Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).
Hangzhou AIMA Maternity Hospital, Hangzhou, Zhejiang, China (mainland).
Med Sci Monit. 2020 Apr 4;26:e921905. doi: 10.12659/MSM.921905.
BACKGROUND Type 2 diabetes mellitus (T2DM) and its comorbidities, including obesity, hypertension, and hyperlipidemia, are commonly associated with non-alcoholic fatty liver disease (NAFLD). Ganoderma lucidum polysaccharide (GDLP) is one of the central bioactive components in Ganoderma lucidum with anti-inflammatory, antioxidant, and hepatoprotective properties. However, the effect and mechanisms of GDLP in hepatic steatosis remain largely unknown. In the present study, we aimed to investigate the function of GDLP in hepatic steatosis and the underlying mechanism. MATERIAL AND METHODS In this study, male db/db mice were received with a high-fat diet (HFD) to investigate the effect of GDLP in T2DM-induced hepatic steatosis. The biological characteristics of the hepatic steatosis were evaluated through the detection of clinical indicators, including biochemical parameters, histopathology, and related cytokine levels. Additionally, the protein expression levels of Nrf2 (nuclear factor E2 (erythroid-derived 2)-related factor-2) signaling pathway were investigated by using western blotting and immunohistochemical staining. RESULTS The levels of food/water intake, body weight, fasting blood glucose, plasma lipids, urinary biomarkers, hepatic lipid accumulation, and tumor necrosis factor (TNF)-alpha were observably decreased in GDLP-treated db/db mice. Additionally, administration of GDLP increased the expression of various antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), whereas it reduced the level of malonaldehyde (MDA). Furthermore, GDLP was significantly promoted protein expression level of Nrf2 and its downstream target gene HO-1 (heme oxygenase-1) while decreased TNF-alpha expression. CONCLUSIONS These results indicate that GDLP against T2DM-induced hepatic steatosis, oxidative stress, and inflammation by improving the Nrf2/HO-1 signaling pathway in db/db mice, suggesting the GDLP may serve as an effective strategy for in fatty liver treatment.
2 型糖尿病（T2DM）及其合并症，包括肥胖症、高血压和高脂血症，通常与非酒精性脂肪性肝病（NAFLD）相关。灵芝多糖（GDLP）是灵芝中的一种主要生物活性成分，具有抗炎、抗氧化和保肝作用。然而，GDLP 在肝脂肪变性中的作用和机制在很大程度上仍不清楚。在本研究中，我们旨在研究 GDLP 在肝脂肪变性中的功能及其潜在机制。
本研究中，雄性 db/db 小鼠接受高脂肪饮食（HFD），以研究 GDLP 对 T2DM 诱导的肝脂肪变性的作用。通过检测生化参数、组织病理学和相关细胞因子水平等临床指标来评估肝脂肪变性的生物学特征。此外，还通过 Western blot 和免疫组织化学染色研究了 Nrf2（核因子 E2（红细胞衍生 2）相关因子-2）信号通路的蛋白表达水平。
GDLP 处理的 db/db 小鼠的食物/水摄入量、体重、空腹血糖、血浆脂质、尿生物标志物、肝脂质积累和肿瘤坏死因子（TNF）-α水平明显降低。此外，GDLP 增加了各种抗氧化酶的表达，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px），同时降低了丙二醛（MDA）水平。此外，GDLP 显著促进了 Nrf2 及其下游靶基因 HO-1（血红素加氧酶-1）的蛋白表达水平，同时降低了 TNF-α的表达。
这些结果表明，GDLP 通过改善 db/db 小鼠的 Nrf2/HO-1 信号通路，对 T2DM 诱导的肝脂肪变性、氧化应激和炎症具有防治作用，提示 GDLP 可能成为治疗脂肪肝的有效策略。
