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. 2024 Feb 20;10(5):e26712.
doi: 10.1016/j.heliyon.2024.e26712. eCollection 2024 Mar 15.

Anti-sepsis effect of Xiaochaihu decoction based on the TLR4/MyD88/NF-κB signalling pathway

Qingxin Yang  1 , Yulong Wang  2 , Gefei Cao  2 , Xiaoqing Li  3 , Tinghui Zhao  4
Affiliations

Anti-sepsis effect of Xiaochaihu decoction based on the TLR4/MyD88/NF-κB signalling pathway

Qingxin Yang et al. Heliyon. .

Abstract

The aims of this study were to explore the protective effect of Xiaochaihu decoction in mice with sepsis induced by intraperitoneal injection; to explore its anti-inflammatory effect on the TLR4-MyD88-NF-κB signalling pathway; and to explore the main material basis of the anti-inflammatory effect of Xiaochaihu decoction, with the aim of supplementing and expanding the associated research and providing a scientific foundation for the clinical use of the decoction. The effects of Xiaochaihu decoction on septic mice were analysed by measurements of white blood cells (WBC) and Platelets (PLT); Nitric Oxide (NO) level in serum; IL-6, IL-1β and TNF-α levels in serum; RT-PCR; Haematoxylin-Eosin (HE) immunohistochemistry; western blotting (WB). The results showed the excellent in vivo anti-inflammatory effects of Xiaochaihu decoction in LPS-induced septic mice, through down regulation of the gene and protein expression of TLR4, MYD88, TRAF6, IKK, IKBα and p65 and the subsequent reduction in the release of inflammatory mediators IL-6, IL-1β, TNF-α and NO. Moreover, significant anti-septic effect was observed from high and medium doses of Xiaochaihu decoction, but not from the low dose.

Keywords: LPS; Mice; MyD88; NF-κB; Sepsis; TLR4; Xiaochaihu decoction.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic of anti-sepsis effectiveness of Xiaochaihu decoction through the TLR4/MyD88/NF-κB signalling pathway.
Fig. 2
Fig. 2
Effects of Xiaochaihu decoction on the evolution of the spleen and thymus index and WBC, PLT, NO, IL-1β, IL-6, TNF-α in septic mice as determined by ELISA. Normal, blank group; LPS, model group; XCHD H, Xiaochaihu decoction high-dose group; XCHD M, Xiaochaihu decoction medium-dose group; and XCHD L, Xiaochaihu decoction low-dose group. Compared with the LPS group, p < 00.05, p < 00.01.
Fig. 3
Fig. 3
Effect of Xiaochaihu decoction on mRNA expression of IL-1β, IL-6, TNF-α, TLR4, MYD88, TRAF6, CHUK, IKB-α and p65 in lung tissue from septicmice. Normal, blank group; LPS, model group; XCHD H, Xiaochaihu decoction high-dose group; XCHD M, Xiaochaihu decoction medium-dose group; and XCHD L, Xiaochaihu decoction low-dose group. Compared with the LPS group, p < 00.05, p < 00.01.
Fig. 4
Fig. 4
Effect of Xiaochaihu decoction HE staining of the lungs of septic mice in various conditions (400× magnification). Normal, blank group; LPS, model group; XCHD H, Xiaochaihu decoction high-dose group; XCHD M, Xiaochaihu decoction medium-dose group; and XCHD L, Xiaochaihu decoction low-dose group.
Fig. 5
Fig. 5
Effects of Xiaochaihu decoction on TLR4, MYD88, TRAF6, IKK, IKKB-α and p65 protein levels in the lung tissues of septic mice determined by immunohistochemical staining (Magnification 400×). Normal, blank group; LPS, model group; XCHD H, Xiaochaihu decoction high-dose group; XCHD M, Xiaochaihu decoction medium-dose group; and XCHD L, Xiaochaihu decoction low-dose group. Data are expressed as the mean ± SEM of 10 mice per group, compared with the LPS group, p < 00.05, p < 00.01.
Fig. 6
Fig. 6
Effects of Xiaochaihu decoction on the expression of TLR4, MYD88, TRAF6, IKK, IKKB-α and p65 in lung tissue of mice (refer to Fig. S1-Fig. S7). Normal, blank group; LPS, model group; XCHD H, Xiaochaihu decoction high-dose group; XCHD M, Xiaochaihu decoction medium-dose group; and XCHD L, Xiaochaihu decoction low-dose group. Comparison with LPS group, p < 00.05, p < 00.01.
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