Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Department of Medicine, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Molecules. 2021 Apr 7;26(8):2106. doi: 10.3390/molecules26082106.
Oxyresveratrol, a stilbene extracted from the plant Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the release of the pro-inflammatory cytokines IL-12, IL-6, and TNF-α by human dendritic cells (DCs). We found that oxyresveratrol did not elicit per se the release of these cytokines, but inhibited their secretion induced upon DC stimulation with R848 (Resiquimod), a well-known immune cell activator engaging receptors recognizing RNA viruses. We then investigated whether the inclusion of oxyresveratrol into nanoparticles promoting its ingestion by DCs could favor its effects on cytokine release. For this purpose we synthesized and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on DCs. We found that bare PLGA nanoparticles did not affect cytokine secretion by resting DCs, but increased IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs, an event known as "priming effect". We then loaded PLGA nanoparticles with oxyresveratrol and we observed that oxyresveratrol-bearing particles did not stimulate the cytokine release by resting DCs and inhibited the PLGA-dependent enhancement of IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs. The results herein reported indicate that oxyresveratrol suppresses the cytokine production by activated DCs, thus representing a good anti-inflammatory and immune-suppressive agent. Moreover, its inclusion into PLGA nanoparticles mitigates the pro-inflammatory effects due to cooperation between nanoparticles and R848 in cytokine release. Therefore, oxyresveratrol can be able to contrast the synergistic effects of nanoparticles with microorganisms that could be present in the patient tissues, therefore overcoming a condition unfavorable to the use of some nanoparticles in biological systems.
氧白藜芦醇是一种从植物 Roxb. 中提取的二苯乙烯，据报道具有显著的抗炎活性。由于这种治疗作用的机制尚未得到充分阐明，我们研究了氧白藜芦醇是否会影响人树突状细胞 (DC) 释放促炎细胞因子 IL-12、IL-6 和 TNF-α。我们发现，氧白藜芦醇本身不会引起这些细胞因子的释放，但可以抑制其在 R848（瑞喹莫德）刺激 DC 时的分泌，R848 是一种众所周知的免疫细胞激活剂，可激活识别 RNA 病毒的受体。然后，我们研究了将氧白藜芦醇纳入促进 DC 摄取的纳米颗粒中是否可以促进其对细胞因子释放的影响。为此，我们合成并表征了聚乳酸-共-羟基乙酸 (PLGA) 纳米颗粒，并评估了它们对 DC 的影响。我们发现，裸 PLGA 纳米颗粒不会影响静止 DC 的细胞因子分泌，但会增加 R848 刺激的 DC 中 IL-12、IL-6 和 TNF-α 的分泌，这一事件被称为“启动效应”。然后，我们将 PLGA 纳米颗粒负载氧白藜芦醇，观察到载氧白藜芦醇的颗粒不会刺激静止 DC 的细胞因子释放，并抑制 PLGA 依赖的 R848 刺激的 DC 中 IL-12、IL-6 和 TNF-α 分泌的增强。本研究表明，氧白藜芦醇抑制激活的 DC 产生细胞因子，因此是一种良好的抗炎和免疫抑制药物。此外，将其纳入 PLGA 纳米颗粒可以减轻由于纳米颗粒与细胞因子释放中的 R848 之间的协同作用而导致的促炎作用。因此，氧白藜芦醇能够抵抗与患者组织中可能存在的微生物协同作用的纳米颗粒的协同作用，从而克服了一些纳米颗粒在生物系统中使用的不利条件。
