Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
Shock. 2018 Aug;50(2):178-186. doi: 10.1097/SHK.0000000000001021.
Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and antibacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture to induce polymicrobial intra-abdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 h for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic tumor necrosis factor without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function, or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at 7 days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.
厚朴酚是从厚朴树皮中提取的一种双酚类单体，在中国传统医学和日本医学中被广泛应用，最近还被研究具有抗炎和抗菌特性。厚朴酚先前已被证明可提高具有快速 100%致死率的败血症模型中的存活率。本研究旨在确定厚朴酚对更接近人类疾病的败血症模型中宿主反应的影响。雄性和雌性 C57BL/6 小鼠接受盲肠结扎和穿刺以诱导多微生物腹腔内败血症。然后，将小鼠随机分为接受厚朴酚（120mg/kg/天）或载体注射的组，并在 24 小时后进行功能研究或 7 天进行存活研究时处死。败血症后给予厚朴酚治疗可增加 CD4 T 细胞的频率，并增加 CD4 T 细胞的激活，如激活标志物 CD69 所测量的那样。厚朴酚还增加了脾脏树突状细胞。厚朴酚同时减少了 CD8 T 细胞的频率和数量。厚朴酚降低了全身肿瘤坏死因子，而不影响其他全身细胞因子。厚朴酚对肾功能、肺功能、肝功能或肠道完整性没有可检测到的影响。与先前关于厚朴酚在致死性败血症模型中的研究相比，厚朴酚在 7 天时并未改变存活率（厚朴酚组的死亡率为 70%，而载体组的死亡率为 60%）。因此，厚朴酚在调节宿主免疫反应和炎症方面是有效的，但其效果不足以改变败血症的存活。
