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Curcumin & Immuno-Modulatory Axis

Today we all know that inflammation marks the initiation of immune defence with phagocytes (neutrophils, monocytes, macrophages) and natural killer cells (NK cells) circulating to encounter and destroy microbes entering the system. Evidence and research experiments have demonstrated the principal mechanism of phagocytosis and destruction of the foreign bodies by neutrophils and other phagocytic cells. It is now known that this process encounters production of highly toxic free radicals, such as hydrogen peroxide, superoxide anion (O2-) and nitric oxide. This initiates the inflammatory processes. It is necessary that immune system remains poised for the internal physiological balance.

The balancing of the immune system is determined in terms of its release of inflammatory factors: pro- (type 1) and anti- (type 2) inflammation factors:

  • Type I response includes production of cytokines, such as interleukin-12 (IL-12), tumour-necrosis factor-α (TNFα); they direct the launch of specific immunity, leading to the production of interferon-γ (IFNγ) and nitric oxide for protection against microbial infections.
  • The type 2 response, IL-10 keeps inflammation in check. Both these responses work together to maintaining balance of the immune system.

Curcumin the natural antioxidant, anti-inflammatory active principal from turmeric is known for its immuno-modulatory properties. Several research programmes are ongoing to evaluate its mechanism of action and clinical usefulness on the several inflammatory processes, pathways and anti-inflammatory properties.

Several research studies support that curcumin prevents the onset of inflammation by inhibiting the activation of nuclear factor-κB (NFκB), the production of TNFα, IFNγ, and nitric oxide, and gene expression of inducible nitric oxide synthase (iNOS) in the cells. More recently, it was found that curcumin activates the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), which has a promising target for switching off inflammation.  In animal studies, it has been demonstrated that when taken orally curcumin, modulates the type 1/type 2 immune balance and influences adaptive immunity. It also seems to provide protection to the cells by attenuating detrimental effects of inflammatory mediators.  These intrinsic activities of curcumin is of immense interest and value for medical innovation and offers hopes for new treatments for several diseases that stem from impaired immune system.

The benefits of curcumin in medical sciences continues to remain limited and not yet fully consolidated. The main reason being poor bioavailability of oral curcumin as most of it gets metabolised via glucuronidation to glucuronide and glucuronide/sulphate metabolites in the intestinal mucosa and liver. This limitation is now being overcome by <<novel drug delivery system>> that completely bypasses gut absorption and delivers bioactive curcumin in systemic circulation instantly.

 

References:

The Molecular Targets and Therapeutic Uses of Curcumin in Health and Diseasepp 321-341. Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 595)

AAPS J. 2013 Jan; 15(1): 195–218. Published online 2012 Nov 10. doi:  10.1208/s12248-012-9432-8

Laboratory Investigation (2008) 88, 1329–1339; doi:10.1038/labinvest.2008.90; published online 15 September 2008

 

 

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