Polysaccharides from Hemp Seed Protect against Cyclophosphamide-Induced Intestinal Oxidative Damage via Nrf2-Keap1 Signaling Pathway in Mice

Abstract

Hemp seed has been used as a traditional oriental medicine and health food in China for centuries. Polysaccharides from hemp seed (HSP) exhibit important properties of intestinal protection, but there are limited data on the specific underlying mechanism. The primary objective of this study was to investigate the protective effect of HSP on intestinal oxidative damage induced by cyclophosphamide (Cy) in mice. The results showed that pretreatment with HSP significantly increased the average daily gain, thymus index, spleen index, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity in serum and ileal homogenate and significantly reduced malondialdehyde (MDA) content in ileal homogenate. In addition, the expression levels of SOD, GSH-Px, Nrf2, heme oxidase-1 (HO-1), and quinoneoxidoreductase-1 (NQO1) mRNA in ileal homogenate were significantly increased. Western blot results showed that HSP significantly upregulated the expression of Nrf2 protein and downregulated the expression of Keap1 protein in the ileum. Collectively, our findings indicated that HSP had protective effects on intestinal oxidative damage induced by Cy in mice, and its mechanism might be related to the activation of Nrf2-Keap1 signaling pathway.

Effects of Exopolysaccharides from Lactiplantibacillus plantarum JLAU103 on Intestinal Immune Response, Oxidative Stress, and Microbial Communities in Cyclophosphamide-Induced Immunosuppressed Mice

“…Xue et al discovered that hemp seed polysaccharides played a protective role against a Cy-triggered intestine oxidation injury via reinforcing the gene expression of antioxidation enzymes and activating the Nrf2/Keap1 signaling pathway. 44 Zhang et al reported that the polysaccharides from Chimonanthus nitens Oliv could decrease oxidation stress and protect the liver in Cy-induced immunocompromised mice by reducing the upstream factor Keap1 and elevating the upstream factor Nrf2, which eventually reinforced the expression of the downstream factors (NQO1, HO-1, GSH-Px, SOD1, and CAT). 45 Moreover, Li et al reported that Ostrea rivularis polysaccharides could effectively attenuate the reproductive oxidative stress injury derived from Cy via activating the Keap1-Nrf2/ARE signaling pathway.…”

“…Both in vitro and in vivo research studies on polysaccharides have displayed that they can defend against oxidation stress via modulating the Nrf2/Keap1 signal path. Xue et al discovered that hemp seed polysaccharides played a protective role against a Cy-triggered intestine oxidation injury via reinforcing the gene expression of antioxidation enzymes and activating the Nrf2/Keap1 signaling pathway . Zhang et al reported that the polysaccharides from Chimonanthus nitens Oliv could decrease oxidation stress and protect the liver in Cy-induced immunocompromised mice by reducing the upstream factor Keap1 and elevating the upstream factor Nrf2, which eventually reinforced the expression of the downstream factors (NQO1, HO-1, GSH-Px, SOD1, and CAT) .…”

Immunomodulatory activity of a water-soluble polysaccharide extracted from mussel on cyclophosphamide-induced immunosuppressive mice models

“…Cyclophosphamide (Cy) is a well-known and potent therapeutic drug 1 with anticancer activity, but its toxic side effects cannot be disregarded 2 . Previous studies have shown that high doses of Cy can damage the gastrointestinal mucosa and induce changes in the composition of the intestinal microbiota, which can then lead to translocation of pathogenic bacteria to vital organs of the body 3 .…”

The Role And Mechanism Of Calcitriol In Promoting Intestinal Injury in AKI By Improving The Intestinal Barrier

“…The intestines are the largest reservoir of bacteria and endotoxins in the body and are considered a driver of sepsis and multiple organ dysfunction syndrome [19]. Intestinal mucosal barrier degradation, increased mucosal permeability, and disruption of intestinal microbiota may result from an excessive buildup of oxygen free radicals, which may also have an impact on the body's homeostasis [20].…”