International Journal of Drug Delivery Technology
Volume 15, Issue 2

Network Pharmacology and Molecular Docking Studies to Explore Mechanistic Insights of Bonnisan, used for Treatment of Infantile Colic 

Deshraj Chumbhale1, Pankaj Chaudhari2, Ashwini Shelke3, Lokesh Barde4

1Department of Pharmacognosy, Amrutvahini College of Pharmacy, Sangamner, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

2Department of Pharmacology, Shatabdi Institute of Pharmacy, Nandurbar, Affiliated to Dr. Babasaheb Ambedkar Technological University, Lonere, Dist. Raigad, Maharashtra, India

3Department of Pharmaceutical Chemistry, Sir Dr. M.S. Gosavi College of Pharmaceutical Education and Research, Nashik, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

4Department of Quality Assurance, Shram Sadhana Bombay Trust’s Institute of Pharmacy, Jalgaon, Affiliated to Dr. Babasaheb Ambedkar Technological University, Lonere, Dist. Raigad, Maharashtra, India 

Received: 2nd Mar, 2025; Revised: 14th May, 2025; Accepted: 29th May, 2025; Available Online: 25th Jun, 2025 

ABSTRACT

Infants with infantile colic, a common gastrointestinal condition, wail uncontrollably and in a painful manner.  The molecular mechanism of action of the Ayurvedic proprietary compound bonnisan, which has been used traditionally to improve infant digestion, has not yet been fully studied.  Therefore, this study intended to investigate the mechanism of action of Bonnisan in infantile colic utilizing network pharmacological and molecular docking techniques.

Bonnisan's active phytoconstituents were found in online databases and literature.  KEGG-pathway analysis, genes ontology (GO) enrichment, proteins-protein interactions (PPI) analysis, and network pharmacology were used to predict the target.  Additionally, studies using molecular docking were conducted to investigate ligand-target interaction.

A total of 62 bioactive compounds and 85 potential targets were yielded, out of which major proteins such as PTGS2, NOS2, TNF, and HTR3A were found to be closely associated with coindexing colic-related inflammation, pain modulation, and gut motility. For KEGG pathway analysis, the enrichment in pathways that were significant included PI3K-Akt signaling, neuroactive ligand-receptor interaction, serotonergic synapse, and inflammatory pathways related to the pathophysiology of colic. Molecular docking results demonstrated strong binding of ligands to targets: oleanolic acid (-9.2 kcal mol-1, PTGS2), ursolic acid (-8.7 kcal mol-1, TNF) and linalool (-7.5 kcal mol-1, HTR3A) were the major bioactive compounds for the observed changes.

The study mechanistically explains the effects of Bonnisan's multiple-target pharmacological activities in managing infantile colic, most notably with anti-inflammatory, gut motility regulation, and neuromodulatory actions. These computational predictions require more experimental validation and eventually enhance their clinical applicability.

Keywords: Bonnisan, Infantile Colic, Network Pharmacology, Molecular Docking, Ayurveda, PI3K-Akt Pathway, PTGS2, NOS2, HTR3A, Phytoconstituents

How to cite this article: Deshraj Chumbhale, Pankaj Chaudhari, Ashwini Shelke, Lokesh Barde. Network Pharmacology and Molecular Docking Studies to Explore Mechanistic Insights of Bonnisan, a Proprietary Ayurvedic Medicine, in Infantile Colic. International Journal of Drug Delivery Technology. 2025;15(2):531-38. doi: 10.25258/ijddt.15.2.21

REFERENCES

  1. Indrio F, Dargenio VN, Francavilla R, Szajewska H, Vandenplas Y. Infantile colic and long-term outcomes in childhood: a narrative synthesis of the evidence. Nutrients. 2023 Jan 25;15(3):615. https://doi.org/10.3390/nu15030615
  2. Gelfand AA. Infantile colic. Handbook of Clinical Neurology. 2023 Jan 1;198:203-7. https://doi.org/10.1016/B978-0-12-823356-6.00010-X
  3. Ünal ET, Bülbül A, Elitok GK, Avşar H, Uslu S. Evaluation of the knowledge level and attitude of mothers about infantile colic. HaydarpaşaNumune Medical Journal. 2021;61(1):38. https://doi.org/10.14744/hnhj.2020.47135
  4. Simonson J, Haglund K, Weber E, Fial A, Hanson L. Probiotics for the management of infantile colic: a systematic review. MCN: The American Journal of Maternal/Child Nursing. 2021 Mar 1;46(2):88-96. https://doi.org/10.1097/NMC.0000000000000691
  5. Yılmaz ÖN. Infantile Colic: Diagnosis and treatment options in Primary Care. The Journal of Turkish Family Physician. 2024 Jun 30;15(2):55-71. https://doi.org/10.15511/tjtfp.24.00255.
  6. Barekatian B, Kelishadi R, Sohrabi F, Yazdi M. Efficiency of Dimethicone and Symbiotic Approaches in Infantile Colic Management. Iranian Journal of Neonatology. 2021 Jul 1;12(3). https://doi.org/22038/ijn.2021.52504.1940
  7. Rajani PS, Martin H, Groetch M, Järvinen KM. Presentation and management of food allergy in breastfed infants and risks of maternal elimination diets. The Journal of Allergy and Clinical Immunology: In Practice. 2020 Jan 1;8(1):52-67. https://doi.org/10.1016/j.jaip.2019.11.007
  8. Perry R, Leach V, Penfold C, Davies P. An overview of systematic reviews of complementary and alternative therapies for infantile colic. Systematic reviews. 2019 Dec;8:1-6. https://doi.org/10.1186/s13643-019-1191-5
  9. Bethi S, Shirole R, Ghangale G. Computational Exploration of Multitarget Effects of Curcumin in Breast Cancer Treatment. Pharmaceutical Fronts 2025 (efirst). https://doi.org/10.1055/a-2522-0009
  10. Kizhakkeveettil A, Parla J, Patwardhan K, Sharma A, Sharma S. History, Present and Prospect of Ayurveda. InHistory, Present and Prospect of World Traditional Medicine 2024 (pp. 1-72). https://doi.org/10.1142/9789811282171_0001
  11. Saravanakumar A, Santhosh Kumar B. A study on female customer satisfaction on hair oil and beauty cream with special reference to Himalaya products in Coimbatore district. Special Is s ue. 2018 Aug;4:23. http://dx.doi.org/10.18843/ijms/v5iS4/03
  12. Bethi S, Shirole R, More V, Thorat M, Mohapatra S, Tare H. Uncovering The Anticonvulsant Mechanisms of Saussurea Lappa: A Network Pharmacology and Molecular Docking Approach. Palestinian Medical and Pharmaceutical Journal (Pal. Med. Pharm. J.). 2025 Jan 1;9999(9999):None-.
  13. Xin WA, Zi-Yi WA, Zheng JH, Shao LI. TCM network pharmacology: a new trend towards combining computational, experimental and clinical approaches. Chinese journal of natural medicines. 2021 Jan 1;19(1):1-1. https://doi.org/10.1016/S1875-5364(21)60001-8
  14. Stanzione F, Giangreco I, Cole JC. Use of molecular docking computational tools in drug discovery. Progress in medicinal chemistry. 2021 Jan 1;60:273-343. https://doi.org/10.1016/bs.pmch.2021.01.004
  15. Muthuramalingam P, Jeyasri R, Varadharajan V, Priya A, Dhanapal AR, Shin H, Thiruvengadam M, Ramesh M, Krishnan M, Omosimua RO, Sathyaseelan DD. Network pharmacology: an efficient but underutilized approach in oral, head and neck cancer therapy—a review. Frontiers in Pharmacology. 2024 Jul 5;15:1410942. https://doi.org/10.3389/fphar.2024.1410942
  16. Huang C, Luo H, Huang Y, Fang C, Zhao L, Li P, Zhong C, Liu F. AURKB, CHEK1 and NEK2 as the potential target proteins of scutellariabarbata on hepatocellular carcinoma: an integrated bioinformatics analysis. International Journal of General Medicine. 2021 Jul 12:3295-312. https://doi.org/10.2147/IJGM.S318077
  17. Tare H, Vaidya V, Fulmali S, Jadhao S, Wankhade M, Bhise M. Transcriptomic insight and structural integration: repositioning FDA-approved methotrexate derivative for precision therapy in lung cancer through drug-drug similarity analysis and cavity-guided blind docking. International Research Journal of Multidisciplinary Scope (IRJMS), 2024; 5(1 ): 631-639. https://doi.org/10.47857/irjms.2024.v05i01.0300
  18. Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P, Jensen LJ. The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic acids research. 2021 Jan 8;49(D1):D605-12. https://doi.org/10.1093/nar/gkaa1074
  19. Syed Zameer Ahmed S, Vetrivel M, Khader SZ, Ragunathan YT, Kumar SK, Prabhu P, Rajaram DL. Exploring gene network and protein interaction analysis of neurotrophin signaling pathway in ameloblastoma. In Silico Pharmacology. 2024 Jun 10;12(1):56. https://doi.org/10.1007/s40203-024-00223-2
  20. Ugurlu SY, McDonald D, Lei H, Jones AM, Li S, Tong HY, Butler MS, He S. Cobdock: an accurate and practical machine learning-based consensus blind docking method. Journal of Cheminformatics. 2024 Jan 11;16(1):5. https://doi.org/10.1186/s13321-023-00793-x
  21. Reddy NS, Raju MG, Anusha V, Gaikwad A, Pulate C, Mahajan K, Tare H. Investigation of potential antiurolithiatic activity and in silico docking studies of Karpura shilajit. International journal of health sciences. 2022;6(S4):8900-16. https://doi.org/10.53730/ijhs.v6nS4.11875
  22. Li S, Xiao W. General expert consensus on the application of network pharmacology in the research and development of new traditional Chinese medicine drugs. Chinese Journal of Natural Medicines. 2025 Feb 1;23(2):129-42. https://doi.org/10.1016/S1875-5364(25)60802-8
  23. Zhai Y, Liu L, Zhang F, Chen X, Wang H, Zhou J, Chai K, Liu J, Lei H, Lu P, Guo M. Network pharmacology: a crucial approach in traditional Chinese medicine research. Chinese Medicine. 2025 Jan 12;20(1):8. https://doi.org/10.1186/s13020-024-01056-z