Research Progress on the Neuroprotective Effect of Leonurine on Ischemic Stroke

Leonurus is one of the commonly used clinical drugs in traditional Chinese medicine.In recent years,leonurus has been widely used for cerebrovascular diseases.With the deepening of research,the effect of its main component,leonurine,on the central nervous system has become clearer,and its mechanism has been confirmed and explained from many aspects.For reference,this paper discusses the latest research on the neuroprotective effect of leonurine on ischemic stroke at home and abroad in recent years.

Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution

The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating strokes.However,the biosynthetic pathway of leonurine remains largely unexplored.Here,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine production.By integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this pathway.Further analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L.japonicus,which contributed to the accumulation of leonurine specifically in L.japonicus.Collectively,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

Leonurine: From Gynecologic Medicine to Pleiotropic Agent

Leonurus japonicus Houtt,a Chinese traditional herbal medicine,has been widely used to cure gynecological diseases,such as incomplete abortion and menoxenia.Leonurine,a major active alkaloid compound only be found in Leonurus japonicus Houtt,has been successfully extracted and purified.Recent evidence has shown that leonurine can regulate a variety of pathologic processes including oxidative stress,inflammation,fibrosis,apoptosis,and multiple metabolic disorders.Here,we have reviewed the pharmacological actions and biological functions of leonurine,with a focus on the role of leonurine in the amelioration of various pathological processes.Insights into the related signaling pathways and molecular mechanisms have strengthened our understanding on the function of leonurine in the alleviation of multiple pathological states.Our summary of the existing researches should help direct future research into the basic science and clinical applications in related diseases.

Leonurine protects ischemia-induced brain injury via modulating SOD, MDA and GABA levels

The present study was designed to investigate the protective effects of leonurine, a compound purified from Herba Leonuri that is active on ischemic rat behavior and cortical neurons, and explore the underlying mechanism. The general rat activity, cortical neuron morphology, superoxide dismutase (SOD), malondialdehyde (MDA),γ- aminobutyric acid (GABA) and glutamate decarboxylase 67 (GAD67) levels were measured. We found leonurine significantly improve the general activity of rats in an opefield test, which was associated with attenuated neuronal damage induced by ischemia. Moreover, serum SOD activity was significantly greater, MDA level lower in the leonurine group as compared with ischemia group. In addition, GABA content in the cerebral cortex was significantly greater in high-dose leonurine group. Correspondingly, GAD67 protein level coincided with the GABA level. Taken together, our results demonstrated that leonurine attenuated brain injury during ischemia via antioxidative and anti-excitotoxicity effects by targeting GABA and leonurine might become a useful adjuvant neuroprotective agent.

Improved synthesis of leonurine as cardioprotective agent

A new synthetic method of leonurine was developed. Leonurine 1 was synthesized from the key intermediates 4 and 5, two compounds with high solubility in dichloromethane which allowed the synthetic procedure to be performed under mild conditions and afforded 1 with a good yield. Comparing the previous methods, the yield was increased from 30% to 54%, time consumed was significantly reduced as well.

Six-step synthesis of Leonurine and toxicity study on zebrafish

Leonurine（1）,an important ingredient in leonurus sibiricus L,can be used for some gynecological disease.We have developed a concise and efficient synthetic route of Leonurine,which can be optimized for mass production.Commercially available compound 6 and 2,3-dihydrofuran（7） were used as starting materials.And the toxicity study on zebrafish shows that Leonurine would promote the hatching of zebrafish embryos at low concentration and result in acute death or chronic lethal toxicity at high concentration.