Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer’s disease

Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.

Pharmacokinetic studies of multi-bioactive components in rat plasma after oral administration of Xintiantai Ⅰ extract and effects of guide drug borneol on pharmacokinetics

Objective:To investigate the in vivo pharmacokinetic characteristics of 17 bioactive components including ginsenoside Rg1,Rb1,Rd,berberine,epiberberine,jatrorrhizine,palmatine,columbamine,coptisine,evodiamine,dehydroevodiamine,rutaecarpine,limonin,hyperin,curcumin,demethoxycurcumin and bisdemethoxycurcumin in rat plasma after oral administration of Xintiantai I extract powder(XI)and Xintiantai I without guide drug borneol extract powder(XI without borneol),and study the compatibility effects of guide drug borneol on the pharmacokinetics.Methods:A UHPLC-MS/MS method was established and fully validated for the comparative pharmacokinetics of 17 bioactive components.The pharmacokinetics parameters of 17 bioactive components after oral administration of XI and XI without borneol were calculated by the software of DAS 3.0 and intercompared.Results:The specificity,linearity,lower limit of quantification(LLOQ),precision,accuracy,extraction recovery rates,matrix effects,and stability of the UHPLC-MS/MS assay were good within the acceptance criteria from FDA guidelines.Guide drug borneol can significantly increase AUC of G-Rd,palmatine,hyperin,curcumin,demethoxycurcumin,bisdemethoxycurcumin and Cmaxof 16 bioactive components except for dehydroevodiamine(P<0.05),decrease Tmaxof G-Rd,berberine,columbamin,coptisine,limonin and MRT of 17 bioactive components in XI group(P<0.05).Conclusion:Guide drug borneol enhanced the absorption of G-Rd,palmatine,hyperin,curcumin,demethoxycurcumin and bisdemethoxycurcumin.

The Mechanism of Panax Notoginseng in the Treatment of Heart Failure Based on Biological Analysis

Objective:This study aimed to explore the mechanism of Panax notoginseng(PNS)in the treatment of heart failure(HF)based on network pharmacology analysis combined with experimental verification.Materials and Methods:The potential targets and key pathways of effective components of PNS in the treatment of HF were revealed using network pharmacology.The postacute myocardial infarction(MI)HF rat model was established by ligating the left anterior descending branch of the coronary artery.The rats were divided into three groups:model,PNS,and fenofibrate groups.PNS(0.75 g/kg)and fenofibrate(10 mg/kg)were administered for 28 days.The efficacy and target mechanism of PNS in the treatment of HF were verified by cardiac ultrasound,Masson staining,and western blotting(WB)techniques.Results:The results of network pharmacology showed that seven potentially active compounds,such as quercetin,were obtained,involving 105 targets of HF;GO function was enriched to 1240 items;and KEGG enrichment covered 1240 signal pathways.The results of echocardiography showed that EF and FS of HF rats after MI were significantly increased,while Left ventricular internal dimension diastole(LVIDd)and Left ventricular internal dimension systole(LVIDs)were significantly decreased(P<0.001,P<0.05).Masson staining showed that PNS could reduce the degree of myocardial fibrosis(MF)in HF.The results of WB showed that PNS could reduce the expression of the p-p38-MAPK,transforming growth factor-beta(TGF-β),and Smad3 in HF rats.Conclusion:PNS inhibited MF and treated HF by regulating p-p38 MAPK-TGF-βpathway,which lays a theoretical foundation for further study of its pharmacological mechanism and key target.