Sparalide B from Sparassis latifolia inhibits early adipogenesis in 3T3-L1 adipocytes via β-catenin-dependent downregulation of PPARγ and C/EBPα

IF 3.9 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2026-02-01 Epub Date: 2026-01-17 DOI:10.1016/j.jff.2026.107167

Hyeok Jin Choi , Jeong Won Choi , So Jung Park , Gyeong Eun Im , Youngki Park , Kyoung Tae Lee , Jin Boo Jeong

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Abstract

Sparalide B, a phthalide isolated from Sparassis latifolia (S. latifolia), was structurally assigned as 4,5,7-trihydroxy-6-ethoxyphthalide by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) (¹H, ¹³C, heteronuclear multiple bond correlation (HMBC)) analyses. In 3T3-L1 adipocytes, sparalide B (2.5–20 μg/mL) significantly reduced lipid droplet accumulation in a dose-dependent manner, as quantified by Oil Red O staining at concentrations that did not affect cell viability. Western blotting showed decreased expression of adipogenic transcription factors (PPARγ, C/EBPα) and lipid droplet-associated/lipolytic proteins (perilipin-1, ATGL, HSL), alongside increased levels of thermogenesis/energy-metabolism markers (UCP2, PGC-1α, p-AMPK, AMPK). Stage-restricted treatments revealed that efficacy was confined to the early differentiation window (D0-D2), with little effect during D2-D4 or D4-D8. Mechanistically, sparalide B elevated β-catenin during D0-D2; β-catenin knockdown abrogated the compound's suppression of PPARγ/C/EBPα and its inhibition of lipid accumulation. These findings indicate that sparalide B targets early adipogenesis through β-catenin-dependent signaling to suppress lipid formation, highlighting this natural phthalide as a promising anti-obesity lead.

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疏树苷B通过β-catenin依赖性下调PPARγ和C/EBPα抑制3T3-L1脂肪细胞的早期脂肪形成

通过高分辨率电喷雾质谱（HR-ESI-MS）和核磁共振（NMR）（1H, 13C，异核多键相关（HMBC））分析，从菝葜（S. latifolia）中分离得到邻苯酞类化合物Sparalide B，结构为4,5,7-三羟基-6-乙氧基邻苯酞。在3T3-L1脂肪细胞中，经油红O染色，在不影响细胞活力的浓度下，稀疏胺B （2.5-20 μg/mL）以剂量依赖性方式显著降低脂滴积累。Western blotting显示，脂肪生成转录因子（PPARγ、C/EBPα）和脂滴相关/脂解蛋白（perilipin-1、ATGL、HSL）的表达下降，产热/能量代谢标志物（UCP2、PGC-1α、p-AMPK、AMPK）水平升高。限期治疗显示，疗效仅限于早期分化窗口（D0-D2），在D2-D4或D4-D8期间效果不大。在机制上，疏肽B在D0-D2期间升高β-catenin；β-catenin的敲除消除了该化合物对PPARγ/C/EBPα的抑制作用及其对脂质积累的抑制作用。这些发现表明，sparalide B通过β-连环蛋白依赖的信号传导抑制脂质形成，靶向早期脂肪形成，突出了这种天然邻苯酞作为一种有希望的抗肥胖先导物。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.