| Gastrodia elata is a perennial herb of the orchid Gastrodia elata Blume The dry tuber of Gastrodia elata is widely used to calm wind and calm alarms.Treat paralysis,vertigo,headache,numbness,language Jian,children epilepsy and other mental brain diseases.In recent years,pharmacological studies have found that it has a variety of central nervous system therapeutic effects,including nerve protection,anti-inflammatory,anti-oxidation,anti-psychotic diseases(anti-Alzheimer’s disease,antiParkinson’s disease,anti-epilepsy,anti-convulsion,anti-anxiety,antidepression,etc.),regulation of the circulatory system,improve learning and memory.While opioid addiction is a serious chronic brain disease,long-term drug abuse may lead to adaptive changes in the metabolites in brain nerve cells,resulting in non-self-conscious drug seeking behavior.Due to its complex pathogenesis,the progress in seeking effective treatment and low toxicity drugs this year is still limited.Gastrodia elata has potential value in the treatment of heroin addiction.In this study,the metabonomics method was used to study the therapeutic effect of Gastrodia elata water extract on the post-withdrawal symptoms of heroin addicted mice,so as to provide a new basis for the clinical treatment of opioid addiction.Methods:(1)Under the condition of water temperature of 100 ℃,the ratio of material to liquid(Gastrodia elata: pure water)was 1 ∶ 30,extracted twice for 4 h,centrifuged for 10 min at 4000 r / min,separated the solid and liquid,concentrated to 200 ml,and then lyophilized to powder solid.The dosage of Gastrodia elata was 2 g/ kg,1 g/kg,0.5 g/kg.(2)Heroin addiction model was established in mice by increasing the dose of heroin for 13 consecutive days,and then the high,medium and low dose groups of Gastrodia elata aqueous extract(the crude dose was 2000mg/kg,1000 mg/kg and 500 mg/kg respectively)were prepared.The model mice were gavaged daily for 7 consecutive days,and the mice in the natural abstinence group were gavaged with a certain volume of normal saline every day.The mice were killed 2 hours after naloxone injection on the 8th day.The antiaddiction effect of water extract of Gastrodia elata Blume was evaluated by observing the weight change,abnormal activity,food intake,symptom score and weight loss before and after naloxone stimulation.(3)The metabolites in brain tissues of blank control mice and heroin addicted mice were detected by UHPLC-Q-TOF/ MS,and the differential metabolites were screened by multivariate analysis based on orthogonal signal partial least squares discriminant analysis(OPLS-DA).The different metabolites were introduced into the pathway analysis in metaboanalyst 5.0 to analyze the metabolites and metabolic pathways related to heroin addiction(4)The effects of different doses of Gastrodia elata on the metabolites of brain tissue samples of heroin addicted mice were studied based on metabolic profile analysis,and the related compounds were identified according to the accurate molecular weight,retention time and ion cleavage law.Principal component analysis(PCA)was used for metabolic profile analysis to explore the effects of different doses of Gastrodia elata aqueous extract on the metabolites of brain tissue samples of heroin addicted mice.Then,the abnormal chemical components of the drug group and the model group were screened through the multivariate analysis of OPLS-DA.Combined with the behavioral indexes of heroin addicted mice after naloxone withdrawal,the causes of behavioral changes before and after administration of Gastrodia elata water extract were analyzed.Result:(1)Compared with the blank control group,the withdrawal score of the model group increased significantly(P < 0.01),indicating that the model group was successful.After administration,it was found that compared with the model group,the treatment groups significantly alleviated naloxone induced withdrawal symptoms and weight loss in heroin addicted mice(P < 0.01),indicating that Gastrodia elata treatment group has a certain therapeutic effect on heroin addicted mice induced withdrawal symptoms.(2)Based on UHPLC-Q-TOF/MS metabonomics technology and pathway analysis,30 different metabolites were preliminarily identified and screened from brain tissue samples of blank and model groups.They are mainly involved in purine metabolism pathway,glyceride metabolism pathway,glutathione metabolism pathway,arginine and proline metabolism pathway,D-glutamine and D-glutamic acid metabolism pathway,and vitamin B6 metabolism pathway.(3)A metabonomics method based on UHPLC-Q-TOF / MS was established to analyze the changes of metabolites in brain tissue of heroin induced chronic poisoning mice and the changes of metabolites in brain tissue of Gastrodia elata after administration.Through metaboanalyst metabolic pathway analysis,we found that Gastrodia elata water extract can reduce the content of glutamate in brain tissue,improve the utilization rate of guanosine,etc.,which are mainly related to the metabolism of glutamate,glutathione and purine.Conclusion:(1)Gastrodia elata water extract can effectively improve the withdrawal symptoms,reduce the withdrawal score,relieve weight loss and improve brain function of heroin induced chronic addiction mice.(2)Gastrodia elata low dose group can by reducing glutamate levels in the brain tissue,improve the utilization rate of guanosine treatment of heroin addiction caused by brain damage,brain lipid classes,vitamins and amino acids,purine metabolites are changed,the analysis results indicate mechanism may be related to metabolism of purine metabolism,glutamate and glutathione metabolism and other metabolic pathways. |
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