Hsu Yin-Chieh, Ou Shih-Ming, Zhuang Kai-Ru, Kuo Ai-Ling, Li Wan-Jhen, Huang Chun-Yi, Lin Chao-Hsiung, Chen Jih-Jung, Fu Shu-Ling
Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
J Tradit Complement Med. 2023 Mar 2;13(4):379-388. doi: 10.1016/j.jtcme.2023.03.002. eCollection 2023 Jul.
Sepsis causes an uncontrolled systemic response characterized by excessive inflammation and immune suppression, leading to multiple organ failure and death. An effective therapeutic strategy for sepsis-related syndromes is urgently needed. Hance (HS) is a folk herbal plant used to treat arthritis and dermatitis, but the anti-inflammatory properties of HS and its related compounds have rarely been investigated. In this study, we aimed to explore the anti-inflammatory effects of HS.
Models of bacterial lipopolysaccharide (LPS)-induced activated macrophages and endotoxemia mice were used, in which the TLR4/NF-κB signaling pathway is upregulated to trigger inflammatory responses. The HS extract (HSE) was delivered into LPS-induced endotoxemia mice via oral administration. Three compounds were purified using column chromatography and preparative thin layer chromatography and were validated by physical and spectroscopic data.
HSE suppressed NF-κB activation and proinflammatory molecules (TNF-α, IL-6, iNOS) in LPS-activated RAW 264.7 macrophages. Furthermore, oral administration of HSE (200 mg/kg) to LPS-treated mice improved the survival rate, restored body temperature, decreased TNF-α and IL-6 in serum, and reduced IL-6 expression in bronchoalveolar lavage fluid (BALF). In lung tissues, HSE reduced LPS-induced leukocyte infiltration and the expression of proinflammatory molecules (TNF-α, IL-6, iNOS, CCL4 and CCL5). Three pure compounds isolated from HSE, including 2,4,6-trihydroxybenzophenone-4-O-geranyl ether, 1-hydroxy-7 methoxyxanthone and euxanthone, were demonstrated to exhibit anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophages.
The present study demonstrated the anti-inflammatory effects of HS and . Further clinical studies of HS in human sepsis are warranted.
脓毒症会引发一种不受控制的全身反应，其特征为过度炎症反应和免疫抑制，进而导致多器官功能衰竭和死亡。因此，迫切需要一种针对脓毒症相关综合征的有效治疗策略。汉防己（HS）是一种用于治疗关节炎和皮炎的民间草药，但HS及其相关化合物的抗炎特性鲜有研究。在本研究中，我们旨在探究HS的抗炎作用。
采用细菌脂多糖（LPS）诱导的活化巨噬细胞模型和内毒素血症小鼠模型，其中TLR4/NF-κB信号通路被上调以触发炎症反应。通过口服给药将HS提取物（HSE）给予LPS诱导的内毒素血症小鼠。使用柱色谱和制备薄层层析法纯化了三种化合物，并通过物理和光谱数据进行了验证。
HSE抑制了LPS激活的RAW 264.7巨噬细胞中NF-κB的激活以及促炎分子（TNF-α、IL-6、iNOS）的产生。此外，对LPS处理的小鼠口服HSE（200mg/kg）可提高存活率、恢复体温、降低血清中的TNF-α和IL-6，并减少支气管肺泡灌洗液（BALF）中IL-6的表达。在肺组织中，HSE减少了LPS诱导的白细胞浸润以及促炎分子（TNF-α、IL-6、iNOS、CCL4和CCL5）的表达。从HSE中分离出的三种纯化合物，包括2,4,6-三羟基二苯甲酮-4-O-香叶基醚、1-羟基-7-甲氧基呫吨酮和呫吨酮，在LPS刺激的RAW 264.7巨噬细胞中表现出抗炎活性。
本研究证明了HS的抗炎作用。HS在人类脓毒症中的进一步临床研究很有必要。
