Screening The Active Components In Chinese Medicine For Parkinson’s Disease With Dopamine Receptor D₁ As The Target

Parkinson’s Disease（PD）is a common neurodegenerative disease.The increased incidence significantly with age,most PD are Sporadic（alled Sporadic Parkinson’s Disease,it has no obvious connection with heredity）,and less than 10%of PD patients have a family history.The main clinical feature of PD is dyskinesia,and the pathological feature is mainly the loss of dopaminergic（DA）neurons in the substantia nigra compact（SNC）of midbrain and the formation of Lewy bodies.The cause of these pathological symptoms is still unclear.However,according to research,the death of DA neurons is related to mitochondrial dysfunction,oxidative stress and abnormal protein aggregation,which may be the result of genetic mutations and environmental stimulation.At present,levodopa is commonly used in the treatment of PD.However,its side effects are uncontrollable,including involuntary movement,aphasia,dystonia and hemicoma.At the same time,the common symptoms of PD cannot be completely eliminated.Therefore,the problems to be solved in the treatment of PD are to improve the therapeutic effect of drugs and reduce the non target effect.At present,Specific enhancement of the function of the DA system is currently the main method of PD treatment.Clinically,dopamine receptor（DAR）agonists are used alone or in combination with other drugs to improve the quality of life of patients with PD.DAR can be divided into two types:D₁-like（D₁ and D₅）and D₂-like（D₂,D₃ and D₄）,which belong to the G Protein-Coupled Receptors（GPCRs）superfamily,and consists of seven transmembrane structures to form three extracellular rings and three intracellular rings.Among them,D₁ has the widest distribution and the highest density in the striatum,which may have a considerable regulatory effect on PD.Studies have shown that activating D₁ can up-regulate the phosphorylation level of extracellular regulated protein kinases（ERK1/2）,while activating the ERK pathway in DA neurons can attenuate the effects of neurotoxins on DA energy in neurodegenerative diseases.Neuronal damage suggests that D₁ agonists may be promising treatments for PD.There are abundant resources of traditional Chinese medicine in China,but the development and utilization of traditional Chinese medicine is limited by the unclear target.In this study,a drug screening system with D₁ as the target was successfully synthesized,and on the basis of the separation,extraction and preliminary identification of the effective ingredients in traditional Chinese medicine for calming the nerves and preliminaries,22plant medicinal ingredients derived from rhubarb,Gastrodia and others above compound monomers provided by Kunming Institute of Botany,Chinese Academy of Sciences.It is found that chrysophanol has a strong activation effect on D₁.Chrysophanol was found to have a strong activation effect on D₁.And chrysophanol can play a role in resisting apoptosis of nerve cells by activating D₁ pathway.This research provides data support for the development of D₁ as a target for the treatment of PD drugs,and also provides a new idea and research platform for the mechanism of the active ingredients of traditional Chinese medicine through D₁ to play a neuroprotective role.