Abstract
Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid–binding protein 4 (FABP4) and sterol regulatory element–binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.
Highlights
The liver is a vital organ of the body, being involved in bile, protein, and clotting factor production and regulating cholesterol and glycogen metabolism
The pathophysiology of Non-alcoholic fatty liver disease (NAFLD) varies from simple steatosis with or without inflammation or fibrosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and, hepatocellular carcinoma (HCC) [5]
After 8 weeks, compared with the TAA group, the SSd group had a 1.09-fold higher body weight with statistical significance (Figure 1a), increased body weight gain by 1.92-fold (Figure 1b), and 1.41-fold higher food intake (Figure 1c). These results were consistent with significant changes in the daily food efficiency in the SSd group, with a 1.42-fold higher daily food efficiency compared with the TAA group (Figure 1d)
Summary
The liver is a vital organ of the body, being involved in bile, protein, and clotting factor production and regulating cholesterol and glycogen metabolism. It is more prone to injuries compared to any other organ of the body. Inflammation and wound healing are interrelated processes, since it is inflammatory signals that stimulate immune cells toward injury sites [3]. Hepatocytes are parenchymal cells of the liver, and their apoptosis is reported in liver injury [4]. Non-alcoholic fatty liver disease (NAFLD), or idiopathic steatosis, is seen in patients without any history of alcohol use. The pathophysiology of NAFLD varies from simple steatosis with or without inflammation or fibrosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and, hepatocellular carcinoma (HCC) [5]. The increased prevalence of NAFLD is a significant public health concern due to increased mortality from liver-related and liver-unrelated causes [6]
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