Protective effect of mussel polysaccharide on cyclophosphamide-induced intestinal oxidative stress injury via Nrf2-Keap1 signaling pathway

Zhen-Lei Zhao; Xiao-Gang Xu; Yun-Chuang Chang; Yi-Peng Xu; Xu-Qiang Zhou; Hui-Li Su; Xiao-Hua Cui; Xiao-Qing Wan; Gen-Xiang Mao

doi:10.1002/fsn3.3453

Protective effect of mussel polysaccharide on cyclophosphamide-induced intestinal oxidative stress injury via Nrf2-Keap1 signaling pathway

Food Sci Nutr. 2023 May 23;11(7):4233-4245. doi: 10.1002/fsn3.3453. eCollection 2023 Jul.

Authors

Zhen-Lei Zhao¹, Xiao-Gang Xu¹, Yun-Chuang Chang², Yi-Peng Xu³, Xu-Qiang Zhou⁴, Hui-Li Su¹, Xiao-Hua Cui¹, Xiao-Qing Wan¹, Gen-Xiang Mao¹

Affiliations

¹ Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang Province, Department of Geriatrics Zhejiang Hospital Hangzhou China.
² College of Biological and Food Engineering Hubei Minzu University Enshi China.
³ The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Institute of Basic Medicine and Cancer (IBMC) Zhejiang Cancer Hospital, Chinese Academy of Sciences Hangzhou China.
⁴ College of Life Science Zhejiang Chinese Medical University Hangzhou China.

Abstract

The hard-shelled mussel (Mytilus coruscus) has been used as a traditional Chinese medicine and health food in China for centuries. Polysaccharides from mussel has been reported to have multiple biological functions, however, it remains unclear whether mussel polysaccharide (MP) exerts protective effects in intestinal functions, and the underlying mechanisms of action remain unclear. The aim of this study was to investigate the protective effects and mechanism of MP on intestinal oxidative injury in mice. In this study, 40 male BALB/C mice were used, with 30 utilized to produce an animal model of intestinal oxidative injury with intraperitoneal injection of cyclophosphamide (Cy) for four consecutive days. The protective effects of two different doses of MP (300 and 600 mg/kg) were assessed by investigating the change in body weight, visceral index, and observing colon histomorphology. Moreover, the underlying molecular mechanisms were investigated by measuring the antioxidant enzymes and related signaling molecules through ELISA, real-time PCR, and western blot methods. The results showed that MP pretreatment effectively protected the intestinal from Cy-induced injury: improved the colon tissue morphology and villus structure, increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and reduced malondialdehyde (MDA) content in serum and colon tissues. Meanwhile, MP also significantly increased the expression levels of SOD, GSH-Px, heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) mRNA in colon tissues. Further, western blot results showed that the expression of Nrf2 protein was significantly upregulated while kelch-like ECH-associated protein 1 (Keap1) was significantly downregulated by MP in the colonic tissues. This study indicates that MP can ameliorate Cy-induced oxidative stress injury in mice, and Nrf2-Keap1 signaling pathway may mediate these protective effects.

Keywords: Nrf2‐Keap1 pathway; cyclophosphamide; intestinal protection; mussel polysaccharide; oxidative stress.