Hypericum sampsonii exhibits anti-inflammatory activity in a lipopolysaccharide-induced sepsis mouse model

Yin-Chieh Hsu; Shih-Ming Ou; Kai-Ru Zhuang; Ai-Ling Kuo; Wan-Jhen Li; Chun-Yi Huang; Chao-Hsiung Lin; Jih-Jung Chen; Shu-Ling Fu

doi:10.1016/j.jtcme.2023.03.002

Hypericum sampsonii exhibits anti-inflammatory activity in a lipopolysaccharide-induced sepsis mouse model

J Tradit Complement Med. 2023 Mar 2;13(4):379-388. doi: 10.1016/j.jtcme.2023.03.002. eCollection 2023 Jul.

Authors

Yin-Chieh Hsu¹, Shih-Ming Ou², Kai-Ru Zhuang¹, Ai-Ling Kuo¹, Wan-Jhen Li², Chun-Yi Huang³, Chao-Hsiung Lin², Jih-Jung Chen^{3

4}, Shu-Ling Fu¹

Affiliations

¹ Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
² Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
³ Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
⁴ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404332, Taiwan.

Abstract

Background and aim: 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. Hypericum sampsonii 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.

Experimental procedure: 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.

Results: 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.

Conclusion: The present study demonstrated the anti-inflammatory effects of HS in vitro and in vivo. Further clinical studies of HS in human sepsis are warranted.

Keywords: Herbal medicine; Hypericum sampsonii; Inflammation; Lipopolysaccharide; NF-κB; Sepsis.