Indirubin is a
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
most often produced as a byproduct of bacterial metabolism. For instance, it is one of the compounds responsible for the generally benign condition
purple urine bag syndrome
Purple urine bag syndrome (PUBS) is a medical syndrome where purple discoloration of urine occurs in people with urinary catheters and co-existent urinary tract infection. Bacteria in the urine produce the enzyme indoxyl sulfatase. This converts In ...
, resulting from bacteria metabolizing
indoxyl sulfate
Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the develop ...
found naturally in urine.
Indirubin is a structural isomer (more precisely is position isomer) of
indigo dye.
Indigo naturalis
Indirubin is a chemical constituent of indigo naturalis (also known as qing dai ), which has been used since 627 AD in
traditional Chinese medicine
Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of acti ...
. It is essentially the indigo dye as traditionally extracted from plants by fermentation and lime treatment.
The dye mixture contains a variety of organic compounds, indirubin and
tryptanthrin being possible sources of some pharmacological actions. It is used in
realgar/Indigo naturalis
Realgar/Indigo naturalis (RIF), also known as Compound Huangdai (), is a medication used to treat acute promyelocytic leukemia. Effectiveness appears similar to arsenic trioxide. It is generally used together with all-trans-retinoic acid (ATRA). ...
, a medication for
acute promyelocytic leukemia.
Research
Indirubin exerts its effects on the human body by downregulating expression of genes. Genes
PLK1
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the ''PLK1'' ( polo-like kinase 1) gene.
Structure
PLK1 consists of 603 am ...
and
PIN1
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 is an enzyme that in humans is encoded by the ''PIN1'' gene.
Pin 1, or peptidyl-prolyl cis/trans isomerase (PPIase), isomerizes only phospho-Serine/Threonine-Proline motifs. The enzyme bi ...
, both oncogenic, have been shown to be affected by indirubin. Indirubin has, ''in vitro'' and ''in vivo'', been shown to reduce expression of the
''CDC25B'' gene, which codes for production of CDC25B enzyme. CDC stands for cell-division-cycle, and is used in cellular reproduction. Studies suggest that mouse cells are viable after the CDC25B (and ''
CDC25C'') genes are "knocked out", but removal of ''
CDC25A
M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A) gene.
Function
CDC25A is a member of the CDC25 family of dual-specificity ...
'' results in non-viable cells.
Indirubin has not been shown to prevent or treat cancer in humans. However, it is being studied for treatment of
small-cell lung cancer
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell c ...
,
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...
, and
chronic myeloid leukemia
Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulati ...
, either alone or in conjunction with more typical cancer management treatments. It has also been studied for potential use in the treatment of
ulcerative colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...
, an immune-modulated disease process.
Indirubin shows
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
and
anti-angiogenesis An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels ( angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...
properties ''
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 ...
''.
See also
*
Realgar/Indigo naturalis
Realgar/Indigo naturalis (RIF), also known as Compound Huangdai (), is a medication used to treat acute promyelocytic leukemia. Effectiveness appears similar to arsenic trioxide. It is generally used together with all-trans-retinoic acid (ATRA). ...
References
{{Aryl hydrocarbon receptor modulators
Enones
Lactams