<i>Lygodium japonicum</i> Herb Ameliorates Nonalcoholic Fatty Liver Disease by Inhibiting Hepatic Lipid Accumulation and Inflammatory Response in ob/ob Mice

The ubiquity of nonalcoholic fatty liver disease (NAFLD) as a chronic metabolic disorder across the globe is currently matched by a dearth of efficacious treatment modalities. <i>Lygodium japonicum</i> (Thunb.) Sw. herb (LJ) extensively employed in the management of hepatitis due to its noted anti-inflammatory properties as per the Chinese Materia Medica presents an interesting potential therapeutic agent. However, its applicability and mechanistic action in NAFLD treatment remain underexplored. To investigate the potential role of LJ in mitigating NAFLD and discern whether this effect is interconnected with lipid metabolism and the inflammatory signaling pathway, the HPLC method was employed to identify potential active ingredients in LJ. Subsequently, ob/ob obese mice were used to simulate a NAFLD model and administered oral doses of LJ (300 and 600 mg/kg) over an 8 week period. Multiple measures, including body and liver weights, the liver-to-body weight ratio, lipid metabolism, and inflammatory cytokines, were evaluated. Histological parameters were assessed using HE staining, Masson's trichrome staining, and Oil red O staining. Additionally, the protein expression levels of TLR4/MyD88/NF-κB and the MAPK pathway as well as transcription factors relevant to lipid metabolism and inflammatory transcription levels were investigated. Five principal chemical components of the LJ were identified through HPLC analysis. The animal experiments demonstrated that LJ could significantly curtail weight gain, lower the liver-to-body weight ratio, decrease transaminase release and serum lipid profile, ameliorate liver histopathology alterations, and attenuate hepatocyte inflammatory infiltration and the release of proinflammatory cytokines in obese mice. Further, it was found that LJ could impede the TLR4/MyD88/NF-κB and MAPK pathway and regulate the inflammatory transcription level, thereby moderating liver inflammation. Additionally, LJ was found to inhibit genes associated with lipid synthesis, while augmenting the expression of those associated with lipid oxidation. These findings, for the first time, endorse the protective effects of LJ on obesity-related NAFLD and provide preliminary evidence that the amelioration of hepatic inflammation and restructuring of lipid metabolism play pivotal roles in LJ's intervention against obesity-related NAFLD. Collectively, our research bolsters the case for the potential clinical application of LJ in NAFLD treatment.