A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus

Milkica Grabež^1,2,*, Ranko Škrbić³, Miloš P Stojiljković³, Vesna Vučić⁴, Vesna Rudić Grujić^1,2, Vladimir Jakovljević^5,6, Dragan M Djuric⁷, Relja Suručić⁸, Katarina Šavikin⁹, Dubravka Bigović⁹, Nađa Vasiljević¹⁰

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¹ Department of Hygiene, Faculty of Medicine University of Banja Luka, 78000 Banja Luka, the Republic of Srpska, Bosnia & Herzegovina

² Department of Hygiene, Public Health Institute of Republic of Srpska, 78000 Banja Luka, the Republic of Srpska, Bosnia & Herzegovina

³ Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine University of Banja Luka, 78000 Banja Luka, the Republic of Srpska, Bosnia & Herzegovina

⁴ Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research University of Belgrade, 11000 Beograd, Serbia

⁵ Department of Physiology, Faculty of Medical Sciences University of Kragujevac, 34000 Kragujevac, Serbia

⁶ Department of Human Pathology, 1st Moscow Medical University ``I.M. Sechenov", 119991 Moscow, Russian Federation

⁷ Institute of Medical Physiology ``Richard Burian", Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia

⁸ Department of Pharmacоgnosy, Faculty of Medicine University of Banja Luka, 78000 Banja Luka, the Republic of Srpska, Bosnia & Herzegovina

⁹ Institute for Medicinal Plant Research ``Dr Josif Pančić", 11000 Belgrade, Serbia

¹⁰ Institute of Hygiene and Medical Ecology, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia

^*Correspondence: milkica.grabez@med.unibl.org (Milkica Grabež)
Academic Editor: Peter A. McCullough

Rev. Cardiovasc. Med. 2022, 23(2), 57; https://doi.org/10.31083/j.rcm2302057

Submitted: 14 October 2021 | Revised: 10 December 2021 | Accepted: 13 December 2021 | Published: 11 February 2022

(This article belongs to the Special Issue Stress and Inflammation in Coronary Artery Disease)

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted. Methods: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor $\alpha{}$ (TNF- $\alpha{}$ ) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO ${}_{2}$ ${}^{-}$ ), superoxide anion radical (O ${}_{2}$ ${}^{-}$ ), hydrogen peroxide (H ${}_{2}$ O ${}_{2}$ ), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed. Results: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF- $\alpha{}$ , hsCRP), oxidative stress biomarkers (TBARS, NO ${}_{2}$ ${}^{-}$ , O ${}_{2}$ ${}^{-}$ ) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group. Conclusions: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients.

Keywords

pomegranate peel extract

polyphenols

oxidative stress

inflammation

lipid profile

diabetes mellitus

Figures

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Fig. 1.

The effects of eight-week PoPEx consumption on the circulating biomarkers of inflammation levels. (A–C) The high sensitivity c-reactive protein (hsCRP), Interleukin 6 (IL-6), and tumor necrosis factor $\alpha{}$ (TNF- $\alpha{}$ ) levels, baseline and after eight-weeks intervention period in the Diabetes mellitus type 2 patients. Wilcoxon signed rank test was done and asterisk (*) indicate significant differences compared with baseline value within the groups *p $<$ 0.05, **p $<$ 0.01. (D–F) The delta values of circulating inflammation biomarkers levels (hsCRP, IL-6, and TNF- $\alpha{}$ ) in the PoPEx group and the Placebo group. Mixed ANOVA was done and sign (†) indicate significant differences between the groups after controlling for the baseline values †p $<$ 0.05, ††p $<$ 0.01.

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Rev. Cardiovasc. Med. Print ISSN 1530-6550 Electronic ISSN 2153-8174