Original articleAnthocyanins reduce inflammation and improve glucose and lipid metabolism associated with inhibiting nuclear factor-kappaB activation and increasing PPAR-γ gene expression in metabolic syndrome subjects
Graphical abstract
Introduction
Metabolic syndrome (MetS) has become a leading health concern due to its link to cardiovascular disease (CVD) [1]. The prevalence of MetS and CVD is expected to rise due to the global obesity epidemic [2]. The main diagnostic components of MetS are identified with reduced HDL-cholesterol, raised triglycerides, blood pressure, and fasting plasma glucose, all of which are related to weight gain, specifically abdominal fat accumulation [3]. Reducing levels of modifiable atherogenic risk factors is an essential goal in the prevention of CVD in metabolic syndrome populations. There is an established relationship between metabolic syndrome, oxidative stress, chronic inflammation, and cardiovascular disease [4]. The pathogenesis of atherosclerotic plaque formation is a multiphase process, including the interaction between immune cells and endothelium [5].
Currently, there is much interest in phytochemicals as bioactive components of food [6]. The roles of fruit and vegetables in disease prevention have been attributed in part to their antioxidant properties [7]. Recent studies have indicated that dietary polyphenolic constituents derived from plants are effective antioxidants in vitro and, as a result, might contribute significantly to the protective effects in vivo [[7], [8], [9]]. Anthocyanins, a category of polyphenolic pigments belong to the flavonoid group, are responsible for a variety of colors present in the plant from red-orange to blue-violet in fruits, flowers, and leaves [10]. The epidemiological study demonstrated that higher consumption of anthocyanin extracts or anthocyanin-rich fruit was attributed to improved cardiovascular risk profile [11]. Results from mechanistic studies suggest that anthocyanin ability to lower CVD risk mediate through the regulation expression of proinflammatory genes and reducing the production of anti-inflammatory molecules [12,13]. Anthocyanins decrease iNOS activity and, consequently, nitric oxide overexpression [14] and attenuate COX-2 activity and accordingly, PGE2 expression [15,16]. Due to their mechanisms of action, plenty of the evidence points to the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Peroxisome proliferator-activated receptors (PPARs) pathways. However, so far, no human studies have systematically investigated the metabolic effect of purified anthocyanin on gene dependent expression of Nrf2, NF-κB and PPAR-γ pathways in a metabolic syndrome population.
Thus, the purpose of this study sought to determine the effect of anthocyanin supplements on cellular oxidative defenses gene pathways via the expression of Nrf2 dependent gene, lipid, and glucose metabolism by PPRA-γ activation, and NF-KB pathways by reducing inflammation in the mRNA levels. This study is part of a larger clinical trial which will be reported at a larger stage.
Section snippets
Materials
Medox is a veg-encapsulated anthocyanin extract which contains 80 mg purified anthocyanins isolated from wild Norwegian bilberries (Vaccinium myrtillus) and blackcurrant (Ribes nigrum). Anthocyanin capsules were provided by Biolink Group and MedPalett Pharmaceuticals and the Biolink Group (Sandnes, NORWAY). Each Anthocyanin capsules comprise a mixture of 32% Cyanidin, 58% Delphinidin, 2.5% Petunidin, 2.5% peonidin, and 3.0% malvidin. Anthocyanin capsules also contained pullulan, maltodextrin,
Demographics of the participants
An initial survey of anthocyanin supplementation was conducted involving 35 male and female adults aged between 25 and 75 years, divided into two groups MetS (n = 20) and Control (n = 15). Demographic data, characteristics of both groups are summarised in Table 2. While the average in the MetS group was 56.2 ± 2.6 year, in the Control group showed the average of 37.3 ± 2.9 years. There were significant differences concerning age, BMI, waist circumference, waist/hip ratio, and blood pressure.
Discussion
The present study showed that the modulatory effect of anthocyanins on cardiometabolic risk factors and the expression of associated genes to indicate the atheroprotective effect of anthocyanin-rich extracts via inhibition of NF-κB and stimulation of PPAR- γ pathways. This study demonstrated that anthocyanin supplementation in MetS subjects exerted favorable metabolic adaptations by improving lipid profile, fasting blood glucose, and inflammatory biomarkers. In addition, it was found that
Author contributions
ANA conceived the study and theoretical model, carried out the experiments, designed the figures and drafted the manuscript. ARA conducted a statistical evaluation of the data and interpreted the results. RM and IS provided feedback on the manuscript.
Declaration of competing interest
Authors have no conflict of interest to be disclosed.
Acknowledgments
The contribution of Mr Almottesembellah Gaiz, Dr Elham Nikbakht, Dr Lada Tucakovic and Dr Avinash Kundur for assistance during data collection and recruitment were acknowledged. The authors would like to acknowledge Dr Jelena Vider for her technical support to operate NanoString nCounter system and Drs Meyer and Singh to provide feedback on the manuscript.
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