Liao Zhengzheng, Li Yuhua, Liao Lihong, Shi Qing, Kong Ying, Hu Jinfang, Cai Yaojun
Department of Pharmacy, the First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, People's Republic of China.
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, People's Republic of China.
Int J Biol Macromol. 2023 May 31;238:124111. doi: 10.1016/j.ijbiomac.2023.124111. Epub 2023 Mar 21.
Okra (Abelmoschus esculentus (L.) Moench) is rich in various bioactive ingredients and used as a medicinal plant in traditional medicine. In the present study, to find the polysaccharide with anti-lipotoxicity effects from okra and clarify its structure, a pectin OP-1 was purified from okra, which had a backbone containing →4)-α-GalpA-(1 → residues, and 1,5-Ara linked the main chain through the O-3 of the residue →3,4)-α-GalpA-(1→, and the C-6 of residue 1, 4-α-GalpA replaced by methyl ester. In vitro experiments showed that OP-1 pretreatment alleviated oleic acid (OA)-induced lipid accumulation, ROS generation, apoptosis, transaminase leakage, and inflammatory cytokine secretion in HepG2 cells, resulting in reduced lipotoxicity. Further molecular results revealed that OP-1 increased Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and affected the expression of AMPK downstream targets, including inhibit SREBP1c and FAS, as well as activate CPT-1A. Impressively, AMPK inhibitor dorsomorphin (Compound C) blocked the effects of OP-1 against lipotoxicity. The effects of OP-1 on lipid metabolism were also diminished by dorsomorphin. Our results demonstrated that OP-1 possesses a potent function in preventing lipotoxicity via regulating AMPK-mediated lipid metabolism and provide a novel insight into the future utilization of okra polysaccharide.
秋葵(Abelmoschus esculentus (L.) Moench)富含多种生物活性成分,在传统医学中被用作药用植物。在本研究中,为了从秋葵中找到具有抗脂毒性作用的多糖并阐明其结构,从秋葵中纯化出一种果胶OP - 1,其主链含有→4)-α-半乳糖醛酸-(1→残基,1,5-阿拉伯糖通过→3,4)-α-半乳糖醛酸-(1→残基的O - 3连接到主链上,1,4-α-半乳糖醛酸残基的C - 6被甲酯取代。体外实验表明,OP - 1预处理减轻了油酸(OA)诱导的HepG2细胞脂质积累、活性氧生成、细胞凋亡、转氨酶泄漏和炎性细胞因子分泌,从而降低了脂毒性。进一步的分子结果显示,OP - 1增加了5'-单磷酸腺苷(AMP)激活的蛋白激酶(AMPK)的磷酸化,并影响了AMPK下游靶点的表达,包括抑制固醇调节元件结合蛋白1c(SREBP1c)和脂肪酸合酶(FAS),以及激活肉碱棕榈酰转移酶1A(CPT - 1A)。令人印象深刻的是,AMPK抑制剂 dorsomorphin(化合物C)阻断了OP - 1对脂毒性的作用。dorsomorphin也削弱了OP - 1对脂质代谢的影响。我们的结果表明,OP - 1通过调节AMPK介导的脂质代谢在预防脂毒性方面具有强大功能,并为秋葵多糖的未来利用提供了新的见解。