Protection by the Total Flavonoids from Rosa laevigata Michx Fruit against Lipopolysaccharide-Induced Liver Injury in Mice via Modulation of FXR Signaling

Abstract

We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining. The results showed that the TFs markedly reduced serum ALT (alanine transferase), AST (aspartate transaminase), TG (total triglyceride), and TC (total cholesterol) levels and relative liver weights and improved liver pathological changes. In addition, the TFs markedly decreased tissue MDA (malondialdehyde) level and increased the levels of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase). A mechanistic study showed that the TFs significantly increased the expression levels of Nrf2 (nuclear erythroid factor2-related factor 2), HO-1 (heme oxygenase-1), NQO1 (NAD(P)H dehydrogenase (quinone 1), GCLC (glutamate-cysteine ligase catalytic subunit), and GCLM (glutamate-cysteine ligase regulatory subunit) and decreased Keap1 (Kelch-like ECH-associated protein 1) level by activating FXR (farnesoid X receptor) against oxidative stress. Furthermore, the TFs markedly suppressed the nuclear translocation of NF-κB (nuclear factor-kappa B) and subsequently decreased the expression levels of IL (interleukin)-1β, IL-6, HMGB-1 (high -mobility group box 1), and COX-2 (cyclooxygenase-2) by activating FXR and FOXO3a (forkhead box O3) against inflammation. Besides, the TFs obviously reduced the expression levels of SREBP-1c (sterol regulatory element-binding proteins-1c), ACC1 (acetyl-CoA carboxylase-1), FASN (fatty acid synthase), and SCD1 (stearoyl-coenzyme A desaturase 1), and improved CPT1 (carnitine palmitoyltransferase 1) level by activating FXR to regulate lipid metabolism. Our results suggest that TFs exhibited protective effect against LPS-induced liver injury by altering FXR-mediated oxidative stress, inflammation, and lipid metabolism, and should be developed as an effective food and healthcare product for the therapy of liver injury in the future.

Lipid-Lowering Effects of Lotus Leaf Alcoholic Extract on Serum, Hepatopancreas, and Muscle of Juvenile Grass Carp via Gene Expression

“…Guo et al (2013) also report that the addition of lotus leaf extract to the diet increased the mRNA levels of genes involved in fatty acid β-oxidation in the liver of hamsters as observed in the present study. Other flavonoid-rich plant extracts also show similar regulation of lipid catabolism (Liu et al, 2017;Dong et al, 2018). These results indicate that AELL, like other flavonoid-rich plant extracts, have positive effects on lipid catabolism through enhancement of fatty acid β-oxidation.…”

trans ‐Chalcone inhibits high‐fat diet‐induced disturbances in FXR/SREBP‐1c/FAS and FXR/Smad‐3 pathways in the kidney of rats

“…Similarly, Dong et al. (2018) indicated that total flavonoids from Rosa laevigata Michx Fruit could exert a hypolipidemic role in liver injury induced by toxicant through modulating FXR/SREBP‐1c pathway. They suggested that total flavonoids had an inhibitory effect on lipopolysaccharides‐induced lipid accumulation in the liver by up‐regulating FXR and decreasing the levels of SREBP‐1c and FAS (Dong et al., 2018).…”

“…(2018) indicated that total flavonoids from Rosa laevigata Michx Fruit could exert a hypolipidemic role in liver injury induced by toxicant through modulating FXR/SREBP‐1c pathway. They suggested that total flavonoids had an inhibitory effect on lipopolysaccharides‐induced lipid accumulation in the liver by up‐regulating FXR and decreasing the levels of SREBP‐1c and FAS (Dong et al., 2018). Since the protective role of FXR against lipid accumulation is linked to the suppression of SREBP‐1c‐mediated lipogenesis (Watanabe et al., 2004; Zhang, Castellani, Sinal, Gonzalez, & Edwards, 2004), it seems that trans ‐chalcone can protect the kidneys of rats against HFD‐induced renal disease through the modulation of FXR/SREBP‐1c/FAS pathway.…”

Hepatoprotective Effect of the Ethanol Extract of Illicium henryi against Acute Liver Injury in Mice Induced by Lipopolysaccharide

“…ALI is a life-threatening disease with high morbidity and mortality rates. Endotoxin-induced hepatotoxicity remains a major source of death [55]. The liver index was usually used to assess liver damage in animal experiments [56].…”