Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

Objective:Osteoporosis has become the biggest cause of non-fatal health issue.Currently,the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance,have raised concerns toward complementary and alternative therapies,particularly herbal medicines and their natural active compounds.Thus,this study aimed to provide an integrative analysis of active chemicals,drug targets and interacting pathways of the herbs for osteoporosis treatment.Methods:Here,we introduced a systematic pharmacology model,combining the absorption,distribution,metabolism,and excretion(ADME)screening model,drug targeting and network pharmacology,to probe into the therapeutic mechanisms of herbs in osteoporosis.Results:We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs.Network analysis revealed that they probably synergistically work through multiple mechanisms,such as suppressing inflammatory response,maintaining bone metabolism or improving organism immunity,to benefit patients with osteoporosis.Furthermore,experimental results showed that all the five compounds(calycosin,asperosaponin VI,hederagenin,betulinic acid and luteolin)enhanced osteoblast proliferation and differentiation in vitro,which corroborated the validity of this system pharmacology approach.Notably,gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis.Conclusion:Herbs and their natural compounds,being characterized as the classical combination therapies,might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms.This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Global gene expression profiling of blast lung injury of goats exposed to shock wave

Purpose:Blast lung injury(BLI)is the most common damage resulted from explosion-derived shock wave in military,terrorism and industrial accidents.However,the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods:In this study,a goat BLI model was established by a fuel air explosive power.The key genes involved in were identified.The goats of the experimental group were fixed on the edge of the explosion cloud,while the goats of the control group were 3 km far away from the explosive environment.After successful modeling for 24 h,all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed to identify the main enriched biological functions of differentially expressed genes(DEGs).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to verify the consistency of gene expression.Results:Of the sampled goat lungs,895 genes were identified to be significantly differentially expressed,and they were involved in 52 significantly enriched GO categories.KEGG analysis revealed that DEGs were highly enriched in 26 pathways,such as cytokine-cytokine receptor interaction,antifolate resistance,arachidonic acid metabolism,amoebiasis and bile secretion,JAK-STAT,and IL-17 signaling pathway.Furthermore,15 key DEGs involved in the biological processes of BLI were confirmed by qRTPCR,and the results were consistent with RNA sequencing.Conclusion:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI,which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.