Network Pharmacology-based Investigations Of Anti-aging Effects And Mechanisms Of Baicalein

Rationales: Aging is the degenerative changes of the tissue and organ functions with increasing age,and is the comprehensive performance of various factors(inheritance,psychentonia,psychology,society,environmental pollution etc.).With the acceleration of aging,aging and aging related diseases seriously endanger the health of the elderly.How to delay the process of aging,improve the life quality and healthy level of the elderly,achieve healthy aging have become one of the major problems in the field of medicine.Exploration of the mechanisms of aging and the mechanism of drug action is an urgent need for improving the health level of the elderly and solving the problem of clinical medication.Scutellaria baicalensis is the dry root of labiatae Scutellaria baicalensis Georgi with long officinal history,which has extensive effects such as free radical scavenging,antioxidant,anti-inflammation.Baicalein is one of the most important flavonoids isolated from Scutellaria baicalensis Georgi.It is also the main active ingredient of Scutellaria baicalensis Georgi.Baicalein has many pharmacological effects,such as antiinflammatory,anti-allergic,free radical scavenging and antipyretic effects.However,there are few reports on the anti-aging effects of the monomer components of Scutellaria baicalensis Georgi,and the anti-aging mechanism has not been studied systematically.As a new discipline,network pharmacology can predict the multi-target mechanism of drugs from the perspective of integrity and system.In current work,network pharmacology was applied to establish the anti-aging prediction model of compounds and investigate the anti-aging mechanisms of baicalein,which would provide new ideas and methods for drug activity prediction and mechanism research.Objective: The aims of this study are to establish anti-aging prediction model of compounds,and predict anti-aging activities of compounds from Scutellaria baicalensis;clarify the anti-aging effects and mechanisms of baicalein in Drosophila melanogaster model and D-galactose induced aging rat model.Methods: 1 The anti-aging prediction model of compounds was built using network pharmacology approach and the model was validated.The model was used to predict the anti-aging activities of compounds from Scutellaria baicalensis Georgi.2 Drosophila melanogaster as a model organism was used to study the effects of baicalein,whose predictive activity was the strongest,on natural aging model and aging models induced by hydrogen peroxide(H2O2)and paraquat.Secondly,the effects of baicalein on food intake and fecundity were examined in natural aging Drosophila melanogaster.Meanwhile,the biochemical and gene expression levels were examined under the guidance of network pharmacology.3 Subcutaneous injection of D-galactose(150 mg/kg)for 8 weeks was used to establish the aging model,meanwhile baicalein(50 mg/kg,100 mg/kg and 200 mg/kg)was gavagely administrated to the rats of baicalein treatment groups.The anti-aging activity of baicalein was evaluated by determination of behaviors,serum inflammatory mediators and endogenous metabolites in the cerebral cortex.Results: 1 The anti-aging prediction model of compounds was established based on network pharmacology and was evaluated by 20 compounds with known anti-aging activities.The results showed that the model has high prediction accuracy.After oral bioavailability(OB)and druglikeness(DL)screening,24 compounds from Scutellaria baicalensis Georgi were retained.The anti-aging activities of these compounds were predicted,which showed that baicalein had the highest anti-aging activity.2 Baicalein extended the mean and maximum lifespans in the natural aging model,and models induced by H2O2 and paraquat.Baicalein might delay aging process of Drosophila melanogaster by increasing the activity of Catalase(CAT)and the content of glutathione(GSH),inhibiting the formation of reactive oxidative species(ROS),decreasing the content of oxidized glutathione(GSSG)and increasing the mRNA expression of superoxide dismutase(SOD)and CAT.3 Baicalein significantly improved learning and memory deficits associated with aging in rats induced by D-galactose,inhibited the releases of inflammatory mediators and attenuated the changes of 10 endogenous metabolites in cerebral cortex including glutamate,glutamine,Nacetylaspartat,aspartate,glycine,choline,myo-inositol,creatine,pyruvate and lactate.These 10 endogenous metabolites were involved in amino acid metabolism and energy metabolism.Conclusion: Baicalein can prolong the lifespan of Drosophila melanogaster,improve the learning and memory deficits associated with aging in rats induced by D-galactose.This might be achieved through scavenging free radical,antioxidation,inhibiting the releases of inflammatory factors,and improving amino acid metabolism and energy metabolism.