Drug Design, Development and Therapy (Jun 2020)
Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy
Abstract
Xiao Ke,1,2,* Yiteng Huang,2,* Liang Li,3 Fuya Xin,3 Luhua Xu,3 Yuangui Zhang,3 Zhicong Zeng,3 Fengxia Lin,3 Yinzhi Song3 1Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, Guangdong 518057, People’s Republic of China; 3Department of Cardiology, Shenzhen Bao’an Traditional Chinese Medicine Hospital Group, The Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen 518133, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengxia LinDepartment of Cardiology, Shenzhen Bao’an Traditional Chinese Medicine Hospital Group, The Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen 518133, People’s Republic of ChinaTel +8617301933930Email [email protected] SongDepartment of Cardiology, Shenzhen Bao’an Traditional Chinese Medicine Hospital Group, The Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen 518133, People’s Republic of ChinaTel +8613760298578Email [email protected]: Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency.Methods: Thirty SD rats were randomly divided into (1) control (CON); (2) damp-heat syndrome atherosclerosis (AS + DH); (3) yang deficiency syndrome atherosclerosis (AS + YX); (4) damp-heat syndrome atherosclerosis + BBR (AS + DH + BBR); (5) yang deficiency syndrome, atherosclerosis + BBR (AS + YX + BBR); and (6) damp-heat syndrome, atherosclerosis + BBR + 3-methyladenine (AS + DH + BBR + 3-MA) (n = 5/group) groups. Pathological morphology, macrophage plaque infiltration, inflammation, and LC3-II and P62 expression were assessed.Results: Compared with the CON group, the AS + DH and AS + YX groups had an increased plaque area in the aortic tissue with substantial foam cell and macrophage infiltration, and increased levels of IL-1β and TNF-α (P < 0.01). After four weeks of BBR intervention, the plaque area in the AS + DH + BBR group was reduced with decreased foam cells and macrophage infiltration, and decreased levels of TNF-α and IL-1β, whereas LC3-II protein expression was increased and P62 protein expression was decreased in the AS + DH + BBR group when compared to AS + DH group. In addition, the AS + DH + BBR + 3-MA group exhibited a significantly enlarged plaque, substantial foam cell and macrophage infiltration, increased levels of IL-1β and TNF-α, and decreased LC3-II and P62 (P < 0.01) expression when compared to the AS + DH + BBR group.Conclusion: Our results indicated that the BBR could inhibit arterial plaque formation and alleviate the inflammatory response in the aortic tissues in the AS rats with damp-heat syndrome possibly via promoting autophagy. The molecular mechanisms of BBR-mediated protective effects in this animal model still require further investigation.Keywords: berberine, autophagy, LC3-II, P62, arterial plaque, damp-heat syndrome
