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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.
Exp Biol Med (Maywood). 2016 Mar; 241(6):667-74.EB

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 high-fat 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 factor-kappa B (NF-κB) 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-κB signal pathway.

Authors+Show Affiliations

Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China luoxuegang@hotmail.com.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Key Lab of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, P. R. China Tianjin Key Lab of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.Hezhou University, Hezhou 542800, P. R. China 805008426@qq.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26825354

Citation

Hu, Hai-Jie, et al. "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." Experimental Biology and Medicine (Maywood, N.J.), vol. 241, no. 6, 2016, pp. 667-74.
Hu HJ, Luo XG, Dong QQ, et al. 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. Exp Biol Med (Maywood). 2016;241(6):667-74.
Hu, H. J., Luo, X. G., Dong, Q. Q., Mu, A., Shi, G. L., Wang, Q. T., Chen, X. Y., Zhou, H., Zhang, T. C., & Pan, L. W. (2016). 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. Experimental Biology and Medicine (Maywood, N.J.), 241(6), 667-74. https://doi.org/10.1177/1535370215627032
Hu HJ, et al. 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. Exp Biol Med (Maywood). 2016;241(6):667-74. PubMed PMID: 26825354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hu,Hai-Jie, AU - Luo,Xue-Gang, AU - Dong,Qing-Qing, AU - Mu,Ai, AU - Shi,Guo-Long, AU - Wang,Qiu-Tong, AU - Chen,Xiao-Ying, AU - Zhou,Hao, AU - Zhang,Tong-Cun, AU - Pan,Li-Wen, Y1 - 2016/01/28/ PY - 2015/09/05/received PY - 2015/12/15/accepted PY - 2016/1/31/entrez PY - 2016/1/31/pubmed PY - 2016/8/3/medline KW - 3-hydroxy-3-methylglutaryl-CoA reductase KW - Zhongtian hawthorn KW - hypocholesteolemic KW - hypolipidemic KW - nuclear factor-kappa B KW - transcriptional regulation SP - 667 EP - 74 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp. Biol. Med. (Maywood) VL - 241 IS - 6 N2 - 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 high-fat 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 factor-kappa B (NF-κB) 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-κB signal pathway. SN - 1535-3699 UR - https://www.unboundmedicine.com/medline/citation/26825354/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_ L2 - http://journals.sagepub.com/doi/full/10.1177/1535370215627032?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -