Leiva-Castro Camila, Múnera-Rodríguez Ana Maria, Martínez-Bailén Macarena, Carmona Ana Teresa, López-Enríquez Soledad, Palomares Francisca
Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Sevilla, Spain.
Br J Pharmacol. 2025 Nov;182(21):5157-5172. doi: 10.1111/bph.70115. Epub 2025 Jun 18.
Sulforaphane (SFN) has notable health benefits but faces challenges due to its poor solubility and delivery. This study investigates SFN-glycoconjugates effects on lipopolysaccharide (LPS)-induced inflammation in dendritic cells (DCs). With the aiming to enhance their therapeutic potential against inflammatory diseases. Novel monovalent SFN-glycoconjugates with mannose (Man) and fucose (0Fuc) were developed and tested for their anti-inflammatory and immune-modulatory properties in DCs from healthy donors under chronic LPS exposure.
By leveraging therapeutic strategies, SFN-glycoconjugates significantly improved the solubility and bioavailability of SFN, thereby overcoming the limitations of traditional delivery methods. Monocyte-derived DCs were treated with SFN-glycoconjugates and subsequently exposed to a chronic inflammatory environment induced by LPS.
Our results showed that SFN-glycoconjugates enhance effectiveness in suppressing inflammation by targeting the p65 NF-κB pathway, without affecting MAPK signalling. SFN-glycoconjugates induce a tolerogenic immune response, characterized by increased IL-10 production and enhanced regulatory T- and B-cell proliferation. These effects surpass those of p65 NF-κB inhibition alone, highlighting a distinct and potent regulatory mechanism independent of MAPK pathways.
The integration of food therapeutic strategies not only enhances the stability and delivery of bioactive compounds but also broadens their potential applications in functional foods and therapeutic approaches. In particular, SFN-glycoconjugates represent a promising option as biologically active compounds for inflammatory diseases, offering enhanced anti-inflammatory and immunomodulatory effects through optimized delivery systems and the activation of specific molecular pathways.
萝卜硫素（SFN）具有显著的健康益处，但因其溶解性和递送性差而面临挑战。本研究调查了SFN-糖缀合物对脂多糖（LPS）诱导的树突状细胞（DCs）炎症的影响，旨在增强其对炎症性疾病的治疗潜力。开发了新型的带有甘露糖（Man）和岩藻糖（Fuc）的单价SFN-糖缀合物，并在慢性LPS暴露下对健康供体的DCs进行抗炎和免疫调节特性测试。
通过利用治疗策略，SFN-糖缀合物显著提高了SFN的溶解性和生物利用度，从而克服了传统递送方法的局限性。单核细胞衍生的DCs用SFN-糖缀合物处理，随后暴露于由LPS诱导的慢性炎症环境中。
我们的结果表明，SFN-糖缀合物通过靶向p65 NF-κB途径增强了抑制炎症的效果，而不影响MAPK信号传导。SFN-糖缀合物诱导了一种耐受性免疫反应，其特征是IL-10产生增加以及调节性T细胞和B细胞增殖增强。这些作用超过了单独抑制p65 NF-κB的作用，突出了一种独立于MAPK途径的独特且有效的调节机制。
食品治疗策略的整合不仅提高了生物活性化合物的稳定性和递送性，还拓宽了它们在功能性食品和治疗方法中的潜在应用。特别是，SFN-糖缀合物作为炎症性疾病的生物活性化合物代表了一个有前景的选择，通过优化递送系统和激活特定分子途径提供增强的抗炎和免疫调节作用。
