Effects Of Ganoderma Lucidum And Cordyceps Militaris Fermentation Process And Products On Lipopolysaccharide-induced Learning And Memory Impairment In Rats

Objective:To optimize the fermentation process of Ganoderma lucidum and Cordyceps militaris for gastrodia,and to investigate the effect of the product of Ganoderma lucidum and Cordyceps militaris on lipopolysaccharide induced learning and memory impairment in rats.Methods:The fermentation time,the inoculation ratio of Ganoderma lucidum and Cordyceps militarium,the amount of gastrodia elata,the carbon source,the nitrogen source and the inorganic salt were used as the research objects.On this basis,box-benhnken experimental design was used to determine the optimal fermentation conditions.The alcohol extracts from fermentation products were then used to study the resistance to the effect of the product of Ganoderma lucidum and Cordyceps militaris on lipopolysaccharide induced learning and memory impairment in rats.High,medium and low dose fermentation product alcohol extract was administered to rats.The general condition,body weight and behavior changes of the Morris water maze experiment and the dark avoidance experiment were observed.The effects of alcohol extracts from fermentation products on the contents of SOD,MDA,IL-6 and IL-10 in serum of experimental rats were determined.Real-time quantitative PCR technology was used to detect the expression levels of TNF-? and BDNF mRNA in the hippocampus of experimental rats.Results:?The optimal fermentation process for the co-culture anf fermentation of Ganoderma lucidum and Cordyceps militarium was:18.2g/L of sucrose,30.0g/L of peptone,0.9g/L of potassium dihydrogen phosphate,and Cordyceps militaris-Ganoderma inoculum ratio of 1:2(inoculation amount of 30mL/L),gastrodia elata dosage of 30.0g/L and the culture time was 15 days.?Compared with the blank group,in the model group the body weight of rats increased slowly(P<0.01),and there was no statistically significant difference in the body weight of rats in other groups(P>0.05).?In the Morris water maze experiment,compared with the blank group,the escape incubation period of rats in the model group was significantly prolonged after the completion of modeling(P<0.01).In the dark avoidance experiment,compared with the blank group,at the end of modeling,the dark avoidance latency period of rats in the model group was shortened(P<0.01),and the number of dark avoidance errors was increased(P<0.01).Compared with the model group,the anti-dark incubation period was increased and the number of memory errors was reduced in the drug administration group.?The results of Elisa test on the serum of experimental rats showed that compared with the model group,the high and medium dose of the product of gastrodia elata fermented by ganoderma lucidum and cordyceps militaris could increase the SOD content of experimental rats(P<0.01).However,there was still a gap with the blank group and the model group(P<0.01).Compared with the model group,the content of MDA in the serum of rats in the high-dose and medium-dose groups could be reduced(P<0.01).However,compared with the blank group,the effect of medium dose was significantly higher.In the detection of serum IL-6 content in rats,it was found that compared with the positive control group,the medium dose of fermented gastrodia elata of ganoderma lucidum and cordyceps militaris could reduce the IL-6 content in alzheimer's disease rats(P<0.01).In the detection of IL-10 content,it was found that compared with the model group,the high-dose and medium-dose groups of the products of gastrodia elata fermented by ganoderma lucidum and cordyceps militaris could increase the serum IL-10 content of the experimental rats(P<0.01).However,compared with the positive control group,the effect of the medium dose group was significant in the higher dose group.?The results of detecting of TNF-? and BDNF mRNA expression levels in the hippocampus of experimental rats showed that compared with the blank group and the positive control group,the medium dose group of the fermented gastrodia elata of ganoderma lucidum and cordyceps militaris could reduce the expression level of TNF-? mRNA in lipopolysaccharide induced learning and memory impairment rats rats and increase the expression level of BDNF mRNA in experimental rats.Conclusion:After optimizing the system of co-culture and fermentation of gastrodia,the biomass(wet weight)of cordyceps militaris and ganoderma lucidum increased.The mycelium of fermented product by methanol extract can improve the learning and memory ability of lipopolysaccharide induced learning and memory impairment rats,its possible mechanism is by increasing the activity of SOD,IL-10,reduce the MDA and the activity of IL-6,remove free radicals,strengthen the body's antioxidant ability,reducing oxidative stress.The alcohol extract from the fermentation product reduced the expression level of TNF-? mRNA in the hippocampus of lipopolysaccharide induced learning and memory impairment rats,and increased the expression level of BDNF mRNA,which promoted the development of the nervous system and maintained the learning and memory function of the nervous system.It may also be one of the mechanisms that alcohol extract from the fermentation product improved the learning and memory ability of rats.