Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

Xinru Gu,Hongjie Wang,Jian Yang,Haiyu Zhao,Baolin Bian,Xiaorui Fan,Junyi Zhou,Yanyan Zhou,Nan Si

doi:10.3389/fphys.2019.01241

Abstract

Huanglian Jiedu decoction (HLJDD) has been used in the clinical treatment of inflammatory conditions. To clarify the mechanism of its comprehensive anti-inflammatory activities, the correlation between lipid homeostasis and the TLR4/MyD88 signaling pathway in zebrafish was established in the present study. In the lipopolysaccharide (LPS)-induced inflammation in zebrafish model, RT-PCR assays of five inflammatory cytokines and six targeted proteins were measured. Lipidomics analysis was conducted to identify potential lipid markers. HLJDD displayed strong efficacies, with a 61% anti-inflammatory rate at a concentration of 50 μg/mL. The activation of TLR4/MyD88 played an essential role in the inflammatory process. All protein indexes in the HLJDD group exhibited a tendency to reverse back to normal levels. Moreover, 79 potential pathological lipid biomarkers were identified. Compared with the model group, 61 therapeutic lipid biomarkers were detected in HLJDD group. Most perturbations of lipids were ameliorated by HLJDD, mainly through the glycerophospholipid metabolic pathway. In the visual network study, the corresponding lipoproteins such as PLA2, SGMS, and SMDP were observed as important intermediates between lipid homeostasis and the TLR4/MyD88 signaling pathway.

Highlights

Inflammation is a complicated pathological process associated with many human diseases
Five concentrations were selected based on the maximum tolerated concentration (MTC) to evaluate the dose-effect relationships of Huanglian Jiedu decoction (HLJDD) (6.25, 12.5, 25, 50, and 100 μg/mL); berberine (3.9, 7.8, 15.6, 31.25, and 62.5 μg/mL); baicalin (15.6, 31.25, 62.5, 125, and 250 μg/mL); and geniposide (31.25, 62.5, 125, 250, and 500 μg/mL)
The results demonstrated that HLJDD had the strongest efficacy at a concentration of 50 μg/mL with 61% antiinflammatory activity among four drugs

Summary

Introduction

Inflammation is a complicated pathological process associated with many human diseases. It is a defense response of tissues against injury or damage (Coussens and Werb, 2002; Ryu et al, 2017). Lipid oxidation and alterations in lipid structures are important triggers of inflammatory diseases, including atherosclerotic diseases, renal failure, and metabolic syndrome (Mi et al, 2012). An exaggerated inflammatory response is able to affect intracellular lipid accumulation (Raetz et al, 2006; Colin et al, 2015). The processes of inflammation and lipid metabolism interact, and both are modulated through specific signaling pathways of NFκB, MAPK, and PPAR (Nakaya et al, 2011; Ayaka et al, 2015; Gong et al, 2017)

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Results

Conclusion