Repositioning of clinically approved drug Bazi Bushen capsule for treatment of Alzheimer′s disease using network pharma⁃cology approach and in vitro experimental validation

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich⁃ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further⁃more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec⁃tion analysis.Two Alzheimer′s disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre⁃liminarily verify the anti-AD efficacy and mecha⁃nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat⁃ment of AD.In vitro experiments showed that BZ⁃BS could significantly reduce the release of TNF-αand IL-6 and the expression of COX-2 and PSEN1 in Aβ25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of Aβ25-35 induced SH-SY5Y cells,significantly increased mitochon⁃drial membrane potential,reduced the expres⁃sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU⁃SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu⁃lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further⁃more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun⁃dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Exploring the mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells by network pharmacology method and verifying it in vitro

OBJECTIVE To explore the key mechanism of Bazi Bushen capsule(BZBS)in delaying the senescence of mesenchymal stem cells(MSCs)through network pharmacology and in vitro experiments.METHODS Network pharmacology was used to predict the mechanism targets of BZBS in delaying MSCs senescence.A MSCs senescence model induced by D-galactose(D-gal)was used to investigate the effect and mechanism of BZBS on MSCs senescence in vitro.RESULTS Network pharmacology analy⁃sis showed that BZSB could delay MSCs senes⁃cence.The experiment showed that BZBS could significantly improve the survival activity of the aged MSCs.It significantly reduced the positive rate ofβ-galactosidase staining and p16,p21 expression in aged MSCs,enhanced the ability of adipogenic differentiation and osteogenic differentiation,and increased expression of Nanog,OCT4 and SOX2 in senescent MSCs.CONCLU⁃SIONS Network pharmacology and in vitro cell experiments verified that BZBS could delay MSCs senescence.

Core mechanism and therapeutic methods of aging revealed by Qi-collateral theory in traditional Chinese medicine

Aging,a complex and multisystem process,has increasingly become a hot issue of global concern.Traditional Chinese medicine has accumulated rich understanding of aging during thousands of years of development,which provides valuable references for the in-depth study of overall aging.According to the Qi-collateral theory in traditional Chinese medicine,essence is the origin of life;Qi is the driving force of life;and spirit is the embodiment of life.This theory interprets key scientific issues such as the formation of life,the driving force of life,the function of Zang-Fu organs,and the spirit and consciousness.Furthermore,it reveals the key mechanism of aging.That is,the deficiency of kidney essence is the root of aging;the loss of vitality is the key of aging;and the depletion of body and spirit is the manifestation of aging.Based on the experience of medical practitioners in the past dynasties,such as nourishing essence,black food tonifying the kidney,and supplementing essence with flesh-blood products,the treatment method of invigorating kidney and supplementing essence,harmonizing Yin and Yang,reinforcing the vitality,and nourishing the body and spirit was proposed.Furthermore,an innovative Chinese patent medicine,Bazi Bushen capsules,is developed,which exerts the antiaging effect by replenishing Qi,invigorating the spirit,and nourishing the body and spirit.Pharmacological and clinical studies have confirmed that this preparation has antiaging effects and are effective in the prevention and treatment of age-related diseases.Experimental studies have shown that Bazi Bushen capsules can delay the overall aging,reduce the DNAmethylation and extend the healthy life of naturally aging mice,mitigate the age-related cognitive dysfunction,improve neurological function,maintain redox homeostasis and telomere integrity,and inhibit apoptosis.Moreover,Bazi Bushen capsules can increase the dermal thickness and the collagen fiber and elastic fiber content to prevent skin aging.In addition,Bazi Bushen capsules can correct the lipid metabolism disorders and ameliorate multisystem age-related diseases such as osteoporosis in surgically induced menopausal rats.This article discusses the pathogenesis,treatment,and prescription of aging and the antiaging theory,aiming to provide a basis for delaying aging and preventing related diseases.