Network pharmacology strategy to investigate the pharmacological effects of Suanzaoren Decoction on insomnia


  • Xiaojian Weng Quzhou Municipal Hospital Of TCM, Quzhou, Zhejiang 324000, P.R. China
  • Jimin Jiang Quzhou Municipal Hospital Of TCM, Quzhou, Zhejiang 324000, P.R. China
  • Hailong Li Zhejiang University of Technology
  • Yi Tan The First People’s Hospital Of Hangzhou Lin An District



Suanzaoren Decoction, Insomnia, Network pharmacology


Suanzaoren Decoction (SZRD) is an ancient prescription used in the treatment of insomnia. This study aimed to investigate the components and targets of SZRD in treating insomnia. First, the compounds of five herbs in SZRD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the putative targets for treating insomnia were obtained from DrugBank to construct the herb-compound-target- disease network. A protein-protein interaction (PPI) network was constructed in the STRING database, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the mechanism of action of intersection target. Finally, 30 mice were divided into five groups: control, model, and quercetin groups (100, 50, 25 mg/kg). The sleep latency and duration of pentobarbital-induced sleeping were measured. The production of interleukin-6 (IL-6) and γ-aminobutyric acid (γ-GABA) was detected by using an enzyme-linked immunosorbent assay kit (ELISA), and Gamma-aminobutyric acid type a receptor subunit alpha1 (GABRA1) was tested by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). A total of 152 active ingredients, including 80 putative targets of SZRD, were obtained. The main active compounds included quercetin and kaempferol, and the key targets involved IL-6 and nitric oxide synthase 3 (NOS3). The results of pathway enrichment analysis indicated that the putative targets of SZRD mainly participated in Neuroactive ligand-receptor interaction. The experiment of P-chlorophenylalanine (PCPA)-induced insomnia model showed that quercetin obviously shortened the sleep latency and prolonged the sleep duration of the insomnia model. The production of IL-6, γ-GABA, and GABRA1 mRNA was significantly increased in mice treated with quercetin. This study predicted the active ingredients and potential targets of SZRD on insomnia on the basis of a systematic network pharmacology approach and illustrated that SZRD might exert hypnotic effects via regulating IL-6, γ-GABA, and GABRA1.


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Afrasiabian F, Mirabzadeh Ardakani M, Rahmani K, Azadi NA, Alemohammad ZB, Bidaki R, et al. Aloysia citriodora Palau (lemon verbena) for insomnia patients: A randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Phytother Res. 2019;33(2):350-359. Epub 2018/11/20.

Berger SI, Iyengar R. Network analyses in systems pharmacology. Bioinformatics. 2009;25(19):2466-2472. Epub 2009/08/04.

Bigelman KA, Chapman DP, Freese EC, Trilk JL, Cureton KJ. Effects of 6 weeks of quercetin supplementation on energy, fatigue, and sleep in ROTC cadets. Mil Med. 2011;176(5):565-572. Epub 2011/06/04.

Costa LG, Garrick JM, Roque PJ, Pellacani C. 2016. Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More. Oxid Med Cell Longev. 2016:2986796. Epub 2016/02/24.

Dixon CL, Harrison NL, Lynch JW, Keramidas A. Zolpidem and eszopiclone prime alpha1beta2gamma2 GABAA receptors for longer duration of activity. Br J Pharmacol. 2015;172(14):3522-3536. Epub 2015/03/31.

Halota W, Lapniewska E, Trzcinski J, Opoka J. [Errors in the diagnosis of chronic intrahepatic cholestasis]. Wiad Lek. 1990;43(14):697-702. Epub 1990/07/15.

Janto K, Prichard JR, Pusalavidyasagar S. An Update on Dual Orexin Receptor Antagonists and Their Potential Role in Insomnia Therapeutics. J Clin Sleep Med. 2018;14(8):1399-1408. Epub 2018/08/11.

Kambe D, Kotani M, Yoshimoto M, Kaku S, Chaki S, Honda K. Effects of quercetin on the sleep-wake cycle in rats: involvement of gamma-aminobutyric acid receptor type A in regulation of rapid eye movement sleep. Brain Res. 2010;1330:83-88. Epub 2010/03/23.

Kanazawa LKS, Vecchia DD, Wendler EM, Hocayen PAS, Dos Reis Livero FA, Stipp MC, Barcaro IMR, Acco A, Andreatini R. Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice. Free Radic Biol Med. 2016; 99:79-86. Epub 2016/10/23.

Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, Roth T. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003;26(7):793-799. Epub 2003/12/06.

Lee AY, Park W, Kang TW, Cha MH, Chun JM. Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. J Ethnopharmacol. 2018;221:151-159. Epub 2018/04/27.

Li F, Xu B, Shi H, Zhang T, Song Z, Chen Y, Liu L, Wang P. Efficacy and safety of TCM Yangxin Anshen Therapy for insomnia: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99(8):e19330. Epub 2020/02/23.

Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013;11(2):110-120. Epub 2013/06/22.

Liu QQ, Zhang J, Guo RJ, Xie YZ, Fu QN, He T, et al. Efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule on primary insomnia: study protocol for a randomised controlled trial. BMJ Open. 2016;6(2);6:e008459. Epub 2016/02/04.

McKernan RM, Whiting PJ. Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci. 1996;19(4):139-143. Epub 1996/04/01.

Mohler H, Fritschy JM, Rudolph U. A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002;300(1):2-8. Epub 2001/12/26.

Ossola B, Kaariainen TM, Mannisto PT. The multiple faces of quercetin in neuroprotection. Expert Opin Drug Saf. 2009;8(4):397-409. Epub 2009/06/23.

Qing C, Weikai W. Study on Chemical Constituents of Zizyphus jujube Seed. Journal of Pharmaceutical Practice; 2009;27(3):209-213. Epub 2009/06//04

Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365-386. Epub 1999/11/05.

Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13. Epub 2014/04/17.

Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med . 2017;13(2):307-349. Epub 2016/12/22.

Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med . 2008;4(5):487-504. Epub 2008/10/16.

Shearer WT, Reuben JM, Mullington JM, Price NJ, Lee BN, Smith EO, et al. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol. 2001;107(1):165-170. Epub 2001/01/10.

Singh A, Zhao K. Treatment of Insomnia With Traditional Chinese Herbal Medicine . Int Rev Neurobiol. 2017;135:97-115. Epub 2017/08/16.

Song Z, Fan P, Zhang Q, Yang Y, Zhan Q, Liu X, Xiong Y. Suan-Zao-Ren decoction for insomnia: A protocol for a systematic review and meta-analysis. Medicine (Baltimore). 2020;99(34):e21658. Epub 2020/08/28.

Spadoni G, Bedini A, Rivara S, Mor M. 2011. Melatonin receptor agonists: new options for insomnia and depression treatment. CNS Neurosci Ther. 2011;17(6):733-741. Epub 2011/05/11.

Spira AP, Kaufmann CN, Kasper JD, Ohayon MM, Rebok GW, Skidmore E, et al. Association between insomnia symptoms and functional status in U.S. older adults. J Gerontol B Psychol Sci Soc Sci. 2014;69(Suppl 1):S35-41. Epub 2014/10/25.

Thimgan MS, Gottschalk L, Toedebusch C, McLeland J, Rechtschaffen A, Gilliland-Roberts M, et al. Cross-translational studies in human and Drosophila identify markers of sleep loss. PLoS One. 2013;8(4):e61016. Epub 2013/05/03.

Xu Y, Li X, Man D, Su X, A G. iTRAQ-based proteomics analysis on insomnia rats treated with Mongolian medical warm acupuncture. Biosci Rep. 2020;40(5):40. Epub 2020/04/07.

Ye MF, Liu Z, Lou SF, Chen ZY, Yu AY, Liu CY, et al. Flos Albiziae aqueous extract and its active constituent quercetin potentiate the hypnotic effect of pentobarbital via the serotonergic system. Biomed Rep. 2015;3(6):835-838. Epub 2015/12/02.

Yu G, Wang W, Wang X, Xu M, Zhang L, Ding L, Guo R, Shi Y. Network pharmacology-based strategy to investigate pharmacological mechanisms of Zuojinwan for treatment of gastritis. BMC Complementary Altern Med. 2018;18(1):292. Epub 2018/11/02.

Zhan LH, Dong YJ, Yang K, Lei SS, Li B, Teng X, et al. Soporific Effect of Modified Suanzaoren Decoction and Its Effects on the Expression of CCK-8 and Orexin-A. Evid Based Complementary Alternat. 2020:6984087. Epub 2020/07/04.

Zijun G, Shunli T, Yan H, Jinlong Z, Guomin C, Jiameng Z, et al. Prediction of active components and target pathway analysis of suanzaoren decoction in treating insomnia. China J Tradit Chin Med Pharm. 2018;33(8):3595-3590. Epub 2018/6/23.




How to Cite

Xiaojian Weng, Jimin Jiang, Hailong Li, & Yi Tan. (2023). Network pharmacology strategy to investigate the pharmacological effects of Suanzaoren Decoction on insomnia. Brazilian Journal of Pharmaceutical Sciences, 59, e21182.



Original Article