Abstract
Purpose: Zhizi-Bopi decoction (ZZBPD) is a classic herbal formula with wide clinical applications in treating liver diseases including hepatitis B. However, the mechanism needs to be elucidated.
Methods: Chemical components of ZZBPD were identified by ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS). Then we used network pharmacology to identify their potential targets. Network construction, coupled with protein–protein interaction and enrichment analysis was used to identify representative components and core targets. Finally, molecular docking simulation was conducted to further refine the drug-target interaction.
Results: One hundred and forty-eight active compounds were identified in ZZBPD, targeting 779 genes/proteins, among which 174 were related to hepatitis B. ZZBPD mainly influences the progression of hepatitis B through the hepatitis B pathway (hsa05161) via core anti-HBV targets (AKT1, PIK3CA, PIK3R1, SRC, TNF, MAPK1, and MAPK3). Enrichment analysis indicated that ZZBPD can also potentially regulate lipid metabolism and enhance cell survival. Molecular docking suggested that the representative active compounds can bind to the core anti-HBV targets with high affinity.
Conclusion: The potential molecular mechanisms of ZZBPD in hepatitis B treatment were identified using network pharmacology and molecular docking approaches. The results serve as an important basis for the modernization of ZZBPD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The intermediate data supporting this paper’s findings are available from the authors upon reasonable request.
Abbreviations
- AKT1:
-
AKT Serine/Threonine Kinase 1
- BP:
-
Biological process
- CC:
-
Cell component;
- cccDNA:
-
Covalently closed circular DNA
- ERK:
-
Extracellular signal-regulated kinase
- FDR:
-
False discovery rate
- Gancao:
-
Dry rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.
- GO:
-
Gene ontology
- Huangbo:
-
Dry bark of Phellodendron chinense Schneid
- HBV:
-
Hepatitis B virus
- HCC:
-
Hepatocellular carcinoma
- HPLC:
-
High performance liquid chromatography
- IDA:
-
Information-dependent acquisition
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- MAPK:
-
Mitogen-activated protein kinase
- MCODE:
-
Molecular complex detection
- MF:
-
Molecular function
- OMIM:
-
Online Mendelian Inheritance in Man database
- PIK3CA:
-
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- PIK3R1:
-
Phosphatidylinositol 3-kinase regulatory subunit alpha
- SRC:
-
Proto-oncogene tyrosine-protein kinase Src
- PPI:
-
Protein–protein interaction
- RCSB:
-
Biological Macromolecular Structures Enabling Breakthroughs in Research and Education
- STAT3:
-
Signal Transducer and Activator of Transcription 3
- STRING:
-
Search Tool for the Retrieval of Interacting Genes/Proteins
- TCM:
-
Traditional Chinese medicine
- TCMSP:
-
Traditional Chinese Medicine System Pharmacology Database
- TNF:
-
Tumor necrosis factor
- TTD:
-
Terapeutic Target Database
- UHPLC-TOF-MS:
-
Ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry
- Zhizi:
-
Dry fruit of Gardenia jasminoides Ellis
- ZZBPD:
-
Zhizi-Bopi decoction
References
Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A (2014) OMIM.org: online mendelian inheritance in man (OMIM®) an online catalog of human genes and genetic disorders. Nucleic Acids Res. https://doi.org/10.1093/nar/gku1205
Bader GD, Hogue CWV (2003) An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform 4(1):2. https://doi.org/10.1186/1471-2105-4-2
Bardou P, Mariette J, Escudié F, Djemiel C, Klopp C (2014) jvenn: an interactive venn diagram viewer. BMC Bioinform 15(1):293. https://doi.org/10.1186/1471-2105-15-293
Brenner D, Blaser H, Mak TW (2015) Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15(6):362–374. https://doi.org/10.1038/nri3834
Burley SK, Bhikadiya C, Bi C, Bittrich S, Chen L, Crichlow GV, Christie CH, Dalenberg K, Di Costanzo L, Duarte JM, Dutta S, Feng Z, Ganesan S, Goodsell DS, Ghosh S, Green RK, Guranović V, Guzenko D, Hudson BP, Lawson Catherine L, Liang Y, Lowe R, Namkoong H, Peisach E, Persikova I, Randle C, Rose A, Rose Y, Sali A, Segura J, Sekharan M, Shao C, Tao Y-P, Voigt M, Westbrook John D, Young JY, Zardecki C, Zhuravleva M (2020) RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. Nucleic Acids Res 49(D1):D437–D451. https://doi.org/10.1093/nar/gkaa1038
Cao X, Sun L, Li D, You G, Wang M, Ren X (2018) Quality evaluation of Phellodendri Chinensis cortex by fingerprint-chemical pattern recognition. Molecules 23(9):2307. https://doi.org/10.3390/molecules23092307
Carvalho-Silva D, Pierleoni A, Pignatelli M, Ong C, Fumis L, Karamanis N, Carmona M, Faulconbridge A, Hercules A, McAuley E, Miranda A, Peat G, Spitzer M, Barrett J, Hulcoop DG, Papa E, Koscielny G, Dunham I (2019) Open targets platform: new developments and updates two years on. Nucleic Acids Res 47(D1):D1056–D1065. https://doi.org/10.1093/nar/gky1133
Chen G, Seukep AJ, Guo M (2020a) Recent advances in molecular docking for the research and discovery of potential marine drugs. Mar Drugs 18(11):545. https://doi.org/10.3390/md18110545
Chen L, Li M, Yang Z, Tao W, Wang P, Tian X, Li X, Wang W (2020b) Gardenia jasminoides Ellis: ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional Chinese medicine. J Ethnopharmacol 257:112829. https://doi.org/10.1016/j.jep.2020.112829
Chin R, Earnest-Silveira L, Koeberlein B, Franz S, Zentgraf H, Dong X, Gowans E, Bock CT, Torresi J (2007) Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus: factors contributing to hepatocarcinogenesis. J Hepatol 47(3):325–337. https://doi.org/10.1016/j.jhep.2007.03.025
Chung T-W, Lee Y-C, Kim C-H (2004) Hepatitis B viral HBx induces matrix metalloproteinase-9 gene expression through activation of ERKs and PI-3K/AKT pathways: involvement of invasive potential. FASEB J 18(10):1123–1125. https://doi.org/10.1096/fj.03-1429fje
Cui X, Wang Y, Kokudo N, Fang D, Tang W (2010) Traditional Chinese medicine and related active compounds against hepatitis B virus infection. Biosci Trends 4(2):39–47
Daina A, Michielin O, Zoete V (2019) SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 47(W1):W357–W364. https://doi.org/10.1093/nar/gkz382
Fan S, Zhang C, Luo T, Wang J, Tang Y, Chen Z, Yu L (2019) Limonin: a review of its pharmacology, toxicity, and pharmacokinetics. Molecules 24(20):3679. https://doi.org/10.3390/molecules24203679
Fang Z, Luo Z, Ji Y, Yang R, Gao J, Zhang N (2022) A network pharmacology technique used to investigate the potential mechanism of Ligustilide’s effect on atherosclerosis. J Food Biochem. https://doi.org/10.1111/jfbc.14146
Fanning GC, Zoulim F, Hou J, Bertoletti A (2019) Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov 18(11):827–844. https://doi.org/10.1038/s41573-019-0037-0
Gao X, Wang W, Wei S, Li W (2009) Review of pharmacological effects of Glycyrrhiza radix and its bioactive compounds. Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China J Chinese Mater Med 34(21):2695–2700. https://doi.org/10.3321/j.issn:1001-5302.2009.21.001
Hers I, Vincent EE, Tavaré JM (2011) Akt signalling in health and disease. Cell Signal 23(10):1515–1527. https://doi.org/10.1016/j.cellsig.2011.05.004
Hopkins AL (2007) Network pharmacology. Nat Biotechnol 25(10):1110–1111. https://doi.org/10.1038/nbt1007-1110
Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4(11):682–690. https://doi.org/10.1038/nchembio.118
Iannacone M, Guidotti LG (2022) Immunobiology and pathogenesis of hepatitis B virus infection. Nat Rev Immunol 22(1):19–32. https://doi.org/10.1038/s41577-021-00549-4
Jiang M, Zhao S, Yang S, Lin X, He X, Wei X, Song Q, Li R, Fu C, Zhang J, Zhang Z (2020) An essential herbal medicine—licorice: a review of phytochemicals and its effects in combination preparations. J Ethnopharmacol 249:112439. https://doi.org/10.1016/j.jep.2019.112439
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M (2020) KEGG: integrating viruses and cellular organisms. Nucleic Acids Res 49(D1):D545–D551. https://doi.org/10.1093/nar/gkaa970
Li S (2007) Framework and practice of network-based studies for Chinese herbal formula. Zhong Xi Yi Jie He Xue Bao = J Chinese Integr Med 5(5):489–493. https://doi.org/10.3736/jcim20070501
Li S, Zhang B (2013) Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 11(2):110–120. https://doi.org/10.3724/sp.J.1009.2013.00110
Li N, Zhou T, Wu F, Wang R, Zhao Q, Zhang J-Q, Yang B-C, Ma B-L (2019) Pharmacokinetic mechanisms underlying the detoxification effect of Glycyrrhizae Radix et Rhizoma (Gancao): drug metabolizing enzymes, transporters, and beyond. Expert Opin Drug Metab Toxicol 15(2):167–177. https://doi.org/10.1080/17425255.2019.1563595
Li S, Ding Q, Wang X (2021) “Network Target” Theory and Network Pharmacology. In: Li S (ed) Network Pharmacology. Springer, Singapore. https://doi.org/10.1007/978-981-16-0753-0_1
Liu W, Guo T-F, Jing Z-T, Yang Z, Liu L, Yang Y-P, Lin X, Tong Q-Y (2018) Hepatitis B virus core protein promotes hepatocarcinogenesis by enhancing Src expression and activating the Src/PI3K/Akt pathway. FASEB J 32(6):3033–3046. https://doi.org/10.1096/fj.201701144R
Liu SX, Li QD, Liu FZ, Cao H, Liu J, Shan JY, Dan WC, Yuan JY, Lin J (2021) Uncovering the mechanism of curcuma in the treatment of Ulcerative Colitis based on network pharmacology, molecular docking technology, and experiment verification. Evid-Based Complement Altern Med. https://doi.org/10.1155/2021/6629761
Lok ASF, McMahon BJ, Brown RS, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K (2016) Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology 63(1):284–306. https://doi.org/10.1002/hep.28280
Lok AS, Zoulim F, Dusheiko G, Ghany MG (2017) Hepatitis B cure: from discovery to regulatory approval. Hepatology 66(4):1296–1313. https://doi.org/10.1002/hep.29323
Lou W, Liu J, Ding B, Chen D, Xu L, Ding J, Jiang D, Zhou L, Zheng S, Fan W (2019) Identification of potential miRNA–mRNA regulatory network contributing to pathogenesis of HBV-related HCC. J Transl Med 17(1):1–14. https://doi.org/10.1186/s12967-018-1761-7
Meng XY, Zhang HX, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7(2):146–157. https://doi.org/10.2174/157340911795677602
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 30(16):2785–2791. https://doi.org/10.1002/jcc.21256
Mubeen S, Hoyt CT, Gemund A, Hofmann-Apitius M, Frohlich H, Domingo-Fernandez D (2019) The impact of pathway database choice on statistical enrichment analysis and predictive modeling. Front Gene. https://doi.org/10.3389/fgene.2019.01203
Oh KK, Adnan M, Cho DH (2021) A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of atherosclerosis. J Food Biochem 45(9):e13906. https://doi.org/10.1111/jfbc.13906
Otasek D, Morris JH, Bouças J, Pico AR, Demchak B (2019) Cytoscape automation: empowering workflow-based network analysis. Genome Biol 20(1):185. https://doi.org/10.1186/s13059-019-1758-4
Panteva M, Korkaya H, Jameel S (2003) Hepatitis viruses and the MAPK pathway: is this a survival strategy? Virus Res 92(2):131–140. https://doi.org/10.1016/S0168-1702(02)00356-8
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—A visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612. https://doi.org/10.1002/jcc.20084
Piñero J, Ramírez-Anguita JM, Saüch-Pitarch J, Ronzano F, Centeno E, Sanz F, Furlong LI (2019) The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res 48(D1):D845–D855. https://doi.org/10.1093/nar/gkz1021
Rawat S, Bouchard MJ (2015) The hepatitis B virus (HBV) HBx protein activates AKT to simultaneously regulate HBV replication and hepatocyte survival. J Virol 89(2):999–1012. https://doi.org/10.1128/JVI.02440-14
Roohbakhsh A, Iranshahy M, Iranshahi M (2016) Glycyrrhetinic acid and its derivatives: anti-cancer and cancer chemopreventive properties, mechanisms of action and structure-cytotoxic activity relationship. Curr Med Chem 23(5):498–517. https://doi.org/10.2174/0929867323666160112122256
Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y (2014) TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 6(1):1–6. https://doi.org/10.1186/1758-2946-6-13
Seto W-K, Lo Y-R, Pawlotsky J-M, Yuen M-F (2018) Chronic hepatitis B virus infection. The Lancet 392(10161):2313–2324. https://doi.org/10.1016/S0140-6736(18)31865-8
Shang Z, Liu C, Qiao X, Ye M (2022) Chemical analysis of the Chinese herbal medicine licorice (Gan-Cao): an update review. J Ethnopharmacol 299:115686. https://doi.org/10.1016/j.jep.2022.115686
Shi X, Yu L, Zhang Y, Liu Z, Zhang H, Zhang Y, Liu P, Du P (2020) Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway. Int Immunopharmacol 84:106578. https://doi.org/10.1016/j.intimp.2020.106578
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D (2016) The genecards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 54(1):1.30.31-31.30.33. https://doi.org/10.1002/cpbi.5
Sun Y, Liu W-Z, Liu T, Feng X, Yang N, Zhou H-F (2015) Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct 35(6):600–604. https://doi.org/10.3109/10799893.2015.1030412
Sun Y, Lenon GB, Yang AWH (2019) Phellodendri cortex: a phytochemical, pharmacological, and pharmacokinetic review. Evid-Based Complement and Altern Med 2019:7621929. https://doi.org/10.1155/2019/7621929
Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P, Jensen LJ, von Mering C (2020) The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 49(D1):D605–D612. https://doi.org/10.1093/nar/gkaa1074
Tang LS, Covert E, Wilson E, Kottilil S (2018) Chronic hepatitis B infection: a review. JAMA 319(17):1802
Tarabasz D, Kukula-Koch W (2020) Palmatine: a review of pharmacological properties and pharmacokinetics. Phytother Res 34(1):33–50. https://doi.org/10.1002/ptr.6504
Tian J, Qin S, Han J, Meng J, Liang A (2022) A review of the ethnopharmacology, phytochemistry, pharmacology and toxicology of Fructus Gardeniae (Zhi-zi). J Ethnopharmacol 289:114984. https://doi.org/10.1016/j.jep.2022.114984
Tornesello ML, Buonaguro L, Tatangelo F, Botti G, Izzo F, Buonaguro FM (2013) Mutations in TP53, CTNNB1 and PIK3CA genes in hepatocellular carcinoma associated with hepatitis B and hepatitis C virus infections. Genomics 102(2):74–83. https://doi.org/10.1016/j.ygeno.2013.04.001
Trott O, Olson AJ (2010) Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2):455–461. https://doi.org/10.1002/jcc.21334
Tsai D-S, Huang M-H, Chang Y-S, Li T-C, Peng W-H (2015) The use of Chinese herbal medicines associated with reduced mortality in chronic hepatitis B patients receiving lamivudine treatment. J Ethnopharmacol 174:161–167. https://doi.org/10.1016/j.jep.2015.08.002
UniProt Consortium T (2018) UniProt: the universal protein knowledgebase. Nucleic Acids Res 46(5):2699–2699. https://doi.org/10.1093/nar/gky092
Wang G, Zhang L, Bonkovsky HL (2012) Chinese medicine for treatment of chronic hepatitis B. Chin J Integr Med 18(4):253–255. https://doi.org/10.1007/s11655-012-1064-4
Wang Y, Zhang S, Li F, Zhou Y, Zhang Y, Wang Z, Zhang R, Zhu J, Ren Y, Tan Y, Qin C, Li Y, Li X, Chen Y, Zhu F (2020) Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res 48(D1):D1031–D1041. https://doi.org/10.1093/nar/gkz981
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M (2017) DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 46(D1):D1074–D1082. https://doi.org/10.1093/nar/gkx1037
Xia JF, Inagaki Y, Song P, Sawakami T, Kokudo N, Hasegawa K, Sakamoto Y, Tang W (2016) Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus. Biosci Trends 10(5):327–336. https://doi.org/10.5582/bst.2016.01110
Xia Y, Cheng X, Li Y, Valdez K, Chen W, Liang TJ, Ou J-HJ (2018) Hepatitis B virus deregulates the cell cycle to promote viral replication and a premalignant phenotype. J Virol 92(19):e00722-e1718. https://doi.org/10.1128/JVI.00722-18
Xiang K, Wang B (2018) Role of the PI3K-AKT-mTOR pathway in hepatitis B virus infection and replication. Mol Med Rep 17(3):4713–4719. https://doi.org/10.3892/mmr.2018.8395
Xiao X, Zhu J-X, Luo G-M, Li L, Zhu Y-Y, Zeng J-X, Wang X-Y, Wu B (2013) Study on the liver-protective and choleretic effect of zhizi baipi soup and its disassembled prescription. Zhong Yao Cai = Zhongyaocai J Chinese Med Mater 36(7):1132–1135
Xu J, Wang F, Guo J, Xu C, Cao Y, Fang Z, Wang Q (2020) Pharmacological mechanisms underlying the neuroprotective effects of Alpinia oxyphylla Miq. on Alzheimer’s disease. Int J Mol Sci 21(6):2071. https://doi.org/10.3390/ijms21062071
Ye YA, Li XK, Zhou DQ, Chi XL, Qin L, Li W, Lu BJ, Mao DW, Wu QK, Wang XB, Zhang MX, Xue JD, Yong L, Lu W, Guo JC, Jiang F, Zhang XW, Du HB, Yang XZ, Guo H, Gan DN, Li ZG (2018) Chinese herbal medicine combined with Entecavir for HBeAg positive chronic hepatitis B: study protocol for a multi-center, double-blind randomized-controlled trial. Chin J Integr Med 24(9):653–660. https://doi.org/10.1007/s11655-018-3011-5
Yuan H, Ma Q, Cui H, Liu G, Zhao X, Li W, Piao G (2017) How can synergism of traditional medicines benefit from network pharmacology? Molecules 22(7):1135. https://doi.org/10.3390/molecules22071135
Yun WY, Dan WC, Liu JL, Guo XY, Li M, He QY (2021) Investigation of the mechanism of traditional Chinese medicines in angiogenesis through network pharmacology and data mining. Evid-Based Complement Altern Med. https://doi.org/10.1155/2021/5539970
Zhang Z (2020) Shang Han Lun of Song, dynastic. Beijing Science and Technology Press, Beijing
Zhang L, Wang G, Hou W, Li P, Dulin A, Bonkovsky HL (2010) Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: an analytical review. Hepatology 51(2):690–698. https://doi.org/10.1002/hep.23384
Zhang J, Ling N, Lei Y, Peng M, Hu P, Chen M (2021) Multifaceted interaction between hepatitis B virus infection and lipid metabolism in hepatocytes: a potential target of antiviral therapy for chronic hepatitis B. Front Microbiol. https://doi.org/10.3389/fmicb.2021.636897
Zhao Q, Ren X, Chen M, Yue S-J, Zhang M-Q, Chen K-X, Guo Y-W, Shao C-L, Wang C-Y (2019) Effects of traditional Chinese medicine formula Le-Cao-Shi on hepatitis B: in vivo and in vitro studies. J Ethnopharmacol 244:112132. https://doi.org/10.1016/j.jep.2019.112132
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10(1):1523. https://doi.org/10.1038/s41467-019-09234-6
Acknowledgements
We appreciate Dr. Sujun Chen for her generous help with draft modification advice. We also acknowledge OriginLab Corporation and Axure Software Solutions Inc. for their offer of software for educational use.
Funding
This research was supported by the P.R.C State Administration of Traditional Chinese Medicine Project [No. LPGZS2012-34].
Author information
Authors and Affiliations
Contributions
HZ: conceptualization, methodology, investigation, visualization, and original draft writing. ZX: investigation. HG: writing—reviewing and editing. QZ: supervision and project administration. All authors have read and approved the final version manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhang, H., Xu, Z., Gao, H. et al. Systematic analysis on the mechanism of Zhizi-Bopi decoction against hepatitis B via network pharmacology and molecular docking. Biotechnol Lett 45, 463–478 (2023). https://doi.org/10.1007/s10529-023-03359-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-023-03359-x