Molecular Biological Mechanisms of Yuan Zhi Powder in the Treatment of Alzheimer's Disease: an Analysis Based on Network Pharmacology

Objective To predict the main active ingredients,potential targets and molecular mechanisms of Yuan Zhi powder in treatment of dementia by using network pharmacology.Methods A database of chemical constituents of Yuan Zhi powder was constructed by using databases and literatures.Potential targets were predicted by reverse molecular docking,and then a component-target network was constructed.The target network of Alzheimer's disease(AD)was mapped and analyzed to obtain the“active ingredient-AD target”network.The key targets were screened through network analysis.Finally,the rationality of the prediction was analyzed by comparing with the target reported in the literatures.Results There were180chemical constituents acting on the AD target,and the targets included three key targets(cyclooxygenase-2,muscarinic acetylcholine receptor M1,and muscarinic acetylcholine receptor M2)and an important target(acetylcholine esterase).Alzheimer's disease may be treated by regulating the activity of acetylcholine receptors and the binding toβ-amyloid protein,and its biological process may be concentrated in the acetylcholine receptor signal pathway,negative regulation of synaptic transmission and so on.Conclusion The fact that Yuan Zhi powder can treat AD is consistent with the characteristics of multi-components-multitargets-multiple pathways of traditional Chinese medicine.The important targets obtained from network analysis have a large proportion in literature research,so network analysis have some rationality.

Quantitative Comparison of Bile Acid Distribution and Intestinal Transport from Native Cow-bezoar and Artificial and in vitro Cultured Substitutes using Caco-2 Cell Monolayer Model

Objective This study was conducted to examine the absorption and translocation of conjugated bile acids(BAs)in Calculus bovis and its substitutes to detect differences in these materials.Methods A Caco-2 monolayer cell model was used to compare the apparent permeability coefficient(Papp)value and efflux ratio(ER)of BAs in natural cow-bezoar(NCB),artificial cow-bezoar(ACB),and in vitro cultured cow-bezoar(Ivt-CCB).Papp and ER values were determined by liquid chromatography-mass spectrometry.Samples were separated on an analytical column.Results The distribution of BAs in NCB was significantly different from that in ACB and Ivt-CCB.The percentages of conjugated BAs were significantly higher in NCB than in the two substitutes.The distribution differences of conjugated and unconjugated BAs can be used to distinguish costly NCB from relatively inexpensive substitutes.Conclusion The transport characteristics of BAs in Ivt-CCB were more consistent with NCB than with ACB,even when the proportions of BAs in Ivt-CCB were closer to those of ACB.

Herb-herb interaction in traditional Chinese medicine：a review of pharmacokinetics-based interaction in Herb-Pairs

"Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility.It is not a random combination of two herbs,nor is the simple accumulation of efficacy,but the simple and delicate experience of ancient Chinese medicine practitioners.As a bridge between single drug and prescriptions,it is the embodiment of the regular and dialectical connotation.Therefore,research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies.However,the interaction between herbs and herbs is an effect with a downside as well as benefits.The beneficial herb-herb interaction in Herb-Pairs include mutual promotion,mutual enhancement,mutual restraint between two drugs and counteract toxicity of another drug.And the harmful herb-herb interaction in Herb-Pairs includes mutual inhibition and antagonism.Al of these interactions areby means of affecting the metabolism of components to play a therapeutic effect.Using the pharmacokinetic-pharmacodynamic(PK-PD)binding model,the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism,which can help elucidate the mechanism of drug action.Consequently,in this review,the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.

Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift

Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high mortality.The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously.This study aimed to evaluate the effect of Jinbei Oral Liquid(JBOL)on IPF and its relationship with Th1/Th2 shift.Methods:Rats were divided into six groups:control group,model group(bleomycin),pirfenidone group(positive group,54 mg/kg,i.g.)and JBOL(5.4,10.8 and 21.6 mL/kg,i.g.)groups.The rat model was established by an intratracheal instillation of bleomycin(BLM,5 mg/kg).One day after injection of BLM,pirfenidone or JBOL was given to rats once daily within 28 consecutive days,respectively.Positron emission tomography/computed tomography(PET/CT)was performed on the treated rats.The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining.The contents of TGF-β1,TNF-α,IL-4 and IFN-γwere further quantified by ELISA assay.Results:PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycininduced alveolitis and fibrosis extent,and the alveolitis lesion score was markedly decreased compared with the model group.The increased expression of inflammatory cytokines TGF-β1 and TNF-αinduced by bleomycin was also suppressed by JBOL.The Th1 response was limited by the reduced IFN-γafter BLM administration,and the Th2 response predominated significantly marked by the increased IL-4.JBOL could increase the level of IFN-γand markedly increased the ratio of IFN-γ/IL-4.Conclusion:These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration,pro-inflammatory cytokine release and excessive collagen deposition in rats.One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.