来自木豆的新型芪类化合物通过下调过氧化物酶体增殖物激活受体γ（PPARγ）抑制3T3-L1脂肪细胞的脂肪生成。

New stilbenes from Cajanus cajan inhibit adipogenesis in 3T3-L1 adipocytes through down-regulation of PPARγ.

作者信息

Yao Liyuan, Zhao Liyun, Liu Fen, Al-Bukhaiti Wedad Q, Huang Xiaobao, Lin Tingting, Qiu Sheng-Xiang

机构信息

Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement, Guangdong Provincial Key Laboratory of Applied Botany, Laboratory of Natural Product Chemical Biology, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, PR China; South China National Botanical Garden, Guangzhou 510650, PR China; Graduate University of Chinese Academy of Sciences, Beijing 100049, PR China.

出版信息

Bioorg Chem. 2024 Dec;153:107851. doi: 10.1016/j.bioorg.2024.107851. Epub 2024 Sep 27.

DOI:10.1016/j.bioorg.2024.107851

PMID:39368142

Abstract

Two new stilbenes, denominated Cajanotone B (CAB) and Cajanotone C (CAC), were isolated from the leaves of Cajanus cajan. In this study, the structures of CAB and CAC were unambiguously elucidated by a combination of various spectral methods. Both compounds significantly inhibited the adipogenesis in 3T3-L1 adipocytes by reducing the lipid accumulation, triglyceride content and FFA secretion. CAB and CAC also substantially inhibit the mRNA expression of HSL, ATGL, C/EBPα and PPARγ as deciphered based by RT-PCR assay. Down-regulation of PPAR is believed to be the primary mechanism underlying which CAB and CAC inhibited adipogenic differentiation because the lipid-promoting activity of PPAR agonists can be counteracted by these compounds. The molecular interaction between CAB/CAC and PPARγ was revealed with the help of molecular docking. Taken together, CAB and CAC could serve as new lead compounds with the potential to speed up the development of novel lipid-lowering and weight-control therapies.

摘要

从木豆叶中分离出两种新的芪类化合物，命名为木豆酮B（CAB）和木豆酮C（CAC）。在本研究中，通过多种光谱方法相结合，明确阐明了CAB和CAC的结构。两种化合物均通过减少脂质积累、甘油三酯含量和游离脂肪酸分泌，显著抑制3T3-L1脂肪细胞的脂肪生成。根据逆转录-聚合酶链反应（RT-PCR）分析结果，CAB和CAC还能大幅抑制激素敏感脂肪酶（HSL）、脂肪甘油三酯脂肪酶（ATGL）、CCAAT增强子结合蛋白α（C/EBPα）和过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA表达。PPAR的下调被认为是CAB和CAC抑制脂肪生成分化的主要机制，因为这些化合物可以抵消PPAR激动剂的促脂活性。借助分子对接揭示了CAB/CAC与PPARγ之间的分子相互作用。综上所述，CAB和CAC可作为新的先导化合物，有可能加速新型降脂和体重控制疗法的开发。