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.

Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways

Dysregulation of mi R-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San(2.835 m L/kg/d) for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, mi RNA microarray, western blot assay and transmission electron microscopy demonstrated that ChaihuShugan-San downregulated mi R-124 expression and upregulated the m RNA and protein levels of mitogen-activated protein kinase 14(MAPK14) and glutamate receptor subunit 3(Gria3). Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together, these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating mi R-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways.

Diagnostic model of saliva protein finger print analysis of patients with gastric cancer

AIM:To explore the method for early diagnosis of gastric cancer by screening the expression spectrum of saliva protein in gastric cancer patients using mass spectrometry for proteomics.METHODS:Proportional peptide mass fingerprints were obtained by analysis based on proteomics matrix-assisted laser desorption ionization time-of-flight/mass spectrometry.A diagnosis model was established using weak cation exchange magnetic beads to test saliva specimens from gastric cancer patients and healthy subjects.RESULTS:Significant differences were observed in the mass to charge ratio(m/z) peaks of four proteins(1472.78 Da,2936.49 Da,6556.81 Da and 7081.17 Da) between gastric cancer patients and healthy subjects.CONCLUSION:The finger print mass spectrum of saliva protein in patients with gastric cancer can be established using gastric cancer proteomics.A diagnostic model for distinguishing protein expression mass spectra of gastric cancer from non-gastric-cancer saliva can be established according to the different expression of proteins 1472.78 Da,2936.49 Da,6556.81 Da and 7081.17 Da.The method for early diagnosis of gastric cancer is of certain value for screening special biological markers.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cvtotoxicitv in PC12 cells

Alpinia oxyphylla,a traditional herb,is widely used for its neuroprotective,antioxidant and memory-improving effects.However,the neuroprotective mechanisms of action of its active ingredients are unclear.In this study,we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro.Alpinia oxyphylla was extracted three times with 95%ethanol(representing extracts 1–3).The third 95%ethanol extract was dried and resuspended in water,and then extracted successively with petroleum ether,ethyl acetate and n-butanol(representing extracts 4–6).The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells.The protective effect of the three ethanol extracts(at tested concentrations of 50,100 and 200μg/mL)against cytotoxicity to PC12 cells increased in a concentration-dependent manner.The ethyl acetate,petroleum ether and n-butanol extracts(each tested at 100,150 and 200μg/mL)had neuroprotective effects as well.The optimum effective concentration ranged from 50–200μg/mL,and the protective effect of the ethyl acetate extract was comparatively robust.These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide.Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

Neuroprotective effect of the Chinese medicine Tiantai No.1 and its molecular mechanism in the senescence-accelerated mouse prone 8

Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8(SAMP8) mice(a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

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.