Root Extract of Polygonum cuspidatum Siebold & Zucc. Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin

Abstract

Background: Polygonum cuspidatum Siebold & Zucc. (PCS) has antibacterial properties and may prevent Ulcerative colitis (UC) but related molecular mechanism remains unknown. NF-κB signaling pathway is associated with inflammatory responses and its inactivation may be critical for effective therapy of UC.Methods: UC mouse (C57BL/6J) model was established by using dextran sulfate sodium (DSS). The extract of PCS (PCSE) was prepared by using ethanol and its main ingredients were measured by HPLC. Thirty-two UC mice were evenly assigned into DG (received vehicle control), LG (0.1 g/kg PCSE daily), MG (0.2 g/kg PCSE daily) and HG (0.4 g/kg PCSE daily) groups. Meanwhile, 8 healthy mice were assigned as a control group (CG). Serum pharmacokinetics of PCS was measured by using HPLC. After 8-day treatment, weight, colon length and disease activity index (DAI) were measured. Inflammatory cytokines and oxidant biomarkers were measured by ELISA kits. The levels of cytokines, and key molecules in NF-κB pathway, were measured by using Western Blot. The effects of main ingredients of PCSE on cytokines and NF-κB signaling pathway were explored by using intestinal cells of a mouse UC model. The normality criterion was evaluated using the Saphiro–Wilk test. The quantitative variables were compared using the paired Student’s-t test.Results: The main ingredients of PCSE were polydatin, resveratrol and emodin. Polydatin may be transformed into resveratrol in the intestine of the mice. PCSE prevented DSS-caused weight loss and colon length reduction, and improved histopathology of UC mice (P < 0.05). PCSE treatment increased the serum levels of IL-10 and reduced the levels of IL-1 beta, IL-6 and TNF-α (P < 0.05). PCSE increased the activities of SOD, CAT, GPX and reduced the level of MDA, BCL-2, beta-arrestin, NF-κB p65 and the activity of MPO (P < 0.05). The combination of polydatin, resveratrol or emodin, and or PCSE exhibited higher inhibitory activities for cytokines and NF-κB signaling related molecules than any one of the three ingredients with same concentration treatment.Conclusion: Oral administration of PCSE suppressed NF-κB signaling pathway and exerts its anti-colitis effects via synergistic effects of polydatin, resveratrol or emodin.

Indigo Naturalis Suppresses Colonic Oxidative Stress and Th1/Th17 Responses of DSS-Induced Colitis in Mice

“…Highly localized concentrations of ROS could attack and inactivate endogenous antioxidant defenses, such as GSH-Px, T-SOD, and CAT, thus preventing the neutralization of ROS [32, 33]. We also observed a decrease in colonic GSH-Px, T-SOD, and CAT activities in DSS-treated mice compared with those in the control mice, which were consistent with previous reports [32, 34]. Notably, administration of QD significantly restrained the elevation of colonic MPO activity and decreased colonic GSH-Px, T-SOD, and CAT activities in DSS-treated mice.…”

Protective Effect of Polydatin on Jejunal Mucosal Integrity, Redox Status, Inflammatory Response, and Mitochondrial Function in Intrauterine Growth-Retarded Weanling Piglets

“…Xu et al [ 27 ] have shown that PD suppresses the secretion of proinflammatory cytokines, including TNF- α , IL-1 β , and IL-6, into the circulation. The available literature has indicated that the anti-inflammatory effects of PD may be attributed to its ability to prevent the overactivation of nuclear factor-kappa B (NF- κ B) signals, as this signaling pathway is responsible for regulating the transcription of proinflammatory mediators during immunological stress [ 10 , 38 , 39 ]. Support for an inhibitory effect of PD on NF- κ B signals has been provided by Wu et al [ 24 ], who observed that PD decreased the DNA binding ability of NF- κ B p65 during intestinal inflammation.…”

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…(PCS) treatment can prevent DSS-caused weight loss and colon length reduction in UC mice, as well as increase the serum levels of IL-10 and reduce the levels of IL-1β, IL-6 and TNF-α. Moreover, whatever PCSE (100, 200 and 400 mg/kg) or the combination of its three extractions: polydatin, resveratrol and emodin exhibit higher inhibitory activities for cytokines and NF-κB signaling related molecules than any one of the three compounds with same concentration treatment [64].…”