Keontae Park , Ranhee Kim , Kyungnam Cho , Chang Hyeon Kong , Mijin Jeon , Woo Chang Kang , Seo Yun Jung , Dae Sik Jang , Jong Hoon Ryu
{"title":"Panaxcerol D from Panax ginseng ameliorates the memory impairment induced by cholinergic blockade or Aβ25–35 peptide in mice","authors":"Keontae Park , Ranhee Kim , Kyungnam Cho , Chang Hyeon Kong , Mijin Jeon , Woo Chang Kang , Seo Yun Jung , Dae Sik Jang , Jong Hoon Ryu","doi":"10.1016/j.jgr.2023.08.002","DOIUrl":"10.1016/j.jgr.2023.08.002","url":null,"abstract":"<div><h3>Background</h3><p>Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of <em>Panax ginseng</em> and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of <em>P. ginseng</em> extract.</p></div><div><h3>Methods</h3><p>We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ<sub>25-35</sub> peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting.</p></div><div><h3>Results</h3><p>We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brain-derived neurotrophic factor (BDNF) expression levels in Aβ<sub>25-35</sub> peptide-treated mice were modulated by sub-chronic administration of panaxcerol D.</p></div><div><h3>Conclusion</h3><p>Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of <em>P. ginseng</em> for improving cognitive function.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 1","pages":"Pages 59-67"},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001070/pdfft?md5=de09289bf38311577e8b1320bfb6921c&pid=1-s2.0-S1226845323001070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46830491","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}
Yifan Wang , Hao Wei , Zhen Song , Liqun Jiang , Mi Zhang , Xiao Lu , Wei Li , Yuqing Zhao , Lei Wu , Shuxian Li , Huijuan Shen , Qiang Shu , Yicheng Xie
{"title":"Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells","authors":"Yifan Wang , Hao Wei , Zhen Song , Liqun Jiang , Mi Zhang , Xiao Lu , Wei Li , Yuqing Zhao , Lei Wu , Shuxian Li , Huijuan Shen , Qiang Shu , Yicheng Xie","doi":"10.1016/j.jgr.2023.09.002","DOIUrl":"10.1016/j.jgr.2023.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied.</p></div><div><h3>Methods</h3><p>A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model.</p></div><div><h3>Results</h3><p>Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation.</p></div><div><h3>Conclusion</h3><p>PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 1","pages":"Pages 77-88"},"PeriodicalIF":6.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001136/pdfft?md5=e370830f9c8bd501572f2b70b485e766&pid=1-s2.0-S1226845323001136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135428499","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}
Bao Ngoc Nguyen , Soyeon Hong , Sowoon Choi , Choong-Gu Lee , GyHye Yoo , Myungsuk Kim
{"title":"Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment","authors":"Bao Ngoc Nguyen , Soyeon Hong , Sowoon Choi , Choong-Gu Lee , GyHye Yoo , Myungsuk Kim","doi":"10.1016/j.jgr.2023.12.004","DOIUrl":"10.1016/j.jgr.2023.12.004","url":null,"abstract":"<div><h3>Background</h3><p>Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation.</p></div><div><h3>Methods</h3><p>Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment.</p></div><div><h3>Results</h3><p>Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco.</p></div><div><h3>Conclusion</h3><p>This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 3","pages":"Pages 310-322"},"PeriodicalIF":6.3,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001938/pdfft?md5=b08271f174874a3072390f6a1c10e296&pid=1-s2.0-S1226845323001938-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139066753","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}
Siyu Cheng , Langqun Chen , Jiahui Ying , Ying Wang , Wenjuan Jiang , Qi Zhang , Hong Zhang , Jiahe Wang , Chen Wang , Huimin Wu , Jing Ye , Liang Zhang
{"title":"20(S)-ginsenoside Rh2 ameliorates ATRA resistance in APL by modulating lactylation-driven METTL3","authors":"Siyu Cheng , Langqun Chen , Jiahui Ying , Ying Wang , Wenjuan Jiang , Qi Zhang , Hong Zhang , Jiahe Wang , Chen Wang , Huimin Wu , Jing Ye , Liang Zhang","doi":"10.1016/j.jgr.2023.12.003","DOIUrl":"10.1016/j.jgr.2023.12.003","url":null,"abstract":"<div><h3>Background</h3><p>20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown.</p></div><div><h3>Methods</h3><p>Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance.</p></div><div><h3>Results</h3><p>Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3.</p></div><div><h3>Conclusions</h3><p>This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 3","pages":"Pages 298-309"},"PeriodicalIF":6.3,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001926/pdfft?md5=71eeb2cee47e4dd010db4132e73d094d&pid=1-s2.0-S1226845323001926-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139066629","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}
{"title":"Foeniculum vulgare essential oil nanoemulsion inhibits Fusarium oxysporum causing Panax notoginseng root-rot disease","authors":"Hongyan Nie, Hongxin Liao, Jinrui Wen, Cuiqiong Ling, Liyan Zhang, Furong Xu, Xian Dong","doi":"10.1016/j.jgr.2023.12.002","DOIUrl":"10.1016/j.jgr.2023.12.002","url":null,"abstract":"<div><h3>Background</h3><p><em>Fusarium oxysporum</em> (<em>F. oxysporum</em>) is the primary pathogenic fungus that causes <em>Panax notoginseng</em> (<em>P. notoginseng</em>) root rot disease. To control the disease, safe and efficient antifungal pesticides must currently be developed.</p></div><div><h3>Methods</h3><p>In this study, we prepared and characterized a nanoemulsion of <em>Foeniculum vulgare</em> essential oil (Ne-FvEO) using ultrasonic technology and evaluated its stability. Traditional <em>Foeniculum vulgare</em> essential oil (T-FvEO) was prepared simultaneously with 1/1000 Tween-80 and 20/1000 dimethyl sulfoxide (DMSO). The effects and inhibitory mechanism of Ne-FvEO and T-FvEO in <em>F. oxysporum</em> were investigated through combined transcriptome and metabolome analyses.</p></div><div><h3>Results</h3><p>Results showed that the minimum inhibitory concentration (MIC) of Ne-FvEO decreased from 3.65 mg/mL to 0.35 mg/mL, and its bioavailability increased by 10-fold. The results of gas chromatography/mass spectrometry (GC/MS) showed that T-FvEO did not contain a high content of estragole compared to <em>Foeniculum vulgare</em> essential oil (FvEO) and Ne-FvEO. Combined metabolome and transcriptome analysis showed that both emulsions inhibited the growth and development of <em>F. oxysporum</em> through the synthesis of the cell wall and cell membrane, energy metabolism, and genetic information of <em>F. oxysporum</em> mycelium. Ne-FvEO also inhibited the expression of 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase and reduced the content of 2-oxoglutarate, which inhibited the germination of spores.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that Ne-FvEO effectively inhibited the growth of <em>F. oxysporum</em> in <em>P. notoginseng</em> in vivo. The findings contribute to our comprehension of the antifungal mechanism of essential oils (EOs) and lay the groundwork for the creation of plant-derived antifungal medicines.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 2","pages":"Pages 236-244"},"PeriodicalIF":6.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001835/pdfft?md5=1e8c6baf1449d2b3126c400b78176e3e&pid=1-s2.0-S1226845323001835-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139030189","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}
BaiCheng Chen , Ajay Vijayakumar , Chul Park , Ulsoo Choi , Seung-Yeol Nah , Jong-Hoon Kim
{"title":"Gintonin upregulates cytokine production and expression of NKp30, NKp44 and NKp44 related to natural killer cell activity on immunosuppressive rat","authors":"BaiCheng Chen , Ajay Vijayakumar , Chul Park , Ulsoo Choi , Seung-Yeol Nah , Jong-Hoon Kim","doi":"10.1016/j.jgr.2023.12.001","DOIUrl":"10.1016/j.jgr.2023.12.001","url":null,"abstract":"<div><p>The objective of the study is to estimate the potential of gintonin, as an immune enhancing agent through natural killer cell (NK cell) activity in cyclophosphamide (CY)-induced immunosuppressive animals. Accumulated results reveals that, gintonin attenuated CY-induced immunosuppression and it might modulate NK cell activity to boost the immunity.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 3","pages":"Pages 341-345"},"PeriodicalIF":6.3,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S122684532300163X/pdfft?md5=cc9b5ef42221829699bbda22894e788f&pid=1-s2.0-S122684532300163X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138572245","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}
Yi Zheng , Yunlong Si , Xuejiao Xu , Hongming Gu , Zhen He , Zihan Zhao , Zhangkai Feng , Jiyong Su , Kevin H. Mayo , Yifa Zhou , Guihua Tai
{"title":"Ginseng-derived type I rhamnogalacturonan polysaccharide binds to galectin-8 and antagonizes its function","authors":"Yi Zheng , Yunlong Si , Xuejiao Xu , Hongming Gu , Zhen He , Zihan Zhao , Zhangkai Feng , Jiyong Su , Kevin H. Mayo , Yifa Zhou , Guihua Tai","doi":"10.1016/j.jgr.2023.11.007","DOIUrl":"10.1016/j.jgr.2023.11.007","url":null,"abstract":"<div><h3>Background</h3><p><em>Panax ginseng</em> Meyer polysaccharides exhibit various biological functions, like antagonizing galectin-3-mediated cell adhesion and migration. Galectin-8 (Gal-8), with its linker-joined <em>N</em>- and <em>C</em>-terminal carbohydrate recognition domains (CRDs), is also crucial to these biological processes, and thus plays a role in various pathological disorders. Yet the effect of ginseng-derived polysaccharides in modulating Gal-8 function has remained unclear.</p></div><div><h3>Methods</h3><p>P. ginseng-derived pectin was chromatographically isolated and enzymatically digested to obtain a series of polysaccharides. Biolayer Interferometry (BLI) quantified their binding affinity to Gal-8, and their inhibitory effects on Gal-8 was assessed by hemagglutination, cell migration and T-cell apoptosis.</p></div><div><h3>Results</h3><p>Our ginseng-derived pectin polysaccharides consist mostly of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG). BLI shows that Gal-8 binding rests primarily in RG-I and its β-1,4-galactan side chains, with sub-micromolar K<sub>D</sub> values. Both <em>N</em>- and <em>C</em>-terminal Gal-8 CRDs bind RG-I, with binding correlated with Gal-8-mediated function.</p></div><div><h3>Conclusion</h3><p>P. ginseng RG-I pectin β-1,4-galactan side chains are crucial to binding Gal-8 and antagonizing its function. This study enhances our understanding of galectin-sugar interactions, information that may be used in the development of pharmaceutical agents targeting Gal-8.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 2","pages":"Pages 202-210"},"PeriodicalIF":6.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001628/pdfft?md5=31e062301051f39999edf4c66358e9d8&pid=1-s2.0-S1226845323001628-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515395","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}
Jing Zhao , Zhandi Wang , Rong Jiao , Qionglian Wan , Lianchun Wang , Liangxing Li , Yali Yang , Shahzad Munir
{"title":"P-hydroxybenzoic acid positively affect the Fusarium oxysporum to stimulate root rot in Panax notoginseng","authors":"Jing Zhao , Zhandi Wang , Rong Jiao , Qionglian Wan , Lianchun Wang , Liangxing Li , Yali Yang , Shahzad Munir","doi":"10.1016/j.jgr.2023.11.005","DOIUrl":"10.1016/j.jgr.2023.11.005","url":null,"abstract":"<div><h3>Background</h3><p>Plant health is directly related to the change in native microbial diversity and changes in soil health have been implicated as one of the main cause of root rot. However, scarce information is present regarding allelopathic relationship of <em>Panax notoginseng</em> root exudates and pathogenic fungi <em>Fusarium oxysporum</em> in a continuous cropping system.</p></div><div><h3>Methods</h3><p>We analyzed <em>P. notoginseng</em> root exudate in the planting soil for three successive years to determine phenolic acid concentration using GC-MS and HPLC followed by effect on the microbial community assembly. Antioxidant enzymes were checked in the roots to confirm possible resistance in <em>P. notoginseng</em>.</p></div><div><h3>Results</h3><p>Total 29 allelochemicals in the planting soil extract was found with highest concentration (10.54 %) of <em>p</em>-hydroxybenzoic acid. The HPLC showing a year-by-year decrease in <em>p</em>-hydroxybenzoic acid content in soil of different planting years, and an increase in population of <em>F. oxysporum</em>. Moreover, community analysis displayed negative correlation with 2.22 mmol. L<sup>−1</sup> of <em>p</em>-hydroxybenzoic acid correspond to an 18.1 % population of <em>F. oxysporum</em>. Furthermore, <em>in vitro</em> plate assay indicates that medium dose of <em>p</em>-hydroxybenzoic acid (2.5–5 mmol. L<sup>−1</sup>) can stimulate the growth of <em>F. oxysporum</em> colonies and the production of macroconidia, as well as cell wall-degrading enzymes. We found that 2–3 mmol. L<sup>−1</sup> of <em>p</em>-hydroxybenzoic acid significantly increased the population of <em>F. oxysporum</em>.</p></div><div><h3>Conclusion</h3><p>In conclusion, our study suggested that <em>p</em>-hydroxybenzoic acid have negative effect on the root system and modified the rhizosphere microbiome so that the host plant became more susceptible to root rot disease.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 2","pages":"Pages 229-235"},"PeriodicalIF":6.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001604/pdfft?md5=40863d9490f606becd93fdf903865631&pid=1-s2.0-S1226845323001604-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515424","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}
Ziyu Song , Meng Jin , Shenglong Wang , Yanzuo Wu , Qi Huang , Wangda Xu , Yongsheng Fan , Fengyuan Tian
{"title":"Reciprocal regulation of SIRT1 and AMPK by Ginsenoside compound K impedes the conversion from plasma cells to mitigate for podocyte injury in MRL/lpr mice in a B cell-specific manner","authors":"Ziyu Song , Meng Jin , Shenglong Wang , Yanzuo Wu , Qi Huang , Wangda Xu , Yongsheng Fan , Fengyuan Tian","doi":"10.1016/j.jgr.2023.11.006","DOIUrl":"10.1016/j.jgr.2023.11.006","url":null,"abstract":"<div><h3>Background</h3><p>Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive.</p></div><div><h3>Methods</h3><p>Female MRL/<em>lpr</em> mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays.</p></div><div><h3>Results</h3><p>CK reduced proteinuria and protected podocyte ultrastructure in MRL/<em>lpr</em> mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO.</p></div><div><h3>Conclusions</h3><p>Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.</p></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"48 2","pages":"Pages 190-201"},"PeriodicalIF":6.3,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845323001616/pdfft?md5=fb5a8168a7f0e7a18108f040467cea70&pid=1-s2.0-S1226845323001616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515469","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}