curcumin (Theracurmin)
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Introduction
A compound with antioxidant properties derived from extracts of turmeric (Curcuma longa) & curry.
Classification
Classified as a diferuloylmethane.
Function
Effect on apoptosis & interaction with chemotherapeutic agents is variable[2][7]
Curcumin inhibits:
- cell proliferation
- cyclin D1 via transcriptional & post-transcriptional mechanisms[1]
- CDK4 mediated phosphorylation of Rb protein
- TNF-alpha induced COX2 gene transcription
- NF kappa B activation
- PMA activation of NF kappa B & AP1
- TNF-alpha induced nuclear translocation & DNA binding of NF kappa B
- catalytic activity of epidermal ERK1/ERK2
- aminopeptidase N, an enzyme that promotes angiogenesis & facilitates tumor invasiveness
- src & focal adhesion kinase[5]
- ubiquitin-proteasome system[8]
- glutathione S-transferase P[9]
- telomerase reverse transcriptase[10]
- cyclooxygenase-2[11]
- sarcoplasmic/endoplasmic reticulum Ca+2 ATPase[13]
Curcumin induces:
- apoptosis through mitochondrial pathway[8]
- heme oxygenase-1 [6a,b]
- via Nrf2 & the antioxidant response element[6]
Pharmacology
- antioxidant with anti-inflammatory properties
- in a single trial, curcumin benefit for major depression not statistically significant[15][16]*
- Theracurmin may lead to improved memory & attention in non-demented adults[14]
* GRS9 concludes curcumin may help with depression[16]
Dosage
Pharmacokinetics
- curcumin is reduced to tetrahydrocurcumin in the GI tract
- curcumin & tetrahydrocurcumin are poorly absorbed from the GI tract
- measurable serum levels from oral intake may be difficult to achieve
Adverse effects
Toxicity:
- a mM concentrations, curcumin is neurotoxic in vitro
- low affinity binding to ATP binding sites of kinases proposed
More general terms
References
- ↑ 1.0 1.1 Mukhopadhyay A et al Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4- mediated retinoblastoma protein phosphorylation. Oncogene 21(57):8852-61, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12483537
- ↑ 2.0 2.1 2.2 Deeb D et al Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2:95-103, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12533677
- ↑ Chemical & Engineering News, Sept 1, 2003, pg 8 Chem Biol 10:695, 2003
- ↑ Nature Reviews Cancer 2003
- ↑ 5.0 5.1 Leu T et al Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity. Biochen Pharmacol 11:1475, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14637190
- ↑ 6.0 6.1 Scapagnini G et al Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 61:554, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11854435
Balogun E et al Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371(pt 3):887, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12570874 - ↑ 7.0 7.1 Bharti AC et al Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101:1053, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12393461
Somasundaram S et al Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62:3868, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12097302 - ↑ 8.0 8.1 8.2 Jana NR et al Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway. J Biol Chem (Epub) 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14701837
- ↑ 9.0 9.1 Duvoix A et al Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition. Biochem Pharmacol 66:1475, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14555224
- ↑ 10.0 10.1 Ramachandran C et al Scientific World Journal 1:1(1 Suppl 3): 109, 2002
- ↑ 11.0 11.1 Shishodia S et al Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24:1269, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12807725
- ↑ Mahady GB et al Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 22(6C):4179, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12553052
- ↑ 13.0 13.1 Egan ME et al Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15105504
- ↑ 14.0 14.1 14.2 14.3 Small GW, Siddarth P, Li Z et al Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. American Journal of Geriatric Psychiatry. 2017 http://www.ajgponline.org/article/S1064-7481(17)30511-0/fulltext
- ↑ 15.0 15.1 Sanmukhani J, Satodia V, Trivedi et al Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014 Apr;28(4):579-85. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23832433
- ↑ 16.0 16.1 16.2 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2889
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=969516
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281767
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=167832
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=150352
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=147439