Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rat...Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rats.Methods:Insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA).The model rats were given Jiaotai pill self-microemulsion and Jiaotai pill suspension.The contents of Berberine,Coptisine,Palmatine and Jatrorrhizine in plasma at different times after administration were determined by UPLC-MS/MS,and calculate pharmacokinetic parameters.Results:Under the set chromatographic conditions,the linear relationship of the four components was good,and the precision,accuracy and stability meet the requirements of biological samples.After intragastric administration of Jiaotai pill self-microemulsion,The C_(max) of Berberine,Coptisine,Palmatine and Jatrorrhizine were(412.68±28.45),(68.65±3.92),(34.06±3.13),(40.60±1.22)ng/mL,and AUC_(0-∞)were(672.70±72.55),(146.04±25.01),(71.49±18.67),(72.25±9.54)ng·mL^(-1)·h^(-1),respectively.Compared with Jiaotai pill suspension,the Cmax,AUC_(0-t) and AUC_(0-∞)of the four components in insomnia rats were significantly increased(P<0.01).Conclusion:Jiaotai pill self-microemulsionl can promote the absorption of effective components in insomnia rats and improve its bioavailability.展开更多
A series of novel derivatives of indirubin were synthesized and evaluated for their anti-proliferative activity against human cancer cell lines of SGC7901,A549,HL-60,SK-BR-3 and HCT116.Most of the compounds displayed ...A series of novel derivatives of indirubin were synthesized and evaluated for their anti-proliferative activity against human cancer cell lines of SGC7901,A549,HL-60,SK-BR-3 and HCT116.Most of the compounds displayed more potent activity than Sunitinib.In addition,the derivatives showed improved water solubility,which may be favorable to their pharmacokinetic performances.展开更多
Objective Indirubin,isolated from Indigo Naturals,has been reported to have the inhibitory activity of MCF-7 human breast cancer cells in vitro.However,studies on its anti-breast cancer activity in vivo and the underl...Objective Indirubin,isolated from Indigo Naturals,has been reported to have the inhibitory activity of MCF-7 human breast cancer cells in vitro.However,studies on its anti-breast cancer activity in vivo and the underlying mechanism are insufficient.We explored whether indirubin could trigger ferroptosis of breast cancer cells to exert anti-tumor activity.Methods Bioinformatical analysis was performed to detect the expression of prostaglandin-endoperoxide synthase 2(Ptgs2)in breast cancer tissues and Ptgs2-related prognosis for patients with breast cancer.The inhibitory effects of indirubin on 4T1 cells were assessed using MTT assay and LDH activity detection.The levels of 4-HNE,GPX4,PTGS2 and GSK-3βproteins were detected by Western blotting,and the mRNA of Ptgs2 was tested by qPCR.The contents of GSH and MDA were determined by commercial kits.Molecular docking was employed to study the interaction between indirubin and GSK-3β.A 4T1 murine breast cancer was adopted to evaluate the in vivo antitumor activity of indirubin.Results Indirubin promoted ferroptosis of 4T1 breast cancer cells with depleting of GSH,increased MDA and 4-HNE levels,as well as decreased GPX4 expression.Indirubin suppressed 4T1 breast tumor in vivo.The mechanism study showed indirubin up-regulated Ptgs2 expression by promoting phosphorylation(Ser 9)of GSK-3β.Conclusion Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis.展开更多
Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer＇s disease. Here, we found that indirubin-3′-monoxime improved th...Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer＇s disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SHSY5 Y cells exposed to amyloid-beta 25–35（Aβ25–35）, and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β（GSK-3β）. Our results suggest that indirubin-3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer＇s disease.展开更多
基金Scientific Research Project of Heilongjiang Provincial Health Commission(No.2018-482)Excellent Discipline Team Project of Jiamusi University(No.JDXKTD-2019005)。
文摘Objective:The pharmacokinetics and relative bioavailability of Jiaotai pill self-microemulsion were evaluated by investigating the blood concentration of Berberine,Coptisine,Palmatine and Jatrorrhizine in insomnia rats.Methods:Insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA).The model rats were given Jiaotai pill self-microemulsion and Jiaotai pill suspension.The contents of Berberine,Coptisine,Palmatine and Jatrorrhizine in plasma at different times after administration were determined by UPLC-MS/MS,and calculate pharmacokinetic parameters.Results:Under the set chromatographic conditions,the linear relationship of the four components was good,and the precision,accuracy and stability meet the requirements of biological samples.After intragastric administration of Jiaotai pill self-microemulsion,The C_(max) of Berberine,Coptisine,Palmatine and Jatrorrhizine were(412.68±28.45),(68.65±3.92),(34.06±3.13),(40.60±1.22)ng/mL,and AUC_(0-∞)were(672.70±72.55),(146.04±25.01),(71.49±18.67),(72.25±9.54)ng·mL^(-1)·h^(-1),respectively.Compared with Jiaotai pill suspension,the Cmax,AUC_(0-t) and AUC_(0-∞)of the four components in insomnia rats were significantly increased(P<0.01).Conclusion:Jiaotai pill self-microemulsionl can promote the absorption of effective components in insomnia rats and improve its bioavailability.
文摘A series of novel derivatives of indirubin were synthesized and evaluated for their anti-proliferative activity against human cancer cell lines of SGC7901,A549,HL-60,SK-BR-3 and HCT116.Most of the compounds displayed more potent activity than Sunitinib.In addition,the derivatives showed improved water solubility,which may be favorable to their pharmacokinetic performances.
基金This work was supported by the Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Yunnan University of Chinese Medicine(2019FF002(-007),2017FF116(-015))National Natural Science Foundation of China(81560661,81960780).
文摘Objective Indirubin,isolated from Indigo Naturals,has been reported to have the inhibitory activity of MCF-7 human breast cancer cells in vitro.However,studies on its anti-breast cancer activity in vivo and the underlying mechanism are insufficient.We explored whether indirubin could trigger ferroptosis of breast cancer cells to exert anti-tumor activity.Methods Bioinformatical analysis was performed to detect the expression of prostaglandin-endoperoxide synthase 2(Ptgs2)in breast cancer tissues and Ptgs2-related prognosis for patients with breast cancer.The inhibitory effects of indirubin on 4T1 cells were assessed using MTT assay and LDH activity detection.The levels of 4-HNE,GPX4,PTGS2 and GSK-3βproteins were detected by Western blotting,and the mRNA of Ptgs2 was tested by qPCR.The contents of GSH and MDA were determined by commercial kits.Molecular docking was employed to study the interaction between indirubin and GSK-3β.A 4T1 murine breast cancer was adopted to evaluate the in vivo antitumor activity of indirubin.Results Indirubin promoted ferroptosis of 4T1 breast cancer cells with depleting of GSH,increased MDA and 4-HNE levels,as well as decreased GPX4 expression.Indirubin suppressed 4T1 breast tumor in vivo.The mechanism study showed indirubin up-regulated Ptgs2 expression by promoting phosphorylation(Ser 9)of GSK-3β.Conclusion Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis.
基金supported by the Nanjing Medical Science and Technique Development Foundation of China,No.QRX11199a grant from the Nanjing Science and Technology Commission Project of China,No.201303010a grant from the Health Research Project in Nanjing City of China,No.YKK14101
文摘Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer＇s disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SHSY5 Y cells exposed to amyloid-beta 25–35（Aβ25–35）, and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β（GSK-3β）. Our results suggest that indirubin-3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer＇s disease.
