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Archive > Volume 15 Issue 3 > 2023,15(3):421-429. DOI:https://doi.org/10.1016/j.chmed.2022.09.006 Prev Next

決明子通過自噬途徑改善非酒精性脂肪肝病

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Cassiae Semen improves non-alcoholic fatty liver disease through autophagy-related pathway

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    摘要:
    目的：決明子在中國古代被用于緩解便秘、改善肝功能和改善視力，已有數(shù)千年的使用歷史。本研究旨在探索決明子對非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）的抗脂肪肝作用及其內(nèi)在機制。 方法：采用高效液相色譜法（High-performance liquid chromatography，HPLC）鑒定決明子水提取物的主要成分。用高脂糖水（ High-fat and sugar-water，HFSW）飲食喂養(yǎng)小鼠以誘導(dǎo)肝臟脂肪變性的發(fā)生，并使用決明子進行治療。通過測定血清生物標(biāo)志物和組織病理學(xué)染色來確定決明子的抗NAFLD 作用。本研究還研究了決明子對油酸和棕櫚酸（oleic acid and palmitic acid，OAPA）處理的 HepG2 細胞活力和脂質(zhì)代謝的影響。此外，本研究探索了參與脂質(zhì)代謝和自噬信號的重要基因和蛋白質(zhì)的表達，以尋找其潛在治療機制。 結(jié)果： 在決明子提取物中同時發(fā)現(xiàn)了五種化合物，包括橙黃決明素、紅鐮霉素龍膽二糖苷、決明子苷 C、大黃素和大黃酸。決明子改善了飲食誘導(dǎo)的體內(nèi)肝脂肪變性，具體表現(xiàn)為脂滴數(shù)量和大小的減少、肝臟和血清甘油三酯（triglycerides，TG）水平的降低，同時也顯著減輕了 OAPA 誘導(dǎo)的肝細胞脂質(zhì)積累。決明子誘導(dǎo)的這些降脂作用主要依賴于抑制脂肪酸合成酶（fatty acid synthase，F(xiàn)ASN）和激活自噬相關(guān)信號，包括 AMP 激活蛋白激酶（AMP-activated protein kinase，AMPK）、輕鏈 3-II （light chain 3-II，LC3-II）/ LC3-1 和自噬相關(guān)基因 5（autophagy-related gene5，ATG5）等。 結(jié)論：我們的研究表明，決明子通過減少與 FASN 相關(guān)的脂肪酸合成和激活 AMPK 介導(dǎo)的自噬，可有效保護肝臟脂肪變性，這可能成為改善非酒精性脂肪肝的潛在治療方案。

    Abstract:
    Objective: Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). Methods: High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. Results: Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). Conclusion: Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.

    關(guān)鍵詞:
    自噬;AMPK;決明子;脂肪酸合成;非酒精性脂肪酸病

    Keywords:


    Project Supported:
    This work was supported by the Beijing Municipal Science & Technology Commission (No. 7212174 to XL); National Natural Science Foundation of China (No. 82004045 to XL); Beijing Nova Program of Science & Technology (No. Z191100001119088 to XL); and the Young Talents Promotion Project of China Association of Traditional Chinese Medicine (No. 2020-QNRC2-01 to XL); Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine. (No. ZYYCXTD-C-202006 to XL).

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