A simple, rapid and sensitive method for the determination of protopanaxadiol in rat plasma with ginsenoside Rh2 as internal standard was developed and validated. The analyte and internal standard were extracted from ...A simple, rapid and sensitive method for the determination of protopanaxadiol in rat plasma with ginsenoside Rh2 as internal standard was developed and validated. The analyte and internal standard were extracted from plasma with ether-dichloromethane（3：2, volume ratio） and then were analyzed by reversed-phase HPLC on a short Zorbax Extend C18 column（50 mm×2.1 mm, 3.5 μm i. d.） eluted with a mobile phase consisting of acetonitrile/methanol 0.10 mmol/L ammonium acetate（45：45：10, volume ratio） at 0.4 mL/min. Detection was performed on an Applied Biosystems Sciex API 4000 mass spectrometer set at unit resolution in the multiple reaction monitoring mode. Electrospray ionization was used for ion production. The assay method shows linear over a range of 5-2000 ng/mL and intra- and inter-day precisions over this range were 〈10.0% with accuracy ranged from 86.3% to 114.1%. The limit of detection was 500 pg/mL in the plasma. The method was successfully applied to a preclinical pharmacokinetic study of protopanaxadiol（17.5 mg/kg） administered as a single oral dose.展开更多
[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was...[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was subjected to structural modification and reacted with acid anhydrides to prepare derivatives,in order to improve the anti-tumor activity of protopanaxadiol.None of the five compounds designed and synthesized had been reported in the literature,and they were novel compounds.The anti-tumor activity of the derivatives was studies using MTS method.Taking cisplatin and paclitaxel as positive control drugs,the bioactivity of the compounds 1-5 on anti-tumor cell lines(HL-60 cells,SMMC-7721 cells,A-549 cells,MCF-7 cells and SW480 cells)in vitro was screened.[Results]The compound 5 showed inhibitory effect on HL-60 cells,SMMC-7721 cells and A-549 cells.[Conclusions]The acid anhydride esterification method is simple to operate and easy to control.This study has reference value for the structural modification and anti-tumor activity research of protopanaxadiol from P.notoginseng(Burk.)FH Chen.展开更多
Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical ...Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical cancer(CC)HeLa cells has yet to be thoroughly understood.In this research,we discovered that PPD effectively inhibits CC HeLa cell proliferation and cause morphological changes,with an IC50 measured at 34.18μM.Based on mRNA-seq analysis,we revealed the mechanism by which PPD inhibits HeLa cell proliferation.The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated significant enrichment of DGEs in the cell cycle and protein processing in the endoplasmic reticulum(PPER)pathway.By inducing DNA damage,PPD resulted in G0/G1 phase cell cycle arrest,inhibited Bcl-2 to cause ROS production,upregulated cytochrome c(Cyto-c)expression,thereby further reducing mitochondrial membrane potential(Δψm),activated the caspase family,and induced cell apoptosis.In addition,PPD promoted Ca^(2+)leakage,downregulated the PPER pathway(PERK,ATF6,and IRE1α),increased Chop expression levels,and mediated programmed cell death.These observations imply that PPD can induce apoptosis in HeLa cells,highlighting its potential as a novel natural therapeutic for cervical cancer.展开更多
Women are more prone to develop a risk of cervical cancer(CC),a cancer with a high metastatic rate and unfavorable prognoses.Novel natural therapeutic agents are urgently needed to potentially prevent the metastasis.T...Women are more prone to develop a risk of cervical cancer(CC),a cancer with a high metastatic rate and unfavorable prognoses.Novel natural therapeutic agents are urgently needed to potentially prevent the metastasis.This study has demonstrated the molecular processes underlying effect of protopanaxadiol(PPD)(molecule produced from ginseng)on HeLa cell metastasis.The results of colony formation assays showed a notable reduction in colony formation that was dose-dependent,peaking at 35μM PPD.5477 differentially expressed genes(DEGs)and 97 differentially expressed microRNAs(DEMs)were found using miRNA-seq and transcriptome analysis;these results were confirmed by RT-PCR.Relationships between these miRNAs and signaling pathways,specifically the PI3K-Akt and MAPK pathways,were revealed by bioinformatics research.Functional experiments verified that PPD inhibits cell metastasis by upregulating E-cadherin expression and downregulating MMP-2,MMP-9,N-cadherin,and vimentin expression levels.Furthermore,as indicated by lower levels of p-PI3K and p-AKT,PPD downregulated the RAS/MEK/ERK,p38 MAPK,and PI3K/AKT pathways.It was confirmed using the AKT activator SC79 that the PI3K/Akt pathway mediates the effects of PPD on migration.Overall,PPD efficiently blocked the advancement of CC through targeting the PI3K/Akt signaling pathway,offering a possible treatment strategy.展开更多
Hepatocellular carcinoma(HCC) is one of the most prevalent malignancies globally, posing a major challenge to global health care. Protopanaxadiol ginsenosides(PDs) have been believed to significantly improve liver dis...Hepatocellular carcinoma(HCC) is one of the most prevalent malignancies globally, posing a major challenge to global health care. Protopanaxadiol ginsenosides(PDs) have been believed to significantly improve liver diseases. PDs, such as Rg_(3), have been developed as a new class of anti-cancer drugs.Ginsenosides Rb_(1), Rd, Rg_(3), and Rh_(2) exhibit effective anti-inflammatory and anti-tumor activities.Studies have confirmed that PDs could be used to treat HCC. However, the mechanism of action of PDs on HCC remains unclear. In the study, we reviewed the anti-HCC effects and mechanisms of PDs including Rb_(1), Rd, Rg_(3), Rg_(5), Rh_(2), Rk_(1), and Compound K(CK). Then, we searched for relevant targets of PDs and HCC from databases and enriched them for analysis. Subsequently, molecular docking was simulated to reveal molecular mechanisms. We found that PDs may treat HCC through multiple signaling pathways and related targets. PDs could inhibit the proliferation, invasion, and metastasis of HCC while promoting apoptosis and inducing differentiation. In conclusion, this review and network pharmacological analysis might offer a direction for in-depth research on related mechanisms. These insights will aid in the direction of further pharmacological studies and the development of safe and effective clinical drugs.展开更多
Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drug...Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drugs delivery.However,cholesterol used as the fluidity buffer in conventional liposomes is a precursor for testosterone biosynthesis,which could convert to dihydrotestosterone,resulting in hair follicle damage and potentiating hair loss.To overcome the limitations,in this study we prepared a cholesterol-free liposome(PPD-Lip)using protopanaxadiol(PPD)instead of cholesterol to avoid the biosynthesis of testosterone which is adverse to alopecia therapy.PPD-Lip also worked as an active ingredient to facilitate hair growth by promoting dermal papilla cells proliferation and migration,upregulating mRNA levels of hair growth-related positive regulators,and accelerating angiogenesis in vitro.Meanwhile,it promoted hair regrowth in telogen and androgenetic alopecia mice models in vivo.In addition,our study showed that as the liposomal vehicle,PPD-Lip loaded with dutasteride exerted a stronger efficacy in the treatment of androgenetic alopecia and such a strategy could extend to other anti-alopecia agents.To the best of our knowledge,being easy for clinical transformation,the PPD-based liposomal delivery system provides a promising and multifunctional alternative platform for the delivery of alopecia treatment agents.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.39930180 and 30070879)
文摘A simple, rapid and sensitive method for the determination of protopanaxadiol in rat plasma with ginsenoside Rh2 as internal standard was developed and validated. The analyte and internal standard were extracted from plasma with ether-dichloromethane（3：2, volume ratio） and then were analyzed by reversed-phase HPLC on a short Zorbax Extend C18 column（50 mm×2.1 mm, 3.5 μm i. d.） eluted with a mobile phase consisting of acetonitrile/methanol 0.10 mmol/L ammonium acetate（45：45：10, volume ratio） at 0.4 mL/min. Detection was performed on an Applied Biosystems Sciex API 4000 mass spectrometer set at unit resolution in the multiple reaction monitoring mode. Electrospray ionization was used for ion production. The assay method shows linear over a range of 5-2000 ng/mL and intra- and inter-day precisions over this range were 〈10.0% with accuracy ranged from 86.3% to 114.1%. The limit of detection was 500 pg/mL in the plasma. The method was successfully applied to a preclinical pharmacokinetic study of protopanaxadiol（17.5 mg/kg） administered as a single oral dose.
基金Supported by Science&Technology Department of Yunnan Province-Kunming Medical University Joint Fund for Applied Basic Research[2017FE468(-001)]NSFC-Yunnan Joint Fund[U1502226].
文摘[Objectives]This paper aimed to prepare derivatives of protopanaxadiol from Panax notoginseng(Burk.)FH Chen with acid anhydrides and study their anti-tumor activity.[Methods]The 3-hydroxyl group of protopanaxadiol was subjected to structural modification and reacted with acid anhydrides to prepare derivatives,in order to improve the anti-tumor activity of protopanaxadiol.None of the five compounds designed and synthesized had been reported in the literature,and they were novel compounds.The anti-tumor activity of the derivatives was studies using MTS method.Taking cisplatin and paclitaxel as positive control drugs,the bioactivity of the compounds 1-5 on anti-tumor cell lines(HL-60 cells,SMMC-7721 cells,A-549 cells,MCF-7 cells and SW480 cells)in vitro was screened.[Results]The compound 5 showed inhibitory effect on HL-60 cells,SMMC-7721 cells and A-549 cells.[Conclusions]The acid anhydride esterification method is simple to operate and easy to control.This study has reference value for the structural modification and anti-tumor activity research of protopanaxadiol from P.notoginseng(Burk.)FH Chen.
基金supported by the National Key Research&Development Program of China(2022YFF1100305)the Juan de la Cierva Incorporación for Hui Cao(IJC2020-046055-I).
文摘Protopanaxadiol(PPD)is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects.However,the detailed anticancer mechanism of this compound in cervical cancer(CC)HeLa cells has yet to be thoroughly understood.In this research,we discovered that PPD effectively inhibits CC HeLa cell proliferation and cause morphological changes,with an IC50 measured at 34.18μM.Based on mRNA-seq analysis,we revealed the mechanism by which PPD inhibits HeLa cell proliferation.The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated significant enrichment of DGEs in the cell cycle and protein processing in the endoplasmic reticulum(PPER)pathway.By inducing DNA damage,PPD resulted in G0/G1 phase cell cycle arrest,inhibited Bcl-2 to cause ROS production,upregulated cytochrome c(Cyto-c)expression,thereby further reducing mitochondrial membrane potential(Δψm),activated the caspase family,and induced cell apoptosis.In addition,PPD promoted Ca^(2+)leakage,downregulated the PPER pathway(PERK,ATF6,and IRE1α),increased Chop expression levels,and mediated programmed cell death.These observations imply that PPD can induce apoptosis in HeLa cells,highlighting its potential as a novel natural therapeutic for cervical cancer.
基金funded by the National Key Research&Development Program of China(2022YFF1100305)the Juan de la Cierva Incorporación for Hui Cao(IJC2020-046055-I).
文摘Women are more prone to develop a risk of cervical cancer(CC),a cancer with a high metastatic rate and unfavorable prognoses.Novel natural therapeutic agents are urgently needed to potentially prevent the metastasis.This study has demonstrated the molecular processes underlying effect of protopanaxadiol(PPD)(molecule produced from ginseng)on HeLa cell metastasis.The results of colony formation assays showed a notable reduction in colony formation that was dose-dependent,peaking at 35μM PPD.5477 differentially expressed genes(DEGs)and 97 differentially expressed microRNAs(DEMs)were found using miRNA-seq and transcriptome analysis;these results were confirmed by RT-PCR.Relationships between these miRNAs and signaling pathways,specifically the PI3K-Akt and MAPK pathways,were revealed by bioinformatics research.Functional experiments verified that PPD inhibits cell metastasis by upregulating E-cadherin expression and downregulating MMP-2,MMP-9,N-cadherin,and vimentin expression levels.Furthermore,as indicated by lower levels of p-PI3K and p-AKT,PPD downregulated the RAS/MEK/ERK,p38 MAPK,and PI3K/AKT pathways.It was confirmed using the AKT activator SC79 that the PI3K/Akt pathway mediates the effects of PPD on migration.Overall,PPD efficiently blocked the advancement of CC through targeting the PI3K/Akt signaling pathway,offering a possible treatment strategy.
基金supported by the grants of National Natural Science Foundation of China (No. 82104465)Changchun Science & Technology Development Plan (No. 21ZGY11)the Scientific Research Planning Project of Jilin Provincial Department of Education (No. JJKH20220371KJ)。
文摘Hepatocellular carcinoma(HCC) is one of the most prevalent malignancies globally, posing a major challenge to global health care. Protopanaxadiol ginsenosides(PDs) have been believed to significantly improve liver diseases. PDs, such as Rg_(3), have been developed as a new class of anti-cancer drugs.Ginsenosides Rb_(1), Rd, Rg_(3), and Rh_(2) exhibit effective anti-inflammatory and anti-tumor activities.Studies have confirmed that PDs could be used to treat HCC. However, the mechanism of action of PDs on HCC remains unclear. In the study, we reviewed the anti-HCC effects and mechanisms of PDs including Rb_(1), Rd, Rg_(3), Rg_(5), Rh_(2), Rk_(1), and Compound K(CK). Then, we searched for relevant targets of PDs and HCC from databases and enriched them for analysis. Subsequently, molecular docking was simulated to reveal molecular mechanisms. We found that PDs may treat HCC through multiple signaling pathways and related targets. PDs could inhibit the proliferation, invasion, and metastasis of HCC while promoting apoptosis and inducing differentiation. In conclusion, this review and network pharmacological analysis might offer a direction for in-depth research on related mechanisms. These insights will aid in the direction of further pharmacological studies and the development of safe and effective clinical drugs.
基金supported by the National Natural Science Foundation of China(Nos.81973264,82104080,and 81773659)Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515010593,2019A1515011954,and 2021A1515012621)Guangdong Provincial Key Laboratory of Construction Foundation(No.2019B030301005).
文摘Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drugs delivery.However,cholesterol used as the fluidity buffer in conventional liposomes is a precursor for testosterone biosynthesis,which could convert to dihydrotestosterone,resulting in hair follicle damage and potentiating hair loss.To overcome the limitations,in this study we prepared a cholesterol-free liposome(PPD-Lip)using protopanaxadiol(PPD)instead of cholesterol to avoid the biosynthesis of testosterone which is adverse to alopecia therapy.PPD-Lip also worked as an active ingredient to facilitate hair growth by promoting dermal papilla cells proliferation and migration,upregulating mRNA levels of hair growth-related positive regulators,and accelerating angiogenesis in vitro.Meanwhile,it promoted hair regrowth in telogen and androgenetic alopecia mice models in vivo.In addition,our study showed that as the liposomal vehicle,PPD-Lip loaded with dutasteride exerted a stronger efficacy in the treatment of androgenetic alopecia and such a strategy could extend to other anti-alopecia agents.To the best of our knowledge,being easy for clinical transformation,the PPD-based liposomal delivery system provides a promising and multifunctional alternative platform for the delivery of alopecia treatment agents.
