Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials
1. Introduction
Inflammation is a physiological response of the immune system induced by various harmful factors such as pathogens, injury, or damaged cells to restore body function [1, 2]. Chronic inflammation is typically characterized by a high number and excessive activation of innate immune cells in tissues and increased release of inflammatory mediators and chemokines at local and systemic levels. In the context of inflammation, interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) are two cytokines that are released in significant amounts. They have been proven to be powerful inducers of C-reactive protein (CRP), which is a major acute-phase reactant produced mostly in the liver and strongly associated with metabolic diseases. It has been widely recognized that autoimmune diseases, atherosclerosis, asthma, type 2 diabetes (T2D), and other conditions can be caused by chronic inflammation [3–5].
A wide range of pharmacotherapies can improve inflammatory biomarkers, but they are also known to cause complications and side effects. Hence, nutraceutical therapies such as dietary supplements can be considered adjunctive or alternative treatments that can be utilized as anti-inflammatory agents [6–8]. Curcumin is remarkable bioactive polyphenol extracted from the rhizome of turmeric (Curcuma longa) [9, 10]. Curcumin has a wide range of medicinal effects such as hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, and antitumor activities [11, 12].
The anti-inflammatory feature of curcumin is mediated by several pathways. Intestinal alkaline phosphatase, an endogenous antioxidant and anti-inflammatory enzyme, is upregulated by curcumin. Moreover, curcumin modulates inflammatory markers through nuclear factor-erythroid factor 2-related factor 2 (NRF2∗)-Keap1 regulatory pathway. The anti-inflammatory and antioxidant effects of Nrf2 in response to stress conditions have been investigated in several studies [13, 14]. Given these effects, curcumin can have regulatory effects on the level of inflammatory biomarkers such as CRP, IL-6, and TNF-α [14–17].
Despite promising results, some studies have found that curcumin supplementation has no considerable efficacy on inflammatory markers [18–20]. Taking into account of inconsistency, the current umbrella of meta-analysis was designed to reevaluate the anti-inflammatory effects of curcumin.