Research On Antidepressant And Congnitive Improvement Effects Of Product Of Soybean Isoflavone Metabolism-S-Equol

Depression is a common mental disease characterized by pessimism,insomnia,anxiety and cognitive impairment.At present,more than 350 million people are suffering from depression,and by 2020,it has become the second largest burden disease in the world.However,the pathogenesis of depression is complex.Most of the antidepressants used in clinical practice have the characteristics of slow onset,great side effects and high recurrence rate,even have little effect on cognitive impairment caused by depression.Cognitive impairment not only affects the clinical cure of depression,but also is closely related to the long-term prognosis of depression.Therefore,it has become a hot spot in academic circles to develop safe and effective antidepressant drugs that can improve cognitive impairment.S-equol(Eq)is the product of soybean isoflavones metabolism and studies have shown that it has higher biological activity than soybean isoflavones.In recent years,soybean isoflavones have been deeply explored in neuroprotection,especially in antidepressant and cognitive improvement.Therefore,we speculate that S-equol also has antidepressant and cognitive improvement effects.In this study,we used two animal modelsintraperitoneal injection of lipopolysaccharide(LPS)and chronic restraint stress(CRS)to explore the effects of S-equol in anti-depression and cognitive improvement and explore the possible mechanism.The specific experimental methods and results are as follows:1.The improvement effects and mechanism research of s-equol on lipopolysaccharide-induced depression and cognitive impairment model mice(1)To explore the best dose of LPS-induced depression and cognitive impairment,we selected three different doses of LPS(0.5,1,2 mg/kg)to inject(i.p)C57BL/6J male mice.The open field test(OFT)was used to observe the spontaneous activity of mice.Sucrose preference test(SPT),tail suspension test(TST)and force swimming test(FST)were used to evaluate the depression behavior of mice.Morris water maze test(MWM)was used to evaluate the cognitive functionofmice.The results showed that LPS(1mg/kg)injection(i.p)could stably induce depression and cognitive impairment of mice without affecting their spontaneous activities.(2)After two weeks treatment with S-equol(10,20,40 mg/kg)by gavage,the mice was injected(i.p)LPS(1 mg/kg)to establish acute depression and cognitive impairment model.The effect of S-equol treatment on spontaneous activities of mice was observed by OPT.SPT、TST and FST were used to evaluate the antidepression effect of S-equol.Step-through passive avoidance test(STT)and MWM were used to evaluate cognitive improvement effect of S-equol.The results showed that the treatment with S-equol did not affect the spontaneous activity of mice,but could significantly improve the sucrose preference index of LPS model mice,significantly shorten the immobility time of LPS model mice in TST and FST,showing antidepressant activity.The results of STT and MWM showed that S-equol could significantly improve the impaired learning and memory ability caused by LPS.(3)Using the biochemical reagent kits determination to explore the possible mechanism of S-equol’s antidepressant and cognitive improvement effects.The results showed that pre-administration of S-equol(10,20,40 mg/kg)for 2 weeks could significantly reduce the levels of IL-6,IL-1β,TNF-α,KYN and significantly increase the level of 5-HT in cortex of LPS model mice.The results indicated that the antidepression and cognitive improvement effect of S-equol may be related to reduce neuroinflammation and balance tryptophan metabolic homeostasis.2.The improvement effects and mechanism research of S-equol on chronic restraint stress-induced depression and cognitive impairment model mice(1)After two weeks treatment with S-equol(10,20,40 mg/kg)by gavage,the model of chronic depression and cognitive impairment was established by chronic restraint for 28 days.The effect of chronic restraint treatment on spontaneous activities of mice was observed by OFT.The antidepressant effect of S-equol was evaluated by SPT and TST.The cognitive improvement effect of S-equol was evaluated by STT and MWM.The results showed that 28-day chronic restraint significantly reduced the weight of mice,but did not affect the spontaneous activities of mice.Pre-administration of S-equol could significantly improve the sucrose preference index and shorten the immobility time of mice in CRS group,showing antidepressant activity.The results of STT and MWM showed that S-equol could prolong the latency into the dark chambers,reduce the error numbers,shorten the darkroom time,significantly shorten the escape latency and increase the crossing numbers,showing the intelligence-improving activity.(2)Using the biochemical reagent kits determination to explore the possible mechanism of S-equol’s antidepressant and cognitive improvement effects.The results showed that pre-administration of S-equol(10,20,40 mg/kg)for 2 weeks could significantly reduce the content of corticosterone in the serum and IL-6,IL-1β,TNF-α and MDA levels in the cortex of model mice.The contents of DA,NE,SOD and CAT in the cortex of model mice were significantly increased.The above results indicated that the antidepression and cognitive improvement effect of S-equol may be related to inhibit HPA axis hyperfunction,reduce neuroinflammation,resist oxidative stress and regulate monoamine transmitter level.This study showed that S-equol,the product of soybean isoflavone metabolism,has good antidepressant and cognitive improvement effects in lipopolysaccharide and chronic restraint animal models,and its mechanism may be related to reduce neuroinflammation,resist oxidative stress,inhibit HPA axis hyperfunction,balance tryptophan metabolism steady state and regulate monoamine transmitter levels.The results provided scientific basis and theoretical support for preventing and treating depression and developing soybean products with neuroprotective effects.