Since the introduction of monoamine oxidase and monoamine neurotransmitter reuptake inhibitors for the treatment of major depression in the 1950s,their strengths and limitations have been fully and accurately determin...Since the introduction of monoamine oxidase and monoamine neurotransmitter reuptake inhibitors for the treatment of major depression in the 1950s,their strengths and limitations have been fully and accurately determined.Therefore,the development of novel drugs for the treatment of depression has become a priority for researchers who aim to address treatment resistance and improve patient out-comes.Panax ginseng C.A.Mey(P.ginseng,Ren Shen)is a Chinese medicine used to treat neurological and psychiatric disorders.Numerous studies have shown that ginsenosides,the primary active constituents of P.ginseng,exert a wide range of effects on the central nervous system.Recent studies have demon-strated that ginsenosides possess significant antidepressant properties in animal models.Ginsenosides,such as Rb1 and Rg1,are steroidal molecules,and steroid derivatives have been successfully used in anesthesia,epilepsy,and more recently,postpartum depression treatment.Based on these findings,ginsenosides are promising candidates for the treatment of depression.This raises the following ques-tion:What are the prospects of using ginsenosides to treat depression?To gain a clearer understanding,this review provides a comprehensive analysis of recent research on the antidepressant potential of ginsenosides,along with insights and suggestions for future development in this field.展开更多
Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredien...Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredient.The anti-aging effect of ginsenosides is considered to be one of the important roles of ginsenosides,and Compound K,as the main deglycosylated metabolite of ginsenosides,has a comprehensive anti-aging effect as a highly active ingredient obtained by transformation under the action of microbiota.Recent studies have shown that ginsenosides have anti-photo-oxidation,anti-skin aging,free radical scavenging and immunostimulatory effects,which can effectively prevent skin photoaging.With the progress of modern natural medicine extraction technology and the deepening of the research on the anti-skin aging of ginsenosides'high active ingredients,it will promote the development and application of natural product protective skin photoaging preparations.The rare ginsenoside Compound K plays an important role in the improvement of skin health and anti-aging,which is mainly realized by increasing the activity of antioxidant enzymes,inducing the expression of related genes,reducing the content of oxidative damage substances,regulating the immune system,and influencing the expression of cell-cycle regulators and aging genes.A more comprehensive and in-depth study of the molecular mechanism of the anti-aging effect of rare ginsenoside Compound K will be one of the focuses of future research.展开更多
Acute kidney injury is a common complication that can arise from improper medication use,mechanical injury,and other underlying conditions,potentially leading to life-threatening situations in severe cases.Ginsenoside...Acute kidney injury is a common complication that can arise from improper medication use,mechanical injury,and other underlying conditions,potentially leading to life-threatening situations in severe cases.Ginsenoside Rg1,a major protopanaxatriol saponin,exhibits pharmacological activities such as antioxidant,anti-inflammatory,and anti-tumor effects,demonstrating significant nephroprotective properties in various renal injury models.This article reviews the mechanisms and recent research advancements of ginsenoside Rg1 in preventing acute kidney injury,focusing on five key areas:antioxidant,anti-inflammatory,anti-apoptotic,anti-podocyte autophagy,and anti-fibrotic activities.These insights provide a valuable foundation for its further development and application.展开更多
Ginsenosides,the bioactive saponins primary found in Panax ginseng,possess a complex structure that underlies their diverse pharmacological properties.Ginsenoside Rg3 stands out for its broad therapeutic potential,inc...Ginsenosides,the bioactive saponins primary found in Panax ginseng,possess a complex structure that underlies their diverse pharmacological properties.Ginsenoside Rg3 stands out for its broad therapeutic potential,including anticancer,anti-inflammatory,neuroprotective,and cardiovascular effects.This review provides a comprehensive overview of the cellular and molecular mechanisms of Rg3,emphasizing its roles in regulating apoptosis,inflammation,oxidative stress,and metabolic pathways relevant to skincare and anticancer applications.The unique biological activities of its isomeric forms,20(S)-Rg3 and 20(R)-Rg3,are highlighted,alongside strategies to enhance its bioavailability,such as nanoencapsulation and prodrug design.Additionally,the synergistic effects of Rg3 when combined with other treatments are discussed,underscoring its promise as a bridging agent between conventional and emerging therapies in dermatology and oncology.Finally,the current research gaps are identified,and future directions are proposed to further optimize the clinical application of Rg3.展开更多
The risk of exposure to particulate matter(PM)has been consistently highlighted globally owing to its detrimental effects on the respiratory and cardiovascular systems and in the development of lung cancer.Additionall...The risk of exposure to particulate matter(PM)has been consistently highlighted globally owing to its detrimental effects on the respiratory and cardiovascular systems and in the development of lung cancer.Additionally,PM promotes cancer cell metastasis;however,research elucidating the precise mechanisms underlying this phenomenon and the strategies to inhibit it remains limited.The aim of this study was to elucidate the mechanism underlying PM-induced cancer metastasis and investigate the preventive role of ginsenoside Rg3.We treated macrophages with PM and confirmed an increase in the expression and secretion of chemokines,such as CCL3,CCL4,and CCL5.This effect was mediated by the MAPK and NF-kB pathways,and Rg3 inhibited this process by suppressing chemokine expression.These chemokines regulate the expression of epithelial-mesenchymal transition(EMT)markers in cancer cells,including Snail,Slug,ZEB1,and E-cadherin.The regulated EMT markers increased the motility of cancer cells in vitro.Furthermore,an increase in CCL3,CCL4,and CCL5 in the bronchoalveolar lavage fluid(BALF)was confirmed in a PM inhalation mouse model,and Rg3 reduced PM-induced cancer metastasis.The study findings suggest the potential use of Rg3 as a therapeutic agent to prevent PM-induced cancer metastasis.展开更多
Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of ...Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.展开更多
Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial...Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].展开更多
Despite the high nucleic acid loading capacity,cationic liposomes(CLs)are facing challenges of insufficient nucleic acid drug release.Ginsenosides,natural product with a steroidal structure similar with cholesterol,no...Despite the high nucleic acid loading capacity,cationic liposomes(CLs)are facing challenges of insufficient nucleic acid drug release.Ginsenosides,natural product with a steroidal structure similar with cholesterol,not only have the potential to replace cholesterol in modulating the mobility of phospholipid bilayer and the release of nucleic acid drugs,but also exhibit therapeutic activities such as anti-fibrosis capacity.In this study,we screened potential ginsenosides and developed an efficient siRNA delivery ginsenoside liposome by replacing cholesterol with preferred ginsenoside Rb1,aiming for enhanced hepatic fibrosis treatment.To further enhance the targeted internalization to the activated hepatic stellate cells,ginsenoside liposomes were further modified with targeting cell penetrating peptide R8-dGR.Compared with cholesterol liposomes,the optimized Rb1 liposomes effectively enhanced the cellular internalization and gene silencing efficiency using Yes-associated protein(YAP)as a target.Mechanism studies reveal that the replacement of cholesterol with ginsenoside Rb1 allows membrane perturbation upon insertion into the phospholipid bilayer,leading to enhanced cell membrane fusion and lysosomal release of siRNA,which may account for enhanced cell internalization and gene silencing.Combined with the internal antifibrotic activity of ginsenoside and the downregulation of YAP,the functionalized liposome inhibited hepatic stellate cell activation and reversed abnormal extracellular matrix deposition,leading to enhanced anti-hepatic fibrosis activity both in vitro and in vivo.Owing to the transfection-promoting effect and pharmacological activity of ginsenoside Rb1,the ginsenoside liposome represents an efficient siRNA delivery approach for the treatment of hepatic fibrosis.展开更多
Gastric cancer is a major global health challenge,associated with high mortality and limited therapeutic options.Ginsenoside Rg3(Rg3),a bioactive compound derived from ginseng,has been shown to possess significant ant...Gastric cancer is a major global health challenge,associated with high mortality and limited therapeutic options.Ginsenoside Rg3(Rg3),a bioactive compound derived from ginseng,has been shown to possess significant anticancer properties,particularly through immune modulation.In this study,we explored the therapeutic potential of Ginsenoside Rg3 hydrogel in the treatment of gastric cancer,focusing on its ability to target fibroblast activation protein(FAP),a key mediator of tumor progression.Using reverse molecular docking and gene expression analysis,we identified FAP as a primary molecular target of Rg3.Preclinical evaluations revealed that Rg3 hydrogel effectively inhibited the proliferation and invasion of gastric cancer cells in vitro.Furthermore,the hydrogel promoted immunogenic cell death,resulting in a robust immune response against the tumor.Our findings suggest that Ginsenoside Rg3 hydrogel holds promise as a novel immune-based therapeutic strategy for gastric cancer,offering a potential pathway to improved clinical outcomes and treatment strategies.展开更多
Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue,leading to progressive architectural remodeling across various tissues a...Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue,leading to progressive architectural remodeling across various tissues and organs.This condition imposes a substantial burden,resulting in considerable morbidity and mortality.Ginseng(Panax ginseng C.A.Meyer),renowned for its medicinal properties,has been incorporated as a key component in Chinese patent medicines to mitigate fibrotic diseases.Ginsenosides,the primary bioactive compounds in ginseng,have garnered significant attention.Over the past five years,extensive research has explored the pharmaceutical potential of ginsenosides in diverse organ fibrosis conditions,including liver,myocardial,renal,and pulmonary fibrosis.Studies have elucidated that ginsenosides demonstrate potential effects on inflammatory responses stemming from parenchymal cell damage,myofibroblast activation leading to extracellular matrix(ECM)production,and myofibroblast apoptosis or inactivation.Additionally,potential downstream targets and pathways associated with these pathological processes have been identified as being influenced by ginsenosides.This review presents a comprehensive overview of the efficacious treatments utilizing ginsenosides for various tissue fibrosis types and their potential antifibrotic mechanisms.Furthermore,it offers a reference for the development of novel candidate drugs for future organ fibrosis therapies.展开更多
Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and ...Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and antioxidative effects.This study is the first to systematically investigate the metabolites of ginsenoside Rb1,specifically F2 and CK,in the context of sepsis-induced ALI modeled by lipopolysaccharide(LPS)administration,a widely used preclinical approach to mimic key inflammatory features of clinical sepsis.Unlike other studies,which primarily focus on ginsenoside Rb1 itself,our research specifically emphasizes the role of its metabolites in this process.We demonstrated that ginsenoside Rb1 significantly improved lung histopathological damage,reduced inflammation,and inhibited cell apoptosis in a sepsis-induced ALI mouse model.Metabolomics and proteomics analyses revealed that Rb1 is metabolized into F2 and CK,which activate the AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling pathway.This activation promotes Forkhead Box O1(FOXO1)deacetylation,inhibiting its cytoplasmic translocation and enhancing mitochondrial unfolded protein response(mtUPR)gene transcription.In vitro experiments confirmed that ginsenoside Rb1 protected alveolar typeⅡ(AT2)cells from oxidative stress and senescence,while restoring mitochondrial function.Blocking the AMPK/SIRT1 pathway or silencing FOXO1 reversed these protective effects,highlighting their crucial roles in Rb1's mitigation of ALI.Our findings provide new insights into the molecular mechanisms by which ginsenoside Rb1 alleviates sepsis-induced ALI and offer a potential therapeutic approach for treating sepsis-related lung injuries.展开更多
Objective To study the key technologies in the field of ginsenosides and to offer a guide for the future development ginsenosides through the main path identification method based on genetic knowledge persistence algo...Objective To study the key technologies in the field of ginsenosides and to offer a guide for the future development ginsenosides through the main path identification method based on genetic knowledge persistence algorithm(GKPA).Methods The global ginsenoside invention authorized patents were used as the data source to construct a ginsenoside patent self-citation network,and to identify high knowledge persistent patents(HKPP)of ginsenoside technology based on the GKPA,and extract its high knowledge persistence main path(HKPMP).Finally,the genetic forward and backward path(GFBP)was used to search the nodes on the main path,and draw the genetic forward and backward main path(GFBMP)of ginsenoside technology.Results and Conclusion The algorithm was applied to the field of ginsenosides.The research results show the milestone patents in ginsenosides technology and the main evolution process of three key technologies,which points out the future direction for the technological development of ginsenosides.The results obtained by this algorithm are more interpretable,comprehensive and scientific.展开更多
BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited...BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited.Ginsenoside F4,as a rare ginsenoside found in Panax ginseng,exhibits stronger antitumor and immunomo-dulatory activities than primary ginsenosides.However,its therapeutic effects on various diseases remain limited.AIM To investigate the antitumor effect of Ginsenoside F4 and mechanism on the maturation of DCs in colorectal cancer(CRC).METHODS The changes in mature DC markers and cytokines generated after DCs were exposed to F4 were assessed using flow cytometry and enzyme-linked immuno-sorbent assay,respectively.The viability of CRC CT26 cells co-cultured with T lymphocytes was monitored by cell counting kit-8 assay.Furthermore,the histopathological characteristics and immune cell infiltration in tumor tissues of CT26-bearing mice were analyzed by hematoxylin-eosin and immuno-fluorescent staining.The expressions of apoptosis-relative proteins were detected by western blot assay.RESULTS Treatment with F4 promoted the maturation of DCs,elevated the expressions of cluster of differentiation(CD)83 and CD86,increased the secretion of interleukin(IL)-2,IL-10,and IL-12 p70,and upregulated the expressions of phosphorylated phosphoinositide 3-kinase,phosphorylated protein kinase B,and nuclear factor kappa-B(NF-κB)phosphorylated p65 in DCs,which enhanced antigen-specific CD8+T-cell responses.However,these benefits could be reversed by the sphingosine-1-phosphate 1(S1PR1)inhibitor fingolimod hydrochloride.Furthermore,oral administration with F4 inhibited tumor growth and increased DC and CD8+T-cell infiltration in the tumor tissues of CT26-bearing mice.CONCLUSION The results demonstrated that F4 inhibited the growth of CRC by maturing DCs through activating S1PR1-mediated phosphoinositide 3-kinase/protein kinase B and NF-κB pathways,which triggered the antitumor effects of CD8+T cells.Therefore,F4 could serve as an antitumor immunomodulator for CRC treatment.展开更多
Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect ...Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.展开更多
The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefo...The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.展开更多
Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component de...Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.展开更多
Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activ...Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains unclear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.展开更多
BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM T...BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
Panax notoginseng saponins(PNS)are the main active components of Panax notoginseng.But after oral administration,they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they c...Panax notoginseng saponins(PNS)are the main active components of Panax notoginseng.But after oral administration,they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects.The sources of rare ginsenosides are extremely limited in P.notoginseng and other medical plants,which hinders their application in functional foods and drugs.Therefore,the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research.During 50 days at 25℃and 150 rpm,A.fumigatus transformed PNS to 14 products(1-14).They were iso-lated by varied chromatographic methods,such as silica gel column chromatography,Rp-C18 reversed phase column chromatography,semi-preparative HPLC,Sephadex LH-20 gel column chromatography,and elucidated on the basis of their 1H-NMR,13C-NMR and ESIMS spectroscopic data.Then,the transformed products(1-14)were isolated and identified as Rk3,Rh4,20(R)-Rh1,20(S)-Protopanaxatriol,C-K,20(R)-Rg3,20(S)-Rg3,20(S)-Rg2,20(R)-R2,Rk1,Rg5,20(S)-R2,20(R)-Rg2,and 20(S)-I,respectively.In addition,all transformed products(1-14)were tested for their antimicrobial activity.Among them,compounds 5(C-K)and 7[20(S)-Rg3]showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25,1.25μg/mL and 1.25,25μg/mL,respectively.This study lays the foundation for production of rare ginsenosides.展开更多
基金supported by the grant International Coop-eration Project of Prevention and Treatment of Major Diseases with Chinese Medicine(GZYYGJ2021047)the High-end Experts Support Program from the Ministry of Science and Technology(DL 2021110001L)+2 种基金the Basic Research Funds from the Ministry of Education(1000061223731)Chinese Medicine Featured Education and Science Cooperation Project(90011662620002)the Ministry of Education of China.
文摘Since the introduction of monoamine oxidase and monoamine neurotransmitter reuptake inhibitors for the treatment of major depression in the 1950s,their strengths and limitations have been fully and accurately determined.Therefore,the development of novel drugs for the treatment of depression has become a priority for researchers who aim to address treatment resistance and improve patient out-comes.Panax ginseng C.A.Mey(P.ginseng,Ren Shen)is a Chinese medicine used to treat neurological and psychiatric disorders.Numerous studies have shown that ginsenosides,the primary active constituents of P.ginseng,exert a wide range of effects on the central nervous system.Recent studies have demon-strated that ginsenosides possess significant antidepressant properties in animal models.Ginsenosides,such as Rb1 and Rg1,are steroidal molecules,and steroid derivatives have been successfully used in anesthesia,epilepsy,and more recently,postpartum depression treatment.Based on these findings,ginsenosides are promising candidates for the treatment of depression.This raises the following ques-tion:What are the prospects of using ginsenosides to treat depression?To gain a clearer understanding,this review provides a comprehensive analysis of recent research on the antidepressant potential of ginsenosides,along with insights and suggestions for future development in this field.
文摘Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredient.The anti-aging effect of ginsenosides is considered to be one of the important roles of ginsenosides,and Compound K,as the main deglycosylated metabolite of ginsenosides,has a comprehensive anti-aging effect as a highly active ingredient obtained by transformation under the action of microbiota.Recent studies have shown that ginsenosides have anti-photo-oxidation,anti-skin aging,free radical scavenging and immunostimulatory effects,which can effectively prevent skin photoaging.With the progress of modern natural medicine extraction technology and the deepening of the research on the anti-skin aging of ginsenosides'high active ingredients,it will promote the development and application of natural product protective skin photoaging preparations.The rare ginsenoside Compound K plays an important role in the improvement of skin health and anti-aging,which is mainly realized by increasing the activity of antioxidant enzymes,inducing the expression of related genes,reducing the content of oxidative damage substances,regulating the immune system,and influencing the expression of cell-cycle regulators and aging genes.A more comprehensive and in-depth study of the molecular mechanism of the anti-aging effect of rare ginsenoside Compound K will be one of the focuses of future research.
基金supported by the National Natural Science Foundation of China(82260812)Youth program of National Natural Science Foundation of China(81803838)+8 种基金Regional fund project of National Natural Science Foundation of China(82060754)Science and technology project of Guizhou health and Health Committee(No.gzwkj 2021-441)Guizhou Provincial Special research project on science and technology of traditional Chinese medicine and ethnic medicine(QZYY-2021-035)Guizhou Province Youth Science and Technology Talent Plan(YQK[2023]038)Guizhou Province Traditional Chinese Medicine and Ethnic Medicine 2011 Collaborative Innovation Center([2022]026)the Guizhou Provincial Department of health outstanding young medical talents fund([2021]3)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302)Science and Technology Department of Zunyi city([2022]419,[2022]420)Postdoctoral initiation program([2020]-044).
文摘Acute kidney injury is a common complication that can arise from improper medication use,mechanical injury,and other underlying conditions,potentially leading to life-threatening situations in severe cases.Ginsenoside Rg1,a major protopanaxatriol saponin,exhibits pharmacological activities such as antioxidant,anti-inflammatory,and anti-tumor effects,demonstrating significant nephroprotective properties in various renal injury models.This article reviews the mechanisms and recent research advancements of ginsenoside Rg1 in preventing acute kidney injury,focusing on five key areas:antioxidant,anti-inflammatory,anti-apoptotic,anti-podocyte autophagy,and anti-fibrotic activities.These insights provide a valuable foundation for its further development and application.
基金supported by the Agricultural Corporation Korean Master Ginseng Co.,Ltd.,Republic of Korea.
文摘Ginsenosides,the bioactive saponins primary found in Panax ginseng,possess a complex structure that underlies their diverse pharmacological properties.Ginsenoside Rg3 stands out for its broad therapeutic potential,including anticancer,anti-inflammatory,neuroprotective,and cardiovascular effects.This review provides a comprehensive overview of the cellular and molecular mechanisms of Rg3,emphasizing its roles in regulating apoptosis,inflammation,oxidative stress,and metabolic pathways relevant to skincare and anticancer applications.The unique biological activities of its isomeric forms,20(S)-Rg3 and 20(R)-Rg3,are highlighted,alongside strategies to enhance its bioavailability,such as nanoencapsulation and prodrug design.Additionally,the synergistic effects of Rg3 when combined with other treatments are discussed,underscoring its promise as a bridging agent between conventional and emerging therapies in dermatology and oncology.Finally,the current research gaps are identified,and future directions are proposed to further optimize the clinical application of Rg3.
基金supported by the KIST Institutional Program(No.2E31700-22-P005)the KRIBB Research Initiative Program(No.KGM5322422)+1 种基金the Technology Innovation Program(No.20008826)funded by the Ministry of Trade,Industry and Energy(MOTIE,Republic of Korea)the National Research Foundation of Korea(NRF)(No.2022R1A2C1091865)funded by the Ministry of Science and ICT(MSIT,Republic of Korea)。
文摘The risk of exposure to particulate matter(PM)has been consistently highlighted globally owing to its detrimental effects on the respiratory and cardiovascular systems and in the development of lung cancer.Additionally,PM promotes cancer cell metastasis;however,research elucidating the precise mechanisms underlying this phenomenon and the strategies to inhibit it remains limited.The aim of this study was to elucidate the mechanism underlying PM-induced cancer metastasis and investigate the preventive role of ginsenoside Rg3.We treated macrophages with PM and confirmed an increase in the expression and secretion of chemokines,such as CCL3,CCL4,and CCL5.This effect was mediated by the MAPK and NF-kB pathways,and Rg3 inhibited this process by suppressing chemokine expression.These chemokines regulate the expression of epithelial-mesenchymal transition(EMT)markers in cancer cells,including Snail,Slug,ZEB1,and E-cadherin.The regulated EMT markers increased the motility of cancer cells in vitro.Furthermore,an increase in CCL3,CCL4,and CCL5 in the bronchoalveolar lavage fluid(BALF)was confirmed in a PM inhalation mouse model,and Rg3 reduced PM-induced cancer metastasis.The study findings suggest the potential use of Rg3 as a therapeutic agent to prevent PM-induced cancer metastasis.
基金financially supported by the Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines(21DZ2270500)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02).
文摘Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.
文摘Myocardial ischemia(MI)is a pathophysiological condition in which the myocardium is unable to maintain normal cardiac function due to insufficient coronary artery blood and oxygen supply,as well as abnormal myocardial energy metabolism[1].Ginsenoside Rbi(Rbi),one of the most abundant natural ingredients in ginseng and Panax notoginseng,has been proven to protect the heart from MI/reperfusion injury(RI)[2].
基金supported by Sichuan Science and Technology program(No.2025ZNSFSC0682)the Program Sichuan Veterinary Medicine and Drug Innovation Group of China,Agricultural Research System(No.SCCXTD-2025-18)the Fundamental Research Funds for the Central Universities.
文摘Despite the high nucleic acid loading capacity,cationic liposomes(CLs)are facing challenges of insufficient nucleic acid drug release.Ginsenosides,natural product with a steroidal structure similar with cholesterol,not only have the potential to replace cholesterol in modulating the mobility of phospholipid bilayer and the release of nucleic acid drugs,but also exhibit therapeutic activities such as anti-fibrosis capacity.In this study,we screened potential ginsenosides and developed an efficient siRNA delivery ginsenoside liposome by replacing cholesterol with preferred ginsenoside Rb1,aiming for enhanced hepatic fibrosis treatment.To further enhance the targeted internalization to the activated hepatic stellate cells,ginsenoside liposomes were further modified with targeting cell penetrating peptide R8-dGR.Compared with cholesterol liposomes,the optimized Rb1 liposomes effectively enhanced the cellular internalization and gene silencing efficiency using Yes-associated protein(YAP)as a target.Mechanism studies reveal that the replacement of cholesterol with ginsenoside Rb1 allows membrane perturbation upon insertion into the phospholipid bilayer,leading to enhanced cell membrane fusion and lysosomal release of siRNA,which may account for enhanced cell internalization and gene silencing.Combined with the internal antifibrotic activity of ginsenoside and the downregulation of YAP,the functionalized liposome inhibited hepatic stellate cell activation and reversed abnormal extracellular matrix deposition,leading to enhanced anti-hepatic fibrosis activity both in vitro and in vivo.Owing to the transfection-promoting effect and pharmacological activity of ginsenoside Rb1,the ginsenoside liposome represents an efficient siRNA delivery approach for the treatment of hepatic fibrosis.
文摘Gastric cancer is a major global health challenge,associated with high mortality and limited therapeutic options.Ginsenoside Rg3(Rg3),a bioactive compound derived from ginseng,has been shown to possess significant anticancer properties,particularly through immune modulation.In this study,we explored the therapeutic potential of Ginsenoside Rg3 hydrogel in the treatment of gastric cancer,focusing on its ability to target fibroblast activation protein(FAP),a key mediator of tumor progression.Using reverse molecular docking and gene expression analysis,we identified FAP as a primary molecular target of Rg3.Preclinical evaluations revealed that Rg3 hydrogel effectively inhibited the proliferation and invasion of gastric cancer cells in vitro.Furthermore,the hydrogel promoted immunogenic cell death,resulting in a robust immune response against the tumor.Our findings suggest that Ginsenoside Rg3 hydrogel holds promise as a novel immune-based therapeutic strategy for gastric cancer,offering a potential pathway to improved clinical outcomes and treatment strategies.
基金the National Natural Science Foundation of China(Nos.82374103、82174036)the Fundamental Research Funds for the Central Universities(No.2632024TD03).
文摘Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue,leading to progressive architectural remodeling across various tissues and organs.This condition imposes a substantial burden,resulting in considerable morbidity and mortality.Ginseng(Panax ginseng C.A.Meyer),renowned for its medicinal properties,has been incorporated as a key component in Chinese patent medicines to mitigate fibrotic diseases.Ginsenosides,the primary bioactive compounds in ginseng,have garnered significant attention.Over the past five years,extensive research has explored the pharmaceutical potential of ginsenosides in diverse organ fibrosis conditions,including liver,myocardial,renal,and pulmonary fibrosis.Studies have elucidated that ginsenosides demonstrate potential effects on inflammatory responses stemming from parenchymal cell damage,myofibroblast activation leading to extracellular matrix(ECM)production,and myofibroblast apoptosis or inactivation.Additionally,potential downstream targets and pathways associated with these pathological processes have been identified as being influenced by ginsenosides.This review presents a comprehensive overview of the efficacious treatments utilizing ginsenosides for various tissue fibrosis types and their potential antifibrotic mechanisms.Furthermore,it offers a reference for the development of novel candidate drugs for future organ fibrosis therapies.
基金supported by the High-Quality Development Projects of China Medical Universitysupported by the Science and Technology Bureau of Liaoning Province(2023JH2/20200121)。
文摘Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and antioxidative effects.This study is the first to systematically investigate the metabolites of ginsenoside Rb1,specifically F2 and CK,in the context of sepsis-induced ALI modeled by lipopolysaccharide(LPS)administration,a widely used preclinical approach to mimic key inflammatory features of clinical sepsis.Unlike other studies,which primarily focus on ginsenoside Rb1 itself,our research specifically emphasizes the role of its metabolites in this process.We demonstrated that ginsenoside Rb1 significantly improved lung histopathological damage,reduced inflammation,and inhibited cell apoptosis in a sepsis-induced ALI mouse model.Metabolomics and proteomics analyses revealed that Rb1 is metabolized into F2 and CK,which activate the AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling pathway.This activation promotes Forkhead Box O1(FOXO1)deacetylation,inhibiting its cytoplasmic translocation and enhancing mitochondrial unfolded protein response(mtUPR)gene transcription.In vitro experiments confirmed that ginsenoside Rb1 protected alveolar typeⅡ(AT2)cells from oxidative stress and senescence,while restoring mitochondrial function.Blocking the AMPK/SIRT1 pathway or silencing FOXO1 reversed these protective effects,highlighting their crucial roles in Rb1's mitigation of ALI.Our findings provide new insights into the molecular mechanisms by which ginsenoside Rb1 alleviates sepsis-induced ALI and offer a potential therapeutic approach for treating sepsis-related lung injuries.
文摘Objective To study the key technologies in the field of ginsenosides and to offer a guide for the future development ginsenosides through the main path identification method based on genetic knowledge persistence algorithm(GKPA).Methods The global ginsenoside invention authorized patents were used as the data source to construct a ginsenoside patent self-citation network,and to identify high knowledge persistent patents(HKPP)of ginsenoside technology based on the GKPA,and extract its high knowledge persistence main path(HKPMP).Finally,the genetic forward and backward path(GFBP)was used to search the nodes on the main path,and draw the genetic forward and backward main path(GFBMP)of ginsenoside technology.Results and Conclusion The algorithm was applied to the field of ginsenosides.The research results show the milestone patents in ginsenosides technology and the main evolution process of three key technologies,which points out the future direction for the technological development of ginsenosides.The results obtained by this algorithm are more interpretable,comprehensive and scientific.
基金Supported by the Science and Technology Project of the Zhejiang Province,No.2020Y.
文摘BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited.Ginsenoside F4,as a rare ginsenoside found in Panax ginseng,exhibits stronger antitumor and immunomo-dulatory activities than primary ginsenosides.However,its therapeutic effects on various diseases remain limited.AIM To investigate the antitumor effect of Ginsenoside F4 and mechanism on the maturation of DCs in colorectal cancer(CRC).METHODS The changes in mature DC markers and cytokines generated after DCs were exposed to F4 were assessed using flow cytometry and enzyme-linked immuno-sorbent assay,respectively.The viability of CRC CT26 cells co-cultured with T lymphocytes was monitored by cell counting kit-8 assay.Furthermore,the histopathological characteristics and immune cell infiltration in tumor tissues of CT26-bearing mice were analyzed by hematoxylin-eosin and immuno-fluorescent staining.The expressions of apoptosis-relative proteins were detected by western blot assay.RESULTS Treatment with F4 promoted the maturation of DCs,elevated the expressions of cluster of differentiation(CD)83 and CD86,increased the secretion of interleukin(IL)-2,IL-10,and IL-12 p70,and upregulated the expressions of phosphorylated phosphoinositide 3-kinase,phosphorylated protein kinase B,and nuclear factor kappa-B(NF-κB)phosphorylated p65 in DCs,which enhanced antigen-specific CD8+T-cell responses.However,these benefits could be reversed by the sphingosine-1-phosphate 1(S1PR1)inhibitor fingolimod hydrochloride.Furthermore,oral administration with F4 inhibited tumor growth and increased DC and CD8+T-cell infiltration in the tumor tissues of CT26-bearing mice.CONCLUSION The results demonstrated that F4 inhibited the growth of CRC by maturing DCs through activating S1PR1-mediated phosphoinositide 3-kinase/protein kinase B and NF-κB pathways,which triggered the antitumor effects of CD8+T cells.Therefore,F4 could serve as an antitumor immunomodulator for CRC treatment.
基金supported by the Pioneer and Leading Goose R&D Program of Zhejiang Province(No.2024C03106)the National Natural Science Foundation of China(No.U23A20513)+1 种基金Ningbo Top Medical and Health Research Program(No.2022030309)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202002).
文摘Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
基金supported by the National Key Research and Development Program,China(Grant Nos.:2021YFC2101500 and 2021YFC2103900)the National Natural Science Foundation of China(Grant Nos.:22278335 and 21978236)the Natural Science Basic Research Program of Shaanxi,China(Grant No.:2023-JC-JQ-17).
文摘The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.
基金funded by the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences(Nos.CI2021A04618 and CI2021A01401).
文摘Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.
基金supported by Wenzhou Municipal Science and technology Bureau,China(Grant No.:Y20220023)the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,China(Grant No.:2022E10022)the Project of Wenzhou Medical University Basic Scientific Research,China(Grant No.:KYYW201904).
文摘Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains unclear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
基金supported by the National Natural Science Foundation of China(Grant number:32060104).
文摘Panax notoginseng saponins(PNS)are the main active components of Panax notoginseng.But after oral administration,they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects.The sources of rare ginsenosides are extremely limited in P.notoginseng and other medical plants,which hinders their application in functional foods and drugs.Therefore,the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research.During 50 days at 25℃and 150 rpm,A.fumigatus transformed PNS to 14 products(1-14).They were iso-lated by varied chromatographic methods,such as silica gel column chromatography,Rp-C18 reversed phase column chromatography,semi-preparative HPLC,Sephadex LH-20 gel column chromatography,and elucidated on the basis of their 1H-NMR,13C-NMR and ESIMS spectroscopic data.Then,the transformed products(1-14)were isolated and identified as Rk3,Rh4,20(R)-Rh1,20(S)-Protopanaxatriol,C-K,20(R)-Rg3,20(S)-Rg3,20(S)-Rg2,20(R)-R2,Rk1,Rg5,20(S)-R2,20(R)-Rg2,and 20(S)-I,respectively.In addition,all transformed products(1-14)were tested for their antimicrobial activity.Among them,compounds 5(C-K)and 7[20(S)-Rg3]showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25,1.25μg/mL and 1.25,25μg/mL,respectively.This study lays the foundation for production of rare ginsenosides.
