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
In the present study, we developed a sensitive and efficient high performance liquid chromatography （HPLC） method for the simultaneous determination of three ginsenosides （Rg1, Re, Rb1） in rat plasma. Chromatograp...In the present study, we developed a sensitive and efficient high performance liquid chromatography （HPLC） method for the simultaneous determination of three ginsenosides （Rg1, Re, Rb1） in rat plasma. Chromatographic separation was performed on a C18 （150 min×4.6 mm） column utilizing gradient elution profile and a mobile phase consisting of （A） water and （B） acetonitrile. The calibration curve, with a great correlation coefficient greater than 0.998, was linear over the range of 1.0-30.0 μg/mL for ginsenoside Rgl, 0.5-15.0 μg/mL for ginsenoside Re, and 0.5-200.0 μg/mL for ginsenoside Rb1. The intra- and inter-day precisions for three ginsenosides （Rg1, Re, Rb1） were all less than 6.0%, and average recovery, examined at three concentration levels, ranged from 96.1% to 118.6%. The samples was stable within 24 h at 4 ℃ storage, and 30 d at -20 ℃ storage with three freeze-thaw-assay cycles. The low limits of quantification （LOQ） were 1.0, 0.5 and 0.5 μg/mL for Rg1, Re and Rb1, respectively. Taken together, the newly developed method was successfully applied to study the pharmacokinetics of ginsenoside Rg1, Re and Rb1 in rat plasma after intravenous administration of SHENMAI injection （SMI）.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
Ginsenosides Rgl, Re, Rb1, Rc, Rb2, Rb3, and Rd in different parts of the American ginseng plant were investigated. The extraction process was a pressurized microwave-assisted extraction（PMAE）. The seven ginsenoside...Ginsenosides Rgl, Re, Rb1, Rc, Rb2, Rb3, and Rd in different parts of the American ginseng plant were investigated. The extraction process was a pressurized microwave-assisted extraction（PMAE）. The seven ginsenosides were separated and determined by high-performance liquid chromatography（HPLC） with a ultraviolet（UV） detector, at 203 nm. The experiment results showed significant variations in the individual ginsenoside contents of the American ginseng in different parts and ages of the plant. The results demonstrated that the leaves, root hairs, and rhizomes of Panax quinquefolius L. contained higher ginsenoside contents, followed by the main roots and stems. The leaves contained dramatically higher levels of ginsenoside Rg1 Rb3, and Rd than the other four parts. Higher contents of Rb1 and Re were present in the main roots, root hairs, and rhizomes. The amount of ginsenoside content in the stems was the lowest. The total content of the seven ginsenosides in main roots, root hairs and rhizomes increased with the age of the plant. In contrast, the ginsenoside contents in the leaves and stems decreased with a year of growth.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
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
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
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
A high performance liquid chromatography coupled with electrospray ionization-tandem mass spectrome try（HPLC-ESI-MS/MS） method was developed for the analysis and identification of ginsenosides in the extracts of raw...A high performance liquid chromatography coupled with electrospray ionization-tandem mass spectrome try（HPLC-ESI-MS/MS） method was developed for the analysis and identification of ginsenosides in the extracts of raw Panax ginseng（RPG） and steamed Panax ginseng at high temperatures（SPGHT）. A total of 25 ginsenosides were extracted include of which 10 low-polar ginsenosides, such as ginsenosides F4, Rk3, Rh4, 20S-Rg3, 20R-Rg3 and so on, were identified according to their HPLC retention time and MS/MS data. The results indicated that the low polar ginsenosides were seldom found in RPG. For the exploration of the transformation pattern of the ginsenosides in steam processing, the standards of ginsenosides Re, Rg1, Rb1, Rc, Rb2, Rb3 and Rd were selected and hydrolyzed at a temperature of 120 oC. The results show that these polar ginsenosides can be converted to low-polar ginsenosides such as Rg2, Rg6, F4, Rk3 and Rg5 by hydrolyzing the sugar chains.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
Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier （BBB） remains unclear. The present study was designed to qualitatively determine the distr...Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier （BBB） remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rgl was detectable and no other ginsenosides or their metabolites were found. No ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed the localization of ginsenosides in brain tissues. Furthermore, immunofluorescence double staining revealed that ginsenosides widely existed in vascular endotheliocytes and astrocytes, and in few neurons. These results indicated that Rgl was the main component that entered the brain after oral administration of ginseng total saponins and that ginsenosides could cross the BBB, although the transport capability ofginsenosides through the BBB may be poor.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
Two new acetylated ginsenosides, 20（S）-protopanaxatriol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-D-6＇-O-acetylglucopyranoside （1） and 20（R）-protopanaxatrol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-o-6＇-O-acetylglu...Two new acetylated ginsenosides, 20（S）-protopanaxatriol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-D-6＇-O-acetylglucopyranoside （1） and 20（R）-protopanaxatrol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-o-6＇-O-acetylglucopyranoside （2）, were isolated from the roots of Panax quinquefolium. The structures were elucidated on the basis of spectroscopic techniques and chemical means.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
AIM: Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routi...AIM: Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routine quality control is restricted by the limited availability of reference substances. Using an easily available single marker as a reference standard to determine multiple or total analogs should be a practical option. METHOD: In this study, the Ultra-HPLC method was used for the baseline separation of the main components in ginseng extracts. Using a plant chemical component database, ginsenosides in ginseng extracts were identified by Ultra-HPLC-MS analysis. The charged aerosol detection(CAD) system with post-column compensation of the gradient generates a similar response for identical amounts of different analytes, and thus, the content of each ginsenoside in ginseng extracts was determined by comparing the analyte peak area with the reference standard(determination of total analogs by single marker, DTSM). The total ginsenoside content was determined by the summation of reference standard and other ginsenoside components. RESULTS: The results showed that DTSM approaches were available for the determination of total ginsenosides in a high purity ginseng extract because of the removal of impurities. In contrast, DTSM approaches might be suitable for determination of multiple ginsenosides without interference from impurities in the crude ginseng extract. CONCLUSION: Future practical studies similar to the present study should be conducted to verify that DTSM approaches based on CAD with post-column inverse gradient for uniform response are ideal for the quality control of plant products.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Science and Technology Research project of Heilongjiang Province Department of Education(Grant No.12541740)
文摘In the present study, we developed a sensitive and efficient high performance liquid chromatography （HPLC） method for the simultaneous determination of three ginsenosides （Rg1, Re, Rb1） in rat plasma. Chromatographic separation was performed on a C18 （150 min×4.6 mm） column utilizing gradient elution profile and a mobile phase consisting of （A） water and （B） acetonitrile. The calibration curve, with a great correlation coefficient greater than 0.998, was linear over the range of 1.0-30.0 μg/mL for ginsenoside Rgl, 0.5-15.0 μg/mL for ginsenoside Re, and 0.5-200.0 μg/mL for ginsenoside Rb1. The intra- and inter-day precisions for three ginsenosides （Rg1, Re, Rb1） were all less than 6.0%, and average recovery, examined at three concentration levels, ranged from 96.1% to 118.6%. The samples was stable within 24 h at 4 ℃ storage, and 30 d at -20 ℃ storage with three freeze-thaw-assay cycles. The low limits of quantification （LOQ） were 1.0, 0.5 and 0.5 μg/mL for Rg1, Re and Rb1, respectively. Taken together, the newly developed method was successfully applied to study the pharmacokinetics of ginsenoside Rg1, Re and Rb1 in rat plasma after intravenous administration of SHENMAI injection （SMI）.
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.20875037)
文摘Ginsenosides Rgl, Re, Rb1, Rc, Rb2, Rb3, and Rd in different parts of the American ginseng plant were investigated. The extraction process was a pressurized microwave-assisted extraction（PMAE）. The seven ginsenosides were separated and determined by high-performance liquid chromatography（HPLC） with a ultraviolet（UV） detector, at 203 nm. The experiment results showed significant variations in the individual ginsenoside contents of the American ginseng in different parts and ages of the plant. The results demonstrated that the leaves, root hairs, and rhizomes of Panax quinquefolius L. contained higher ginsenoside contents, followed by the main roots and stems. The leaves contained dramatically higher levels of ginsenoside Rg1 Rb3, and Rd than the other four parts. Higher contents of Rb1 and Re were present in the main roots, root hairs, and rhizomes. The amount of ginsenoside content in the stems was the lowest. The total content of the seven ginsenosides in main roots, root hairs and rhizomes increased with the age of the plant. In contrast, the ginsenoside contents in the leaves and stems decreased with a year of growth.
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Supported by the Key Project of Jilin Provincial Science and Technology Department, China(No.20090908)the Project of Changchun Science and Technology Bureau, China(No.2008256)the Special Cooperative Project for Hitech Industrializa-tion of Jilin Provincial Science and Chinese Academy of Sciences, China(No.2009SYHZ0026)
文摘A high performance liquid chromatography coupled with electrospray ionization-tandem mass spectrome try（HPLC-ESI-MS/MS） method was developed for the analysis and identification of ginsenosides in the extracts of raw Panax ginseng（RPG） and steamed Panax ginseng at high temperatures（SPGHT）. A total of 25 ginsenosides were extracted include of which 10 low-polar ginsenosides, such as ginsenosides F4, Rk3, Rh4, 20S-Rg3, 20R-Rg3 and so on, were identified according to their HPLC retention time and MS/MS data. The results indicated that the low polar ginsenosides were seldom found in RPG. For the exploration of the transformation pattern of the ginsenosides in steam processing, the standards of ginsenosides Re, Rg1, Rb1, Rc, Rb2, Rb3 and Rd were selected and hydrolyzed at a temperature of 120 oC. The results show that these polar ginsenosides can be converted to low-polar ginsenosides such as Rg2, Rg6, F4, Rk3 and Rg5 by hydrolyzing the sugar chains.
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 the National Natural Science Foundation of China(Nos.81303246,81703732)Projects of Priority-Discipline for Colleges and Universities of Jiangsu Province(integration of traditional Chinese and western medicine)
文摘Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier （BBB） remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rgl was detectable and no other ginsenosides or their metabolites were found. No ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed the localization of ginsenosides in brain tissues. Furthermore, immunofluorescence double staining revealed that ginsenosides widely existed in vascular endotheliocytes and astrocytes, and in few neurons. These results indicated that Rgl was the main component that entered the brain after oral administration of ginseng total saponins and that ginsenosides could cross the BBB, although the transport capability ofginsenosides through the BBB may be poor.
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the National Basic Research Program of China(No.2005CB523301).
文摘Two new acetylated ginsenosides, 20（S）-protopanaxatriol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-D-6＇-O-acetylglucopyranoside （1） and 20（R）-protopanaxatrol-6-O-α-L-rhamnopyranosyl （1 → 2）-β-o-6＇-O-acetylglucopyranoside （2）, were isolated from the roots of Panax quinquefolium. The structures were elucidated on the basis of spectroscopic techniques and chemical means.
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 National Natural Science Foundation of China(81303246)the Jiangsu Provincial Natural Science Foundation of China(BK2011815)+1 种基金the ‘Qing Lan’ Project from Jiangsu Provincial Framework Teacher Support Schemethe Projects of priority-discipline for colleges and universities of Jiangsu Province
文摘AIM: Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routine quality control is restricted by the limited availability of reference substances. Using an easily available single marker as a reference standard to determine multiple or total analogs should be a practical option. METHOD: In this study, the Ultra-HPLC method was used for the baseline separation of the main components in ginseng extracts. Using a plant chemical component database, ginsenosides in ginseng extracts were identified by Ultra-HPLC-MS analysis. The charged aerosol detection(CAD) system with post-column compensation of the gradient generates a similar response for identical amounts of different analytes, and thus, the content of each ginsenoside in ginseng extracts was determined by comparing the analyte peak area with the reference standard(determination of total analogs by single marker, DTSM). The total ginsenoside content was determined by the summation of reference standard and other ginsenoside components. RESULTS: The results showed that DTSM approaches were available for the determination of total ginsenosides in a high purity ginseng extract because of the removal of impurities. In contrast, DTSM approaches might be suitable for determination of multiple ginsenosides without interference from impurities in the crude ginseng extract. CONCLUSION: Future practical studies similar to the present study should be conducted to verify that DTSM approaches based on CAD with post-column inverse gradient for uniform response are ideal for the quality control of plant products.
