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
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
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
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
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
The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed o...The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed on an Alltech Adsorbosphere HS C_(18) column,using 5×10^(-3)M NaH_2PO_4-H_3PO_4 buffer solution(pH 3.0)and acetonitrile-water(50:50)as gradient eluents. The baseline separation of ginsenosides Rb_1,Rb_2,Rb_1,Rc,Rd,Rf,Ro,and Re+Rg_1 was obtained in one analytical run.The ginsenosides are directly detected at 203 nm.The detection limit is 40μg at a signal to noise ratio of 3:1.The improved sample preparation and clean-up prior to injection with SEP-PAK C_(18)cartridge strongly reduced the front peaks caused by the impurities in the methanolic extracts of samples to afford a smooth baseline and clear background.The HPLC patterns of methanolic extracts mainly including the ginsenosides were found capable of serving as chemical fingerprints to differentiate the three species from each other.It was also found that there are no significant diffe- rences of the HPLC patterns between the wild Panax ginseng and the cultivated,the white and the red ginsengs,Chinese and Korean red ginsengs,and the tap roots of Panax ginseng collected in four consecutive months,only certain differences in contents of ginsenosides do exist.The contents of the nine major ginsenosides present in the rhizome,tap root and rootlet as well as the leaf of Panax quinquefolium were also determined and compared.展开更多
To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
Ginsenosides are a series of glycosylated triterpenoids predominantly originated from Panax species with multiple pharmacological activities such as anti-aging, mediatory effect on the immune system and the nervous sy...Ginsenosides are a series of glycosylated triterpenoids predominantly originated from Panax species with multiple pharmacological activities such as anti-aging, mediatory effect on the immune system and the nervous system. During the biosynthesis of ginsenosides, glycosyltransferases play essential roles by transferring various sugar moieties to the sapogenins in contributing to form structure and bioactivity diversified ginsenosides, which makes them important bioparts for synthetic biology-based production of these valuable ginsenosides. In this review, we summarized the functional elucidated glycosyltransferases responsible for ginsenoside biosynthesis, the advance in the protein engineering of UDP-glycosyltransferases(UGTs) and their application with the aim to provide in-depth understanding on ginsenoside-related UGTs for the production of rare ginsenosides applying synthetic biology-based microbial cell factories in the future.展开更多
BACKGROUND Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality.The pathogenesis of liver cancer is closely associated with inflammation and immu...BACKGROUND Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality.The pathogenesis of liver cancer is closely associated with inflammation and immune response in the tumor microenvironment.New therapeutic agents for liver cancer,which can control inflammation and restore cellular immunity,are required.Curcumin(Cur)is a natural anti-inflammatory drug,and total ginsenosides(TG)are a commonly used immunoregulatory drug.Of note,both Cur and TG have been shown to exert anti-liver cancer effects.AIM To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer.METHODS A subcutaneous liver cancer model was established in BALB/c mice by a subcutaneous injection of hepatoma cell line.Animals were treated with Cur(200 mg/kg per day),TG(104 mg/kg per day or 520 mg/kg per day),the combination of Cur(200 mg/kg per day)and TG(104 mg/kg per day or 520 mg/kg per day),or 5-fluorouracil combined with cisplatin as a positive control for 21 d.Tumor volume was measured and the protein expression of programmed cell death 1 and programmed cell death 1 ligand 1(PD-L1),inflammatory indicators Toll like receptor 4(TLR4)and nuclear factor-κB(NF-κB),and vascular growth-related factors nitric oxide synthases(iNOS)and matrix metalloproteinase 9 were analyzed by Western blot analysis.CD4+CD25+Foxp3+regulatory T cells(Tregs)were counted by flow cytometry.RESULTS The combination therapy of Cur and TG significantly inhibited the growth of liver cancer,as compared to vehicle-treated animals,and TG showed dose dependence.Cur combined with TG-520 markedly decreased the protein expression of PD-L1(P<0.0001),while CD4+CD25+Foxp3+Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1.Cur combined with TG-520 also inhibited the cascade action mediated by NF-κB(P<0.0001),thus inhibiting the TLR4/NF-κB signalling pathway(P=0.0088,P<0.0001),which is associated with inflammation and acts on PD-L1.It also inhibited the NF-κB-MMP9 signalling pathway(P<0.0001),which is associated with tumor angiogenesis.CONCLUSION Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-κB-mediated inflammation and angiogenesis.展开更多
The effect of ginsenosides on proliferation of type A spermatogonia was investigated in 7-day-old mice. Spermatogonia were characterized by c-kit expression and cell proliferation was assessed by immunocytochemical de...The effect of ginsenosides on proliferation of type A spermatogonia was investigated in 7-day-old mice. Spermatogonia were characterized by c-kit expression and cell proliferation was assessed by immunocytochemical demonstration of proliferating cell nuclear antigen (PCNA). After 72-h culture, Sertoli cells formed a confluent monolayer to which numerous spermatogonial colonies attached. Spermatogonia were positive for c-kit staining and showed high proliferating activity by PCNA expression. Ginsenosides (1.0～10 μg/ml) significantly stimulated proliferation of spermatogonia. Activation of protein kinase C (PKC) elicited proliferation of spermatogonia at 10-8 to 10-7 mol/L and the PKC inhibitor H7 inhibited this effect. Likewise, ginsenosides-stimulated spermatogonial proliferation was suppressed by combined treatment of H7. These results indicate that the proliferating effect of ginsenosides on mouse type A spermatogonia might be mediated by a mechanism involving the PKC signal transduction pathway.展开更多
Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technologic...Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical applications.Ginseng extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary supplements.Despite the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic instability.Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled release.This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.展开更多
Ginseng(Panax ginseng C.A.Meyer)as a common dietary adjunct is widely applied in Traditional Chinese Medicine due to its health-promoting properties,but the differences between white ginseng and red ginseng was rarely...Ginseng(Panax ginseng C.A.Meyer)as a common dietary adjunct is widely applied in Traditional Chinese Medicine due to its health-promoting properties,but the differences between white ginseng and red ginseng was rarely studied.In the present study,color parameters and scanning electron microscope(SEM)were determined to evaluate the differences of ginseng color and microstructure induced by processing procedure.Quantitative analysis of multi-components by a single-marker(QAMS)method and anti-α-amylase activity test were used to assess variations of chemical ingredients and pharmacological activity between white and red ginseng.Finally,molecular docking studies were carried out to screen out the most effective compound againstα-amylase.Results indicated that processing had a significant impact on the physicochemical properties and pharmacological activity of white and red ginseng.After processing,the color value of L*declined significantly.Red ginseng sample displayed a compact structure and presented of a gel layer on the surface compared to white ginseng.Additionally,the content of ginsenosides and the activity of anti-α-amylase decreased.The contents of total ginsenosides were positively correlated with the anti-α-amylase activities of ginseng,and ginsenoside Rb1 might be the most effective compound to inhibit the activity ofα-amylase.展开更多
Ocotillol(OT)-type ginsenosides,one subtype of ginsenosides,consist of a dammarane skeleton and a tetrahydrofuran ring.Most naturally-occurring OT-type ginsenosides exist in Panax species,particularly in Panax quinque...Ocotillol(OT)-type ginsenosides,one subtype of ginsenosides,consist of a dammarane skeleton and a tetrahydrofuran ring.Most naturally-occurring OT-type ginsenosides exist in Panax species,particularly in Panax quinquefolius,which may be attributed to the warm and humid climate of its native areas.Till now,merely 28 types of naturally-occurring OT-type ginsenosides have been isolated.In contrast,semi-synthesized OT-type ginsenosides are attracted considerable attentions.These ginsenosides can be obtained through oxidation and cyclization of side chains of dammarane-type ginsenosides,and other methods,which may change their physical and chemical properties and further improve their bioavailabilities.It is also notable that the pharmacological activities of ginsenosides are closely related to the stereoisomers caused by the configuration at C-20.Semi-synthesis of OT-type ginsenosides can facilitate our understanding of the biosynthesis,transformation and metabolism of OT-type ginsenosides in the body.This review will systematically summarize the research progress on naturally-occurring and semi-synthetic OT-type ginsenosides,which provides a theoretical basis for their bioactivity-guided research.展开更多
Enrichment of trace bioactive constituents and metabolites from complex biological samples is challenging.This study presented a one-pot synthesis of magnetic polydopamine nanoparticles(Fe3O4@-SiO2@PDA NPs)with multip...Enrichment of trace bioactive constituents and metabolites from complex biological samples is challenging.This study presented a one-pot synthesis of magnetic polydopamine nanoparticles(Fe3O4@-SiO2@PDA NPs)with multiple recognition sites for the magnetic dispersive solid-phase extraction(MDSPE)of ginsenosides from rat plasma treated with white ginseng.The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a highresolution mass spectrometry with supplemental UNIFI libraries.Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides.The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80%after recycling 6 times.Furthermore,the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma.In comparison,conventional methanol method can only detect 8 ginsenosides from the same plasma samples.The proposed approach can provide methodological reference for the trace determination and characterization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.展开更多
A high-performance liquid chromatography method for the simultaneous determination of seven bioactive ginsenosides with diol stationary phase and isocratic elution was used to determin the ginsenosides in ginseng prod...A high-performance liquid chromatography method for the simultaneous determination of seven bioactive ginsenosides with diol stationary phase and isocratic elution was used to determin the ginsenosides in ginseng products. The optimization of the chromatographic separation was performed and the effect of temperature on separation was investigated. Using the validated procedure, the developed method was demonstrated to be more sensitive and effective than the conventional reversed-phase chromatography, where the chromatographic run is time-consuming to analyze a large number of ginsenosides. The results indicated that the developed method can be used for the quantitative determination of ginsenosides in complex ginseng samples.展开更多
A dynamic microwave-assisted extraction（DMAE） method is established for the extraction of total ginsenosides from ginseng fibrous roots. The extraction process has been simulated and its main affection factors（liqu...A dynamic microwave-assisted extraction（DMAE） method is established for the extraction of total ginsenosides from ginseng fibrous roots. The extraction process has been simulated and its main affection factors（liquid/solid ratio K of solvent to ginseng powders（V/m）, irradiation time, irradiation temperature, extracting solution concentration, flow rate of solvent and microwave power） have been optimized by response surface methodology（RSM）. The optimum conditions of extraction are the liquid/solid ratio of 270 m L/g, the extraction temperature of 75 ℃, the extraction time of 35 min, ethanol concentration of 70%（V/V）, the solvent flow rate of 1.3 m L/min, and the microwave power of 500 W. The yield of ginsenosides obtained by the proposed DAME method is（15.0±0.7） %, which is well agreement with the yield predicted by the model. Compared with static microwave-assisted extraction, DMAE has a higher extraction yield and can avoid the degradation of ginsenoside.展开更多
Ginsenosides are the main active components of ginseng,which have been reported to target brain tissues and produce multiple neuroprotective effects.Ginsenosides have been shown to improve learning ability and memory ...Ginsenosides are the main active components of ginseng,which have been reported to target brain tissues and produce multiple neuroprotective effects.Ginsenosides have been shown to improve learning ability and memory in normal aged animals,and in an animal model of memory impairment.However,its underlying pharmacological mechanisms are very complicated,especially with regard to its effects on the activation of protein kinases in neurons.Previous reports have shown that some protein kinases may be affected by ginsenosides,including protein kinase C,calcium/calmodulin-dependent protein kinase Ⅱ,c-Jun-N terminal kinase,and protein tyrosine kinase.In this paper,protein kinases that may underlie the mechanisms of ginsenosides will be discussed.展开更多
Six hours after smoke inhalation injury in rabbits, the permeability of pulmonary vesselsand the aggregation of circulating platelets increased markedly accompanied with apparent patholog-ical changes in the trachea a...Six hours after smoke inhalation injury in rabbits, the permeability of pulmonary vesselsand the aggregation of circulating platelets increased markedly accompanied with apparent patholog-ical changes in the trachea and lungs. Fifteen minutes after smoke inhalation injury in rabbits, an intravenous dose of ginsenosides or ketoprofenwas given to the animals respectively. 6 hours after medication, it was found that both the drugscould significantly alleviate the platelet aggregation, but only ginsenosides could alleviate theaugmentation of pulmonary vascular permeability and the pathological lesions in the trachea andlungs. In those rats injured by smoke inhalation, l hour after an intravenous dose of ginsenosides, theplasma PGI<sub>2</sub> level was elevated and TXA<sub>2</sub>/PGI<sub>2</sub> ratio decreased significantly.展开更多
Objective To investigate possible mechanisms underlying the antioxidant property(1)and the in vitro vasodilator effects(2)of the two ginsenosides,Rb1 and Rg1,in isolated rat renal and cerebral arteries.Methods Arteria...Objective To investigate possible mechanisms underlying the antioxidant property(1)and the in vitro vasodilator effects(2)of the two ginsenosides,Rb1 and Rg1,in isolated rat renal and cerebral arteries.Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension.To examine the antioxidant activity,some rings were exposed to a free radical-generating reaction(hypoxanthine and xanthine oxidase)with and without pre-treatment with ginsenosides.The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions,a condition that promoted Ca2+ influx in vascular smooth muscle cells.Results Ginsenosides protected endothelial function(endothelial nitric oxide-dependent relaxation)against oxidative stress;(2)ginsenoside Rb1 reduced the high K+-induced contractions of both renal and cerebral arteries while ginsenoside Rg1 relaxed the rat cerebral artery but not the renal artery.Conclusions Ginsenosides are vaso-protective via(1)the antioxidant activity which protects endothelial cell function and(2)the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle.The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.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.
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 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.
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 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.
文摘The compositions and contents of ginsenbsides in Panax ginseng,P.quinquefolium and P.notoginseng were determined and compared by reversed-phase High-Performance Liquid Chro- matography(HPLC).The method was performed on an Alltech Adsorbosphere HS C_(18) column,using 5×10^(-3)M NaH_2PO_4-H_3PO_4 buffer solution(pH 3.0)and acetonitrile-water(50:50)as gradient eluents. The baseline separation of ginsenosides Rb_1,Rb_2,Rb_1,Rc,Rd,Rf,Ro,and Re+Rg_1 was obtained in one analytical run.The ginsenosides are directly detected at 203 nm.The detection limit is 40μg at a signal to noise ratio of 3:1.The improved sample preparation and clean-up prior to injection with SEP-PAK C_(18)cartridge strongly reduced the front peaks caused by the impurities in the methanolic extracts of samples to afford a smooth baseline and clear background.The HPLC patterns of methanolic extracts mainly including the ginsenosides were found capable of serving as chemical fingerprints to differentiate the three species from each other.It was also found that there are no significant diffe- rences of the HPLC patterns between the wild Panax ginseng and the cultivated,the white and the red ginsengs,Chinese and Korean red ginsengs,and the tap roots of Panax ginseng collected in four consecutive months,only certain differences in contents of ginsenosides do exist.The contents of the nine major ginsenosides present in the rhizome,tap root and rootlet as well as the leaf of Panax quinquefolium were also determined and compared.
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
基金supported by the National Natural Science Foundation of China (Nos. 81673540,81530096,81573581,and 81920108033)the Natural Science Foundation of Shanghai (No. 16ZR1434100)。
文摘Ginsenosides are a series of glycosylated triterpenoids predominantly originated from Panax species with multiple pharmacological activities such as anti-aging, mediatory effect on the immune system and the nervous system. During the biosynthesis of ginsenosides, glycosyltransferases play essential roles by transferring various sugar moieties to the sapogenins in contributing to form structure and bioactivity diversified ginsenosides, which makes them important bioparts for synthetic biology-based production of these valuable ginsenosides. In this review, we summarized the functional elucidated glycosyltransferases responsible for ginsenoside biosynthesis, the advance in the protein engineering of UDP-glycosyltransferases(UGTs) and their application with the aim to provide in-depth understanding on ginsenoside-related UGTs for the production of rare ginsenosides applying synthetic biology-based microbial cell factories in the future.
基金the National Natural Science Foundation of China,No.81473617the Science and Technology Department of Hunan Province,No.2017SK50310the Hunan Education Department’s Science and Research Project,No.16K066.
文摘BACKGROUND Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality.The pathogenesis of liver cancer is closely associated with inflammation and immune response in the tumor microenvironment.New therapeutic agents for liver cancer,which can control inflammation and restore cellular immunity,are required.Curcumin(Cur)is a natural anti-inflammatory drug,and total ginsenosides(TG)are a commonly used immunoregulatory drug.Of note,both Cur and TG have been shown to exert anti-liver cancer effects.AIM To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer.METHODS A subcutaneous liver cancer model was established in BALB/c mice by a subcutaneous injection of hepatoma cell line.Animals were treated with Cur(200 mg/kg per day),TG(104 mg/kg per day or 520 mg/kg per day),the combination of Cur(200 mg/kg per day)and TG(104 mg/kg per day or 520 mg/kg per day),or 5-fluorouracil combined with cisplatin as a positive control for 21 d.Tumor volume was measured and the protein expression of programmed cell death 1 and programmed cell death 1 ligand 1(PD-L1),inflammatory indicators Toll like receptor 4(TLR4)and nuclear factor-κB(NF-κB),and vascular growth-related factors nitric oxide synthases(iNOS)and matrix metalloproteinase 9 were analyzed by Western blot analysis.CD4+CD25+Foxp3+regulatory T cells(Tregs)were counted by flow cytometry.RESULTS The combination therapy of Cur and TG significantly inhibited the growth of liver cancer,as compared to vehicle-treated animals,and TG showed dose dependence.Cur combined with TG-520 markedly decreased the protein expression of PD-L1(P<0.0001),while CD4+CD25+Foxp3+Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1.Cur combined with TG-520 also inhibited the cascade action mediated by NF-κB(P<0.0001),thus inhibiting the TLR4/NF-κB signalling pathway(P=0.0088,P<0.0001),which is associated with inflammation and acts on PD-L1.It also inhibited the NF-κB-MMP9 signalling pathway(P<0.0001),which is associated with tumor angiogenesis.CONCLUSION Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-κB-mediated inflammation and angiogenesis.
基金Project supported by the Program for New Century Excellent Talents in University of the Ministry of Education of China (No. NCET-05-0514)the Science and Technology Department of Zhejiang Province, China (No. 2008C22040)
文摘The effect of ginsenosides on proliferation of type A spermatogonia was investigated in 7-day-old mice. Spermatogonia were characterized by c-kit expression and cell proliferation was assessed by immunocytochemical demonstration of proliferating cell nuclear antigen (PCNA). After 72-h culture, Sertoli cells formed a confluent monolayer to which numerous spermatogonial colonies attached. Spermatogonia were positive for c-kit staining and showed high proliferating activity by PCNA expression. Ginsenosides (1.0～10 μg/ml) significantly stimulated proliferation of spermatogonia. Activation of protein kinase C (PKC) elicited proliferation of spermatogonia at 10-8 to 10-7 mol/L and the PKC inhibitor H7 inhibited this effect. Likewise, ginsenosides-stimulated spermatogonial proliferation was suppressed by combined treatment of H7. These results indicate that the proliferating effect of ginsenosides on mouse type A spermatogonia might be mediated by a mechanism involving the PKC signal transduction pathway.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.22078264,21978235,21776227 and 21706211)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2019JQ259)Northwest Northwest University Graduate Innovation Project(Grant No.YZZ17128).
文摘Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical applications.Ginseng extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary supplements.Despite the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic instability.Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled release.This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.
基金supported by Tianjin Key R&D Plan-Key Projects Supported by Science and Technology (19YFZCSN00010)
文摘Ginseng(Panax ginseng C.A.Meyer)as a common dietary adjunct is widely applied in Traditional Chinese Medicine due to its health-promoting properties,but the differences between white ginseng and red ginseng was rarely studied.In the present study,color parameters and scanning electron microscope(SEM)were determined to evaluate the differences of ginseng color and microstructure induced by processing procedure.Quantitative analysis of multi-components by a single-marker(QAMS)method and anti-α-amylase activity test were used to assess variations of chemical ingredients and pharmacological activity between white and red ginseng.Finally,molecular docking studies were carried out to screen out the most effective compound againstα-amylase.Results indicated that processing had a significant impact on the physicochemical properties and pharmacological activity of white and red ginseng.After processing,the color value of L*declined significantly.Red ginseng sample displayed a compact structure and presented of a gel layer on the surface compared to white ginseng.Additionally,the content of ginsenosides and the activity of anti-α-amylase decreased.The contents of total ginsenosides were positively correlated with the anti-α-amylase activities of ginseng,and ginsenoside Rb1 might be the most effective compound to inhibit the activity ofα-amylase.
基金supported by the National Key R&D Program of China(No.2017YFC1702302)。
文摘Ocotillol(OT)-type ginsenosides,one subtype of ginsenosides,consist of a dammarane skeleton and a tetrahydrofuran ring.Most naturally-occurring OT-type ginsenosides exist in Panax species,particularly in Panax quinquefolius,which may be attributed to the warm and humid climate of its native areas.Till now,merely 28 types of naturally-occurring OT-type ginsenosides have been isolated.In contrast,semi-synthesized OT-type ginsenosides are attracted considerable attentions.These ginsenosides can be obtained through oxidation and cyclization of side chains of dammarane-type ginsenosides,and other methods,which may change their physical and chemical properties and further improve their bioavailabilities.It is also notable that the pharmacological activities of ginsenosides are closely related to the stereoisomers caused by the configuration at C-20.Semi-synthesis of OT-type ginsenosides can facilitate our understanding of the biosynthesis,transformation and metabolism of OT-type ginsenosides in the body.This review will systematically summarize the research progress on naturally-occurring and semi-synthetic OT-type ginsenosides,which provides a theoretical basis for their bioactivity-guided research.
基金This work was supported by grants from the National Natural Science Foundation of China Key Program(NO.81530094)General Program(NO.81573574,81873193)the Science and Technology Development Project of Jilin Province(20190201283JC).
文摘Enrichment of trace bioactive constituents and metabolites from complex biological samples is challenging.This study presented a one-pot synthesis of magnetic polydopamine nanoparticles(Fe3O4@-SiO2@PDA NPs)with multiple recognition sites for the magnetic dispersive solid-phase extraction(MDSPE)of ginsenosides from rat plasma treated with white ginseng.The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a highresolution mass spectrometry with supplemental UNIFI libraries.Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides.The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80%after recycling 6 times.Furthermore,the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma.In comparison,conventional methanol method can only detect 8 ginsenosides from the same plasma samples.The proposed approach can provide methodological reference for the trace determination and characterization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.
基金supported by the postdoctoral fellowship of Jilin Institute of Chemical Technology
文摘A high-performance liquid chromatography method for the simultaneous determination of seven bioactive ginsenosides with diol stationary phase and isocratic elution was used to determin the ginsenosides in ginseng products. The optimization of the chromatographic separation was performed and the effect of temperature on separation was investigated. Using the validated procedure, the developed method was demonstrated to be more sensitive and effective than the conventional reversed-phase chromatography, where the chromatographic run is time-consuming to analyze a large number of ginsenosides. The results indicated that the developed method can be used for the quantitative determination of ginsenosides in complex ginseng samples.
基金Supported by the National Natural Science Foundation of China(21006075)the Natural Science Foundation of Hubei Province(2014CFA115)+1 种基金the New Century Excellent Talents in University(NCET-11-0966)the Key Project of Chinese Ministry of Education(213024A)
文摘A dynamic microwave-assisted extraction（DMAE） method is established for the extraction of total ginsenosides from ginseng fibrous roots. The extraction process has been simulated and its main affection factors（liquid/solid ratio K of solvent to ginseng powders（V/m）, irradiation time, irradiation temperature, extracting solution concentration, flow rate of solvent and microwave power） have been optimized by response surface methodology（RSM）. The optimum conditions of extraction are the liquid/solid ratio of 270 m L/g, the extraction temperature of 75 ℃, the extraction time of 35 min, ethanol concentration of 70%（V/V）, the solvent flow rate of 1.3 m L/min, and the microwave power of 500 W. The yield of ginsenosides obtained by the proposed DAME method is（15.0±0.7） %, which is well agreement with the yield predicted by the model. Compared with static microwave-assisted extraction, DMAE has a higher extraction yield and can avoid the degradation of ginsenoside.
基金National Natural Science Foundation of China(the Study of Electrochemical Mechanism on the Common Syndrome Factors Concerning Alzheimer's Disease and Parkinson's Disease,No.81273629)Prescription-syndrome Effect of Dihuang Yinzi Treating Alzheimer Disease and Parkinson Disease Based on the Theory of Syndrome Factor,No.81273898+2 种基金Study on the Synergistic Mechanism of Polygala Tenuifolia and Acorus Gramineus Improving Memory Through Modulating Synaptic Plasticity Molecular Network,No.81473375Shanxi Scholarship Council of China(the Study of Electrochemical Mechanism on the Common Syndrome Factors Concerning Brain Degenerative Diseases,No.2013-134)Shanxi Provincial Project of International Science Technology Cooperation(R&D of Screen System for Chinese Medicines of Anti-Neuronal Apoptosis Based on the Modulation Mechanism of Neuroglial Cells,No.2010081065)
文摘Ginsenosides are the main active components of ginseng,which have been reported to target brain tissues and produce multiple neuroprotective effects.Ginsenosides have been shown to improve learning ability and memory in normal aged animals,and in an animal model of memory impairment.However,its underlying pharmacological mechanisms are very complicated,especially with regard to its effects on the activation of protein kinases in neurons.Previous reports have shown that some protein kinases may be affected by ginsenosides,including protein kinase C,calcium/calmodulin-dependent protein kinase Ⅱ,c-Jun-N terminal kinase,and protein tyrosine kinase.In this paper,protein kinases that may underlie the mechanisms of ginsenosides will be discussed.
文摘Six hours after smoke inhalation injury in rabbits, the permeability of pulmonary vesselsand the aggregation of circulating platelets increased markedly accompanied with apparent patholog-ical changes in the trachea and lungs. Fifteen minutes after smoke inhalation injury in rabbits, an intravenous dose of ginsenosides or ketoprofenwas given to the animals respectively. 6 hours after medication, it was found that both the drugscould significantly alleviate the platelet aggregation, but only ginsenosides could alleviate theaugmentation of pulmonary vascular permeability and the pathological lesions in the trachea andlungs. In those rats injured by smoke inhalation, l hour after an intravenous dose of ginsenosides, theplasma PGI<sub>2</sub> level was elevated and TXA<sub>2</sub>/PGI<sub>2</sub> ratio decreased significantly.
文摘Objective To investigate possible mechanisms underlying the antioxidant property(1)and the in vitro vasodilator effects(2)of the two ginsenosides,Rb1 and Rg1,in isolated rat renal and cerebral arteries.Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension.To examine the antioxidant activity,some rings were exposed to a free radical-generating reaction(hypoxanthine and xanthine oxidase)with and without pre-treatment with ginsenosides.The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions,a condition that promoted Ca2+ influx in vascular smooth muscle cells.Results Ginsenosides protected endothelial function(endothelial nitric oxide-dependent relaxation)against oxidative stress;(2)ginsenoside Rb1 reduced the high K+-induced contractions of both renal and cerebral arteries while ginsenoside Rg1 relaxed the rat cerebral artery but not the renal artery.Conclusions Ginsenosides are vaso-protective via(1)the antioxidant activity which protects endothelial cell function and(2)the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle.The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.
