<i>p</i>-Coumaroyl Anthocyanin Mixture Isolated from Tuber Epidermis of <i>Solanum tuberosum</i> Attenuates Reactive Oxygen Species and Pro-inflammatory Mediators by Suppressing NF-κB and STAT1/3 Signaling in LPS-Induced RAW264.7 Macrophages

Abstract

Previously, we first reported the identification of four p-coumaroyl anthocyanins (petanin, peonanin, malvanin, and pelanin) from the tuber epidermis of colored potato (Solanum tuberosum L. cv JAYOUNG). In this study, we investigated the anti-oxidative and anti-inflammatory effects of a mixture of peonanin, malvanin, and pelanin (10 : 3 : 3; CAJY). CAJY displayed considerable radical scavenging capacity of 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase, and subsequent cellular glutathione content. These increases preceded the inhibition of lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production. CAJY inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner at the protein, mRNA, and promoter activity levels. These inhibitions caused attendant decreases in the production of prostaglandin E 2 (PGE 2 ). CAJY suppressed the production and mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Molecular data revealed that CAJY inhibited the transcriptional activity and translocation of nuclear factor κB (NF-κB) and phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3. Taken together, these results suggest that the anthocyanin mixture exerts anti-inflammatory effects in macrophages, at least in part by reducing ROS production and inactivating NF-κB and STAT 1/3. Key words anthocyanin; macrophage; antioxidant; anti-inflammatory; nuclear factor κB; signal transducer and activator of transcription Reactive oxygen species (ROS) are important in various biological processes at the levels of gene expression, protein translation, post-translational modification, and protein interactions.1) Cell-derived ROS independently or cooperatively regulate cellular signaling in response to environmental cues. 1)A sustained pro-inflammatory state characterized by excessive ROS production is the common aspect in the development, progression, and complication of obesity, infections, cardiovascular and neurodegenerative diseases, and cancer.2-4) The shift in the balance between oxidants and anti-oxidants in favor of oxidants is termed oxidative stress. This stress contributes to many pathological conditions.Aerobic organisms have integrated anti-oxidant systems, which include enzymatic and non-enzymatic antioxidants, that are usually effective in blocking harmful effects of ROS. 5)Anti-oxidant defense systems comprise glutathione (GSH) and its synthesis, phase II detoxifying enzymes, and ROS inactivating enzymes, which play key roles in protecting cells upon oxidative damage. 6) GSH effectively protects cells from various oxidative stresses caused by scavenging free radicals, suppression of lipid peroxidation, and removal of hydrogen peroxides in cells.7) Glutamate cysteine ligase (GCL) is the rate-limiting enzyme for de novo GSH synthesis and comprises a heterodimer formed of a catalytic subunit (GCLC) and a modulator...

The Anti-inflammatory Effects of Dietary Anthocyanins against Ulcerative Colitis

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Antioxidant and Anti-Inflammatory Activity of Combined Phycocyanin and Palmitoylethanolamide in Human Lung and Prostate Epithelial Cells

“…This observation is novel for the two molecules, but is similar to what was reported for other natural compounds such as anthocyanins and flavonoids. In fact, it has been shown that a mixture of anthocyanins has antioxidative properties resulting from radical scavenging activity, increased intracellular GSH through induction of GCL and recovery of intracellular ROS [ 53 ]. Moreover, various flavonoids and quercetin were able to increase the intracellular concentration of glutathione and regulated GCL gene expression [ 54 ].…”

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