Leonurine

Leonurine weakly binds to multiple GABA receptor sites including the GABA_A receptor.^[2][3] However, it shows much higher affinity as a 5-HT3A receptor antagonist.^[4] 5-HT3A antagonists have been shown to help prevent nausea and vomiting as well as the negative effects of serotonin in the gastrointestinal tract.^[5][6]

Leonurine can regulate a variety of functions including oxidative stress, inflammation, fibrosis, apoptosis, and metabolic disorder.^[7][8][9]

Leonurine has demonstrated antidepressant-like action and has been shown to increase levels of serotonin, noradrenaline, and dopamine in chronic mild stress studies on mice and inhibits the production of pro-inflammatory cytokines.^[10][11][12]

Leonurine has been investigated as a potential treatment for cardiovascular disorders.^{[13][14][15][16]} It protects against oxidative damage from ischemic stroke and demonstrates neuroprotective activity against focal cerebral ischemia brain injury induced on rats.^[17][18][19]

Leonurine protects mice from pneumonia induced by influenza A.^[20]

Leonurine has demonstrated anti-cancer activity in vitro and in animal studies.^{[21][22][23][24][25]}

Metabolites of leonurine in rats dosed orally include leonurine-10-O-sulfate (the sulfate conjugate of leonurine), leonurine-10-O-β-D-glucuronide (the glucuronide metabolite of leonurine) and an O-demethylated leonurine analog that has not yet had its structure definitively confirmed.^[26]

Leonurine can be synthesized starting from eudesmic acid. Reaction with sulfuric acid produces syringic acid. Protection with ethyl chloroformate followed by reaction with thionyl chloride (SOCl₂) and then tetrahydrofuran yields 4-carboethoxysyringic acid 4-chloro-1-butyl ester. The chloride is then converted to an amino group via a Gabriel synthesis (with potassium phthalimide) followed by hydrazinolysis (Ing–Manske procedure). The final step is reaction of the amine with S-methylisothiourea hemisulfate salt.