Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9

Abstract

Numerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis regulation. The inducement of PCSK9 expression is also an important reason for statin intolerance. The Di’ao Xinxuekang (DXXK) capsule extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product used in atherosclerotic cardiovascular disease. Although DXXK has been widely used in atherosclerotic cardiovascular treatment for nearly 30 years, studies on the potential mechanisms of the lipid-lowering effect are very limited. The purpose of the present study was to demonstrate the possible involvement of the PCSK9/LDLR signaling pathway in the lipid-lowering and antiatherosclerotic effect of DXXK in high-fat diet-fed ApoE–/– mice. The results showed that DXXK treatment alleviated hyperlipidemia, fat accumulation, and atherosclerosis formation in ApoE–/– mice. Furthermore, changes in the expression of PCSK9 mRNA in liver tissue and the circulating PCSK9 level in ApoE–/– mice were both reversed after DXXK treatment, and upregulation of LDLR in the liver was also detected in the protein level in DXXK-treated mice. Our study is the first to show that DXXK could alleviate lipid disorder and ameliorate atherosclerosis with downregulation of the PCSK9 in high-fat diet-fed ApoE–/– mice, suggesting that DXXK may be a potential novel therapeutic treatment and may support statin action in the treatment of atherosclerosis.

Effect of the polyphenol‐rich extract fromAllium cepaon hyperlipidemic sprague‐dawley rats

“…The development of atherosclerosis is modulated by disturbances of lipid metabolism, oxidative stress, etc (Rzepecka‐Stojko et al., 2017). Moreover, accumulating data show that, during atherosclerosis progression, hyperlipidemia is a critical issue (Qu et al., 2018). Furthermore, oxidative stress is discovered to be related to hyperlipidemia (Cheng et al., 2017).…”

The proatherosclerotic function of indoleamine 2, 3-dioxygenase 1 in the developmental stage of atherosclerosis

“…Hypercholesterolemia, defined by an overload of lipids, as well as an imbalance of lipoproteins, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), acts as a driving force and plays a vital role in the development and progression of atherosclerosis. 51,52 Herein, the in vivo study showed that serum TC and LDL-C were significantly increased in ApoE −/− mice fed a HFD 53 (Fig. 8d, f), while serum HDL-C was decreased (Fig.…”

Atheroprotective Effects and Mechanisms of Postmarketing Chinese Patent Formulas in Atherosclerosis Models: A Systematic Review

“…Among these, five low-risk studies [ 40 , 42 , 43 , 66 , 68 ] used the “random number table” in the assessment of sequence generation, seven high-risk studies [ 24 , 33 , 34 , 49 , 59 , 75 , 76 ] did not report the entry, and the remaining 48 studies had unclear detailed random methods. Although none of the studies mentioned random housing, the outcome measures in the 19 studies [ 20 , 23 , 26 , 27 , 29 , 30 , 34 – 36 , 38 , 41 , 45 , 46 , 48 , 50 , 52 , 59 , 73 , 75 ] were not influenced since the feeding conditions (such as temperature, lighting, and humidity) were described, and the bias was evaluated as low risk. The incomplete outcome data were detected in 27 high-risk articles [ 19 – 21 , 23 , 26 , 32 – 36 , 39 , 45 – 47 , 50 – 53 , 55 , 56 , 60 , 61 , 68 , 74 – 77 ] without any reason or appropriate method for describing the missing data, while 18 articles [ 22 , 24 , 25 , 27 – 31 , 38 , 41 , 49 , 54 , 57 , 64 , 70 – 72 , ...…”