College of Life Science, Shandong Agricultural University, PR China.
College of Life Science, Shandong Agricultural University, PR China.
J Ethnopharmacol. 2023 Jun 12;309:116321. doi: 10.1016/j.jep.2023.116321. Epub 2023 Mar 1.
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.
This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism.
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.
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.
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.
作为一种传统药用真菌，灵芝已在中国被用作民间药物，用于治疗多种代谢疾病，因为其具有卓越的生物活性。最近，越来越多的报道研究了灵芝多糖（GLP）对改善血脂异常的保护作用。然而，GLP 改善血脂异常的确切机制尚不完全清楚。
本研究旨在探讨 GLP 对高脂饮食诱导的高血脂的保护作用，并探讨其潜在机制。
成功从灵芝菌丝体中获得 GLP。用高脂饮食对小鼠进行处理，建立高血脂模型。生化测定、组织学分析、免疫荧光、Western blot 和实时 qPCR 用于评估 GLP 干预后高脂饮食处理的小鼠的变化。
结果发现，GLP 给药可显著降低体重增加和脂质水平升高，并部分缓解组织损伤。通过激活 Nrf2-Keap1 抑制 NF-κB 信号通路，GLP 可有效改善氧化应激和炎症。GLP 通过 LXRα-ABCA1/ABCG1 信号促进胆固醇逆向转运，增加负责胆汁酸生成的 CYP7A1 和 CYP27A1 的表达，同时抑制肠道 FXR-FGF15 水平。此外，在 GLP 的干预下，多种参与脂质代谢的靶蛋白也显著调节。
综上所述，我们的结果表明 GLP 具有潜在的降脂作用，其可能的作用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、促进胆固醇逆向转运，从而表明 GLP 可能可作为高血脂辅助治疗的膳食补充剂或药物。
