Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway

Abstract

Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the highfat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factorkappa B (NF-jB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the extract of Crataegus could suppress the transcription of HMGCR via NF-jB signal pathway.

Fruits for Prevention and Treatment of Cardiovascular Diseases

“…It has been used as food or a traditional medicine to improve digestion for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat CVDs, especially hyperlipidemia and atherosclerosis [ 78 ]. A study investigated the hypolipidemic effect of hawthorn fruit compounds (HFC, including hawthorn and kiwi fruit extract) in apoE −/− atherosclerotic mice with high blood lipid levels.…”

The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism

“…Tanshinone ⅡA and Crataegus pinnatifida Bunge can regulate the expressions of LDLR in the liver ( Hu et al, 2016 ; Jia et al, 2016b ). The Ldlr mRNA level was significantly higher in rats by treatment with an n -butanol extract (NE3) of Panax notoginseng (Burkill) F.H.…”

Hawthorn (Crataegus spp.): An Updated Overview on Its Beneficial Properties

“…As indicated above, many beneficial properties have been attributed to hawthorn, including anticancer [55], anti-HIV, anti-diabetic [56], and anticoagulant activity [57], cardioprotective effects [58][59][60][61][62][63][64][65], hepatoprotective effects, antihyperglycemic and antihyperlipidemic activities, wound healing effects [66], antimicrobial effects, gastroprotective effects, treatment of metabolic syndrome [67], regulation of cholesterol homeostasis [68], anti-atherosclerosis effects [69][70][71][72], anti-aging effects [73], ischemia protective effects [74], treatment of cognitive disorders, neuroprotective effects, regulating gastrointestinal motility [75], anti-inflammatory activities [76,77], regulation of the gut-brain axis [78], treatment of hypertension [79], antioxidant activity [80][81][82][83][84][85], anti-hypoxic activities [86], antidepressant effects [87], anti-Alzheimer's effects, and treatment of intestinal microbial disorder [88].…”