Dendrobium Officinale Polysaccharides Protect against MNNG-Induced PLGC in Rats via Activating the NRF2 and Antioxidant Enzymes HO-1 and NQO-1

• Published in: Oxidative medicine and cellular longevity 2019-01, Vol.2019 (2019), p.1-11
• Main Authors: Ge, Shucao, Wang, Gaoyu, Sun, You-Zhi, Zhao, Yi, Liu, Hong-Ning
• Format: Article
• Language: English
• Subjects: Alcohol; Animals; Antioxidants; Chromatography; Cysteine; Dendrobium - chemistry; Enzymes; Epidermal growth factor; Gastric cancer; Gene expression; Heme; Heme Oxygenase-1 - metabolism; Hyperplasia; Immunohistochemistry; Laboratory animals; Life sciences; Liver cancer; Male; Medical research; Molecular weight; NAD(P)H Dehydrogenase (Quinone) - metabolism; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Polysaccharides; Polysaccharides - metabolism; Prevention; Rats; Reactive oxygen species; Stomach cancer; Uric acid
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2019/9310245

Dendrobium officinale polysaccharides (DOP) are the main effective ingredient in Dendrobium officinale. Nuclear factor erythroid 2-related factor 2 (NRF2) signaling is regarded as an important way to mitigate the effects of reactive oxygen species (ROS) damage and inhibit gastric cancer progress. This study introduces a previously unknown effect of DOP on precancerous lesions of gastric cancer (PLGC). The mechanism discussed herein is based on the NRF2 signal pathway as well as its downstream antioxidant enzymes heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1). DOP was prepared by the alcohol deposition method, and its molecular weight was determined using High-Performance Gel-Permeation Chromatography (HPGPC). Sixty male rats were randomly divided into five groups: normal control group (NC), PLGC model group (PLGC), model treated with low dose (2.4 g/kg) of DOP (L-DOP), model treated with middle dose (4.8 g/kg) of DOP (M-DOP), and model treated with high dose (9.6 g/kg) of DOP (H-DOP). DOP was orally administered to rats for 15 consecutive days prior to the start of a seven-month course of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) exposure. Histological evaluation was observed by hematoxylin and eosin (HE) and alcian blue/periodic acid-Schiff (AB-PAS) staining. Alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (Scr), serum uric acid (UA), blood urea nitrogen (BUN), and HE staining were detected for liver and kidney function. The level of 8-hydroxy-deoxyguanosine (8-OHdG) in serum was detected by kits. The NRF2 protein expression was detected by immunohistochemistry, and western blotting was utilized to compare differential protein expression levels among cytoplasmic and nuclear cell fractions. Expression levels of antioxidant enzymes heme oxygenase 1 (HO-1), Glutamate-Cysteine Ligase Catalytic Subunit (GCLC), Glutamate-Cysteine Ligase Modifier Subunit (GCLM), and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); furthermore, the protein expression of NRF2, HO-1, and NQO-1 was detected by western blotting. The results showed that the average content of DOP is 83%, and its molecular weight is mainly contained within 3500 and 1000000. The H-DOP experimental group exhibited noticeable weight gain after seven months, reduced intestinal metaplasia, and made the atypical hyperplasia to be kept in moderate or mild degree. Data also showed DOP to be c