Pycnogenol protects against diet-induced hepatic steatosis in apolipoprotein-E-deficient mice

Abstract

Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg·kg·day for 2 wk in advance and were then fed a high-cholesterol and -fat diet (HCD) for 8 wk. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD. Short-term treatment with HCD in ApoE-deficient mice induced hepatic injuries, such as lipid metabolism disorder and hepatic histopathological changes. We found that PYC reduced body weight and the increase of serum lipids that had been caused by HCD. Supplementation of PYC significantly reduced lipid deposition in the liver, as shown by the lowered hepatic lipid content and histopathological lesions. We subsequently detected genes related to lipid metabolism and inflammatory cytokines. The study showed that PYC markedly suppressed the expression of genes related to hepatic lipogenesis, fatty acid uptake, and lipid storage while increasing the lipolytic gene, which thus reduced hepatic lipid content. Furthermore, PYC mainly reduced the expression of inflammatory cytokines and the infiltration of inflammatory cells, which were resistant to the development of hepatic steatosis. These results demonstrate that PYC protects against the occurrence and development of hepatic steatosis and may provide a new prophylactic approach for nonalcoholic fatty liver disease (NAFLD).

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

“…Flavonoids product has numerous biological properties, which may be promising therapeutic agents for NASH (Li and Schluesener, 2017). Many natural products are rich in flavonoids and possess anti-oxidative and anti-inflammatory activities against NASH (Jian et al, 2018;Parafati et al, 2018;Wang et al, 2018). Various flavonoid compounds have been identified, such as flavones, flavanones, flavanols, flavonols, and chalcones (Rzepecka-Stojko et al, 2015).…”

The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects

“…As mentioned earlier, PYC contains various compounds such as flavonoids, polyphenols, and procyanidins, which have prophylactic and curative attributes in chronic diseases (including liver diseases) through their antiinflammatory and antioxidant effects (Cho et al, 2001; Fan et al, 2015; Malekahmadi et al, 2019). Previous cellular, animal, and human studies have evaluated the effects of PYC on liver diseases, such as fatty liver disease (Mei, Mochizuki, & Hasegawa, 2012; Wang et al, 2018) and hepatitis (Ezzikouri et al, 2015), directly or as a prophylactic agent to decrease the hepatotoxic effects of other compounds (e.g., chemotherapeutic agents) (Kondo, Ishimi, Takebayashi, & Tousen, 2020).…”

“…PYC has been reported to exert protective effects against hepatic steatosis in animal and cellular studies owing to the phenol and polyphenol content (Fan et al, 2009; Mei et al, 2012; Wang et al, 2018). Accordingly, supplementation with pine bark extract could decelerate the development of hepatic fibrosis and slightly reduce the triglycerides (TGs) and liver index of rats (Mei et al, 2012).…”

“…Nevertheless, some mechanisms have been proposed in this regard. For instance, PYC has been shown to decrease lipid accumulation (especially TGs) in the NMuLi cells of the liver in mice (Fan et al, 2009) and hepatocytes in in‐vivo models (Wang et al, 2018). Moreover, PYC affects lipid metabolism by regulating major enzymes in synthetic and catabolic paths.…”

“…PYC has been reported to exert protective effects against hepatic steatosis in animal and cellular studies owing to the phenol and polyphenol content (Fan et al, 2009;Mei et al, 2012;Wang et al, 2018).…”