Sulforaphane-rich aqueous broccoli seed extract suppresses diet-induced obesity ...

연구 요약

Sulforaphane-rich aqueous broccoli seed extract suppresses diet-induced obesity via 5-HT2A/AMPK signaling in mice.

Phytomedicine : international journal of phytotherapy and phytopharmacology 학술지에 발표된 이 연구는 Jeon YJ, Park J, Park KT 외 연구팀이 수행하였습니다.

이 연구는 'Sulforaphane-rich aqueous broccoli seed extract suppresses diet-induced obesity via 5-HT2A/AMPK signaling in mice.'에 대한 과학적 분석을 제공합니다.

핵심 내용

BACKGROUND: Obesity remains a major global health challenge, and current pharmacotherapies have limitations in long-term efficacy, safety, and cost. Broccoli (Brassica oleracea L. var. italica) seeds are a rich source of sulforaphane (SFN), which has demonstrated anti-obesity effects. However, the bioavailability of SFN from broccoli seeds is limited by suboptimal conversion conditions and competing nitrile-formation pathways. PURPOSE: This study aims to standardize a high-yield, SFN-rich broccoli seed hydrolysate (BSH), to evaluate its anti-obesity efficacy in mice fed a high-fat diet (HFD), and to elucidate its mechanism via molecular docking and molecular dynamics (MD). METHODS: SFN hydrolysis was optimized by Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and High-performance liquid chromatography (HPLC) across pH, temperature, time, and L-ascorbic acid; 5-hydroxytryptamine receptor 2A (5-HT2A) binding was probed by network pharmacology, molecular docking, and 100 ns MD. HFD-fed male C57BL/6 mice (n = 6 per group) received oral broccoli seed water extract (BWE), BSH, or SFN for 8 weeks. Anti-obesity efficacy was assessed by body/tissue weights, micro-computed tomography (Micro-CT), histology, and serum lipid profiling, while 5-HT2A, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and other markers in epididymal white adipose tissue (eWAT) and liver were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. RESULTS: SFN production from broccoli seeds was maximized under two hydrolysis regimes: short-term (pH 4 at 35°C for 2 h) and long-term (pH 5 at 25°C for 24 h). In silico analyses predicted stable binding of the sulforaphane-glutathione conjugate (SFN-GSH) to 5-HT2A. In HFD-fed mice, BSH (40-800 mg/kg, p.o.) dose-dependently attenuated HFD-induced body weight gain (800 mg/kg vs HFD, p < 0.001). BWE 400 mg/kg and BSH 40 mg/kg showed broadly comparable effects on body weight. Furthermore, gene and protein analyses in eWAT and liver showed 5-HT2A (Htr2a) suppression, restored AMPK phosphorylation, and downregulation of lipogenic regulators. However, co-administration of the AMPK inhibitor Compound C (5 mg/kg, i.p.) with BSH abolished these BSH-induced effects. Oral administration of a sulforaphane standard (1-10 mg/kg) produced similar effects to BSH (10 mg/kg vs HFD, p < 0.01), suggesting that the anti-obesity effect of BSH is mediated primarily by SFN. CONCLUSIONS: In this study, SFN-rich BSH ameliorated obesity in HFD-fed mice via a peripheral 5-HT2A suppression-AMPK activation axis. However, further mechanistic clarification will require studies to more precisely define the role of 5-HT2A in adipocytes.

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