Artesunate Inhibits Lipid Accumulation and Inflammation by Regulating the NLRP3 Inflammasome in Nonalcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD), recognized as a chronic liver condition, has emerged as one of the most prevalent worldwide. This study explores the impact of artesunate (ART) on lipid accumulation and inflammatory factors within NAFLD model cells. Methods: LO2 cells were subjected to treatment with oleic acid (OA) to establish NAFLD cell model. Subsequently, these cells were categorized into distinct groups: a control group, an OA group, an OA + 2.5 μm ART group, and an OA + 5 μm ART group. The activity of LO2 cells was determined using the Cell Counting Kit-8 (CCK-8) method. The presence of intracellular lipid droplets was examined through oil red O staining. Levels of triglycerides (TG), total cholesterol (TC), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated using enzyme-linked immunosorbent assay (ELISA). Additionally, the protein expressions of nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3), Cleaved caspase-1, N-terminus of Gasdermin-D (GSDMD-N), and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) were measured via Western blot assay. Results: In comparison to the control group, the OA group exhibited a significant increase in the contents of lipid droplets, TC, and TG (p < 0.01). Notably, ART effectively reversed the impact of OA (p < 0.01). Following OA stimulation, there was a pronounced elevation in the levels of IL-6 (p < 0.01), IL-1β (p < 0.01), and TNF-α (p < 0.05). In comparison to the OA group, the 2.5 μm ART group showed no significant difference in TNF-α content (p > 0.05), while the 5 μm ART group significantly reduced TNF-α content (p < 0.05). Furthermore, both the 2.5 μm ART (p < 0.05) and 5 μm ART (p < 0.01) groups notably reduced IL-1β and IL-6 content. When compared to the control group, the expressions of NLRP3, ASC, GSDMD-N, and Cleaved caspase-1 in the OA group significantly increased (p < 0.01). ART, however, mitigated this heightened expression trend (p < 0.05). Conclusions: ART demonstrated a reduction in TC and TG content, improvement in the deposit of intracellular lipid droplets, and a decrease in the release of inflammatory factors in LO2 cells. This effect was achieved through the regulation of the NLRP3 inflammasome, presenting a novel approach to the treatment of NAFLD.