function via activation of the mitochondrial unfolded protein response (mtUPR), and alleviated mitochondrial structural damage. In vivo, a murine model of sepsis-induced ALI was used to evaluate therapeutic outcomes. Treatment with Rb1-loaded dECM-gel improved lung histopathology, decreased oxidative stress, and reduced apoptosis, largely through activation of the AMPK/SIRT1 signaling pathway.
Conclusion
Rb1-loaded dECM-gel mitigates sepsis-induced ALI by enhancing mtUPR and activating the AMPK/SIRT1 pathway, offering a promising therapeutic strategy for lung injury. These findings underscore the potential of ginsenoside-based biomaterials in the clinical management of ALI.
{"title":"Ginsenoside Rb1-enhanced decellularized extracellular matrix hydrogels ameliorates mitochondrial dysfunction and cellular aging in sepsis-induced acute lung injury","authors":"Linlin Gao , Fushuang Zheng , Zhiling Fu , Wei Wang","doi":"10.1016/j.jgr.2025.10.003","DOIUrl":"10.1016/j.jgr.2025.10.003","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced acute lung injury (ALI) is a life-threatening condition with high mortality and limited effective treatments. Aging of alveolar type II (AT2) epithelial cells and mitochondrial dysfunction are key contributors to ALI pathogenesis. Ginsenoside Rb1, a major bioactive component of ginseng, has shown potential in modulating cellular senescence and mitochondrial health. This study aimed to evaluate the therapeutic efficacy of Rb1-loaded lung tissue-derived decellularized extracellular matrix hydrogel (dECM-gel) in alleviating sepsis-induced ALI.</div></div><div><h3>Methods and results</h3><div>Rb1-loaded dECM-gel was formulated and characterized for its rheological properties. In vitro, primary AT2 cells were treated with lipopolysaccharide (LPS) to mimic ALI conditions. The impact of Rb1-loaded dECM-gel on cellular senescence, mitochondrial function, and oxidative stress was assessed using β-galactosidase staining, JC-1 dye for mitochondrial membrane potential, ATP quantification assays, and transmission electron microscopy. Results demonstrated that Rb1-loaded dECM-gel significantly reduced AT2 cell senescence, improved mitochondrial function via activation of the mitochondrial unfolded protein response (mtUPR), and alleviated mitochondrial structural damage. In vivo, a murine model of sepsis-induced ALI was used to evaluate therapeutic outcomes. Treatment with Rb1-loaded dECM-gel improved lung histopathology, decreased oxidative stress, and reduced apoptosis, largely through activation of the AMPK/SIRT1 signaling pathway.</div></div><div><h3>Conclusion</h3><div>Rb1-loaded dECM-gel mitigates sepsis-induced ALI by enhancing mtUPR and activating the AMPK/SIRT1 pathway, offering a promising therapeutic strategy for lung injury. These findings underscore the potential of ginsenoside-based biomaterials in the clinical management of ALI.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100906"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877056","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}
Pub Date : 2026-01-01Epub Date: 2025-11-29DOI: 10.1016/j.jgr.2025.11.010
Su-Min Baek , Young-Jin Lee , Jae-Hyuk Yim , Tae-Un Kim , Woo Jun Kim , Seoung-Woo Lee , Hee-Yeon Kim , Kyung-Ku Kang , Kyeong-Min Lee , Seong-Kyoon Choi , Sung Dae Kim , Man-Hee Rhee , Jin-Kyu Park
Background
Impaired intestinal mucosal barrier in alcoholic liver disease leads to the entry of toxic substances into the liver parenchyma. Ingestion of microplastics (MPs; plastic particles sized <5 mm) can induce inflammation, metabolic disorders, oxidative stress, and cancer. Red ginseng extract (RGE) is a widely used herbal medicine globally. The effects of RGE on the accumulation of MPs and the underlying mechanisms remain unclear.
Methods
Nine-week-old male wild-type C57BL/6 mice were fed a control liquid diet or ethanol diet with or without MP and RGE. MPs (fluorescent-tagged 2.16-μm polystyrene MP; dose: 0.1 mg/kg body weight) and RGE (dose: 250 or 500 mg/kg body weight) were orally administered five times a week.
Results
RGE treatment markedly reduced MP accumulation in the liver and intestines. In the intestines, RGE protected tight junctions, as shown by ZO-1 and F-actin expression, and prevented MP translocation into the lamina propria. It also inhibited ethanol- and MP-induced villi fusion, epithelial detachment, and vacuolization. In the liver, RGE attenuated ethanol-mediated steatosis, lobular inflammation, and ballooning degeneration. In vitro, RGE restored tight junction integrity in Caco-2 cells by upregulating ZO-1 while reducing MP accumulation. However, its effect on goblet cell differentiation (MUC-2) in HT-29 cells was minimal, suggesting that in vivo goblet cell regeneration occurred secondarily to tight junction protection.
Conclusion
Disruption of the gut–liver axis leads to increased translocation of MPs into the lamina propria and their secondary accumulation in the intestines and liver. RGE inhibits the accumulation of MPs by protecting the intestinal epithelial mucosal barrier.
{"title":"Korean red ginseng extract inhibits microplastic translocation via the gut−liver axis by ameliorating alcohol-induced intestinal disruption","authors":"Su-Min Baek , Young-Jin Lee , Jae-Hyuk Yim , Tae-Un Kim , Woo Jun Kim , Seoung-Woo Lee , Hee-Yeon Kim , Kyung-Ku Kang , Kyeong-Min Lee , Seong-Kyoon Choi , Sung Dae Kim , Man-Hee Rhee , Jin-Kyu Park","doi":"10.1016/j.jgr.2025.11.010","DOIUrl":"10.1016/j.jgr.2025.11.010","url":null,"abstract":"<div><h3>Background</h3><div>Impaired intestinal mucosal barrier in alcoholic liver disease leads to the entry of toxic substances into the liver parenchyma. Ingestion of microplastics (MPs; plastic particles sized <5 mm) can induce inflammation, metabolic disorders, oxidative stress, and cancer. Red ginseng extract (RGE) is a widely used herbal medicine globally. The effects of RGE on the accumulation of MPs and the underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>Nine-week-old male wild-type C57BL/6 mice were fed a control liquid diet or ethanol diet with or without MP and RGE. MPs (fluorescent-tagged 2.16-μm polystyrene MP; dose: 0.1 mg/kg body weight) and RGE (dose: 250 or 500 mg/kg body weight) were orally administered five times a week.</div></div><div><h3>Results</h3><div>RGE treatment markedly reduced MP accumulation in the liver and intestines. In the intestines, RGE protected tight junctions, as shown by ZO-1 and F-actin expression, and prevented MP translocation into the lamina propria. It also inhibited ethanol- and MP-induced villi fusion, epithelial detachment, and vacuolization. In the liver, RGE attenuated ethanol-mediated steatosis, lobular inflammation, and ballooning degeneration. <em>In vitro</em>, RGE restored tight junction integrity in Caco-2 cells by upregulating ZO-1 while reducing MP accumulation. However, its effect on goblet cell differentiation (MUC-2) in HT-29 cells was minimal, suggesting that <em>in vivo</em> goblet cell regeneration occurred secondarily to tight junction protection.</div></div><div><h3>Conclusion</h3><div>Disruption of the gut–liver axis leads to increased translocation of MPs into the lamina propria and their secondary accumulation in the intestines and liver. RGE inhibits the accumulation of MPs by protecting the intestinal epithelial mucosal barrier.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100922"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877039","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}
Pub Date : 2026-01-01Epub Date: 2025-10-28DOI: 10.1016/j.jgr.2025.10.009
Cheol Park , Hee-Jae Cha , Kyoung-Seob Song , Heui-Soo Kim , EunJin Bang , Hyesook Lee , Cheng-Yun Jin , Gi-Young Kim , Yung Hyun Choi
{"title":"Corrigendum to “Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells” [J. Ginseng Res. 47 (2) (March 2023) 311]","authors":"Cheol Park , Hee-Jae Cha , Kyoung-Seob Song , Heui-Soo Kim , EunJin Bang , Hyesook Lee , Cheng-Yun Jin , Gi-Young Kim , Yung Hyun Choi","doi":"10.1016/j.jgr.2025.10.009","DOIUrl":"10.1016/j.jgr.2025.10.009","url":null,"abstract":"","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 1","pages":"Article 100912"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877040","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}
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