NaoXinTong Enhances Atorvastatin-induced Plaque Stability While Ameliorating Atorvastatin-induced Hepatic Inflammation

Abstract

Buchang NaoXinTong (NXT) is a Chinese medicine that has been used for many years for treatment of patients with coronary heart disease (CHD) in China. Statins substantially reduce hypercholesterolemia and CHD mortality and morbidity. However, there is still a lot of CHD patients who do not respond well to statin therapy. Herein, we report the effects of NXT on atorvastatin-inhibited atherosclerosis and atorvastatin-induced hepatic side effects. After 10 weeks of high-fat diet (HFD) feeding, apoE-deficient mice were randomly divided into 4 groups and received the following treatment for another 8 weeks: group 1, HFD; group 2, HFD containing NXT; group 3, HFD containing atorvastatin; and group 4, HFD containing both NXT and atorvastatin. After treatment, serum lipid profiles, atherosclerotic lesions, and hepatic lipid content and inflammation were determined. NXT moderately increased high-density lipoprotein cholesterol levels, although had little effect on atorvastatin-induced reduction of low-density lipoprotein cholesterol levels. Both NXT and atorvastatin reduced en face lesions and sinus lesions of aortic root. In addition, NXT enhanced atorvastatin-induced lesion plaque stability by increasing smooth muscle cell/collagen content and reducing macrophage accumulation and calcification in lesion areas. The co-treatment of NXT and atorvastatin further reduced hepatic triglyceride levels by downregulating acyl-CoA:diacylglycerol acyltransferase 1 while activating hormone-sensitive lipase, adipose triglyceride lipase, and comparative gene identification-58 expression. The AMPKα pathway was also further activated by the co-treatment. More importantly, the liver injuries caused by atorvastatin, such as hepatic inflammation and elevated serum aminotransferase activities, were substantially attenuated by NXT. Therefore, our study demonstrates that NXT enhances atorvastatin-induced plaque stability and ameliorates atorvastatin-induced hepatic side effects.

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

“…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 , 78 ] were unclear of the attrition bias. Although none of the studies provided any protocol, almost all had reported the expected outcome indicators, and most of them were evaluated as the low-risk bias.…”

“…In addition to the reduction in APA, Zhixiong capsule altered the artery structure of attenuating intima thickening (IT), intimal area (IA), and IA/MA (intimal area/medial area) ratio [ 20 , 78 ]; Danlou tablet reduced luminal occlusion (LO) and lipid content in the artery [ 24 , 75 , 77 ]; Naoxintong capsule, ginkgo biloba tablet, Tongxinluo capsule, and Fufang Danshen dropping pill also decreased LO [ 32 , 37 , 69 , 70 ]; Angong Niuhuang pill attenuated IT and media thickness (MT) [ 35 ]; ginkgo biloba tablet, Danlou tablet, Tongxinluo capsule, Fufang Danshen dropping pill, and Xuefu Zhuyu granule reduced IT [ 37 , 40 , 46 , 68 ]; Tongxinluo capsule decreased IA and the IA/MA ratio [ 49 ] and attenuated the external elastic membrane area (EEMA) and intima-media thickness (IMT) [ 71 , 72 ].…”

NaoXinTong Capsules inhibit the development of diabetic nephropathy in db/db mice

“…In H9c2 cardiomyocytes, NXT reduces H 2 O 2 -induced oxidative injury 25 . We previously reported that NXT inhibited diabetes-induced retinal vascular abnormalities, and hepatic inflammation induced by a long-term statin treatment 26 , 27 . Based on the protections of NXT on vascular system above, in this study, we attempted to investigate the effects of NXT on serum glucose levels, lipid profiles and DN development in db/db mice, a typical type 2 diabetic animal model.…”

Evaluation of the anti-inflammatory and antioxidant pharmcodynamic compoents of naoxintong capsules as a basis of broad spectrum effects

“…NXT was developed from Buyang Huanwu decoction and is composed of 16 ingredients (Table 1). It has been widely used to treat CHD for more than 20 years in China (Yang et al 2017). NXT can exert a cardioprotective effect by inhibiting NLRP3 inflammasome activation in the ischemia/reperfusion injury model (Wang et al 2017).…”