Network Pharmacology: An Emphasis on Traditional Chinese Medicines and Its Adaptability for Ayurveda Medicines in India

Main Article Content

Neela Bhatia
Asma Mokashi
Nazeen Nathore
Aliraza Nathore

Abstract

Network pharmacology is expanding as a comprehensive paradigm and becoming a breakthrough research topic of pharmaceutical research by providing an extraordinary potential for the comprehensive examination of conventional treatments. The development of network pharmacology has paved the way for the implementation of the complex phytochemical constituents found in diverse natural products. Network pharmacology is a burgeoning field of study that has linked its legs not just to Traditional Chinese Medicine, but also to other natural products, herbs, and ayurvedic medicine. By being a multidisciplinary area that includes network biology, system pharmacology, and even omics, it has demonstrated its unimaginable potential for future research. It is, in particular, a network-based science. Natural products have long served an important role in the advancement of pharmaceutical research, with all the supplementary immense expertise that has yet to be demonstrated, which can be established with the help of this application, which in turn may demonstrate the potential of these natural products to be multitargets, multicomponent characteristics of them rather than the solitary target that is becoming a dilemma in developing drugs. In this review paper, we summarised the notion of network pharmacology and discussed the newer features of how this concept might be used to natural products as well as drug discovery.

Article Details

How to Cite
Bhatia, N. ., Mokashi, A., Nathore, N., & Nathore, A. . (2022). Network Pharmacology: An Emphasis on Traditional Chinese Medicines and Its Adaptability for Ayurveda Medicines in India. International Journal of Medical Science and Clinical Research Studies, 2(12), 1608–1620. https://doi.org/10.47191/ijmscrs/v2-i12-40
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References

I. Burger A. Approaches to drug discovery. New England Journal of Medicine. 1964;270(21):1098–101.

II. Zeng X, Zhu S, Liu X, Zhou Y, Nussinov R, Cheng F. DeepDR: A network-based deep learning approach to in Silico Drug Repositioning. Bioinformatics. 2019;35(24):5191–8.

III. Zhou W, Wang Y, Lu A, Zhang G. Systems pharmacology in small molecular drug discovery. International Journal of Molecular Sciences. 2016;17(2):246.

IV. Buriani A, Garcia-Bermejo ML, Bosisio E, Xu Q, Li H, Dong X, et al. OMIC techniques in systems biology approaches to traditional Chinese medicine research: Present and future. Journal of Ethnopharmacology. 2012;140(3):535–44.

V. Yuan H, Ma Q, Cui H, Liu G, Zhao X, Li W, et al. How can synergism of traditional medicines benefit from network pharmacology? Molecules. 2017;22(7):1135.

VI. Gogoi B, Gogoi D, Silla Y, Kakoti BB, Bhau BS. Network pharmacology-based virtual screening of natural products from Clerodendrum species for identification of novel anti-cancer therapeutics. Molecular BioSystems. 2017;13(2):406–16.

VII. Gu J, Gui Y, Chen L, Yuan G, Lu H-Z, Xu X. Use of natural products as Chemical Library for drug discovery and network pharmacology. PLoS ONE. 2013;8(4).

VIII. Thomford N, Senthebane D, Rowe A, Munro D, Seele P, Maroyi A, et al. Natural products for drug discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences. 2018;19(6):1578.

IX. Lai X, Wang X, Hu Y, Su S, Li W, Li S. Editorial: Network Pharmacology and traditional medicine. Frontiers in Pharmacology. 2020;11.

X. Hopkins AL. Network pharmacology. Nature Biotechnology. 2007;25(10):1110–1.

XI. LI S, ZHANG B. Traditional Chinese Medicine Network Pharmacology: Theory, methodology and application. Chinese Journal of Natural Medicines. 2014;11(2):110–20.

XII. Chen Y, Bi F, Sun Z. A network pharmacology approach to determine the underlying mechanisms of action of Yishen Tongluo formula for the treatment of oligoasthenozoospermia. PLOS ONE. 2021;16(6).

XIII. Li R, Li Y, Liang X, Yang L, Su M, Lai KP. Network pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets. Briefings in Bioinformatics. 2020;22(2):1279–90.

XIV. Rai A, Kumar V, Jerath G, Kartha CC, Ramakrishnan V. Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy. npj Systems Biology and Applications. 2021;7(1).

XV. Yang M, Chen J-L, Xu L-W, Ji G. Navigating traditional chinese medicine network pharmacology and computational tools. Evidence-Based Complementary and Alternative Medicine. 2013;2013:1–23.

XVI. Azmi AS. Network pharmacology for Cancer Drug Discovery: Are we there yet? Future Medicinal Chemistry. 2012;4(8):939–41.

XVII. Rai A, Kumar V, Jerath G, Kartha CC, Ramakrishnan V. Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy. npj Systems Biology and Applications. 2021;7(1).

XVIII. Ning K, Zhao X, Poetsch A, Chen WH, Yang J. Computational Molecular Networks and Network Pharmacology. Biomed Res Int. 2017;2017:7573904. doi: 10.1155/2017/7573904. Epub 2017 Nov 8. PMID: 29250548; PMCID: PMC5698785.

XIX. Xinqiang S, Yu Z, Ningning Y, Erqin D, Lei W, Hongtao D. Molecular mechanism of celastrol in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking technology. Life Sci. 2020 Jan 1;240:117063. doi: 10.1016/j.lfs.2019.117063. Epub 2019 Nov 14. PMID: 31734262.

XX. Maron BA, Altucci L, Balligand JL, Baumbach J, Ferdinandy P, Filetti S, Parini P, Petrillo E, Silverman EK, Barabási AL, Loscalzo J; International Network Medicine Consortium. A global network for network medicine. NPJ Syst Biol Appl. 2020 Aug 31;6(1):29. doi: 10.1038/s41540-020-00143-9. PMID: 32868765; PMCID: PMC7459285.

XXI. Chopra B, Dhingra AK. Natural products: A lead for drug discovery and development. Phytother Res. 2021 Sep;35(9):4660-4702. doi: 10.1002/ptr.7099. Epub 2021 Apr 13. PMID: 33847440.

XXII. Rodrigues T, Reker D, Schneider P, Schneider G. Counting on natural products for drug design. Nat Chem. 2016 Jun;8(6):531-41. doi: 10.1038/nchem.2479. Epub 2016 Apr 25. PMID: 27219696.

XXIII. Gu J, Gui Y, Chen L, Yuan G, Lu H-Z, Xu X. Use of natural products as Chemical Library for drug discovery and network pharmacology. PLoS ONE. 2013;8(4).

XXIV. Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network pharmacology. Innovative Approaches in Drug Discovery. 2017;:127–64.

XXV. Atanasov AG, Zotchev SB, Dirsch VM; International Natural Product Sciences Taskforce, Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021 Mar;20(3):200-216. doi: 10.1038/s41573-020-00114-z. Epub 2021 Jan 28. PMID: 33510482; PMCID: PMC7841765.

XXVI. Vallance P, Smart TG. The future of pharmacology. Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S304-7. doi: 10.1038/sj.bjp.0706454. PMID: 16402118; PMCID: PMC1760753.

XXVII. Winquist RJ, Mullane K, Williams M. The fall and rise of pharmacology--(re-)defining the discipline? Biochem Pharmacol. 2014 Jan 1;87(1):4-24. doi: 10.1016/j.bcp.2013.09.011. Epub 2013 Sep 23. PMID: 24070656.

XXVIII. Fotis C, Antoranz A, Hatziavramidis D, Sakellaropoulos T, Alexopoulos LG. Network-based technologies for early drug discovery. Drug Discov Today. 2018 Mar;23(3):626-635. doi: 10.1016/j.drudis.2017.12.001. Epub 2017 Dec 30. PMID: 29294361.

XXIX. Leung EL, Cao ZW, Jiang ZH, Zhou H, Liu L. Network-based drug discovery by integrating systems biology and computational technologies. Brief Bioinform. 2013 Jul;14(4):491-505. doi: 10.1093/bib/bbs043. Epub 2012 Aug 9. PMID: 22877768; PMCID: PMC3713711.

XXX. Koutrouli M, Karatzas E, Paez-Espino D, Pavlopoulos GA. A Guide to Conquer the Biological Network Era Using Graph Theory. Front Bioeng Biotechnol. 2020 Jan 31;8:34. doi: 10.3389/fbioe.2020.00034. PMID: 32083072; PMCID: PMC7004966.

XXXI. Emmert-Streib F, Dehmer M. Biological networks: the microscope of the twenty-first century? Front Genet. 2015 Oct 13;6:307. doi: 10.3389/fgene.2015.00307. PMID: 26528327; PMCID: PMC4602153.

XXXII. Barabási AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet. 2011 Jan;12(1):56-68. doi: 10.1038/nrg2918. PMID: 21164525; PMCID: PMC3140052.

XXXIII. Tavassoly I, Goldfarb J, Iyengar R. Systems biology primer: The basic methods and approaches. Essays in Biochemistry. 2018;62(4):487–500.

XXXIV. Berger SI, Iyengar R. Network analyses in systems pharmacology. Bioinformatics. 2009 Oct 1;25(19):2466-72. doi: 10.1093/bioinformatics/btp465. Epub 2009 Jul 30. PMID: 19648136; PMCID: PMC2752618.

XXXV. Yadav BS, Tripathi V. Recent advances in the system biology-based target identification and Drug Discovery. Current Topics in Medicinal Chemistry. 2018;18(20):1737–44.

XXXVI. Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network pharmacology. Innovative Approaches in Drug Discovery. 2017;:127–64.

XXXVII. Anighoro A, Bajorath J, Rastelli G. Polypharmacology: challenges and opportunities in drug discovery. J Med Chem. 2014 Oct 9;57(19):7874-87. doi: 10.1021/jm5006463. Epub 2014 Jun 25. PMID: 24946140.

XXXVIII. Chaudhari R, Tan Z, Huang B, Zhang S. Computational polypharmacology: a new paradigm for drug discovery. Expert Opin Drug Discov. 2017 Mar;12(3):279-291. doi: 10.1080/17460441.2017.1280024. Epub 2017 Jan 23. PMID: 28067061; PMCID: PMC7241838.

XXXIX. Reddy AS, Zhang S. Polypharmacology: drug discovery for the future. Expert Rev Clin Pharmacol. 2013 Jan;6(1):41-7. doi: 10.1586/ecp.12.74. PMID: 23272792; PMCID: PMC3809828.

XL. Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008 Nov;4(11):682-90. doi: 10.1038/nchembio.118. PMID: 18936753.

XLI. Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network pharmacology. Innovative Approaches in Drug Discovery. 2017;:127–64.

XLII. Hao da C, Xiao PG. Network pharmacology: a Rosetta Stone for traditional Chinese medicine. Drug Dev Res. 2014 Aug;75(5):299-312. doi: 10.1002/ddr.21214. PMID: 25160070.

XLIII. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for Traditional Chinese Medicine: Review and assessment. Frontiers in Pharmacology. 2019;10.

XLIV. Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013 Mar;11(2):110-20. doi: 10.1016/S1875-5364(13)60037-0. PMID: 23787177.

XLV. Ideker T, Galitski T, Hood L. A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet. 2001;2:343-72. doi: 10.1146/annurev.genom.2.1.343. PMID: 11701654.

XLVI. Zhu F, Shi Z, Qin C, Tao L, Liu X, Xu F, Zhang L, Song Y, Liu X, Zhang J, Han B, Zhang P, Chen Y. Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. doi: 10.1093/nar/gkr797. Epub 2011 Sep 24. PMID: 21948793; PMCID: PMC3245130.

XLVII. He R, Ou S, Chen S, Ding S. Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Compound Kushen Injection in Anti-Cancer Effect. Med Sci Monit. 2020 Jan 1;26:e918520. doi: 10.12659/MSM.918520. PMID: 31892693; PMCID: PMC6977710.

XLVIII. Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8 Suppl 4(Suppl 4):S11. doi: 10.1186/1752-0509-8-S4-S11. Epub 2014 Dec 8. PMID: 25521941; PMCID: PMC4290687.

XLIX. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 Nov;13(11):2498-504. doi: 10.1101/gr.1239303. PMID: 14597658; PMCID: PMC403769.

L. Hu QN, Deng Z, Tu W, Yang X, Meng ZB, Deng ZX, Liu J. VNP: Interactive Visual Network Pharmacology of Diseases, Targets, and Drugs. CPT Pharmacometrics Syst Pharmacol. 2014 Mar 12;3(3):e105. doi: 10.1038/psp.2014.1. PMID: 24622768; PMCID: PMC4039393.

LI. Pavlopoulos GA, Paez-Espino D, Kyrpides NC, Iliopoulos I. Empirical Comparison of Visualization Tools for Larger-Scale Network Analysis. Adv Bioinformatics. 2017;2017:1278932. doi: 10.1155/2017/1278932. Epub 2017 Jul 18. PMID: 28804499; PMCID: PMC5540468.

LII. Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, Myung P, Plikus MV, Nie Q. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021 Feb 17;12(1):1088. doi: 10.1038/s41467-021-21246-9. PMID: 33597522; PMCID: PMC7889871.

LIII. Lagunin A, Filimonov D, Poroikov V. Multi-targeted natural products evaluation based on biological activity prediction with PASS. Curr Pharm Des. 2010 May;16(15):1703-17. doi: 10.2174/138161210791164063. PMID: 20222853.

LIV. Ji HF, Li XJ, Zhang HY. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep. 2009 Mar;10(3):194-200. doi: 10.1038/embor.2009.12. Epub 2009 Feb 20. PMID: 19229284; PMCID: PMC2658564.

LV. Schmidt BM, Ribnicky DM, Lipsky PE, Raskin I. Revisiting the ancient concept of botanical therapeutics. Nat Chem Biol. 2007 Jul;3(7):360-6. doi: 10.1038/nchembio0707-360. PMID: 17576417.

LVI. Gomez-Cadena A, Barreto A, Fioretino S, Jandus C. Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment. Cell Stress. 2020 May 18;4(7):154-166. doi: 10.15698/cst2020.07.224. PMID: 32656498; PMCID: PMC7328673.

LVII. Leung EL, Cao ZW, Jiang ZH, Zhou H, Liu L. Network-based drug discovery by integrating systems biology and computational technologies. Brief Bioinform. 2013 Jul;14(4):491-505. doi: 10.1093/bib/bbs043. Epub 2012 Aug 9. PMID: 22877768; PMCID: PMC3713711.

LVIII. Wang E, Wang L, Ding R, Zhai M, Ge R, Zhou P, Wang T, Fang H, Wang J, Huang J. Astragaloside IV acts through multi-scale mechanisms to effectively reduce diabetic nephropathy. Pharmacol Res. 2020 Jul;157:104831. doi: 10.1016/j.phrs.2020.104831. Epub 2020 Apr 24. PMID: 32339782.

LIX. Pei L, Bao Y, Liu S, Zheng J, Chen X. Material basis of Chinese herbal formulas explored by combining pharmacokinetics with network pharmacology. PLoS One. 2013;8(2):e57414. doi: 10.1371/journal.pone.0057414. Epub 2013 Feb 28. PMID: 23468985; PMCID: PMC3585395.

LX. Chen Y, Chen X, Luo G, Zhang X, Lu F, Qiao L, He W, Li G, Zhang Y. Discovery of Potential Inhibitors of Squalene Synthase from Traditional Chinese Medicine Based on Virtual Screening and In Vitro Evaluation of Lipid-Lowering Effect. Molecules. 2018 Apr 28;23(5):1040. doi: 10.3390/molecules23051040. PMID: 29710800; PMCID: PMC6102583.

LXI. Li M, Zhou J, Jin W, Li X, Zhang Y. Danhong Injection Combined With t-PA Improves Thrombolytic Therapy in Focal Embolic Stroke. Front Pharmacol. 2018 Apr 6;9:308. doi: 10.3389/fphar.2018.00308. PMID: 29681849; PMCID: PMC5897498.

LXII. Wang J, Zhang L, Liu B, Wang Q, Chen Y, Wang Z, Zhou J, Xiao W, Zheng C, Wang Y. Systematic investigation of the Erigeron breviscapus mechanism for treating cerebrovascular disease. J Ethnopharmacol. 2018 Oct 5;224:429-440. doi: 10.1016/j.jep.2018.05.022. Epub 2018 May 19. PMID: 29783016.

LXIII. Li X, Wu L, Fan X, Zhang B, Gao X, Wang Y, Cheng Y. [Network pharmacology study on major active compounds of Fufang Danshen formula]. Zhongguo Zhong Yao Za Zhi. 2011 Nov;36(21):2911-5. Chinese. PMID: 22308672.

LXIV. Li H, Zhao L, Zhang B, Jiang Y, Wang X, Guo Y, Liu H, Li S, Tong X. A network pharmacology approach to determine active compounds and action mechanisms of ge-gen-qin-lian decoction for treatment of type 2 diabetes. Evid Based Complement Alternat Med. 2014;2014:495840. doi: 10.1155/2014/495840. Epub 2014 Jan 16. PMID: 24527048; PMCID: PMC3914348.

LXV. Liu X, Wu J, Zhang D, Wang K, Duan X, Zhang X. A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer. Evid Based Complement Alternat Med. 2018 Feb 12;2018:6517034. doi: 10.1155/2018/6517034. PMID: 29619072; PMCID: PMC5829364.

LXVI. Li S, Wang N, Hong M, Tan HY, Pan G, Feng Y. Hepatoprotective Effects of a Functional Formula of Three Chinese Medicinal Herbs: Experimental Evidence and Network Pharmacology-Based Identification of Mechanism of Action and Potential Bioactive Components. Molecules. 2018 Feb 7;23(2):352. doi: 10.3390/molecules23020352. PMID: 29414910; PMCID: PMC6017312.

LXVII. Meng Z, Liu X, Wu J, Zhou W, Wang K, Jing Z, Liu S, Ni M, Zhang X. Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology. Evid Based Complement Alternat Med. 2019 May 28;2019:4637839. doi: 10.1155/2019/4637839. PMID: 31275410; PMCID: PMC6558614.

LXVIII. Lien AS, Jiang YD, Mou CH, Sun MF, Gau BS, Yen HR. Integrative traditional Chinese medicine therapy reduces the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus. J Ethnopharmacol. 2016 Sep 15;191:324-330. doi: 10.1016/j.jep.2016.06.051. Epub 2016 Jun 20. PMID: 27340102.

LXIX. Jiao J, Wu J, Wang J, Guo Y, Gao L, Liang H, et al. Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway. Pharmaceutical Biology. 2018;56(1):580–93.

LXX. Chen L, Zhang L, Fang Z, Li C, Yang Y, You X, et al. Naoxintong restores collateral blood flow in a murine model of hindlimb ischemia through PPARΔ-dependent mechanism. Journal of Ethnopharmacology. 2018;227:121–30.

LXXI. Zheng CS, Xu XJ, Ye HZ, Wu GW, Xu HF, Li XH, Huang SP, Liu XX. Computational pharmacological comparison of Salvia miltiorrhiza and Panax notoginseng used in the therapy of cardiovascular diseases. Exp Ther Med. 2013 Nov;6(5):1163-1168. doi: 10.3892/etm.2013.1291. Epub 2013 Sep 10. PMID: 24223639; PMCID: PMC3820668.

LXXII. Ren W, Ma Y, Wang R, Liang P, Sun Q, Pu Q, Dong L, Mazhar M, Luo G, Yang S. Research Advance on Qingfei Paidu Decoction in Prescription Principle, Mechanism Analysis and Clinical Application. Front Pharmacol. 2021 Jan 27;11:589714. doi: 10.3389/fphar.2020.589714. PMID: 33584265; PMCID: PMC7873690.

LXXIII. Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, Chen SJ, Chen Z. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31. doi: 10.1073/pnas.0712365105. Epub 2008 Mar 14. PMID: 18344322; PMCID: PMC2290784.

LXXIV. Zeng S, Yu Z, Xu X, Liu Y, Li J, Zhao D, Song C, Lu H, Zhao Y, Lu W, Zou X. Identification of the Active Constituents and Significant Pathways of Shen-qi-Yi-zhu Decoction on Antigastric Cancer: A Network Pharmacology Research and Experimental Validation. Evid Based Complement Alternat Med. 2021 Nov 22;2021:6642171. doi: 10.1155/2021/6642171. PMID: 34853601; PMCID: PMC8629626.

LXXV. Zheng CS, Xu XJ, Ye HZ, Wu GW, Li XH, Xu HF, Liu XX. Network pharmacology-based prediction of the multi-target capabilities of the compounds in Taohong Siwu decoction, and their application in osteoarthritis. Exp Ther Med. 2013 Jul;6(1):125-132. doi: 10.3892/etm.2013.1106. Epub 2013 May 9. PMID: 23935733; PMCID: PMC3735841.

LXXVI. Wang L, Li Z, Zhao X, Liu W, Liu Y, Yang J, Li X, Fan X, Cheng Y. A network study of chinese medicine xuesaitong injection to elucidate a complex mode of action with multicompound, multitarget, and multipathway. Evid Based Complement Alternat Med. 2013;2013:652373. doi: 10.1155/2013/652373. Epub 2013 Aug 24. PMID: 24058375; PMCID: PMC3766588.

LXXVII. Zeng L, Yang K. Exploring the pharmacological mechanism of Yanghe Decoction on HER2-positive breast cancer by a network pharmacology approach. J Ethnopharmacol. 2017 Mar 6;199:68-85. doi: 10.1016/j.jep.2017.01.045. Epub 2017 Jan 24. PMID: 28130113.

LXXVIII. An L, Feng F. Network pharmacology-based antioxidant effect study of zhi-zi-da-huang decoction for alcoholic liver disease. Evid Based Complement Alternat Med. 2015; 2015:492470. doi: 10.1155/2015/492470. Epub 2015 Apr 2. PMID: 25922610; PMCID: PMC4398926.

LXXIX. Klee R, Töllner K, Rankovic V, Römermann K, Schidlitzki A, Bankstahl M, Löscher W. Network pharmacology for antiepileptogenesis: Tolerability of multitargeted drug combinations in nonepileptic vs. post-status epilepticus mice. Epilepsy Res. 2015 Dec;118:34-48. doi: 10.1016/j.eplepsyres.2015.11.003. Epub 2015 Nov 10. PMID: 26600369.

LXXX. Gu J, Gui Y, Chen L, Yuan G, Lu H-Z, Xu X. Use of natural products as Chemical Library for drug discovery and network pharmacology. PLoS ONE. 2013;8(4).

LXXXI. Sharma H, Keith Wallace R. Ayurveda and Epigenetics. Medicina (Kaunas). 2020 Dec 11;56(12):687. doi: 10.3390/medicina56120687. PMID: 33322263; PMCID: PMC7763202.

LXXXII. Lagunin AA, Ivanov SM, Gloriozova TA, Pogodin PV, Filimonov DA, Kumar S, Goel RK. Combined network pharmacology and virtual reverse pharmacology approaches for identification of potential targets to treat vascular dementia. Sci Rep. 2020 Jan 14;10(1):257. doi: 10.1038/s41598-019-57199-9. PMID: 31937840; PMCID: PMC6959222.

LXXXIII. Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13. doi: 10.4314/ajtcam. v8i5S.9. Epub 2011 Jul 3. PMID: 22754076; PMCID: PMC3252722.

LXXXIV. Choudhary N, Singh V. Insights about multi-targeting and synergistic neuromodulators in Ayurvedic herbs against epilepsy: integrated computational studies on drug-target and protein-protein interaction networks. Sci Rep. 2019 Jul 22;9(1):10565. doi: 10.1038/s41598-019-46715-6. PMID: 31332210; PMCID: PMC6646331.

LXXXV. Chikhale RV, Sinha SK, Khanal P, Gurav NS, Ayyanar M, Prasad SK, Wanjari MM, Patil RB, Gurav SS. Computational and network pharmacology studies of Phyllanthus emblica to tackle SARS-CoV-2. Phytomed Plus. 2021 Aug;1(3):100095.

doi: 10.1016/j.phyplu.2021.100095. Epub 2021 Jul 13. PMID: 35399824; PMCID: PMC8276571.

LXXXVI. Patil R, Chikhale R, Khanal P, Gurav N, Ayyanar M, Sinha S, Prasad S, Dey YN, Wanjari M, Gurav SS. Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19. Inform Med Unlocked. 2021; 22:100504.

doi: 10.1016/j.imu.2020.100504. Epub 2020 Dec 23. PMID: 33363251; PMCID: PMC7756171.

LXXXVII. Chikhale R, Sinha SK, Wanjari M, Gurav NS, Ayyanar M, Prasad S, Khanal P, Dey YN, Patil RB, Gurav SS. Computational assessment of saikosaponins as adjuvant treatment for COVID-19: molecular docking, dynamics, and network pharmacology analysis. Mol Divers. 2021 Aug;25(3):1889-1904. doi: 10.1007/s11030-021-10183-w. Epub 2021 Jan 25. PMID: 33492566; PMCID: PMC7829483.

LXXXVIII. Zhang XR, Kaunda JS, Zhu HT, Wang D, Yang CR, Zhang YJ. The Genus Terminalia (Combretaceae): An Ethnopharmacological, Phytochemical and Pharmacological Review. Nat Prod Bioprospect. 2019 Dec;9(6):357-392. doi: 10.1007/s13659-019-00222-3. Epub 2019 Nov 6. PMID: 31696441; PMCID: PMC6872704.

LXXXIX. Choudhary N, Singh V. A census of P. longum's phytochemicals and their network pharmacological evaluation for identifying novel drug-like molecules against various diseases, with a special focus on neurological disorders. PLoS One. 2018 Jan 10;13(1): e0191006.

doi: 10.1371/journal.pone.0191006.

PMID: 29320554; PMCID: PMC5761900.

XC. Zhao Y, Wang M, Tsering J, Li H, Li S, Li Y, Liu Y, Hu X. An Integrated Study on the Antitumor Effect and Mechanism of Triphala Against Gynecological Cancers Based on Network Pharmacological Prediction and In Vitro Experimental Validation. Integr Cancer Ther. 2018 Sep;17(3):894-901.

doi: 10.1177/1534735418774410. Epub 2018 May 10. PMID: 29742928; PMCID: PMC6142109.

XCI. Noor F, Tahir ul Qamar M, Ashfaq UA, Albutti A, Alwashmi AS, Aljasir MA. Network Pharmacology Approach for medicinal plants: Review and assessment. Pharmaceuticals. 2022;15(5):572.

XCII. Zhang G-biao, Li Q-ya, Chen Q-long, Su S-bing. Network pharmacology: A new approach for Chinese Herbal Medicine Research. Evidence-Based Complementary and Alternative Medicine. 2013; 2013:1–9.