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
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 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.
