Experimental study of the effect of compound combination of traditional Chinese medicine on atherosclerosis

doi:10.16138/j.1673-6087.2021.04.008

Abstract

Abstract:

Objective To explore a combination of resveratrol, berberine, curcumin and artesunate with a reasonable dose ratio to obtain the most effective and safest compound combination to provide an alternative selection for the patients with atherosclerosis and statin intolerance. Methods The atherosclerotic model in apolipoprotein E-knockout (ApoE^-/-) mice was established by high fat diet. Four compound of Chinese medicine including resveratrol, berberine, curcumin and artesunate were divided into 9 groups according to orthogonal test table L₉(3⁴). Through evaluating the degree of atherosclerosis and the level of low-density lipoprotein cholesterol（LDL-C） in each group, the most effective and safest combination of 4 compounds were obtained and verified. Results According to the therapeutic effect on blood LDL-C and aortic atherosclerotic plaque, the range analysis of orthogonal experiment suggested the best compound combination, which was: resveratrol 1.25 mg/(kg·d), berberine 0.625 mg/(kg·d), curcumin 12.5 mg/(kg·d), artesunate 6.25 mg/(kg·d). In verification phase, it was shown that the traditional Chinese medicine combination group had smaller atherosclerotic plaque areas, lower liver injury than the single drug group (all P<0.05). Conclusions Through orthogonal test, we obtained a best compound combination of traditional Chinese medicine in all combination groups, which could prevent atherosclerosis and was verified to be effective and safe. This study provided a reference method in clinical transformation for traditional Chinese medicine.

Key words: Atherosclerosis, Resveratrol, Berberine, Curcumin, Artesunate, Orthogonal experiment

CLC Number:

R543

WANG Shun, ZHU Huafang, MAO Chengyu, LI Dongjiu, WANG Changqian. Experimental study of the effect of compound combination of traditional Chinese medicine on atherosclerosis[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(04): 261-266.

Figures/Tables 6

References 21

[1]	Libby P. The changing landscape of atherosclerosis[J]. Nature, 2021, 592(7855): 524-533. doi: 10.1038/s41586-021-03392-8 URL
[2]	Task Force Members, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk[J]. Atherosclerosis, 2019, 290: 140-205. doi: 10.1016/j.atherosclerosis.2019.08.014 URL
[3]	Ward NC, Watts GF, Eckel RH. Statin toxicity[J]. Circ Res, 2019, 124(2): 328-350. doi: 10.1161/CIRCRESAHA.118.312782 URL
[4]	Adhyaru BB, Jacobson TA. Safety and efficacy of statin therapy[J]. Nat Rev Cardiol, 2018, 15(12): 757-769. doi: 10.1038/s41569-018-0098-5 pmid: 30375494
[5]	Zhou L, Long J, Sun Y, et al. Resveratrol ameliorates atherosclerosis induced by high-fat diet and LPS in ApoE^-/- mice and inhibits the activation of CD4⁺ T cells[J]. Nutr Metab (Lond), 2020, 17: 41. doi: 10.1186/s12986-020-00461-z URL
[6]	Lu L, Huang J, Xue X, et al. Berberine regulated miR150-5p to inhibit P2X7 receptor, EMMPRIN and MMP-9 expression in oxLDL induced macrophages[J]. Front Pharmacol, 2021, 12: 639558. doi: 10.3389/fphar.2021.639558 URL
[7]	任晓娜, 张晓丽, 宋超. 小檗碱抗动脉粥样硬化的效果及作用机制研究[J]. 河北医药, 2021, 43(1): 115-118.
[8]	侯梦琳. 姜黄素抑制动脉粥样硬化的研究进展[J]. 临床医药文献电子杂志, 2020, 7(34): 190.
[9]	Jiang W, Cen Y, Song Y, et al. Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines[J]. Phytomedicine, 2016, 23(11): 1259-1266. doi: 10.1016/j.phymed.2016.06.004 URL
[10]	蒋林, 随家宁, 冯婷, 等. 正交试验设计法优选益根调理膏水提工艺[J]. 广东化工, 2020, 47(11): 15-18.
[11]	王青, 赵林华, 邸莎. 黄芪的临床应用及其用量探究[J]. 吉林中医药, 2018, 38(12): 1450-1454.
[12]	朱梦鸷, 张喜奎, 林勇. 桂枝汤类方证的临证思维探析[J]. 国医论坛, 2021, 36(1):4-6.
[13]	刘签兴, 路志正. 小建中汤证治辨析[J]. 中华中医药杂志, 2020, 35(10): 5006-5008.
[14]	李忠轩. 从《伤寒论》分析小柴胡汤在临床中的应用[J]. 中医临床研究, 2020, 12(34): 83-85.
[15]	谢海波, 周岚, 李杨, 等. 不同剂量活血破血药对对动脉粥样硬化小鼠主动脉PLEK及PLK3基因表达的影响[J]. 时珍国医国药, 2018, 29(2): 278-280.
[16]	邵建伟, 胡赟赟, 倪通天, 等. 急性脑梗死患者神经功能缺损与颈动脉粥样硬化斑块关系的临床研究[J]. 内科理论与实践, 2021, 16(1): 32-36.
[17]	张飞, 陈翠玲, 刘俏贤, 等. 阿托伐他汀钙片辅助治疗高血压肾病的效果和安全性观察[J]. 智慧健康, 2021, 7(7): 132-134.
[18]	Hsu CN, Hou CY, Tain YL. Preventive aspects of early resveratrol supplementation in cardiovascular and kidney disease of developmental origins[J]. Int J Mol Sci, 2021, 22(8): 4210. doi: 10.3390/ijms22084210 URL
[19]	Kumacs M, Ecsrefoiglu M, Karatacs E, et al. Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats[J]. Nefrologia(Engl Ed), 2019, 39(4): 411-423.
[20]	Iqbal M, Shah MD, Vun-Sang S, et al. The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: implications for cancer chemoprevention[J]. Biomed Pharmacother, 2021, 139: 111636. doi: 10.1016/j.biopha.2021.111636 URL
[21]	Wen Y, Pan MM, Lv LL, et al. Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF-κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy[J]. J Cell Biochem, 2019, 120(3): 4291-4300. doi: 10.1002/jcb.27714 pmid: 30260039

药物	2（中剂量）	3（高剂量）
白藜芦醇（A）	1.25	5
小檗碱（B）	0.625	2.5
姜黄素（C）	12.5	50
青蒿琥酯（D）	6.25	25

项目	白藜芦醇组	小檗碱组	姜黄素组	青蒿琥酯组	中药复合物组	阿托伐他汀钙组	高脂饲料组	F	P
斑块面积占比(%)	16.97±0.06¹⁾	15.41±1.18¹⁾	15.59±0.72¹⁾	15.28±0.87¹⁾	10.75±0.93	9.53±1.26	25.96±2.25¹⁾	88.827	<0.001
ALT(U/L)	34.68±6.82	36.52±6.39	37.58±6.38	39.44±3.84	36.40±7.01	57.56±5.64²⁾	42.89±5.33	8.623	<0.001
Cr（μmol/L）	38.60±6.19	42.60±8.02	43.00±5.92	42.80±4.76	40.60±7.57	41.20±5.07	41.20±8.47	0.269	0.947