PEA/Polydatin: Anti-Inflammatory and Antioxidant Approach to Counteract DNBS-Induced Colitis

Abstract

Palmitoylethanolamide (PEA) has well-known anti-inflammatory effects. However, PEA does not possess an antioxidant ability. A comicronized formulation of ultramicronized PEA (um-PEA) and polydatin (Pol) PEA/Pol, a biological precursor of resveratrol with antioxidant activity, could have protective effects on oxidative stress produced by inflammatory processes. We evaluated the effects of a comicronized PEA/Pol 10 mg/kg (9 mg of um-PEA+1 mg of polydatin) in a model of Dinitrobenzene sulfonic acid (DNBS)-induced colitis. Ulcerative colitis was induced in mice by intrarectally injection of DNBS (4 mg in 100 µL of 50% ethanol per mouse). Macroscopic and histologic colon alterations and marked clinical signs were observed four days after DNBS and elevated cytokine production. The myeloperoxidase (MPO) activity assessed for neutrophil infiltration was associated with ICAM-1 and P-selectin adhesion controls in colons. Oxidative stress was detected with increased poly ADP-ribose polymerase (PARP) and nitrotyrosine positive staining and malondialdehyde (MDA) levels in inflamed colons. Macroscopic and histologic alterations minimized by oral PEA/Pol, as well as neutrophil infiltration, inflammatory cytokine release, MDA, nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. The mechanism of action of PEA/Pol could be related to the sirtuin 1/nuclear factor erythroid 2-related factor 2 (SIRT-1/Nrf2) pathway and nuclear factor (NF)-κB. PEA/Pol administration inhibited NF-κB and increased SIRT-1/Nrf2 expressions. Our results show that PEA/Pol is capable of decreasing inflammatory bowel disease (IBD) DNBS-induced in mice.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

“…Polydatin (PD, C 20 H 22 O 8 ) is a natural active ingredient extracted from the dried roots of the perennial herb Polygonum cuspidatum Sieb. et Zucc., which might play a potential therapeutic role in various kidney disorders, such as AKI [7][8][9][10][11][12][13][14][15][16], diabetic nephropathy [17][18][19][20][21][22][23][24], lupus nephritis [25], and hyperuricemia [26][27][28], and has been used to treat patients with irritable bowel syndrome in Europe [29]; moreover, PD has been shown to exhibit mechanisms to antioxidant stress, anti-inflammation, and antifibrosis characteristics; improvement of mitochondrial damage; and regulation of autophagy [9,30,31]. Resveratrol, an aglycone of PD, has been verified to ameliorate myocardial and liver damage caused by iron overload [32][33][34]; moreover, it has been confirmed that resveratrol can reduce iron load in hemodialysis patients in clinical studies [35].…”

Hidrox® Roles in Neuroprotection: Biochemical Links between Traumatic Brain Injury and Alzheimer’s Disease

“…In particular, the role of Nrf2 in the defense against TBI-induced neuroinflammation is of particular interest [57][58][59][60]. Many pieces of evidence confirm the role of the Nrf2 pathway in modulating both oxidative stress and inflammation [61][62][63][64][65][66][67]. Hidrox ® is known to influence the promotion of the transcription of genes downstream of Nrf2 activation [41].…”

Coriolus Versicolor Downregulates TLR4/NF-κB Signaling Cascade in Dinitrobenzenesulfonic Acid-Treated Mice: A Possible Mechanism for the Anti-Colitis Effect

“…The intra-rectal injection of DNBS (4 mg in 100 μL of 50% ethanol per mouse) was executed on day 0 for induction of colitis as previously reported [ 22 ].…”

“…In the colon tissues obtained after sacrifice, TNF-α (Ray Bio ELISA Kit Mouse TNF-alpha, Norcross, GA, USA), IL-1β, CCL2, and PGE2 (R&D Systems, Milan, Italy) levels were evaluated using a colorimetric commercial kit [ 22 ].…”