Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies have demonstrated that MMPs are in most cases upregulated in various inflammatory diseases, including osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer’s disease. Studies using patient-derived human samples, animal studies, and cellular experiments have suggested that polyphenols may be beneficial against inflammatory diseases by suppressing MMP gene expression and enzyme activity. One important mechanism by which polyphenols exert their activity is the downregulation of reactive oxygen species that promote MMP expression. Another important mechanism is the direct binding of polyphenols to MMPs and their inhibition of enzyme activity. Molecular docking analyses have provided a structural basis for the interaction between polyphenols and MMPs and will help to explore new polyphenol-based drugs with anti-inflammatory properties.

Inhibition of MMP-2 and MMP-9 by Dietary Antioxidants in THP-1 Macrophages and Sera from Patients with Breast Cancer

“…As a result of our experiments, RSV inhibited MMP-9 in THP-1 supernatants but not in "in-gel" zymography, suggesting that this antioxidant only exerted its inhibitory action on the expression of the enzyme. This result is consistent with previous studies showing the ability of RSV to downregulate MMP-9 expression by inhibiting the activation of the transcription factors NF-kB and AP-1 [30,40]. Differently, we found that GTE was able to inhibit, in a dose-dependent manner, both the activity and expression of MMP-2 and MMP-9 as assessed by the "in-gel" zymography and by the analysis of the THP-1 supernatants, respectively.…”

“…At the molecular level, polyphenols may downregulate the ROS-induced activation of ERK 1/2, p38 and JNK, as well as PI3K/AKT, preventing the nuclear translocation of NF-kB and the downstream activation of the transcription factor AP-1. The consequent downregulation of MMP gene transcription results in the inhibition of tumor cell growth, metastasis, angiogenesis and inflammation [22,40,41]. As a result of our experiments, RSV inhibited MMP-9 in THP-1 supernatants but not in "in-gel" zymography, suggesting that this antioxidant only exerted its inhibitory action on the expression of the enzyme.…”

“…All of these considerations could explain the reason why, in our experiments, GTE is the most active "in-gel" inhibitor of MMPs even at the lowest concentrations. However, as reported by Suzuki et al [40], another important mechanism to explain the inhibitory activity of polyphenols towards MMPs might be their direct binding to MMPs, as demonstrated by several molecular docking studies [47][48][49][50].…”

The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats

“…However, studies in the literature have already suggested that the daily optimal consumption of fruits and vegetables high in polyphenol compounds decreases the risk of developing specific chronic and degenerative diseases with an inflammatory component, via MMPs regulation [ 62 , 63 , 64 ]. Accordingly, multiple studies have examined the chemical composition of the raspberry leaf extract, uncovering a wide range of bioactive compounds that have prompted research into its potential uses in several diseases, especially those related to inflammation and metabolic disorders [ 22 , 65 ].…”