The 22+ Benefits Of Oxymatrine (With Natural Sources, Synergies, And Mechanisms)

Oxymatrine: A Sophora Alkaloid

 
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Oxymatrine has shown to have anti-arrhythmic, immune regulatory, and anti-tumor properties and is used in China for treatment of viral hepatitis, cancer, cardiac diseases (such as viral myocarditis), and skin diseases (such as psoriasis and eczema). R

In this post, we will discuss the many benefits of oxymatrine, its natural sources, and its mechanisms.

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Basics Of Oxymatrine

Oxymatrine (matrine oxide, matrine N-oxide, matrine 1-oxide) is an alkaloid extracted from the Chinese herb family of SophoraeR

Oxymatrine has shown to have anti-arrhythmic, immune regulatory, and anti-tumor properties. R

It is extensively used in China for treatment of viral hepatitis, cancer, cardiac diseases (such as viral myocarditis), and skin diseases (such as psoriasis and eczema). R

Oxymatrine is very similar in structure to Matrine, but has an extra oxygen molecule and within ~3 hours of ingestion oxymatrine increases blood levels of matrine (via metabolism of human microbiome). R R

 
 

Benefits Of Oxymatrine

1. Abolishes Neuroinflammation And Excitotoxcity

Oxymatrine is neuroprotective able to prevent neuroinflammation (inflammation in the brain). R R

Microglial cells play a pivotal role in the Central Nervous System's (CNS) innate immune response and act as the first line of defense against microorganism invasion and injury in the brain. R

Oxymatrine can inhibit Heat Shock Protein 60 (HSP60) induction of Toll-Like Receptor 4 (TLR4) in microglial cells. R

Activation of TLR4 is a major player of initiating inflammation following neurodegeneration and oxymatrine can inhibit this activation. R

Oxymatrine can also protect neurons by downregulating 12/15-Lipooxygenase (12/15-lox), phospho-p38 Mitogen-Activated Protein Kinase (p38-MAPK) and Cytosolic Phospholipase A2 (CPLA2). R

Oxymatrine can also protect hippocampal neurons from cell death. R

Oxymatrine may prevent excitotoxicity in the brain by protecting neurons against N-methyl-D-aspartate (NMDA) exposure-induced neurotoxicity. R

2. Alleviates Endotoxemia And Inflammation

Sepsis (endotoxemia) is a major cause of many chronic health problems. 

Oxymatrine can prevent sepsisR R

For example, oxymatrine can prevent Lipopolysaccharide (LPS)-induced inflammation in/of:

  • Breast - lightens immune response from Mastitis R
  • Gut R
  • Heart (reduces TNF-α/p38-MAPK/caspase-3) R R
  • Hippocampus (reduces TLR4) R
  • Kidneys (reduces JAK2/STAT3) R
  • Liver (induces Nrf2/HO‑1/NADPH/GSH-PX/SOD, reduces TLR4/PI3K/Akt/GSK-3β and ROS)R R R
  • Lung (reduces JNK) R
  • Macrophages (reduces TLR4) R
  • Microglia (reduces TLR4) R R
  • Pancreas (reduces TLR4/MyD88/NF-κB) R

By reducing Aquaporin 1 (AQP1) expression in vascular endothelial cells, oxymatrine can reduce inflammatory cellular edema. R

3. Fights Cancer

 
 https://link.springer.com/article/10.1007%2Fs13277-014-1680-z

https://link.springer.com/article/10.1007%2Fs13277-014-1680-z

 

Oxymatrine is a powerful chemotherapeutic agent - it inhibits cancer cell proliferation, induces cell cycle arrest, accelerates apoptosis, restrains angiogenesis, induces cell differentiation, inhibits cancer metastasis and invasion, reverses multidrug resistance, and prevents/reduces chemotherapy- or radiotherapy-induced toxicity. R

Oxymatrine has cancer-fighting properties against:

  • Bladder Cancer (increases caspase-3 and Bax; downregulates survivin, increases Bcl-2 and p53) R
  • Breast Cancer (increases bax, reduces Bcl-2) R R
  • Cervical Cancer (reduces HPV16E7) R R
  • Colorectal Carcinoma (reduces TGF-β1/Smad and EMT) R R R R
  • Gallbladder carcinoma (increases PTEN, reduces PI3K/AKT) R R
  • Gastric Cancer (inhibits EGFR/Cyclin D1/CDK4/6, EGFR/Akt and MEK-1/ERK1/2/MMP2) R
  • Glioblastoma (via Bax/Bcl2/Caspase-3) R
  • Laryngeal Cancer (reduces HPV16E7) R R R
  • Leukemia (increases Caspase-3 and Caspese-9) R
  • Liver Cancer (reduces bcl-2 and up-regulates p53R R
  • Lung Cancer (reduces EGFR) R R R R
  • Osteosarcoma (increases PTEN, reduces PI3K/Akt) R R
  • Ovarian Cancer (reduces MMP‑2) R
  • Pancreatic Cancer (reduces Livin, Survivin and VEGF; increases release of cytochrome c) R R
  • Prostate Cancer (increases p53 and bax, reduces Bcl-2) R
  • Synovial cell sarcoma + Akt/mTOR inhibition R

Oxymatrine can also prevent the development of hemangiomas (by reducing HIF-1a, VEGF, Bcl-2, and CyclinD1, and increasing p53). R

4. Ameliorates Arthritis

Oxymatrine may have a protective effect on Rheumatoid Arthritis (RA) through the inhibition of inflammation and regulation of Treg/Th17. R

Mxymatrine may also protect joint destruction in RA by inhibiting synoviocyte activation, migration, invasion, and proliferation. R

5. Protects The Liver

By inducing the transcription factor NRF2 and suppressing TLR4, oxymatrine can protect against Acute Liver Failure (ALF). R R

Oxymatrine also increases antioxidants such as Glutathione (GSH) and Superoxide Dismutase (SOD). R

By activating Peroxisome Proliferator-Activated Receptor-α (PPAR-alpha), oxymatrine helps prevent Non-Alcoholic Fatty Liver Disease (NAFLD). R R

For example, in models of NAFLD fed a high fat diet or high fructose diet, oxymatrine administration for 4 weeks was able to reduced body weight gain and visceral fat weight, as well as improve serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) and fasting serum insulin (FinS) levels. R R

Oxymatrine can prevent fibrosis (cirrhosis) of the liver (via Smad3/Smad7/TGFb1 and MMP2/TIMP1). R R R R

Oxymatrine fights Hepatitis B Virus (HBV) replication. R

Also, oxymatrine can protect the liver from Alcohol-induced damage. R

Oxymatrine may also promote Mesenchymal Stem Cells (MSC) in the liver. R

6. Strengthens The Gut

Oxymatrine can ameliorates acute intestinal inflammation (prevents NF-kB nuclear translocation and inhibits LPO). R R

For example, oxymatrine can prevent cirrhosis-associated intestinal mucosal damage, thus protecting the gut lining. R

Oxymatrine may be therapeutic in treatment of Ulcerative Colitis (UC). R R R

Oxymatrine can attenuate the development of UC by regulating DOR/β-arrestin1/Bcl-2 and β2AR/β-arrestin2/NF-κB signal transduction pathways. R R R

7. Has Antimicrobial Properties

Oxymatrine has antiviral effects against:

  • Coxsackievirus B3 (CB3) - protects against CB3 induced myocarditis R
  • Hepatitis B Virus (HBV) - improves TLR9 signalling and also prevents Lamivudine-induced YMDD mutations R R R R R R R 

Oxymatrine has antifungal effects against:

  • Cladosporium oxysporum R
  • Fusarium oxysporum R
  • Marssonina brunnea R
  • Mycobacterium tuberculosis (MTB) - protects against mycobacterial Trehalose Dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages R
  • Sphaeropsis sapinea R
  • Valsa pini R

Oxymatrine also have antiparasitic effects aganst Toxoplasma gondii (strong protection in liver) and insecticidal properties against two-spotted spider mite (Tetranychus urticae Koch). R R

8. Protects The Lungs

 
 

Oxymatrine can protect the lungs from Acute Lung Injury (ALI) by activating the epithelial sodium channel and suppressing the JNK signaling pathway. R

Oxymatrine treatment protects against the effects of Cardiopulmonary Resuscitation (CPR) as it significantly improves troponin I levels, the ejection fraction, hydroxyproline content and the myocardial performance index while inhibiting TGFb1 levels. R

Oxymatrine prevents fibrosis of the lungs. R R

Oxymatrine may also protect the lungs from mycobacterium bacteria (Mycobacterium aurum) infection. R

Oxymatrine can also protect damage from loss of blood to the lungs. R R

Oxymatrine can also prevent pulmonary hypertension (hypoxia induced). R

9. Fortifies The Vascular System

Oxymatrine has strong effects on the vascular system. R

Oxymatrine can protect the heart against sepsis-induced shock. R R

Oxymatrine also protects the heart against arrhythmias (irregular heartbeats). R R

It also prevents heart failure by inhibiting Cyclooxygenase-1 (COX-1), COX-2, and Brain Natruretic Peptide (BNP) as well as increasing Dimethylarginine Dimethylaminohydrolase 2 (DDAH2) expression. R R R R

It may also prevent heart attack. R

Oxymatrine can also prevent the development of fibrosis of the heart (via TGF-b1) and reduce hypertension (via ACE). R R R R

Oxymatrine can also protect the heart against high levels of Aldosterone (ALD). R R

Oxymatrine can also protect against doxorubicin-induced cardiotoxicity by inhibiting  cell death and oxidative stress. R

By antagonizing the Adenosine A2B Receptor (A2BR), oxymatrine can protect the heart form high levels of glucose. R

Oxymatrine can also protect against high homocysteine levels-induced cell death. R

In mice, oxymatrine has shown to protect against Coxsackievirus B3-induced myocarditis. R

Oxymatrine is also effective at reducing vascular calcification. R

10. Protects The Kidneys

Oxymatrine is powerful at protecting the kidneys from inflammation (inhibits JAK2 and STAT3). R

Oxymatrine can protect the kidneys from high levels of glucose (inhibits production of Advanced Glycation End-Products, AGEs) and may be useful for Diabetic Neuropathy (DN). R R

Oxymatrine can also increase antioxidant levels in the kidneys and protect them from hypoxia (increases NRF2/HO-1). R R

Oxymatrine is also able to prevent fibrosis of the kidneys. R 

11. Combats Diabetes And Obesity

Oxymatrine can ameliorate insulin resistance/glucose intolerance and may improve Diabetes. R

For example, in diabetic rats, oxymatrine can significantly decrease fasting blood glucose, glycosylated hemoglobin (GHb), food and water intake, non-esterified fatty acid (NEFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol levels (LDL-c), and increase serum insulin, liver and muscle glycogen, high density lipoprotein cholesterol (HDL-c), glucagon-like peptide-1 (GLP-1) and muscle glucose transporter-4 (GLUT-4) content. R

12. May Help Spinal Cord Injury Treatment

In vitro, oxymatrine can enhance axonal growth and may be useful for Spinal Cord Injuries (SCI). R

13. Reduces Withdrawal And Tolerance

Oxymarine may help reduce morphine tolerance, but without affecting the magnitude of the analgesic effect of morphine. R

High doses of oxymatrine can inhibit the development of morphine tolerance (similar to the NMDAR antagonist memantine). R

High dose of oxymatrine (30 mg/kg) can also significantly inhibit the increase in expression of morphine-induced P-glycoprotein (P-gp). R

14. Helps With Stroke

Oxymatrine is neuroprotective during stroke. R

For example, in animal models subjected to Middle Cerebral Artery Occlusion (MCAO), oxymatrine protected the brain from damage caused by MCAO (via downregulation of the TLR4, TLR2, MyD88, and NF-kB). R

In hemorrhagic stroke models, oxymatrine can reduce inflammatory responses, oxidative injury, and neuronal cell apoptosis. R

In ischemic stroke models, oxymatrine can increase antioxidant levels in the brain and prevents cell death. R

15. Ameliorates Psoriasis

 
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Oxymatrine can effectively ameliorate severe plaque PsoriasisR R

For example, in a 8 week trial, patients given oxymatrine injections had significantly decreased PASI score, skin classification grade and DLQI score. R

Compared to acitretin capsules 24 weeks later, oxymatrine patients had less chance of relapse. R

16. Helps Reduce Allergies

Oxymatrine can help with allergies. R R

For example, oxymatrine can reduce skin allergy in models of eczema and atopic dermatitis. R

Oxymatrine can also improve allergic asthma by regulation of CD40 signaling. R

17. Stops Pain

By modulating calcium release and increasing GABA in the brain, oxymatrine has pain-reducing effects. R R R

Oxymatrine may also help with neuropathies (by modulating NMDA NR2B receptor-ERK/CREB signaling). R

In the gut, oxymatrine also regulates Delta Opioid Receptors (DOR). R R

18. Combats Arsenic Poisoning

Oxymatrine can protect the heart from Arsenic-induced Long QT Syndrome (LQTS). R

Oxymatrine can also protect the liver against Arsenic-induced liver injury (by increasing Nrf2 and HO-1). R

19. May Help Prevent Stress Ulcers

Oral oxymatrine may help prevent the formation of stress ulcers. R

20. Reduces Scarring

On the skin, oxymatrine may help reduce scarring. R

21. Reduces Cognitive Loss 

In aging mice, can improve the learning and memory ability by increasing antioxidant levels and reducing lipid peroxidation. R

Oxymatrine can also attenuate diabetes-associated cognitive deficits in rats. R

22. Protects Pancreas

Oxymatrine can protect the pancreas from inflammation. R

My Experience With Oxymatrine

I've tried oxymatrine and have seen a reduction in acne and increase in energy levels. 

It is considerably more tolerable with Licorice (important see below).

Natural Sources Of Oxymatrine

 
 

Pure oxymatrine can be bought here.

Natural sources of oxymatrine:

Oxymatrine Synergies

 
 

Oxymatrine goes well with:

  • Chitosan - may help with gastric retention and sustaining release R
  • Dong Quai (Sodium ferulate) - protects against sepsis, lung injury, and alcohol-induced liver injury R R R
  • Fluorouracil R
  • Licorice - protects against liver toxicity R
  • Matrine R
  • Oxaliplatin - Oxymatrine synergistically enhances antitumor activity of oxaliplatin in colon carcinoma R
  • Phosphatidylcholine (liposomal) - Helps with liver delivery and retention time R

Caveats

Oxymatrine is dependent on CYP2B1 and CYP3A2 and can inhibit hOCT1 (SLC22A1), so drug-drug interactions may occur during hOCT1-mediated hepatic and renal uptake and during hOCT3-mediated intestinal absorption. R R R

In mice, high doses (at a dose of 320 mg/kg) can lead to liver damage (via activation of JNK) although adding Licorice (diammonium glycyrrhizinate) can remarkably reduces the toxicity of oxymatrine. R R

Oxymatrine may inhibit the therapeutic benefits of Ribavirin. R

Mechanism Of Action

Simple:

  • Increases Acox1 R
  • Increases AMACR R
  • Increases APOA4 R
  • Increases APOM R
  • Increases ATF2 R
  • Increases Akt (reduces in cancer though) R
  • Increases Bcl-2 R R R
  • Increases β2AR R
  • Increases β-arrestin1 R
  • Increases β-arrestin2 R
  • Increases CAR R
  • Increases CAT R R
  • Increases CPT1A R R
  • Increases CYP17A1 R
  • Increases CYP2B1 R
  • Increases CYP2C18 R
  • Increases CYP2C19 R 
  • Increases CYP450 R
  • Increases DOR R R
  • Increases ENaC R
  • Increases ETA R
  • Increases E-cadherin R
  • Increases FOXP3 R
  • Increases GABA R
  • Increases GABAAR2 R
  • Increases HDL-c R
  • Increases GLP-1 R
  • Increases GLUT-4 R
  • Increases GSH-PX R R
  • Increases GSK-3beta R
  • Increases HO-1 R R
  • Increases Hsp90a R
  • Increases IFN-γRα R
  • Increases IL-4 R 
  • Increases IL-10 R
  • Increases IL-12 R
  • Increases INHBC R
  • Increases INHBE R
  • Increases MTTP R
  • Increases NRF2 R R 
  • Increases OAT R
  • Increases PPARα R 
  • Increases PTEN R R
  • Increases p53 R R
  • Increases Smad7 R
  • Increases SOD R R R
  • Increases SULT1A2 R
  • Increases TLR-9 R
  • Increases Tregs R
  • Increases UCH-L1 R
  • Reduces Acc R
  • Reduces ACE R
  • Reduces ADMA R
  • Reduces AIF R
  • Reduces AKT R
  • Reduces Albumin R
  • Reduces ALP R
  • Reduces ALT R
  • Reduces AQP1 R
  • Reduces Arkadia R 
  • Reduces AST R
  • Reduces α-SMA R R 
  • Reduces A2BR R
  • Reduces Bax R R
  • Reduces BNP R
  • Reduces BUN R R
  • Reduces Cadherin 22 R
  • Reduces Calbindin 3 R
  • Reduces Calpain R
  • Reduces Caspase-3 R R R R
  • Reduces Caspase-9 R
  • Reduces CDK4 R
  • Reduces CDK6 R 
  • Reduces CD44 R
  • Reduces COL1A1 R
  • Reduces COL1A2 R
  • Reduces COL5A2 R
  • Reduces COX-1 R
  • Reduces COX-2 R R
  • Reduces cPLA2 R
  • Reduces CPT1A R
  • Reduces Creatinine R
  • Reduces CRP R
  • Reduces CTGF R
  • Reduces Cyclin D1 R R 
  • Reduces DDAH2 R
  • Reduces Decorin R 
  • Reduces EGF1 R
  • Reduces EGFR R
  • Reduces ERK R R
  • Reduces Fasn R
  • Reduces FFA R
  • Reduces FN R R
  • Reduces GAT-1 R
  • Reduces HIF-1a R
  • Reduces HMGb1 R
  • Reduces hOCT1 (SLC22A1) R
  • Reduces HPV16E7 R
  • Reduces HSP60 R
  • Reduces ICAM-1 R
  • Reduces IgE R
  • Reduces IGFBP-2 R 
  • Reduces IL-1b R R R R
  • Reduces IL-4 R
  • Reduces IL-5 R
  • Reduces IL-6 R R R
  • Reduces IL-8 R R
  • Reduces IL-13 R
  • Reduces IL-17 R
  • Reduces iNOS R R
  • Reduces Insulin (fasting) R
  • Reduces ITGA6 R
  • Reduces ITGB1 R
  • Reduces I-κBα R
  • Reduces JAK2 R R
  • Reduces JNK R R
  • Reduces Keratin 10 R
  • Reduces Laminin Receptor 1 R
  • Reduces LDL-c R
  • Reduces Livin R
  • Reduces LPO R
  • Reduces MAPK R R
  • Reduces MDA R
  • Reduces MDC R
  • Reduces MEK-1 R
  • Reduces MIF R
  • Reduces MMP-2 R
  • Reduces MMP-9 R
  • Reduces mTOR R
  • Reduces MyD88 R R
  • Reduces NF-kB R R
  • Reduces NMDAR R
  • Reduces NO R
  • Reduces NR2B R R
  • Reduces PAI-1 R 
  • Reduces Pan-Cytokeratin R
  • Reduces PAP R
  • Reduces PGE2 R
  • Reduces PI3K R R
  • Reduces pro‑collagen I R
  • Reduces p38 R R R
  • Reduces p63 R
  • Reduces p65 R
  • Reduces P-gp R
  • Reduces RORγt R
  • Reduces ROS R
  • Reduces Smad2 R R
  • Reduces Smad3 R R
  • Reduces Smad4 R 
  • Reduces Snon R
  • Reduces SOCS1 R
  • Reduces Srebf1 R
  • Reduces STAT3 R R
  • Reduces Survivin R R
  • Reduces TC R
  • Reduces TG R
  • Reduces TGFb1 R R R R
  • Reduces TH17 R
  • Reduces TIMP1 R R
  • Reduces TNF-α R R R R R
  • Reduces TLR-2 R
  • Reduces TLR-4 R R R R
  • Reduces VEGF R R
  • Reduces Y-B1 R
  • Reduces 12/15-LOX R

Advanced:

  • The absorption rate and permeability of OMT is not dependent on concentration, but through passive absorption in intestine (P > 0.05). In the rat intestine, the absorbed amount of OMT was significantly different in four sections of the intestine in an order of duodenum > jejunum > ileum > colon (P < 0.05). OMT is metabolized into two metabolites in duodenum and jejunum, and matrine (MT) is the major one. R
  • In the brain, OMT is neuroprotective as it can inhibit the HSP60-TLR-4-MYD88-NF-κB pathway. R
  • OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family. R
  • In RA models, OMT treatment enhanced the differentiation of Treg cells and inhibited Th17 cells. R
  • Oxymatrine can induce human constitutive androstane (CAR) and CYP2B1 in a dose-dependent manner. R
  • OMT suppressed the expression of TLR4 and its downstream pro-inflammatory cytokines, lowered the level of HMGB1, TGF-β1 in macrophages. R
  • In skin cells in models of psoriasis, OMT significantly suppresses the expression of Pan-Cytokeratin, p63 and keratin 10. R
  • OMT may have tyrosinase inhibition (simulation of molecular docking). R
  • In pain models, compared with the model group, mRNA levels of Cavl.2, Cavl.3, Cav2.1, and Cav2. 3 in brain tissues were decreased, and those of Cav2.2 were increased significantly in the OMT group (P < 0.05). In spinal cord tissues of the OMT group, mRNA levels of Cav1.3 decreased and those of Cav2.1, Cav2.2, and Cav2.3 increased significantly with statistical difference, when compared with those of the model group (P < 0.05)...increases GABA in brain but not spinal cord tissues. R
  • In neuropathic pain, OMT reduces GAT-1 and increases expression of GABAAR2. R
  • Oxymatrine combats HPV by a few mechanisms: increasing TH1 cytokines/decreasing TH2 cytokines. R
  • Also in HPV - OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-γ (IFN-γ) in a dose-dependent manner in CD4+ T cells. R
  • OMT can significantly ameliorate UC through anti-inflammatory, pro-apoptotic, down-regulating the differentiation of Th1 and Th17 cells via PI3K/AKT pathway. R
  • By scavenging oxygen free radicals, OMT can inhibit apoptosis, increase Hsp90a expression, and reduce the injury caused by lung ischemia reperfusion. R
  • In the heart, oxymatrine significantly delayed the initial time and shortened the duration time of rat arrhythmias induced by coronary artery ligation. R
  • OMT treatment aslo inhibited CFB proliferation and the CFB‑myofibroblast transition induced by TGF‑β1, at least in part through inhibition of ERK1/2 and p38MAPK signaling...oxymatrine attenuated aldosterone-induced Smad-2, Smad-3, and Smad-4 expression in cardiac fibroblasts. R R
  • Oxymatrine could ameliorate the hypertrophy and dysfunction of left ventricle of rats with heart failure, which is attributed to modulation of dimethylarginine dimethylaminohydrolase 2 (DDAH2)/asymmetric dimethylarginine (ADMA) metabolism pathway by oxymatrine. R
  • Oxymatrine blocked Hep-2 cells in G0/G1 phase, resulting in an obvious accumulation of G0/G1 phase cells while decreasing S phase cells. R

More Research

  • Oxymatrine may also act as a fertilizer and plant defense. R R