Cinnamaldehyde Attenuates Hepatic Fibrosis in NAFLD Rats by Inhibiting the SphK1/S1P Signaling Pathway
10.13359/j.cnki.gzxbtcm.2025.09.028
- VernacularTitle:肉桂醛通过抑制SphK1、S1P信号通路减轻非酒精性脂肪肝大鼠肝纤维化
- Author:
Junlin WU
1
;
Bo XU
Author Information
1. 武汉市第五医院内分泌科,湖北武汉 430050
- Keywords:
cinnamaldehyde;
non-alcoholic fatty liver disease(NAFLD);
hepatic fibrosis;
SphK1/S1P pathway;
rats
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2025;42(9):2288-2294
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects and mechanisms of cinnamaldehyde(CA)on hepatic fibrosis in non-alcoholic fatty liver disease(NAFLD)rats.Methods A NAFLD rat model was established using a high-fat diet.Successfully modeled rats were randomly divided into:model group,low-and high-dose CA groups,and high-dose CA+K6PC-5[a sphingosine kinase-1(SphK1)activator]group,with healthy rats as normal controls.After intervention,serum lipid profiles[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)]and liver function markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST)]were measured using an automated biochemical analyzer.Serum inflammatory cytokines(TNF-α,IL-6,IFN-γ)were quantified by ELISA.Hepatic histopathology was evaluated via hematoxylin-eosin(HE)and Masson staining.Immunohistochemistry detected fibrosis-related proteins(COL1A1,α-SMA),while Western Blot analyzed SphK1 and sphingosine-1-phosphate(S1P)expression.Results Compared with the normal group,the model group showed significant destruction of hepatic lobule structure,hepatocyte swelling and degeneration,disordered cell arrangement,abundant lipid vacuoles in cytoplasm,obvious inflammatory cell infiltration,extensive blue collagen fiber deposition,and severe fibrosis.Moreover,the levels of TC,TG,LDL-C,ALT,AST,TNF-α,IL-6,IFN-γ,COL1A1,α-SMA,SphK1,and S1P were significantly increased,while HDL-C levels were decreased,with statistically significance(P＜0.05).Compared with the model group,both low-and high-dose CA groups demonstrated alleviated liver histopathological changes,reduced blue collagen fiber deposition,and improved fibrosis.These groups also showed significantly decreased levels of TC,TG,LDL-C,ALT,AST,TNF-α,IL-6,IFN-γ,COL1A1,α-SMA,SphK1,and S1P,along with increased HDL-C levels(P＜0.05).However,compared with the high-dose CA group,the high-dose CA+K6PC-5 group exhibited more severe destruction of hepatic lobule structure,aggravated hepatocyte swelling and degeneration,dramatically increased cytoplasmic lipid vacuoles,significant inflammatory cell infiltration,increased blue collagen fiber deposition,and worsened fibrosis.This group also had significantly elevated levels of TC,TG,LDL-C,ALT,AST,TNF-α,IL-6,IFN-γ,COL1A1,α-SMA,SphK1,and S1P,along with reduced HDL-C levels(P＜0.05).Conclusion CA alleviates hepatic fibrosis in NAFLD rats by inhibiting the SphK1/S1P signaling pathway.
