Two Triterpenoids, ARM-2 and RA-5, From Protorhus longifolia Exhibit the Potential to Modulate Lipolysis and Lipogenesis in Cultured 3T3-L1 Adipocytes.

IF 5.9 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Lipids Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI:10.1155/2024/3972941
Musawenkosi Ndlovu, June C Serem, Megan J Bester, Zeno Apostolides, Andrew R Opoku, Rebamang A Mosa
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Abstract

Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP-1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with Ki and IC50 values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.

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长叶原木中的两种三萜类化合物 ARM-2 和 RA-5 具有调节培养的 3T3-L1 脂肪细胞中脂肪分解和脂肪生成的潜力。
三萜类化合物已被确定为治疗高甘油三酯血症的潜在新型降脂药物。本研究调查了从长叶原木(Protorhus longifolia (Benrh.)Engl)茎皮中分离出的两种三萜类化合物(ARM-2 和 RA-5)的潜在抗脂生成和/或抗脂肪分解作用。 本研究结合了硅学预测和体外试验,调查了这些三萜类化合物与参与脂肪生成和脂肪分解的关键蛋白质之间的相互作用。根据硅学分子对接分析预测,这两种三萜类化合物与 PPARγ、SREBP-1 和 AMPK 的结合亲和力较高,而与 C/EBPα、胰脂肪酶和激素敏感性脂肪酶(HSL)的结合亲和力较低。这两种三萜类化合物都具有体外抑制胰脂肪酶的作用,其 Ki 值和 IC50 值分别为 28.7 至 52.9 μM 和 27.6 至 35.8 μM。分化的 3T3-L1 脂肪细胞和油酸诱导的 HepG2 细胞模型中的总脂质和中性脂质积累均受到抑制,ARM-2 的抑制效果优于 RA-5。在 HepG2 模型中,两种三萜类化合物(25 μM 和 100 μM)的抑制活性与 50 μM 洛伐他汀相当,但后者具有细胞毒性,而 ARM-2 和 RA-2 均无细胞毒性。相关基因的表达与辛伐他汀的作用相似,其中 SREBP-1、PPARγ、C/EBPα 和 HSL 的表达减少,而 AMPK 的表达不变。体外研究证实,ARM-2 和 RA-5 还能抑制脂肪细胞的脂肪分解,25 μM 和 100 μM 的甘油释放减少量与 50 μM 的洛伐他汀和辛伐他汀相似。这项研究表明,三萜类化合物 ARM-2 和 RA-5 具有调节脂肪生成和脂肪分解的潜力。
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来源期刊
Journal of Lipids
Journal of Lipids BIOCHEMISTRY & MOLECULAR BIOLOGY-
自引率
0.00%
发文量
7
审稿时长
12 weeks
期刊介绍: Journal of Lipids is a peer-reviewed, Open Access journal that publishes original research articles and review articles related to all aspects of lipids, including their biochemistry, synthesis, function in health and disease, and nutrition. As an interdisciplinary journal, Journal of Lipids aims to provide a forum for scientists, physicians, nutritionists, and other relevant health professionals.
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