Volume 8 Issue 3 Article 22

Integrated Network Pharmacology and In-Silico Molecular Docking Studies to Unveil Mechanism of Action of Polyphenolic Compounds of Psidium Guajava for The Management of Thrombocytopenia

Authors: Adil Ahamad1 & Kamran Javed Naquvi2 & Mohd. Javed Naeem3 & Javed Ahamad4 & S. H. Ansari5 & Sayeed Ahmad6
1Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
2Institute of Biomedical Education and Research, Department of Pharmacy, Mangalayatan University, Beswan, Aligarh, UP, India
3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan region, Iraq
4Department of Pharmacognosy, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan region, Iraq
5Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
6Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

Abstract: Despite considerable studies, thrombocytopenia is still affecting millions of people with an increasing rate of morbidity and mortality around the globe. Therefore, we aimed to identify pharmacologically active polyphenolic compounds such as quercetin, apigenin and kaempferol in Psidium guajava for the management of thrombocytopenia using network pharmacology and in-silico molecular docking. The results of ADME/Tox screening revealed that all the polyphenolic compounds possess the drug-likeness activity and were found safe. Moreover, network pharmacology revealed that polyphenolic compounds of Psidium guajava may combat diabetes by acting on key targets, such as MAPK, TP53 and TNF-α which were strongly involved in oxidative stress, inflammatory responses and blood-related parameters involved in thrombocytopenia. Further, a mechanistic approach through molecular docking also supports the strong binding sites of quercetin, apigenin and kaempferol. Conclusively, in-silico ADME, molecular docking and network pharmacology study revealed that identified compounds are safe and pharmacologically effective. These identified compounds could be a great source for the development of new anti-thrombocytopenic drugs in the future.

Keywords: Psidium Guajava, Polyphenol, Network Pharmacology, Docking, Anti-Thrombocytopenic

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Doi: 10.23918/eajse.v8i3p283

Published: January 4, 2023

References

Ahmad, A., Ibrahim, M., Ansari, S. H., Taleuzzaman, M., and Ahmad, S. (2021). Antithrombocytopenic potential of metabolically characterized extract and fractions of Momordica charantia L. fruits by in vivo study. Ann. Phytomedicine An Int. J. 10, doi: 10.21276/ap.2021.10.2.35.

Ahmad, A., Ibrahim, M., Chester, K., Khan, W., Ahmad, S., and Ansari, S. (2019). Antithrombocytopenic potential of bioactivity guided fractions of traditionally used Psidium guajava Linn. leaves in busulfan induced-thrombocytopenic rats. Pharmacogn. Mag. 15, 440, doi: 10.4103/pm.pm_608_18.

Jackie, B., Sagar, S., Alamgir, H., Razowanul, Md.F., Sumaiya, F., et al. (2018) In silico Molecular Docking and ADME/T Analysis of Some Selected Isolated Compounds of Phyllanthus emblica against Type 2 Diabetics. Am J Ethnomed, 5(2), 3–7, doi: 10.21767/2348-9502.100009.

Chandran, U., Mehendale, N., Patil, S., Chaguturu, R., and Patwardhan, B. (2017). “Network Pharmacology,” in Innovative Approaches in Drug Discovery: Ethnopharmacology, Systems Biology and Holistic Targeting, doi: 10.1016/B978-0-12-801814-9.00005-2.

Chu, M., Gao, T., Zhang, X., Kang, W., Feng, Y., Cai, Z., et al. (2022). Elucidation of Potential Targets of San-Miao-San in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking Analysis. Evidence-based Complement. Altern. Med, doi: 10.1155/2022/7663212.

Daswani, P. G., Gholkar, M. S., and Birdi, T. J. (2017). Psidium guajava: A single plant for multiple health problems of rural Indian population. Pharmacogn. Rev. 11, 167–174, doi: 10.4103/phrev.phrev_17_17.

Fahim, M., Ibrahim, M., Zahiruddin, S., Parveen, R., Khan, W., Ahmad, S., et al. (2019). TLC-bioautography identification and GC-MS analysis of antimicrobial and antioxidant active compounds in Musa × paradisiaca L. fruit pulp essential oil. Phytochem. Anal, doi: 10.1002/pca.2816.

Hong, Z., Duan, X., Wu, S., Yanfang, Y., and Wu, H. (2020). Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 Mechanism of Qing-Fei-Da-Yuan Granules. Nat. Prod. Commun. 15, doi: 10.1177/1934578X20934219.

Huang, Q., Liu, R., Liu, J., Huang, Q., Liu, S., and Jiang, Y. (2020). Integrated network pharmacology analysis and experimental validation to reveal the mechanism of anti-insulin resistance effects of moringa oleifera seeds. Drug Des. Devel. Ther, doi: 10.2147/DDDT.S265198.

Ibrahim, M., Parveen, B., Zahiruddin, S., Gautam, G., Parveen, R., Khan, M. A., et al. (2022). Analysis of polyphenols in Aegle marmelos leaf and ameliorative efficacy against diabetic mice through restoration of antioxidant and anti-inflammatory status. J. Food Biochem, 46. doi: 10.1111/jfbc.13852.

Izak, M., and Bussel, J. B. (2014). Management of thrombocytopenia. F1000Prime Rep. 6, doi: 10.12703/P6-45.

Jiang, Y., Liu, N., Zhu, S., Hu, X., Chang, D., and Liu, J. (2019). Elucidation of the mechanisms and molecular targets of Yiqi Shexue formula for treatment of primary immune thrombocytopenia based on network pharmacology. Front. Pharmacol, 10. doi: 10.3389/fphar.2019.01136.

Johnson, J. L., Rupasinghe, S. G., Stefani, F., Schuler, M. A., and Gonzalez De Mejia, E. (2011). Citrus flavonoids luteolin, apigenin, and quercetin inhibit glycogen synthase kinase-3β enzymatic activity by lowering the interaction energy within the binding cavity. J. Med. Food ,14, 325–333. doi: 10.1089/jmf.2010.0310.

Li, H., Zhao, L., Zhang, B., Jiang, Y., Wang, X., Guo, Y., et al. (2014). A network pharmacology approach to determine active compounds and action mechanisms of Ge-Gen-Qin-Lian decoction for treatment of type 2 diabetes. Evidence-based Complement. Altern. Med, doi: 10.1155/2014/495840.

Li, W., Yuan, G., Pan, Y., Wang, C., and Chen, H. (2017). Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Front. Pharmacol, doi: 10.3389/fphar.2017.00074.

Madaan, R., Bansal, G., Kumar, S., and Sharma, A. (2011). Estimation of total phenols and flavonoids in extracts of Actaea spicata roots and antioxidant activity studies. Indian J. Pharm. Sci, 73, 666–669. doi: 10.4103/0250-474X.100242.

Pan, S. Y., Litscher, G., Gao, S. H., Zhou, S. F., Yu, Z. L., Chen, H. Q., et al. (2014). Historical perspective of traditional indigenous medical practices: The current renaissance and conservation of herbal resources. Evidence-based Complement. Altern. Med. doi: 10.1155/2014/525340.

Qu, X., Tang, Y., and Hua, S. (2018). Immunological approaches towards cancer and inflammation: A cross talk. Front. Immunol. 9. doi: 10.3389/fimmu.2018.00563.

Reardon, J. E., and Marques, M. B. (2006). Evaluation of thrombocytopenia. Lab. Med, 37, 248–250. doi: 10.1309/R7P79KERAJHPRHLT.

Ren, W., Luo, Z., Pan, F., Liu, J., Sun, Q., Luo, G., et al. (2020). Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in venenum bufonis for ameliorating heart failure. PeerJ, 8. doi: 10.7717/peerj.10107.

Sanda, K. A., Grema, H. A., Geidam, Y. A., and Bukar-Kolo, Y. M. (2011). Pharmacological aspects of Psidium guajava: An Update. Int. J. Pharmacol, 7, 316–324. doi: 10.3923/ijp.2011.316.324.

Vauzour, D., Rodriguez-Mateos, A., Corona, G., Oruna-Concha, M. J., and Spencer, J. P. E. (2010). Polyphenols and human health: Prevention of disease and mechanisms of action. Nutrients. doi: 10.3390/nu2111106.

Yi, F., Li, L., Xu, L. jia, Meng, H., Dong, Y. mao, Liu, H. bo, et al. (2018). In silico approach in reveal traditional medicine plants pharmacological material basis. Chinese Med. (United Kingdom). doi: 10.1186/s13020-018-0190-0.