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
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 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
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
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
Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosi...Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosides exert an effective antitumor role. Ginsenosides are a class of triterpenoid saponins primarily found in the plant genus Panax. Many monomer components are studied, the most often investigated are Rg3, and Rh2, etc. Reports have shown that ginsenosides can inhibit tumor cells by suppressing proliferation and metastasis, and promoting apoptosis. In addition, ginsenosides can enhance sensitivity to conventional chemotherapeutic drugs. In this review, the recent articles about anti-tumor of ginsenosides were reviewed to promote the further development of anti-tumor therapy.展开更多
A rat model was used to explore the therapeutic effects of ginsenosides (GS)on smoke inhalation long injury.It was found that GS could markedly alleviate the in-crease of pulmonary microvascular permeability (PMVP),re...A rat model was used to explore the therapeutic effects of ginsenosides (GS)on smoke inhalation long injury.It was found that GS could markedly alleviate the in-crease of pulmonary microvascular permeability (PMVP),reduction of protein and leu-cocyte content in the bronchoalveolar lavage fluid (BALF) of the smoke inhalation injur-ed rats.Histopathological studies of the lungs revealed that GS could distinctly reduceleucocyte accumulation in the vessels,interstitial infiltration of leucocytes,interstitial andintra-alveolar edema,hemorrhage and vascular congestion.Meanwhile,GS could inhibitthe elevation of malondialdehyde (MDA) in the lungs and serum and reverse the decrea-sed activity of superoxide dismutase (SOD) in the lungs after smoke inhalation.In addi-tion experiments in vitro also showed the inhibition of lipid peroxidation in lung homo-genate and elimination of superoxide anions hydroxyl radicals effectively by GS in properdoses.These results imply that there is close interrelationship between the therapeuticefficiency of GS on smoke inhalation lung injury and its capability of antioxidation.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
Objective: To examine the anti-obesity effects of ginsenosides in Korea Red Ginseng(KRG, Panax ginseng) in rats fed with a high-fat diet(HFD). Methods: Twenty-five 4-week-old obesity rats after receiving an HFD for 5 ...Objective: To examine the anti-obesity effects of ginsenosides in Korea Red Ginseng(KRG, Panax ginseng) in rats fed with a high-fat diet(HFD). Methods: Twenty-five 4-week-old obesity rats after receiving an HFD for 5 weeks;subsequently, they were additionally treated with ginsenosides Rb1, Rd, Rg1, or Re(10 mg/kg, intraperitoneal injection) for a further 3 weeks(n=5 in each group). The control rats were fed a normal diet. The food consumption, body weight, locomotor activity, serum lipids, adipose tissues, nitric oxide(NO) expression, leptin, neuropeptide Y(NPY), cholecystokinin(CCK) in the brains were measured. Results: In the HFD-fed rats, body weight, body fat mass, serum levels of leptin and NO were significantly higher than in the control rats(P<0.05 or P<0.01). However, the treatment of Rd, Re, and Rb1 markedly decreased body fat mass and body weight(P<0.05). The serum level of leptin and NO in ginsenoside-treated rats were markedly lower than the control group(P<0.01). The expression of NPY and CCK in the hypothalamic nuclei showed insignificant difference among groups. However, the expression of NPY immunoreactive neurons in the hypothalamus was significantly reduced in the Rb1-treated group(P<0.05). Conclusion: PD-type ginsenoside Rb1 from the crude saponins of KRG may be a useful compound for the treatment of obesity and related disorders through the modulation of peripheral and central appetite-regulating signals.展开更多
Objective:Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation.Both pathogens and antagonistic fungi have been reported to induce plant resistance responses,thereby promoting the accumulation of sec...Objective:Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation.Both pathogens and antagonistic fungi have been reported to induce plant resistance responses,thereby promoting the accumulation of secondary metabolites.The purpose of this experiment is to compare the advantages of one of the two fungi,in order to screen out more effective elicitors.The mechanism of fungal elicitor-induced plant resistance response is supplemented.Methods:A gradient dilution and the dural culture were carried out to screen strains.The test strain was identified by morphology and 18 s rDNA.The effect of different concentrations(0,50,100,200,400 mg/L)ofPenicillium sp.YJM-2013 and F.oxysporum on fresh weight and ginsenosides accumulation were tested.Signal molecules transduction,expression of transcription factors and functional genes were investigated to study the induction mechanism of fungal elicitors.Results:Antagonistic fungi ofF.oxysporum was identified as Penicillium sp.YJM-2013,which reduced root biomass.The total ginsenosides content of Panax ginseng adventitious roots reached the maximum(48.95±0.97 mg/g)treated with Penicillium sp.YJM-2013 at 200 mg/L,higher than control by 2.59-fold,in which protopanoxadiol-type ginsenosides(PPD)were increased by 4.57 times.Moreover,Penicillium sp.YJM-2013 activated defense signaling molecules,up-regulated the expression of PgWRKY 1,2,3,5,7,9 and functional genes in ginsenosides synthesis.Conclusion:Compared with the pathogenic fungi F.oxysporum,antagonistic fungi Penicillium sp.YJM-2013 was more conducive to the accumulation of ginsenosides in P.ginseng adventitious roots.Penicillium sp.YJM-2013 promoted the accumulation of ginsenosides by intensifying the generation of signal molecules,activating the expression of transcription factors and functional genes.展开更多
Objective:To develop a reversed-phase high-performance liquid chromatography method for the quantification of major ginsenosides in red ginseng(RG,the steamed and dried root of the cultivar of Panax ginseng C.A.Mey).M...Objective:To develop a reversed-phase high-performance liquid chromatography method for the quantification of major ginsenosides in red ginseng(RG,the steamed and dried root of the cultivar of Panax ginseng C.A.Mey).Methods:A feasible method was developed in strict accordance with chromatographic properties of eight ginsenosides.Their contents could be unveiled with conventional external standard method,or as an alternative,using ginsenoside Rg1 as the single reference standard by means of seven conversion factors.Those parameters had been validated on different chromatographic columns and instruments.Results:Twenty-one batches of RG samples were determined.In addition,the chromatograms of RG and confusing species,including Panax ginseng,Panax quinquefolium,and Panax notoginseng,were apparently different.Conclusions:The method was proved to be efficient for the quality control of RG.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
Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from ...Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.展开更多
Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but als...Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but also controlled by a variety of structural genes.Nonetheless,the molecular mechanism underlying ginsenoside biosynthesis has always been a topic in the discussion of ginseng secondary metabolites.Squalene epoxidase(SQE)is a key enzyme in the mevalonic acid pathway,which affects the biosynthesis of secondary metabolites such as terpenoid.Using ginseng transcriptome,expression,and ginsenoside content databases,this study employed bioinformatic methods to systematically analyze the genes encoding SQE in ginseng.We first selected six PgSQE candidates that were closely involved in ginsenoside biosynthesis and then identified PgSQE08-01 to be highly associated with ginsenoside biosynthesis.Next,we constructed the overexpression vector pCAMBIA3301-PgSQE08-01 and the RNAi vector pART27-PgSQE08-01 and transformed ginseng adventitious roots using Agrobacterium rhizogenes,to obtain positive hairy-root clones.Thereafter,quantitative reverse transcriptionpolymerase chain reaction and high-performance liquid chromatography were used to determine the expression of relevant genes and ginsenoside content,respectively.Then,we focused on the function of PgSQE08-01 gene,which was noted to be involved in ginsenoside biosynthesis.Thus,these findings not only provided a molecular basis for the identification of important functional genes in ginseng but also enriched genetic resources for the biosynthesis of ginsenosides using synthetic biology.展开更多
Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accu...Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accumulated in plant roots,stems,leaves,and flowers.The content and composition of ginsenosides are varied in different ginseng species,and in different parts of a certain plant.In this review,we summarized the representative saponins structures,their distributions and the contents in nearly 20 Panax species,and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis.We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants,and highlighted the current three major biotechnological applications for ginsenosides production.This review covered advances in the past four decades,providing more clues for chemical discrimination and assessment on certain ginseng plants,new perspectives for rational evaluation and utilization of ginseng resource,and potential strategies for production of specific ginsenosides.展开更多
Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity.Traditional approaches for producing them rely on direct extraction from Panax ginseng,enzymatic c...Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity.Traditional approaches for producing them rely on direct extraction from Panax ginseng,enzymatic catalysis or chemical synthesis,all of which result in low yield and high cost.Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products.Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-OGlc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system.The titers of F2 and 3β,20S-Di-O-GlcDM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level,respectively,by multistep metabolic engineering strategies.Additionally,pharmacological evaluation showed that both F2and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-GlcDM was even better.Furthermore,the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor.To our knowledge,this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM,and achieving their de novo biosynthesis by the engineered yeasts.Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass,which lays a foundation for drug research and development.展开更多
Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,...Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.展开更多
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 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.
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.
文摘Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosides exert an effective antitumor role. Ginsenosides are a class of triterpenoid saponins primarily found in the plant genus Panax. Many monomer components are studied, the most often investigated are Rg3, and Rh2, etc. Reports have shown that ginsenosides can inhibit tumor cells by suppressing proliferation and metastasis, and promoting apoptosis. In addition, ginsenosides can enhance sensitivity to conventional chemotherapeutic drugs. In this review, the recent articles about anti-tumor of ginsenosides were reviewed to promote the further development of anti-tumor therapy.
文摘A rat model was used to explore the therapeutic effects of ginsenosides (GS)on smoke inhalation long injury.It was found that GS could markedly alleviate the in-crease of pulmonary microvascular permeability (PMVP),reduction of protein and leu-cocyte content in the bronchoalveolar lavage fluid (BALF) of the smoke inhalation injur-ed rats.Histopathological studies of the lungs revealed that GS could distinctly reduceleucocyte accumulation in the vessels,interstitial infiltration of leucocytes,interstitial andintra-alveolar edema,hemorrhage and vascular congestion.Meanwhile,GS could inhibitthe elevation of malondialdehyde (MDA) in the lungs and serum and reverse the decrea-sed activity of superoxide dismutase (SOD) in the lungs after smoke inhalation.In addi-tion experiments in vitro also showed the inhibition of lipid peroxidation in lung homo-genate and elimination of superoxide anions hydroxyl radicals effectively by GS in properdoses.These results imply that there is close interrelationship between the therapeuticefficiency of GS on smoke inhalation lung injury and its capability of antioxidation.
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Supported by the a grant from Integrative Medicine Research Project through Wonkwang University Jangheung Integrative Medical Hospital,funded by the Ministry of Health&Welfare,Republic of Korea(No.1465027127)Kyung Hee University in 2019(KHU-20191211)
文摘Objective: To examine the anti-obesity effects of ginsenosides in Korea Red Ginseng(KRG, Panax ginseng) in rats fed with a high-fat diet(HFD). Methods: Twenty-five 4-week-old obesity rats after receiving an HFD for 5 weeks;subsequently, they were additionally treated with ginsenosides Rb1, Rd, Rg1, or Re(10 mg/kg, intraperitoneal injection) for a further 3 weeks(n=5 in each group). The control rats were fed a normal diet. The food consumption, body weight, locomotor activity, serum lipids, adipose tissues, nitric oxide(NO) expression, leptin, neuropeptide Y(NPY), cholecystokinin(CCK) in the brains were measured. Results: In the HFD-fed rats, body weight, body fat mass, serum levels of leptin and NO were significantly higher than in the control rats(P<0.05 or P<0.01). However, the treatment of Rd, Re, and Rb1 markedly decreased body fat mass and body weight(P<0.05). The serum level of leptin and NO in ginsenoside-treated rats were markedly lower than the control group(P<0.01). The expression of NPY and CCK in the hypothalamic nuclei showed insignificant difference among groups. However, the expression of NPY immunoreactive neurons in the hypothalamus was significantly reduced in the Rb1-treated group(P<0.05). Conclusion: PD-type ginsenoside Rb1 from the crude saponins of KRG may be a useful compound for the treatment of obesity and related disorders through the modulation of peripheral and central appetite-regulating signals.
基金The work was supported by National Natural Science Foundation of China NSFC(No.81703639).
文摘Objective:Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation.Both pathogens and antagonistic fungi have been reported to induce plant resistance responses,thereby promoting the accumulation of secondary metabolites.The purpose of this experiment is to compare the advantages of one of the two fungi,in order to screen out more effective elicitors.The mechanism of fungal elicitor-induced plant resistance response is supplemented.Methods:A gradient dilution and the dural culture were carried out to screen strains.The test strain was identified by morphology and 18 s rDNA.The effect of different concentrations(0,50,100,200,400 mg/L)ofPenicillium sp.YJM-2013 and F.oxysporum on fresh weight and ginsenosides accumulation were tested.Signal molecules transduction,expression of transcription factors and functional genes were investigated to study the induction mechanism of fungal elicitors.Results:Antagonistic fungi ofF.oxysporum was identified as Penicillium sp.YJM-2013,which reduced root biomass.The total ginsenosides content of Panax ginseng adventitious roots reached the maximum(48.95±0.97 mg/g)treated with Penicillium sp.YJM-2013 at 200 mg/L,higher than control by 2.59-fold,in which protopanoxadiol-type ginsenosides(PPD)were increased by 4.57 times.Moreover,Penicillium sp.YJM-2013 activated defense signaling molecules,up-regulated the expression of PgWRKY 1,2,3,5,7,9 and functional genes in ginsenosides synthesis.Conclusion:Compared with the pathogenic fungi F.oxysporum,antagonistic fungi Penicillium sp.YJM-2013 was more conducive to the accumulation of ginsenosides in P.ginseng adventitious roots.Penicillium sp.YJM-2013 promoted the accumulation of ginsenosides by intensifying the generation of signal molecules,activating the expression of transcription factors and functional genes.
基金supported by the National Natural Science Foundation of China(No.81530095,81673591)。
文摘Objective:To develop a reversed-phase high-performance liquid chromatography method for the quantification of major ginsenosides in red ginseng(RG,the steamed and dried root of the cultivar of Panax ginseng C.A.Mey).Methods:A feasible method was developed in strict accordance with chromatographic properties of eight ginsenosides.Their contents could be unveiled with conventional external standard method,or as an alternative,using ginsenoside Rg1 as the single reference standard by means of seven conversion factors.Those parameters had been validated on different chromatographic columns and instruments.Results:Twenty-one batches of RG samples were determined.In addition,the chromatograms of RG and confusing species,including Panax ginseng,Panax quinquefolium,and Panax notoginseng,were apparently different.Conclusions:The method was proved to be efficient for the quality control of RG.
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supported by the grant International Cooperation 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)the Basic Research Funds from the Ministry of Education(1000061223731).
文摘Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.
基金This work was supported by an award from the Department of Science and Technology of Jilin Province(20210402043GH and 20210204063YY).
文摘Panax ginseng C.A.Mey.is an important plant species used in traditional Chinese medicine,whose primary active ingredient is a ginsenoside.Ginsenoside biosynthesis is not only regulated by transcription factors but also controlled by a variety of structural genes.Nonetheless,the molecular mechanism underlying ginsenoside biosynthesis has always been a topic in the discussion of ginseng secondary metabolites.Squalene epoxidase(SQE)is a key enzyme in the mevalonic acid pathway,which affects the biosynthesis of secondary metabolites such as terpenoid.Using ginseng transcriptome,expression,and ginsenoside content databases,this study employed bioinformatic methods to systematically analyze the genes encoding SQE in ginseng.We first selected six PgSQE candidates that were closely involved in ginsenoside biosynthesis and then identified PgSQE08-01 to be highly associated with ginsenoside biosynthesis.Next,we constructed the overexpression vector pCAMBIA3301-PgSQE08-01 and the RNAi vector pART27-PgSQE08-01 and transformed ginseng adventitious roots using Agrobacterium rhizogenes,to obtain positive hairy-root clones.Thereafter,quantitative reverse transcriptionpolymerase chain reaction and high-performance liquid chromatography were used to determine the expression of relevant genes and ginsenoside content,respectively.Then,we focused on the function of PgSQE08-01 gene,which was noted to be involved in ginsenoside biosynthesis.Thus,these findings not only provided a molecular basis for the identification of important functional genes in ginseng but also enriched genetic resources for the biosynthesis of ginsenosides using synthetic biology.
基金supported by National Natural Science Foundation of China(No.81673540,No.81530096)Natural Science Foundation of Shanghai(No.16ZR1434100,China)Shanghai local Science and Technology Development Fund Program guided by the Central Government(YDZX20203100002948,China)
文摘Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accumulated in plant roots,stems,leaves,and flowers.The content and composition of ginsenosides are varied in different ginseng species,and in different parts of a certain plant.In this review,we summarized the representative saponins structures,their distributions and the contents in nearly 20 Panax species,and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis.We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants,and highlighted the current three major biotechnological applications for ginsenosides production.This review covered advances in the past four decades,providing more clues for chemical discrimination and assessment on certain ginseng plants,new perspectives for rational evaluation and utilization of ginseng resource,and potential strategies for production of specific ginsenosides.
基金financially supported by the grants of CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-029,China)the Beijing Natural Science Foundation(7212158,China)+1 种基金the National Natural Science Foundation of China(81673341)PUMC Disciplinary Development of Synthetic Biology(201920100801,China)。
文摘Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity.Traditional approaches for producing them rely on direct extraction from Panax ginseng,enzymatic catalysis or chemical synthesis,all of which result in low yield and high cost.Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products.Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-OGlc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system.The titers of F2 and 3β,20S-Di-O-GlcDM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level,respectively,by multistep metabolic engineering strategies.Additionally,pharmacological evaluation showed that both F2and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-GlcDM was even better.Furthermore,the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor.To our knowledge,this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM,and achieving their de novo biosynthesis by the engineered yeasts.Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass,which lays a foundation for drug research and development.
基金supported by the National Key R&D Program of China(Grant No.:2021YFC2101500)the National Natural Science Foundation of China(Grant Nos.:22078264,21978235,22108224,and 21978236)+2 种基金the Natural Science Basic Research Program of Shaanxi,China(Grant Nos.:2023-JC-JQ-17 and 2023-JCQN-0109)the Xi'an Science and Technology Project,China(Project No.:20191422315KYPT014JC016)Key Research and Development Program of Shaanxi,China(Grant No.:2022ZDLSF05-12).
文摘Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.
