Naringin Alleviates Atherosclerosis in ApoE^–/– Mice by Regulating Cholesterol Metabolism Involved in Gut Microbiota Remodeling

Abstract

Naringin, a major flavonoid in citrus, has potential for preventing atherosclerosis. The presence in the colon of a large amount of naringin after oral intake might affect the gut microbiota. We investigated the role of gut microbiota remodeling in the alleviation of atherosclerosis by naringin. Naringin significantly alleviated atherosclerosis and lowered the serum and liver cholesterol levels by 24.04 and 28.37% in ApoE −/− mice fed with a high-fat diet. Nontarget metabolomics showed that naringin modulated the hepatic levels of cholesterol derivatives and bile acids. Naringin increased the excretion of bile acids and neutral sterols by 1.6-and 4.3-fold, respectively. The main potential pathway by which naringin alleviated atherosclerosis was the gut microbiota−liver− cholesterol axis. Naringin modulated the abundances of bile salt hydrolase-and 7α-dehydroxylase-producing bacteria, promoting bile acid synthesis from cholesterol by upregulating CYP7A1 via suppression of the FXR/FGF15 pathway. In addition, naringin facilitated reverse cholesterol transport by downregulating PCSK9/IDOL. The results provide insight into the atherosclerosisalleviation mechanisms of citrus flavonoids and a scientific basis for the development of functional foods containing citrus flavonoids.

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

“…Our previous study revealed eight new ene-yne hydroquinones derived from marine fungus Pestalotiopsis neglecta SCSIO41403, one of them, pestalotioquinoside C (102), functioning as a potential LXRα agonist via upregulating the mRNA level of the target gene ABCA1. Using SPR assay, 102 interacted with LXRα dose-dependently with the K D of 50.0 μM ( Wang F. et al, 2020 ). Further study discovered pestalotiochromones A (103) as a potential LXRs agonist, remarkably upregulated LXRβ and downstream gene ABCA1.…”

Potential of Naringin in Reducing Aorta Lesion Atherosclerosis in Hypercholesterolemia: A Systematic Review

“…The final 3 articles selected are from Korea (2001) 8 , China (2020) 9 , and France (2012) 10 . A total of 92 animal models used in these studies were hypercholesterolemia.…”

Painong San, a Traditional Chinese Compound Herbal Medicine, Restores Colon Barrier Function on DSS-Induced Colitis in Mice

“…PNS regulates the balance of intestinal flora and is an important starting point for repairing the mucosal barrier. Its main ingredients include paeoniflorin, naringin, hesperidin, and neohesperidin which also play an important role in the regulation of intestinal flora [42][43][44][45]. is study confirmed that compared with the DSS group, the diversity of intestinal flora increased after PNS administration (Figure 3(a)), and the abundance Evidence-Based Complementary and Alternative Medicine of Bacteroides, Staphylococcus, Odoribacter, Lactobacillus, Isobacterium, and other bacteria increased, while Escherichia-Shigella bacteria, Helicobacter, Streptococcus, and other bacteria were significantly reduced (Figure 3(c)).…”