NEWS

Novel small molecules found in Magnolia officinalis for the treatment of central nervous system diseases

Release time:

2018-07-27 11:21

Depression is a common mental illness, with more3Hundreds of millions of people suffer from depression, distributed in all age groups. At its worst, depression can lead to suicide.80Thousands of people died by suicide. According to news from the Kunming Institute of Botany, Chinese Academy of Sciences, researchers at the institute have found new small molecules with antidepressant effects that act on melatonin receptors through the study of traditional Chinese medicine Magnolia officinalis, which can be used for the development of new antidepressant drugs.

Previously, the Chen Jijun research team of the Kunming Institute of Botany, Chinese Academy of Sciences used the anti-mental disease cell and overall animal research platform established by this research team to study traditional Chinese medicines such as Radix Paeoniae Rubra, Radix Bupleuri, Semen Ziziphi Spinosae, Alcifera, and Polygala. A series of active compounds.

Melatonin(N-acetyl-5-Methoxytryptamine,Melatonin)Is mainly produced by the human pineal gland of an amine hormone, melatonin receptor mainlyMT1,MT2andMT3Composed of three subtypes, the modulatory effects of melatonin produce different physiological responses by binding to different receptors. Melatonin andMT1receptor binding, can reducecAMPgeneration and suppressionPKAactivity, thereby regulating the biological clock;MT2The main role of the receptor may be synchronization and vasodilation. In addition, melatonin also has antioxidant effect, hypnotic effect, immune regulation and regulation of human emotions and behavior. Decreased production of melatonin or reduced expression of melatonin receptors is one of the main factors leading to breast cancer, as well as a series of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, chronic insomnia and depression. Using an in vitro screening model for melatonin receptors, the researchers learned from Magnolia officinalis(Laughter, Rehder and Wilson)In order to find highly active compounds, they modified and optimized the structure of magnolol and synthesized a series of derivatives. Through in vitro activity assay, they found magnolol glucoside (7c) is the most active, and the agonistic effect of magnolol on melatonin receptors is enhanced.2.5To7.5times, at the same time, in vivo efficacy evaluation results also show that the compound.7cPotential antidepressant effects may be exerted by affecting neurotransmitter levels in the mouse brain.

Subsequent to the compound7cIn vivo metabolite study and preliminary safety evaluation were carried out, from mice plasma, urine and feces25The acute toxicity test shows that the compound has good safety and has the potential application prospect of developing into new antidepressant drugs.

This achievement has been published in the European Journal of Medicinal Chemistry, the top journal in the subject field, and applied for a Chinese patent on "Application of Magnolol Glycosides in the Preparation of Drugs for the Treatment of Central Nervous System Diseases" earlier this year. Its main claim is "Compound Magnolol;4;O;β;D;Glucopyranoside(See structural formula below)or its medicinal salts in the preparation of melatonin receptor agonists ", has now entered the trial stage.