背景:作为一种传统的药用真菌,灵芝由于其优越的生物活性,在中国已被用作治疗多种代谢疾病的民间药物。最近,已有研究表明灵芝多糖(GLP)对血脂异常的保护作用。然而,GLP改善血脂异常的具体机制尚不完全清楚.
目的:本研究旨在探讨GLP对高脂饮食诱导的高脂血症的保护作用及其机制。
方法:从灵芝菌丝体中成功获得GLP。高脂饮食小鼠建立高脂血症模型。生化测定,组织学分析,免疫荧光,在GLP干预后的高脂饮食治疗小鼠中,采用Westernblot和实时qPCR评估这些变化.
结果:发现GLP显著降低了体重增加和脂质水平过高,部分减轻了组织损伤。GLP治疗后通过激活Nrf2-Keap1和抑制NF-κB信号通路有效改善了氧化应激和炎症。GLP通过LXRα-ABCA1/ABCG1信号促进胆固醇反向转运,增加了负责胆汁酸产生的CYP7A1和CYP27A1的表达,伴随着肠道FXR-FGF15水平的抑制。此外,参与脂质代谢的多种靶蛋白在GLP的干预下也被显著调节。
结论:综合来看,我们的研究结果表明,GLP具有潜在的降脂作用,其可能机制涉及改善氧化应激和炎症反应,调节胆汁酸合成和脂质调节因子,促进胆固醇的逆向运输,因此表明GLP可能用作膳食补充剂或药物用于高脂血症的辅助治疗。
BACKGROUND: As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear.
OBJECTIVE: This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism.
METHODS: The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fatdiet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fatdiet-treated mice after the GLP intervention.
RESULTS: It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP.
CONCLUSIONS: Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.