leonurine

Leonurine weakly binds to multiple GABA receptor sites including the GABA_A receptor.{{cite journal | vauthors = Çiçek SS | title = Structure-Dependent Activity of Natural GABA(A) Receptor Modulators | journal = Molecules | volume = 23 | issue = 7 | page = 1512 | date = June 2018 | pmid = 29932138 | pmc = 6100244 | doi = 10.3390/molecules23071512 | doi-access = free }}{{cite journal | vauthors = Rauwald HW, Savtschenko A, Merten A, Rusch C, Appel K, Kuchta K | title = GABAA Receptor Binding Assays of Standardized Leonurus cardiaca and Leonurus japonicus Extracts as Well as Their Isolated Constituents | journal = Planta Medica | volume = 81 | issue = 12–13 | pages = 1103–1110 | date = August 2015 | pmid = 26218338 | doi = 10.1055/s-0033-1352395 }} However, it shows much higher affinity as a 5-HT3A receptor antagonist.{{cite journal | vauthors = Hoffmann KM, Herbrechter R, Ziemba PM, Lepke P, Beltrán L, Hatt H, Werner M, Gisselmann G | display-authors = 6 | title = Kampo Medicine: Evaluation of the Pharmacological Activity of 121 Herbal Drugs on GABAA and 5-HT3A Receptors | journal = Frontiers in Pharmacology | volume = 7 | pages = 219 | year = 2016 | pmid = 27524967 | pmc = 4965468 | doi = 10.3389/fphar.2016.00219 | doi-access = free }} 5-HT3A antagonists have been shown to help prevent nausea and vomiting as well as the negative effects of serotonin in the gastrointestinal tract.{{cite book | vauthors = Theriot J, Wermuth HR, Ashurst JV |title=StatPearls |date=2022 |publisher=StatPearls Publishing |url=https://www.ncbi.nlm.nih.gov/books/NBK513318/ |chapter=Antiemetic Serotonin-5-HT3 Receptor Blockers |pmid=30020690 }}{{cite web | url=https://www.drugs.com/drug-class/5ht3-receptor-antagonists.html | title=List of 5HT3 receptor antagonists (5hydroxytryptamine receptor antagonists) }}

Leonurine can regulate a variety of functions including oxidative stress, inflammation, fibrosis, apoptosis, and metabolic disorder.{{cite journal | vauthors = Li YY, Lin YK, Liu XH, Wang L, Yu M, Li DJ, Zhu YZ, Du MR | display-authors = 6 | title = Leonurine: From Gynecologic Medicine to Pleiotropic Agent | journal = Chinese Journal of Integrative Medicine | volume = 26 | issue = 2 | pages = 152–160 | date = February 2020 | pmid = 31069695 | doi = 10.1007/s11655-019-3453-0 | s2cid = 148571306 }}{{cite journal | vauthors = Li N, Xu Q, Liu Q, Pan D, Jiang Y, Liu M, Liu M, Xu H, Lin C | display-authors = 6 | title = Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation and joint destruction in rheumatoid arthritis | journal = Rheumatology | volume = 56 | issue = 8 | pages = 1417–1427 | date = August 2017 | pmid = 28431044 | doi = 10.1093/rheumatology/kex142 | doi-access = free }}{{cite journal | vauthors = Zheng S, Zhuang T, Tang Y, Wu R, Xu T, Leng T, Wang Y, Lin Z, Ji M | display-authors = 6 | title = Leonurine protects against ulcerative colitis by alleviating inflammation and modulating intestinal microflora in mouse models | journal = Experimental and Therapeutic Medicine | volume = 22 | issue = 5 | pages = 1199 | date = November 2021 | pmid = 34584544 | pmc = 8422400 | doi = 10.3892/etm.2021.10633 }}

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.{{cite journal | vauthors = Jia M, Li C, Zheng Y, Ding X, Chen M, Ding J, Du R, Lu M, Hu G | display-authors = 6 | title = Leonurine Exerts Antidepressant-Like Effects in the Chronic Mild Stress-Induced Depression Model in Mice by Inhibiting Neuroinflammation | journal = The International Journal of Neuropsychopharmacology | volume = 20 | issue = 11 | pages = 886–895 | date = November 2017 | pmid = 29016795 | pmc = 5737563 | doi = 10.1093/ijnp/pyx062 | doi-access = free }}{{cite journal | vauthors = Shi XR, Hong ZY, Liu HR, Zhang YC, Zhu YZ | title = Neuroprotective effects of SCM198 on 6-hydroxydopamine-induced behavioral deficit in rats and cytotoxicity in neuronal SH-SY5Y cells | journal = Neurochemistry International | volume = 58 | issue = 8 | pages = 851–860 | date = July 2011 | pmid = 21093517 | doi = 10.1016/j.neuint.2010.11.007 | s2cid = 33986318 }}{{cite journal | vauthors = Liao L, Zhou M, Wang J, Xue X, Deng Y, Zhao X, Peng C, Li Y | display-authors = 6 | title = Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade | journal = Frontiers in Pharmacology | volume = 12 | pages = 742954 | date = 4 November 2021 | pmid = 34803688 | pmc = 8600049 | doi = 10.3389/fphar.2021.742954 | doi-access = free }}

Leonurine has been investigated as a potential treatment for cardiovascular disorders.{{cite journal | vauthors = Huang L, Xu DQ, Chen YY, Yue SJ, Tang YP | title = Leonurine, a potential drug for the treatment of cardiovascular system and central nervous system diseases | journal = Brain and Behavior | volume = 11 | issue = 2 | pages = e01995 | date = February 2021 | pmid = 33300684 | pmc = 7882174 | doi = 10.1002/brb3.1995 }}{{cite journal | vauthors = Wang R, Peng L, Lv D, Shang F, Yan J, Li G, Li D, Ouyang J, Yang J | display-authors = 6 | title = Leonurine Attenuates Myocardial Fibrosis Through Upregulation of miR-29a-3p in Mice Post-myocardial Infarction | journal = Journal of Cardiovascular Pharmacology | volume = 77 | issue = 2 | pages = 189–199 | date = February 2021 | pmid = 33235025 | doi = 10.1097/FJC.0000000000000957 | s2cid = 227168673 }}{{cite journal | vauthors = Zhu Q, Cai W, Sha X, Ma G, Zheng Y, Shi X, Zhu Y | title = Quantification of leonurine, a novel potential cardiovascular agent, in rat plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in rats | journal = Biomedical Chromatography | volume = 26 | issue = 4 | pages = 518–523 | date = April 2012 | pmid = 21882210 | doi = 10.1002/bmc.1699 }}{{cite journal | vauthors = Liu XH, Pan LL, Deng HY, Xiong QH, Wu D, Huang GY, Gong QH, Zhu YZ | display-authors = 6 | title = Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4 | journal = Free Radical Biology & Medicine | volume = 54 | pages = 93–104 | date = January 2013 | pmid = 23127783 | doi = 10.1016/j.freeradbiomed.2012.10.555 }} It protects against oxidative damage from ischemic stroke and demonstrates neuroprotective activity against focal cerebral ischemia brain injury induced on rats.{{cite journal | vauthors = Xie YZ, Zhang XJ, Zhang C, Yang Y, He JN, Chen YX | title = Protective effects of leonurine against ischemic stroke in mice by activating nuclear factor erythroid 2-related factor 2 pathway | journal = CNS Neuroscience & Therapeutics | volume = 25 | issue = 9 | pages = 1006–1017 | date = September 2019 | pmid = 31087454 | pmc = 6698971 | doi = 10.1111/cns.13146 }}{{cite journal | vauthors = Li F, Zhu S, Jiang Q, Hou C, Pang T, Zhang L, Li W | title = Novel Stachydrine-Leonurine Conjugate SL06 as a Potent Neuroprotective Agent for Cerebral Ischemic Stroke | journal = ACS Chemical Neuroscience | volume = 12 | issue = 13 | pages = 2478–2490 | date = July 2021 | pmid = 34180238 | doi = 10.1021/acschemneuro.1c00200 | s2cid = 235660771 }}{{cite journal | vauthors = Liu H, Zhang X, Du Y, Ji H, Li S, Li L, Xing Y, Zhang X, Dong L, Wang C, Zhao K, Ji Y, Cao X | display-authors = 6 | title = Leonurine protects brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke | journal = Brain Research | volume = 1474 | pages = 73–81 | date = September 2012 | pmid = 22842526 | doi = 10.1016/j.brainres.2012.07.028 | s2cid = 24119195 }}

Leonurine protects mice from pneumonia induced by influenza A.{{cite journal | vauthors = Qiu LN, Tan YR, Luo YJ, Chen XJ | title = Leonurine protects against influenza A virus infection-induced pneumonia in mice | journal = Pathogens and Disease | volume = 79 | issue = 7 | pages = ftab045 | date = September 2021 | pmid = 34543397 | doi = 10.1093/femspd/ftab045 }}

Leonurine has demonstrated anti-cancer activity in vitro and in animal studies.{{cite journal | vauthors = Zhuang Q, Ruan L, Jin T, Zheng X, Jin Z | title = Anti-leukaemia effects of leonurine in vitro and in vivo | journal = General Physiology and Biophysics | volume = 40 | issue = 5 | pages = 397–407 | date = September 2021 | pmid = 34602453 | doi = 10.4149/gpb_2021018 | doi-access = free }}{{cite journal | vauthors = Liu HM, Guo CL, Zhang YF, Chen JF, Liang ZP, Yang LH, Ma YP | title = Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy | journal = Frontiers in Pharmacology | volume = 12 | pages = 657724 | year = 2021 | pmid = 33935775 | pmc = 8087248 | doi = 10.3389/fphar.2021.657724 | doi-access = free }}{{cite journal | vauthors = Mao F, Zhang L, Cai MH, Guo H, Yuan HH | title = Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria-dependent pathway | journal = Pharmaceutical Biology | volume = 53 | issue = 11 | pages = 1684–1690 | date = 2 November 2015 | pmid = 25856714 | doi = 10.3109/13880209.2014.1001406 | s2cid = 207526411 | doi-access = free }}{{cite journal | vauthors = Lin M, Pan C, Xu W, Li J, Zhu X | title = Leonurine Promotes Cisplatin Sensitivity in Human Cervical Cancer Cells Through Increasing Apoptosis and Inhibiting Drug-Resistant Proteins | journal = Drug Design, Development and Therapy | volume = 14 | pages = 1885–1895 | date = 15 May 2020 | pmid = 32523334 | pmc = 7237110 | doi = 10.2147/DDDT.S252112 | doi-access = free }}{{cite journal | vauthors = Li X, Xie Y, Qu W, Ou X, Ou X, Wang C, Qi X, Wang Y, Liu Z, Zhu L | display-authors = 6 | title = Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Mediate the Disposition of Leonurine-10-O-β-glucuronide | journal = Current Drug Metabolism | volume = 21 | issue = 13 | pages = 1060–1067 | date = November 2020 | pmid = 33198612 | doi = 10.2174/1389200221999201116142742 | s2cid = 226985047 }}

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.{{cite journal | vauthors = Zhu Q, Zhang J, Yang P, Tan B, Liu X, Zheng Y, Cai W, Zhu Y | display-authors = 6 | title = Characterization of metabolites of leonurine (SCM-198) in rats after oral administration by liquid chromatography/tandem mass spectrometry and NMR spectrometry | journal = TheScientificWorldJournal | volume = 2014 | pages = 947946 | date = 2014 | pmid = 24772041 | pmc = 3956552 | doi = 10.1155/2014/947946 | doi-access = free }}

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.

:File:Leonurinesynthesis.svg{{clear-left}}

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• {{cite journal | vauthors = Cheng KF, Yip CS, Yeung HW, Kong YC | title = Leonurine, an improved synthesis | journal = Experientia | volume = 35 | issue = 5 | pages = 571–572 | date = May 1979 | pmid = 446644 | doi = 10.1007/BF01960323 | s2cid = 22601565 }}
• {{cite journal | vauthors = Huang L, Xu DQ, Chen YY, Yue SJ, Tang YP | title = Leonurine, a potential drug for the treatment of cardiovascular system and central nervous system diseases | journal = Brain and Behavior | volume = 11 | issue = 2 | pages = e01995 | date = February 2021 | pmid = 33300684 | pmc = 7882174 | doi = 10.1002/brb3.1995 }}

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Category:Alkaloids

Category:Guanidines

Category:Benzoate esters

Category:Phenols

Category:Phenol ethers