Beneficial Herb-Drug Interaction of Shenqi Oral Liquid on Atorvastatin: A Pharmacokinetic and Pharmacodynamic Investigation in Rats with Hyperlipidemia

HU Xian-run; LI Man-lin; LIU Wen-kang; ZHANG Si-tong; LEI Jin-chun; WANG Jun-yi; Bahatijiang Mi-re-yi; CHENG Xue-mei; WANG Chang-hong

doi:10.1007/s11655-026-4031-1

Your Location：

Home >

Browse articles >

Beneficial Herb-Drug Interaction of Shenqi Oral Liquid on Atorvastatin: A Pharmacokinetic and Pharmacodynamic Investigation in Rats with Hyperlipidemia

Original Article | Updated：2026-11-13

- Beneficial Herb-Drug Interaction of Shenqi Oral Liquid on Atorvastatin: A Pharmacokinetic and Pharmacodynamic Investigation in Rats with Hyperlipidemia
- Chinese Journal of Integrative Medicine Vol. 32, Issue 11, Pages: 979-987(2026)
- Affiliations：
  
  Key Laboratory for Standardization of Chinese Medicines, Ministry of Education, Shanghai Key Laboratory for Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
- Author bio：
  
  Correspondence to: Prof. WANG Chang-hong, E-mail: wchcxm@shutcm.edu.cn
- Funds：
- DOI：10.1007/s11655-026-4031-1
  CLC：
- Accepted：10 September 2025，
  
  Published：2026-11
- Accepted：
Scan QR Code
HU Xian-run, LI Man-lin, LIU Wen-kang, et al. Beneficial Herb-Drug Interaction of Shenqi Oral Liquid on Atorvastatin: A Pharmacokinetic and Pharmacodynamic Investigation in Rats with Hyperlipidemia[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 979-987.
DOI：

HU Xian-run, LI Man-lin, LIU Wen-kang, et al. Beneficial Herb-Drug Interaction of Shenqi Oral Liquid on Atorvastatin: A Pharmacokinetic and Pharmacodynamic Investigation in Rats with Hyperlipidemia[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 979-987. DOI： 10.1007/s11655-026-4031-1.

摘要

目的：研究参芪口服液（SQ）与阿托伐他汀（ATV）在高脂血症大鼠中的药效学与药动学相互作用，探讨SQ对ATV相关转运体及代谢酶的调节作用，为两者临床联合用药的安全性和合理性提供实验依据。方法：采用高脂饮食诱导高脂血症大鼠模型，按血清总胆固醇水平随机分组。药效学研究中，大鼠分别给予ATV（10 mg/kg）、SQ（0.68、1.68、3.38 g/kg）及ATV联合SQ，连续灌胃4周，检测血脂、肝功能、肝脏组织病理学变化；药动学研究中，比较ATV单用与ATV联合SQ（1.68 g/kg）后ATV及其活性代谢物o-ATV、p-ATV的血药浓度和药动学参数；采用定量PCR检测空肠、回肠和肝脏中Bcrp、Mrp2、Oatp2b1、Oatp1b2、CYP3A2等表达，采用鸡尾酒探针法和原代大鼠肝细胞评价CYP2C11、CYP3A2活性及SQ活性成分的作用。结果：ATV联合SQ可显著改善高脂血症大鼠血脂水平，减轻肝细胞肿胀、脂滴蓄积和肝脏损伤，联合组调脂及保肝趋势优于ATV单用组。SQ显著提高ATV活性代谢物的全身暴露：o-ATV的Cmax和AUC0-t分别增加97.02%和119.01%，p-ATV分别增加73.22%和63.39%（均P<0.05）。机制上，SQ下调空肠Bcrp、Mrp2及回肠Oatp2b1、Bcrp、Mrp2表达，上调肝脏Oatp1b2和CYP3A2表达；并增强CYP2C11和CYP3A2酶活性。原代肝细胞实验显示，SQ、党参和黄芪提取物可剂量依赖性诱导CYP3A2 mRNA表达，党参苷I、党参炔苷和芒柄花苷为其潜在活性成分。结论：SQ与ATV联用具有增益性中药-药物相互作用，可通过调节药物转运体和代谢酶，协同改善脂质代谢并减轻肝脏损伤；同时可增加ATV活性代谢物暴露，提示临床联合用药时宜关注潜在相互作用并优化ATV剂量。

Abstract

Objective: To investigate the pharmacodynamic and pharmacokinetic interactions between Shenqi Oral Liquid (SQ) and atorvastatin (ATV) in hyperlipidemic rats

explore the impact of SQ on ATV-related transporters and metabolic enzymes

the potential implications for the safety and rationality of their combined administration based on pharmacodynamic

pharmacokinetic

transporter

and metabolic enzyme data. Methods: Hyperlipidemic rats were induced using a high-fat diet and randomized according to serum total cholesterol levels using a randomized block design into model

ATV (10 mg/kg)

SQ (0.68

1.68

3.38 g/kg)

and combination groups

and treated for 4 weeks. Serum lipid profiles

liver histopathological changes

pharmacokinetic parameters of ATV

mRNA expression levels of transporters (including Bcrp

Mrp2

etc.) and metabolic enzymes (CYP2C11

CYP3A2)

enzyme activities

as well as the effects of SQ's active ingredients were assessed using quantitative PCR

cocktail probe assays

and primary hepatocyte studies. Results: The combination therapy significantly reduced serum lipid levels and improved liver histology

as evidenced by a more organized cellular structure and reduced accumulation of lipid droplets. SQ significantly increased systemic exposure of ATV metabolites

elevating the maximum plasma concentration (C

max

) and area under the curve from time 0 to time t (AUC

0-t

) of o-ATV by 97.02% and 119.01%

and of p-ATV by 73.22% and 63.39%

respectively (all P＜0.05). SQ downregulated the e

xpressions of Bcrp and Mrp2 in the jejunum and Oatp2b1

Bcrp

and Mrp2 in the ileum

while upregulating Oatp1b2 and CYP3A2 in the liver (all P＜0.05). Additionally

it enhanced the enzymatic activities of CYP2C11 and CYP3A2

as shown by significantly reduced AUC

0-∞

of omeprazole (P＜0.01) and AUC

0-t

of midazolam (P＜0.05). Notably

tangshenoside Ⅰ

lobetyolin

and ononin were found to promote CYP3A2 mRNA expression (P＜0.05). Conclusions: SQ synergizes with ATV in lipid regulation and hepatoprotection through modulation of drug transporters and metabolic enzymes. These findings suggest that dose adjustment of ATV may be necessary during combination therapy

thereby providing a scientific basis for the rational co-administration of these agents.

关键词

Keywords

references

Karr S. Epidemiology and management of hyperlipidemia. Am J Manag Care 2017;23:S139-S148.

Adams S, Tsang M, Wright JM. Lipid-lowering efficacy of atorvastatin. Cochrane Database Syst Rev 2015;2015:CD008226.

Hu N, Chen C, Wang J, Huang J, Yao D, Li C. Atorvastatin ester regulates lipid metabolism in hyperlipidemia rats via the PPAR-signaling pathway and HMGCR expression in the liver. Int J Mol Sci 2021;22:11107.

Zhao Y, Yin J, Zhang L, Zhang Y, Chen X. Drug-drug interaction prediction: databases, web servers and computational models. Brief Bioinform 2023;25:bbad445.

Toth PP, Banach M. Statins: then and now. Methodist Debakey Cardiovasc J 2019;15:23-31.

National Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China. The first part of the 2020 ed. Beijing: China Medical Science and Technology Press; 2020:1215.

Feng LM, Du WX, Zhu MD, Zhang SQ, Zhang CY, Guo FJ. Effect of Qishen Yiqi Dropping Pills on L-FABP and A-FABP in hyperlipidemia with qi deficiency and blood stasis syndrome and its lipid-lowering effect. Liaoning J Tradit Chin Med (Chin) 2015;42:1267-1269.

Zhang J, Li BB, Huang MY, Tan LP, Xiao X, Zhang GM. Mechanism of Shenqi Jiangtang Granules in the treatment of type 2 diabetes mellitus based on network pharmacology. Chin Tradit Herbal Drugs (Chin) 2020;51:4873-4883.

Esteves F, Rueff J, Kranendonk M. The central role of cytochrome P450 in xenobiotic metabolism-a brief review on a fascinating enzyme family. J Xenobiot 2021;11:94-114.

Xiao M, Qian C, Luo X, Yang M, Zhang Y, Wu C. Impact of the Chinese herbal medicines on dual antiplatelet therapy with clopidogrel and aspirin: pharmacokinetics and pharmacodynamics outcomes and related mechanisms in rats. J Ethnopharmacol 2019;235:100-110.

Chen J, Chen R, Meng X, Yang ZF, Wang D, Lu WJ. Simultaneous determination of three index components in Codonopsis Pilosula by high-performance liquid chromatography. China Pharmaceut 2021;30:69-72.

Cui M, Zhu F, Yin Y, Sui Y, Yan X, Chen T. Influence of Gegenqinlian Decoction on pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemic rats. Eur J Drug Metab Pharmacokinet 2022;47:117-126.

Wu F, Cui M, Wang S, Yu C, Yin W, Li J. Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats. Xenobiotica 2023;53:644-652.

Zheng TH, Liu W, Li SP, Yang T, Wang CH, Liu CH. Effect of Fuzheng Huayu Formula on CYP450 enzyme in normal and hepatic fibrosis rats. China J Chin Mater Med (Chin) 2015;40:1166-1172.

Huang CS, Chen HW, Lin TY, Lin AH, Lii CK. Shikonin upregulates the expression of drug-metabolizing enzymes and drug transporters in primary rat hepatocytes. J Ethnopharmacol 2018;216:18-25.

Neuvonen PJ. Drug interactions with HMG-CoA reductase inhibitors (statins): the importance of CYP enzymes, transporters and pharmacogenetics. Curr Opin Investig Drugs 2010;11:323-332.

Khan AA, Ahmed S, Mohammed A, Elzouki ANY. Autoimmunelike drug-induced liver injury caused by atorvastatin and demonstration of the safety profile of pravastatin: a case report and literature review. Cureus 2020;12:e7299.

FULL TEXT LINK

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Mechanisms of Different Brainstem Nuclei Involved in Electroacupuncture-Induced Analgesia

Naoxueshu Oral Liquid Promotes Hematoma Absorption and Relieves Neurological Symptoms in Chronic Subdural Hematoma Patients: A Prospective, Single-Arm, Self-Controlled Study

Antidepressant and Anxiolytic Effects of Intranasal Curcumin in Parkinson's Disease Model Rats: Inhibition of Neuroinflammation and Oxidative Stress

Andrographolide Sulfonate Injection for Adjunctive Treatment of Non-severe Community-Acquired Pneumonia in Adults: A Multicenter, Double-Blind, Randomized Controlled Trial

Astragaloside Ⅳ Mitigates Subarachnoid Hemorrhage-Induced Brain Injury via Regulating Microglial Polarization and Neuroinflammation Mediated by cGAS/STING Pathway

Related Author

No data

Related Institution

No data

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰