The Hypolipidemic Effect of Hawthorn Leaf Flavonoids through Modulating Lipid Metabolism and Gut Microbiota in Hyperlipidemic Rats

Abstract

Objective. The purpose of this study was to explore the potential mechanisms of the lipid-regulating effects and the effect on modulating the gut microbiota of hawthorn leaf flavonoids (HLF) in the high-fat diet-induced hyperlipidemic rats. Methods. The hypolipidemic effect of HLF was investigated in the high-fat diet-induced hyperlipidemic rats. The action targets of HLF in the treatment of hyperlipidemia were predicted by network pharmacology and KEGG enrichment bubble diagram, which were verified by the test of western blotting. Meanwhile, we used 16S rRNA sequencing to evaluate the effects of HLF on the microbes. Results. The results of animal experiments showed that HLF could reduce the body weight and regulate the levels of serum lipid in high-fat diet (HFD) rats. Meanwhile, for the related targets of cholesterol metabolism, HLF could significantly upregulate the expression of LDLR, NR1H3, and ABCG5/ABCG8; reduce the expression of PCSK9; and increase the level of CYP7A1 in the intestinal tissue, whereas cholesterol biosynthetic protein expressions including HMGCR and SCAP were lowered by HLF. In addition, HLF increased the activities of plasma SOD, CAT, and GSH-Px and decreased the levels of Casp 1, NLRP3, IL-1β, IL-18, and TNF-α, improving the degree of hepatocyte steatosis and inflammatory infiltration of rats. Notably, HLF significantly regulated the relative abundance of major bacteria such as g_Lactobacillus, g_Anaerostipes, g_[Eubacterium]_hallii_group, g_Fusicatenibacter, g_Akkermansia, and g_Collinsella. Synchronously, we found that HLF could regulate the disorder of plasma HEPC and TFR levels caused by HFD. Conclusion. This study demonstrates that HLF can regulate metabolic hyperlipidemia syndromes and modulate the relative abundance of major bacteria, which illustrated that it might be associated with the modulation of gut microbiota composition and metabolites.

Effects of sex on fat deposition through gut microbiota and short-chain fatty acids in weaned pigs

“…In addition, the relative abundance of Peptostreptococcaceae has been significantly and positively correlated with back-fat thickness ( Soares et al., 2021 ). In a study by Hu et al. (2022b) , the high-fat group exhibited a greater abundance of Collinsella in the gut compared to the control group ( Hu et al., 2022b ).…”

“…In a study by Hu et al. (2022b) , the high-fat group exhibited a greater abundance of Collinsella in the gut compared to the control group ( Hu et al., 2022b ). Another experiment revealed that relative weights of mesenteric white adipose tissue (mWAT), epididymal white adipose tissue (eWAT), and renal white adipose tissue (kWAT) were increased in mice related with low relative abundance of Ralstonia .…”

Synergistic mediating effect of edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids in hyperlipidemic rats

“…Flavonoids can promote the decomposition of cholesterol and triglyceride to improve liver function and lipid metabolism (Huiming et al, 2022;Lanlan et al, 2022). In order to evaluate the synergistic effects of polysaccharide and flavonoid, the hyperlipidemia model Clostridium is a large and important group of bacteria in Firmicutes, containing a variety of intestinal pathogenic bacteria, which can produce exotoxins and have strong toxic effects on both humans and animals (Kociolek & Gerding, 2016).…”

“…Edible fungi polysaccharides can improve lipid metabolism disorders mainly by inhibiting or promoting the expression of related lipid metabolism enzymes and related factors, improving the activity of bile acid synthesis, regulating intestinal flora, and alleviating oxidative stress reaction (Yin et al, 2020; Zhao et al, 2023). Flavonoids can promote the decomposition of cholesterol and triglyceride to improve liver function and lipid metabolism (Huiming et al, 2022; Lanlan et al, 2022). In order to evaluate the synergistic effects of polysaccharide and flavonoid, the hyperlipidemia model was established.…”

Polydatin combined with hawthorn flavonoids alleviate high fat diet induced atherosclerosis by remodeling the gut microbiota and glycolipid metabolism

“…(P. cuspidatum) (28) and Crataegus pinnatifida Bunge (C. pinnatifida) as representative detoxifying and blood-activating herbs (29) , are known for their efficacy in blood activation and resolving stasis, clearing heat, and detoxification (30). Extensive evidence has shown that polydatin (31) or hawthorn flavonoids (32) could exert cardioprotective effects and alleviate metabolic disorders, partially via the gut microbiota. Previously, our team combined hawthorn to promote blood circulation and resolving blood stasis with P. cuspidatum to clear heat and detoxify (33), applied it to the treatment of acute coronary syndrome, and achieved great clinical efficacy (34).…”