Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, P. R. China.
J Leukoc Biol. 2020 Dec;108(6):1829-1839. doi: 10.1002/JLB.3AB0820-576RRR. Epub 2020 Sep 6.
Sepsis was redefined as life-threatening organ dysfunction caused by a dysregulated host response to infection in 2016. One of its most common causes is Staphylococcus aureus, especially methicillin-resistant Staphylococcus aureus (MRSA), which leads to a significant increase in morbidity and mortality. Therefore, innovative and effective approaches to combat MRSA infection are urgently needed. Recently, host-directed therapy (HDT) has become a new strategy in the treatment of infectious diseases, especially those caused by antibiotic-resistant bacteria. Baicalin (BAI) is the predominant flavonoid and bioactive compound isolated from the roots of Radix Scutellariae (Huang Qin), a kind of traditional Chinese medicine. It has been reported that BAI exhibits multiple biological properties such as anti-oxidant, antitumor, and anti-inflammatory activities. However, the therapeutic role of BAI in MRSA infection is still unknown. In this study, it is found that BAI treatment inhibited the production of IL-6, TNF-α, and other cytokines from MRSA- or bacterial mimics-stimulated Mϕs and dendritic cells (DCs). BAI played an anti-inflammatory role by inhibiting the activation of ERK, JNK MAPK, and NF-κB pathways. Moreover, the serum level of TNF-α was decreased, whereas IL-10 was increased, in mice injected with MRSA. Furthermore, the bacterial load in livers and kidneys were further decreased by the combination of BAI and vancomycin (VAN), which might account for the amelioration of tissue damage. BAI reduced the high mortality rate caused by MRSA infection. Collectively, the results suggested that BAI may be a viable candidate of HDT strategy against severe sepsis caused by antibiotic-resistant bacteria such as MRSA.
2016 年，脓毒症被重新定义为一种危及生命的器官功能障碍，由宿主对感染的失调反应引起。其最常见的原因之一是金黄色葡萄球菌，特别是耐甲氧西林金黄色葡萄球菌（MRSA），这导致发病率和死亡率显著增加。因此，急需创新有效的方法来对抗 MRSA 感染。最近，宿主导向治疗（HDT）已成为治疗传染病的一种新策略，尤其是对抗生素耐药菌引起的传染病。黄芩苷（BAI）是从黄芩（黄芩）根中分离出来的主要黄酮类和生物活性化合物，黄芩是一种中药。据报道，BAI 具有多种生物学特性，如抗氧化、抗肿瘤和抗炎活性。然而，BAI 在 MRSA 感染中的治疗作用尚不清楚。在这项研究中，发现 BAI 治疗抑制了 MRSA 或细菌模拟物刺激的 Mϕ 和树突状细胞（DC）中 IL-6、TNF-α 和其他细胞因子的产生。BAI 通过抑制 ERK、JNK MAPK 和 NF-κB 途径的激活发挥抗炎作用。此外，MRSA 注射小鼠的血清 TNF-α 水平降低，而 IL-10 水平升高。此外，BAI 与万古霉素（VAN）联合使用进一步降低了肝脏和肾脏中的细菌负荷，这可能是组织损伤改善的原因。BAI 降低了由 MRSA 感染引起的高死亡率。总之，这些结果表明 BAI 可能是一种可行的宿主导向治疗策略候选药物，可用于治疗由抗生素耐药菌（如 MRSA）引起的严重脓毒症。
