Turmeric is well known for giving curry its yellow colour, and although subtle in flavour, its medicinal properties certainly match its boldness. Curcumin is the main active ingredient in turmeric, which has proven anti-inflammatory and anti-oxidant properties.
This naturally sourced and bioactive compound is easy to produce, has no side effects and can help to reduce inflammation in an array of inflammatory diseases; including obesity and diabetes.
But the question still remains, how does curcumin work at a molecular level and what can be done to enhance its credentials?
Scientists from Shandong University in Jinan, China found that curcumin improved glucose tolerance and insulin sensitivity in mice that were fed a high fat diet; and that blocking activation of the NLRP3 inflammasome was key to preventing high fat diet-induced insulin resistance.
Inflammasomes are part of the innate immune system (first-line defence) which act as sensors to monitor for infection or damage. Once activated, they control the production of pro-inflammatory cytokines resulting in inflammation which helps the body fight against infection.
Chronic (long term) stimulation of NLRP3 could result in low grade metabolic inflammatory signalling contributing to obesity and insulin resistance, and so regulating its activation is an attractive therapeutic strategy for many inflammatory diseases.
Curcumin Mode Of Action
Given the plethora of research into curcumin and its obvious beneficial effects, it is key to understand precisely what it targets to allow scientist to develop a suitable compound for clinical delivery.
The NLRP3 inflammasome is split into three main units which assemble in response to inflammatory molecules. It is composed of the NLRP3 scaffold, the inflammatory protease, caspase-1 and ASC.
Priming with an external stimuli such as liposaccharide (endotoxin) causes the NLRP3 and caspase-1 to begin assembly, and activation with nigericin (microbial toxin) encourages ASC oligomerisation and formation of the inflammasome complex.
As a result caspase-1 becomes active and pro-inflammatory cytokines, interleukin (IL)-1 and IL-18 are generated and secreted from the cell. Nigericin can also stimulate potassium movement out of cells (efflux) which is thought to act as a trigger for NLRP3 activation.
In this study, the authors show that curcumin blocks potassium efflux and ASC oligomerisation thereby preventing NLRP3 activation. The researchers conclude:
“It may provide a low-cost, well tolerated addition to a high calorie diet for preventing chronic, low-grade, metabolic inflammation.”
Curcumin appears to have variable effects in other research studies on blood glucose in which the outcomes aren’t as compelling.
However, the researchers in this study highlight that the mode of drug delivery, disease models and bioavailability of the drug can all contribute to these differences.
More investigation is therefore required to improve the understanding of curcumin and facilitate successful translation to human diseases.
Haipeng Yin, Qiang Guo, Xin Li, Tiantian Tang, Cuiling Li, Hengxiao Wang, Yuanxin Sun, Qi Feng, Chunhong Ma, Chengjiang Gao, Fan Yi and Jun Peng Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome The Journal of Immunology April 15, 2018. DOI: https://doi.org/10.4049/jimmunol.1701495
Author: Heledd Jarosz-Griffiths; Faculty of Medicine & Health, University of Leeds. Image: Steven Jackson/Flickr