OBJECTIVE Bergapten(BG),is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immun...OBJECTIVE Bergapten(BG),is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg^(-1)) subcutaneous injections for 30 d.To evaluate the establishment of the agingrelated effect in mice,serum samples of BALB/c mice were collected from tail vein.Aging BALB/c mice were freely divided into three groups:negative control group received 1% Tween 80 solution only,named D-gal group.Positive groups were received BG administration at the dose of 20 and 100 mg·kg^(-1),named D-gal+BG(20) group and D-gal+BG(100) group,respectively.Effects of bergapten on T lympho.cyte proliferation and flow cytometry were assessed by using the splenic cell suspension.Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ) and interleukin-4(IL-4)levels of the isolated serum.Immunophenotype was determined by using mixture of antibodies includ.ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg^(-1)) therapy can modulate immu.nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat.ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1) and T helper 2(Th2) cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg^(-1)) restored antigen-specific CD4+ and CD8+ T cells in aging models(P<0.05,P<0.01),which may help to curing chronic infections.CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.展开更多
Acute lung injury(ALI)or its more severe form,acute respiratory distress syndrome,is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization.However,current therapeutic strateg...Acute lung injury(ALI)or its more severe form,acute respiratory distress syndrome,is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization.However,current therapeutic strategies for ALI are controversial due to their side effects,restricted administration routes,or poor targeted delivery.The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy.One such compound is the bergapten,a coumarin,which has been isolated from Ficus simplicissima Lour.However,it’s been used as an anti-cancer drug and it’s effects on ALI remain unexplored.The poor solubility and biodistribution of bergapten heavily limit its application.In this timely report,we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome,named as Ber-lipo.A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial-endothelial integrity.In a lipopolysaccharide(LPS)-induced ALI mouse model,Ber-lipo can target inflamed lungs and significantly improve lung edema,tissue injury,and pulmonary function,relieve body weight loss,pulmonary permeability,and proinflammatory status,and especially maintain a balance of M1/M2 macrophage polarization.Furthermore,RNA sequencing analysis showed Ber-lipo’s potential in effectively treating inflammatory lung diseases such as pneumonia,inhibiting proinflammatory signals,and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues.Molecular docking and Western blot analyses validated that Ber-lipo suppressed the acti-vation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression.In conclusion,this study demonstrates for the first time that new inhalable nanomedicine(Ber-lipo)can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway,hence providing a promising strategy for enhanced ALI therapy in the clinic.展开更多
Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vin...Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vincristine through the membrane of MDCK-MDR1 cells was used as an indicator of the effect of bergapten on vincristine transport.Molecular docking was employed to predict the binding force between bergapten and P-glycoprotein(Pgp). The effects of bergapten on P-gp function and P-gp ATPase activity were determined by rhodamine123(Rho123) accumulation and activity analysis, respectively. 1,6-Diphenyl-1,3,5-hexatriene(DPH) was used to study the effects of bergapten on membrane fluidity, and Western blotting and quantitative realtime PCR assays were performed to analyze the effect of bergapten on the protein and mRNA expression of P-gp, respectively. These experiments clarified the effects of bergapten on the transport of vincristine and allowed exploration of the possible mechanism underlying the effects of bergapten.Results: The results showed that bergapten could inhibit the transport of vincristine in MDCK-MDR1 cells,and the binding force between bergapten and P-gp was weaker. Bergapten could reduce the accumulation of Rh123 in MDCK-MDR1 cells, increase the membrane fluidity, and upregulate P-gp protein and mRNA expression but it had no effect on P-gp ATPase activity.Conclusions: Overall, we concluded that the possible mechanism through which bergapten inhibits vincristine transport was related to the bergapten-mediated upregulation of P-gp protein and mRNA expression, membrane fluidity or P-gp enzyme activity.展开更多
基金supported by Shenzhen Longhua District Science and Technology Innovation Fund Projects(20160523A1030149)
文摘OBJECTIVE Bergapten(BG),is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg^(-1)) subcutaneous injections for 30 d.To evaluate the establishment of the agingrelated effect in mice,serum samples of BALB/c mice were collected from tail vein.Aging BALB/c mice were freely divided into three groups:negative control group received 1% Tween 80 solution only,named D-gal group.Positive groups were received BG administration at the dose of 20 and 100 mg·kg^(-1),named D-gal+BG(20) group and D-gal+BG(100) group,respectively.Effects of bergapten on T lympho.cyte proliferation and flow cytometry were assessed by using the splenic cell suspension.Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ) and interleukin-4(IL-4)levels of the isolated serum.Immunophenotype was determined by using mixture of antibodies includ.ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg^(-1)) therapy can modulate immu.nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat.ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1) and T helper 2(Th2) cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg^(-1)) restored antigen-specific CD4+ and CD8+ T cells in aging models(P<0.05,P<0.01),which may help to curing chronic infections.CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.
基金supported by grants from the National Natural Science Foundation of China(52173150,82374392)Guangdong Provincial Key Laboratory of Research on Emergency in TCM(2023B1212060062)+3 种基金Innovation Team and Talents Cultivation Program of National Admin-istration of Traditional Chinese Medicine(ZYYCXTD-D-202203)Guangzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Emerging in-fectious diseases(202201020382)Guangdong Provincial Bureau of Chinese Medicine(20241121)Postdoctoral Program of Guangdong Provincial Hospital of Chinese Medicine(B1),the Guangzhou Science and Technology Program City-University Joint Funding Project(2024A03J0604).
文摘Acute lung injury(ALI)or its more severe form,acute respiratory distress syndrome,is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization.However,current therapeutic strategies for ALI are controversial due to their side effects,restricted administration routes,or poor targeted delivery.The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy.One such compound is the bergapten,a coumarin,which has been isolated from Ficus simplicissima Lour.However,it’s been used as an anti-cancer drug and it’s effects on ALI remain unexplored.The poor solubility and biodistribution of bergapten heavily limit its application.In this timely report,we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome,named as Ber-lipo.A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial-endothelial integrity.In a lipopolysaccharide(LPS)-induced ALI mouse model,Ber-lipo can target inflamed lungs and significantly improve lung edema,tissue injury,and pulmonary function,relieve body weight loss,pulmonary permeability,and proinflammatory status,and especially maintain a balance of M1/M2 macrophage polarization.Furthermore,RNA sequencing analysis showed Ber-lipo’s potential in effectively treating inflammatory lung diseases such as pneumonia,inhibiting proinflammatory signals,and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues.Molecular docking and Western blot analyses validated that Ber-lipo suppressed the acti-vation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression.In conclusion,this study demonstrates for the first time that new inhalable nanomedicine(Ber-lipo)can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway,hence providing a promising strategy for enhanced ALI therapy in the clinic.
基金supported by a project of the National Natural Science Foundation of China(Grant No.81303237)the Training Project of Young Scientists in Jiangxi Province(No.20153BCB23019)+1 种基金China Postdoctoral Science Foundation(2016M590606)the National Natural Science Foundation of Jiangxi Province(20161ACB21020)
文摘Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vincristine through the membrane of MDCK-MDR1 cells was used as an indicator of the effect of bergapten on vincristine transport.Molecular docking was employed to predict the binding force between bergapten and P-glycoprotein(Pgp). The effects of bergapten on P-gp function and P-gp ATPase activity were determined by rhodamine123(Rho123) accumulation and activity analysis, respectively. 1,6-Diphenyl-1,3,5-hexatriene(DPH) was used to study the effects of bergapten on membrane fluidity, and Western blotting and quantitative realtime PCR assays were performed to analyze the effect of bergapten on the protein and mRNA expression of P-gp, respectively. These experiments clarified the effects of bergapten on the transport of vincristine and allowed exploration of the possible mechanism underlying the effects of bergapten.Results: The results showed that bergapten could inhibit the transport of vincristine in MDCK-MDR1 cells,and the binding force between bergapten and P-gp was weaker. Bergapten could reduce the accumulation of Rh123 in MDCK-MDR1 cells, increase the membrane fluidity, and upregulate P-gp protein and mRNA expression but it had no effect on P-gp ATPase activity.Conclusions: Overall, we concluded that the possible mechanism through which bergapten inhibits vincristine transport was related to the bergapten-mediated upregulation of P-gp protein and mRNA expression, membrane fluidity or P-gp enzyme activity.
