Andrographolide Inhibits the NF-κB Signaling Pathway and Alleviates High-Fat Diet-Induced Hepatic Inflammation in a Mouse Model of Nonalcoholic Fatty Liver Disease

Background High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) is a key link between several medical conditions and is becoming a major health concern affecting thousands of people globally. Andrographolide, an active ingredient extracted from Andrographis paniculate, has shown anti-inflammatory and anti-fibrosis effects in recent studies. Objective This study aims to explore whether andrographolide can mitigate HFD-induced NAFLD and the underlying mechanism. Methods We treated C57B/6 mice consuming a high-fat diet (HFD) with varying concentrations of andrographolide. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate liver function indicators in circulating blood. Haematoxylin and Eosin and Oil Red O staining were used to assess inflammation infiltration and lipid deposits in liver tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunoblotting were used to analyze the expression levels of genes and proteins. Results ELISA revealed that andrographolide dose-dependently mitigated the HFD-induced elevations of glucose, alanine aminotransferase, and aspartate aminotransferase in circulating blood. Histological analysis indicated that andrographolide dose-dependently reduced HFD-induced inflammation infiltration and lipid deposition. RT-qPCR and immunoblotting analyses showed that andrographolide dose-dependently inhibited the HFD-induced overproduction of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and the up-regulation of p-p65 and NLRP3 proteins. Conclusion Together, these results suggest that andrographolide treatment can dose-dependently mitigate HFD-induced liver function impairments, lipid accumulation, pro-inflammatory cytokine overproduction, and inflammatory responses in the liver of mice by regulating the NF-κB signaling pathway. However, it is important to note that our results are observational and do not conclusively demonstrate the necessity of the NF-κB signaling pathway's involvement in the NAFLD-alleviating effects of andrographolide. This highlights the need for further validation at both the gene and protein levels through additional in vitro and in vivo experiments.