Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.Th...Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.展开更多
The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membr...The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.展开更多
Platycodon grandiflorus polysaccharide(PGP)is one of the main components of P.grandiflorus,but the mechanism of its anti-inflammatory effect has not been fully elucidated.The aim of this study was to evaluate the ther...Platycodon grandiflorus polysaccharide(PGP)is one of the main components of P.grandiflorus,but the mechanism of its anti-inflammatory effect has not been fully elucidated.The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and explore the underlying mechanisms.The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice,increased colon length,and reduced DAI,spleen index,and pathological damage within the colon.PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity.Meanwhile,PGP restored the levels of Th1,Th2,Th17,and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity.Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation.Taken together,PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.展开更多
Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berb...Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82104701)Science Fund Program for Outstanding Young Scholars in Universities of Anhui Province(Grant No.2022AH030064)+3 种基金Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(Grant No.2060302)Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(Grant No.2021KFKT10)China Agriculture Research System of MOF and MARA(Grant No.CARS-21)Talent Support Program of Anhui University of Chinese Medicine(Grant No.2020rcyb007).
文摘Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.
基金Supported by Anhui University of Chinese Medicine Foundation(No.2019zrzd13)the Key Project of Anhui Province Department of Education(No.KJ2019A0471)+1 种基金the Key Project of Liaoning Province Department of Education(No.2017LZD03)the National Nature Science Foundation of China(Nos.81473164,81703451,81873019 and 81873351,U1608283).
文摘The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.
基金supported by the National Science Foundation of China(No.81874348)the Academic Funding for Top Talents in Disciplines(Specialties)of Anhui Provincial Higher Education Institutes(No.gxbjZD2021056)the Exploratory Fund of Anhui University of Chinese Medicine(No.2021zxts31)。
文摘Platycodon grandiflorus polysaccharide(PGP)is one of the main components of P.grandiflorus,but the mechanism of its anti-inflammatory effect has not been fully elucidated.The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and explore the underlying mechanisms.The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice,increased colon length,and reduced DAI,spleen index,and pathological damage within the colon.PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity.Meanwhile,PGP restored the levels of Th1,Th2,Th17,and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity.Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation.Taken together,PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.
基金supported by the National Natural Science Foundation of China(grant numbers 81874348,81303239)the Natural Science Foundation of Anhui Province(grant numbers 1908085J29)+3 种基金the Key Research and Development Plan of Anhui Province(grant number 201904b11020023)the Open Project of State Key Laboratory of Natural Medicines(grant number SKLNMKF202007)the Provincial Foundation for Excellent Young Talents of Colleges and Universities of Anhui Province(grant number gxyqZD2018052)the Anhui Provincial Department of Education(grant number KJ2018A0282)。
文摘Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.