Oxymatrine (matrine oxide, matrine ''N''-oxide, matrine 1-oxide) is one of many

quinolizidine alkaloid Quinolizidine (norlupinane, octahydro-2''H''-quinolizine) is a nitrogen-containing heterocyclic compound. Some alkaloids (e.g. cytisine and sparteine) are derivatives of quinolizidine. Quinolizidine alkaloids Quinolizidine alkaloids, such as ...

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. It mainly occurs in India, Japan, Korea and Russia. Description ''Sophora flavescens'' c ...

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

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

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

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

'' 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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, 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 ...

(decreased blood perfusion), myocardial injury,

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

s (irregular heartbeats), and improve

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

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 A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

produce excessive amounts of

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

(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 Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

, deposition of

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

, wall thickening, and

ventricular remodeling In cardiology, ventricular remodeling (or cardiac remodeling) refers to changes in the size, shape, structure, and function of the heart. This can happen as a result of exercise (physiological remodeling) or after injury to the heart muscle (patho ...

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 (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish 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 ''Dr ...

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 (protein), SMAD family of proteins. It acts as a mediator of the signal ...

, 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 Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

pathway. A

dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the Stimulus–response model, response of an organism, as a Function (mathematics), function of exposure (or Dose (biochemistry), doses) to a Sti ...

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. In a 2010 study, Oxymatrine was shown to inhibit the development of morphine-induced tolerance associated with decreased expression of

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

in rat

References

{{reflist Quinolizidine alkaloids Alkaloids found in Fabaceae Amine oxides