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Ethnopharmacological Relevance: Traditional Chinese medicine (TCM) has shown notable effectiveness and safety in managing illnesses linked to cytokine storm(CS). Bailixiang tea (BLX), an herbal medicine formula, which is a compound Chinese medicine composed of Thymus mongolicus (Ronniger) Ronniger (Bailixiang), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi), Cyperus rotundus L. (Xiangfu), and Perilla frutescens (L.) Britton (Zisu). The objective of this study was to explore the capacity of BLX in improving LPS-induced CS., Aim of the Study: This study aimed to validate the mitigating effect of BLX on CS and to further investigate its mechanism., Materials and Methods: mice were orally administered BLX for 24 h after being treated with 5 mg/kg lipopolysaccharide (LPS). Histopathological observations further confirmed the significant protective effect of BLX treatment against LPS-induced lung and spleen damage. Additionally, we aimed to explore the molecular mechanism underlying its effects through blood proteomics and transcriptomics analyses. Real-Time Quantitative PCR (RT-qPCR) was utilized to detect the levels of Toll-like receptor 2 (TLR2), Matrix metalloproteinase 8 (MMP8), Matrix metalloproteinase 9 (MMP9), Integrin beta 2 (ITGB2), Mitogen-activated protein kinase 8 (MAPK8), Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE), Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)expressions in the lung tissue., Results: The results demonstrated that BLX effectively down-regulated the overproduction of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in both the serum and lung and spleen tissues. Furthermore, BLX effectively mitigated the overproduction of monocyte chemoattractant protein-1 (MCP-1) in the serum. Through comprehensive multi-omics analysis, it was revealed that BLX specifically targeted and regulated TLR2/MAPK8 and TLR2/NF-κB signaling pathways, which play a crucial role in the production of key cytokines., Conclusions: The findings of this study demonstrate that Bailixiang tea possesses the ability to alleviate lung tissue damage and inhibit the development of LPS-induced cytokine storm in mice. These effects are attributed to the tea's ability to suppress the TLR2/MAPK8 and TLR2/NF-κB pathways. Consequently, this research highlights the potential application of Bailixiang tea as a treatment option for cytokine storm., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)