Oxymatrine (matrine oxide, matrine ''N''-oxide, matrine 1-oxide) is one of many quinolizidine alkaloid compounds extracted from the root of ''

Sophora flavescens ''Sophora flavescens'', the shrubby sophora, is a species of plant in the genus ''Sophora'' of the family Fabaceae. This genus contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceania, and the P ...

'', a Chinese herb. It is very similar in structure to

matrine Matrine is an alkaloid found in plants from the genus ''Sophora''. It has a variety of pharmacological effects, including anti-cancer effects, as well as κ-opioid and μ-opioid receptor agonism. Matrine possesses strong antitumor activities '' ...

, which has one less oxygen atom. Oxymatrine has a variety of effects ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' and in

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s, including protection against apoptosis, tumor and fibrotic tissue development, and inflammation. Furthermore, oxymatrine has been shown to decrease cardiac

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

(decreased blood perfusion), myocardial injury,

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s (irregular heartbeats), and improve

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

by increasing cardiac function.

Role in cardiac fibrosis

Recent research has shown that oxymatrine prevents

cardiac fibrosis Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic c ...

in rats.Shen, X, Yang, Y, Xiao, T, Peng, J, Liu, X. (2011) Protective effect of oxymatrine on myocardial fibrosis induced by acute myocardial infarction in rats involved in TGF-b1-Smads signal pathway. Journal of Asian Natural Products Research 13: 215-224 The development of fibrotic tissue in the heart occurs when fibroblasts produce excessive amounts of

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

(particularly types I and III), which accumulate and deposit in the heart. The excessive transformation to fibrotic tissue negatively affects the function and structure of the heart. Additionally, excessive amounts of collagen in the ventricles lead to alterations in gene expression, deposition of

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

, wall thickening, and ventricular remodeling in a manner that promotes dysfunction.Huang, X, Chen, X. (2012) Effect of oxymatrine, the active component from Radix Sophorae flavescentis (Kushen), on ventricular remodeling in spontaneously hypertensive rats. Phytomedicine 20: 202-212. The

mechanism Mechanism may refer to: *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that a ...

by which oxymatrine may inhibit fibrosis is still unidentified. One theory that has been proposed is that oxymatrine inhibits a key signaling pathway involved in collagen production. One of the main signaling receptors involved in this pathway is the TGF-β1 co-receptor (complex of type I and type II receptors), which acts as a trans-membrane protein serine/threonine kinase. A receptor assembly factor first activates TGF-β1 type I receptor and then type II. Receptor I is then able to bind proteins

Smad2 Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the ''SMAD2'' gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the ''Dros ...

and

Smad3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...

, which form a complex with

Smad4 SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, ...

. This complex accumulates in the nucleus, and binds to promoter elements of the collagen gene, stimulating the production of collagen.S.J. Wicks, T. Grocott, K. Haros, M. Maillard, P. ten Dijke, and A. Chantry (2006) Reversible ubiquitination regulates the Smad/TGF-beta signalling pathway. Biochem. Soc. Trans. 34: 761-763 In rats, oxymatrine also inhibits the expression of the Smad3 ligand which binds to TGF-β1 type I and activates the signal transduction pathway. A

dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. ...

was observed with increasing intragastric concentrations of oxymatrine resulting in decreased expression of Smad3. By inhibiting this pathway, less collagen was produced and deposited in the heart, preventing the formation of cardiac fibrosis. Huang and Chen (2013) claim that oxymatrine may even be involved in inhibiting the expression of TGF-β1 receptors, which would further support that oxymatrine attenuates the signal transduction pathway involved in collagen production. They also reported that inhibition of the TGF-β1 receptor may also prevent ventricular remodeling.

Future studies

Effects of oxymatrine on heart disease in humans has not been studied and the long term side-effects of clinical oxymatrine use have not yet been identified.

References

{{reflist Quinolizidine alkaloids Alkaloids found in Fabaceae Amine oxides