| Cognitive dysfunction of the elderly is a prominent problem in China’s aging society.Cognitive dysfunction can occur in postmenopausal women,and even severe ones can develop into dementia,which seriously affects the quality of life of elderly women and places a heavy burden on the family and society.The incidence of cognitive dysfunction in postmenopausal women is 2-3 times higher than that of men of the same age.Therefore,it is important to prevent and treat cognitive dysfunction in postmenopausal women.Traditional Chinese medicine Eclipta herba can nourish the liver and kidney yin.It is commonly used in the treatment of bleeding diseases,skin diseases,respiratory diseases,coronary heart disease,hair loss,vitiligo,snake bites and senile degenerative diseases.As a coumarin compound,wedelolactone is one of the main components of Eclipta esculenta,which is a typical phytoestrogen.It has liver protection,bone protection,blood sugar lowering,anti-inflammatory,anti-microbial,blood lipid lowering,and anti-cancer.,Promote hair growth,restore physical vitality and neuroprotective effect.The structure and biological activity of wedelolactone are similar to estrogen,but its adverse reactions are far less than estrogen.Ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS)uses chromatography as a separation system and mass spectrometry as a detection system.It is a highly selective and sensitive analytical detection technology.In recent years,LC-MS technology has been widely used in modern research of traditional Chinese medicine,including traditional Chinese medicine syndrome research,syndrome standardization research,traditional Chinese medicine prescription compatibility research,traditional Chinese medicine active ingredient screening research,and traditional Chinese medicine mechanism research.Objective: To verify the effects of wedelolactone on brain metabolism in mice induced by estrogen deficiency,the team used bilateral ovariectomy to induce behavioral and intellectual decline in mice.The effects of brain metabolism in mice,and then to explore the effects of cognitive function and brain metabolism in postmenopausal women and related mechanisms,so as to provide a reasonable basis for the treatment of postmenopausal mental retardation patients with wedelolactone.Materials and methods: 8-week-old female C57 BL mice were randomly divided into sham operation group,surgery group and drug group.After relevant surgery,the drug group was subcutaneously injected with wedelolactone(25mg / kg)every other day.The rats in the group and the surgery group were injected with the same dose of normal saline at the same site.After 30 consecutive days,the mice’s behavioral water maze experiment was observed.The brain regions of the mouse hippocampus were extracted.Time-of-flight secondary mass spectrometry(UHPLC-QTOF-MS)related metabolomics technology to analyze and identify small differentially metabolized molecules in the hippocampus of mice.Metabo Analyst 4.0,KEGG database,METLIN database,and HMDB database were used to analyze relevant data and metabolic pathway.Results: Animal experiments(1)The search strategy of postmenopausal cognitive dysfunction mice treated with wedelolactone was better than that of the model group,and the escape latency was shorter in localized cruise than in the model group(p <0.05).In the experiment,the swimming time was longer in the quadrant of the original platform(p<0.05),and the number of times of crossing the platform was more(p <0.05).Analysis and identification experiment(2)9 compounds were identified: progesterone,corticosterone,aldosterone,LPC(16:0),LPC(18:1),LPC(18:2),LPC(20:4),phytosphingosine andoleamide,these compounds all returned to normal trends after mice took sterolide(p <0.05).Metabolic pathway analysis experiment(3)The metabolic pathway may involve steroid hormone biosynthesis,sphingolipid metabolism,and glycerophospholipid metabolism.Conclusions:(1)Wedelolactone,an effective component of Eclipta prostrata,can significantly improve the spatial learning and memory ability of estrogen-deficient mice after menopause.(2)Wedelolactone can restore the related metabolites in the hippocampal brain region of mice to close to normal levels.(3)Maybe wedelolactone may play a protective role by regulating steroid hormone metabolism and protecting membrane lipid perturbations. |