Network pharmacology-based prediction of efficacy and mechanism of Myrrha acting on Allergic Rhinitis

Yebin Lim; Bitna Kweon; Dong-Uk Kim; Gi-Sang Bae; Lim, Yebin; Kweon, Bitna; Kim, Dong-Uk; Bae, Gi-Sang

doi:10.13048/jkm.24007

JKM > Volume 45(1); 2024 > Article

Lim, Kweon, Kim, and Bae: Network pharmacology-based prediction of efficacy and mechanism of Myrrha acting on Allergic Rhinitis

Original Article

The Journal of Korean Medicine 2024; 45(1): 113-124.

Published online: March 1, 2024

DOI: https://doi.org/10.13048/jkm.24007

Network pharmacology-based prediction of efficacy and mechanism of Myrrha acting on Allergic Rhinitis

Yebin Lim¹^{, a}

, Bitna Kweon¹^{, 2}^{, a}

, Dong-Uk Kim¹

, Gi-Sang Bae¹^{, 2}^{, 3}^{, *}

¹Department of Pharmacology, School of Korean Medicine, Wonkwang University

²Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University

³Research center of Traditional Korean medicine, Wonkwang University

Correspondence to: Gi-Sang Bae, Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, 54538 Jeonbuk, South Korea, Tel: +82-63-850-6842, E-mail: baegs888@wku.ac.kr

a Equally contributed

Received January 15, 2024 Revised February 7, 2024 Accepted February 16, 2024

Abstract

Objectives

Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking.

Methods

Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock.

Results

The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including ‘Fc epsilon RI signaling pathway’ and ‘JAK-STAT signaling pathway’. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha.

Conclusion

Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

Keywords: Myrrha, Allergic Rhinitis (AR), Network pharmacology, Molecular docking

Supplementary Information

jkm-45-1-113-Supplementary-Fig-1,2.pdf

Fig. 1

(A) Network of Myrrha with 55nodes and 478edges. (B) Veen-diagram of intersection targets between Myrrha network and gene sets of Allergic Rhinitis (AR). (C) Network of intersection targets of Myrrha and AR.

Fig. 2

GO biological process analysis of the intersection targets.

Fig. 3

KEGG pathway analysis of the intersection targets.

Fig. 4

The herb, compound, target and pathway network of Myrrha in the treatment of AR

Fig. 5

Molecular docking Diagrams show the interaction of AA with (A)AKT1, (B)IL6 and DA with (C)AKT1

Table 1

List of Compounds from Myrrha

Compound	Pubchem ID
Abietic Acid	10569
Dehydroabietic Acid	94391
Mansumbinone	128179
Sandaracopimaric Acid	221580

Table 2

List of the common genes of Myrrha and Allergic Rhinitis (AR) gene set

33 common Genes of Myrrha and Allergic Rhinitis
ADIPOQ, AKT1, ALOX5, BCL2, BIRC5, CASP3, CCL2, CD83, CD86, CEBPA, HSD11B1, HSD11B2, PLAU, MMP2, MMP1, FASLG, FOXO1, GPT, HMOX1, IL13, IL23A, IL5, IL6, INS, MRC1, NFATC1, NOS3, PPARG, PTGS2, SMAD3, SYK, TNF, TNFRSF11A

Table 3

Molecular docking results for core bioactive components of Myrrha and the corresponding target proteins

Components	protein	Binding Energies (kJ/mol)	Center (x, y, z)	Size (x, y, z)
Abietic Acid(AA)	AKT1	−9.7	(109, 144, 96)	(21, 21, 28)
Abietic Acid(AA)	IL6	−7.6	(4, −2, 10)	(27, 21, 21)
Dehydroabietic Acid(DA)	AKT1	−9.3	(109, 144, 96)	(20, 20, 28)

참고문헌

1. Koh Y.-I.(2013). Diagnosis of allergic rhinitis. The Korean Journal of Medicine;85(5):452-456. https://doi.org/10.3904/kjm.2013.85.5.4521

2. Kim C.-W.(2012). Current update on allergic rhinitis. The Korean Journal of Medicine;82(3):298-303. https://doi.org/10.3904/kjm.2012.82.3.298

3. Meltzer E. O.(2016). Allergic rhinitis: Burden of illness, quality of life, comorbidities, and control. Immunology and Allergy Clinics;36(2):235-248. https://doi.org/10.1016/j.iac.2015.12.002

4. Choi J.-H.(2013). Allergic rhinitis and comorbidities. The Korean Journal of Medicine;85(5):457-462. https://doi.org/10.3904/kjm.2013.85.5.457

5. Zou Q.-Y., Shen Y., Ke X., Hong S.-L., & Kang H.-Y.(2018). Exposure to air pollution and risk of prevalence of childhood allergic rhinitis: A meta-analysis. International journal of pediatric otorhinolaryngology;112(82–90): https://doi.org/10.1016/j.ijporl.2018.06.039

6. Kim M., Kim H.-H., Kim H.-B., Ho R. Y., Park Y., & Sung M., et al(2021). Main epidemiological characteristics and natural history of pediatric allergic rhinitis. Allergy Asthma & Respiratory Diseases;9(4):203-207. https://doi.org/10.4168/aard.2021.9.4.203

7. Alnahas S., Abouammoh N., Althagafi W., & Abd-Ellatif E. E.(2023). Prevalence, severity, and risk factors of allergic rhinitis among schoolchildren in saudi arabia: A national cross-sectional study, 2019. World Allergy Organization Journal;16(10):100824 https://doi.org/10.1016/j.waojou.2023.100824

8. herbology, T. t. c. c. o. K. (2004). Herbology. Seoul. Young Lim Sa;p. 604-606.

9. Jung D.-H., Chang S.-K., Cho C.-S., & Kim C.-J.(2006). Effects of commiphora myrrha (cm) on the monosodium urate (msu)-induced gout model in rats. The Journal of Internal Korean Medicine;27(3):715-724.

10. Kim K.-S.(2005). Acceleration of wound healing on scald burn skin using irradiation of tdp and skin spread of myrrha. J. Exp. Biomed. Sci;11(2):243-248.

11. Jung Y. H., Roh Y. W., Chong M., Jung Y. H., Roh Y. W., & Chong M.(2022). Anti-inflammatory effects of myrrh ethanol extract on particulate matter-induced skin injury. Journal of Korean Medicine;43(3):1-15. https://doi.org/10.13048/jkm.22026

12. Shin J. Y., Che D. N., Cho B. O., Kang H. J., Kim J., & Jang S. I.(2019). Commiphora myrrha inhibits itch-associated histamine and il-31 production in stimulated mast cells. Exp Ther Med;18(3):1914-1920. https://doi.org/10.3892/etm.2019.7721

13. Han S. Y., & Kim Y. K.(2016). New approach for herbal formula research: Network pharmacology. Journal of Physiology & Pathology in Korean Medicine;30(6):385-396. https://doi.org/10.15188/kjopp.2016.12.30.6.385

14. Hopkins A. L.(2008). Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol;4(11):682-690. https://doi.org/10.1038/nchembio.118

15. Teng B., Zhang X., Yi C., Zhang Y., Ye S., & Wang Y., et al(2017). The association between ambient air pollution and allergic rhinitis: Further epidemiological evidence from changchun, northeastern china. International journal of environmental research and public health;14(3):226 https://doi.org/10.3390/ijerph14030226

16. Lee K. S., Kim K., Choi Y. J., Yang S., Kim C. R., & Moon J. H., et al(2021). Increased sensitization rates to tree pollens in allergic children and adolescents and a change in the pollen season in the metropolitan area of seoul, korea. Pediatric Allergy and Immunology;32(5):872-879. https://doi.org/10.1111/pai.13472

17. Lee K. S., Kim M., Kim H. H., Kim H.-B., Rha Y.-H., & Park Y. M., et al(2023). Associations between pollen and allergic rhinitis in children and adolescents. Allergy, Asthma & Respiratory Disease;11(1):3-8. https://doi.org/10.4168/aard.2023.11.1.3

18. Kaaaci allergic rhinitis guidelines. The korean academy of asthma, allergy and clinical immunology. 2022. [cited 2024 jan 11]. Available from: www.allergy.or.kr

19. Service, N. H. I. Available from: https://www.nhis.or.kr/nhis/together/wbhaea01600m01.do?mode=view&articleNo=136900&article.offset=260&articleLimit=10

20. Kang C.-Y., Kim H.-J., Kim J.-H., Hwang J.-S., & Lee D.-H.(2021). Outcomes analysis for western medicine and korean medicine using the propensity score matching in allergic rhinitis: Data from the health insurance review and assessment service. The journal of Korean Medicine Ophthalmology & Otolaryngology & Dermatology;34(2): https://doi.org/10.6114/jkood.2021.34.2.053

21. Kakli H. A., & Riley T. D.(2016). Allergic rhinitis. Primary Care: Clinics in Office Practice;43(3):465-475. https://doi.org/10.1016/j.pop.2016.04.009

22. Kim H. H.(2007). Allergic rhinitis, sinusitis and asthma-evidence for respiratory system integration. Clinical and Experimental Pediatrics;50(4):335-339.

23. Chung Y. S.(2010). Allergic rhinitis and sleep-disordered breathing. Allergy, Asthma & Immunology Research;30(4):271-274.

24. Liu X., Yang Y., Li Y., Zhang Q., Wang J., & Guo J., et al(2023). Network pharmacology-based approach for investigating the role of xanthii fructus in treatment of allergic rhinitis. Chemistry & Biodiversity;20(4):e202200785 https://doi.org/10.1002/cbdv.202200785

25. Shin M.(2010). Clinical traditional herbalogy. Seoul. Yeong. Lim Publishing;p. 748-749.

26. Ahmad A., Raish M., Ganaie M. A., Ahmad S. R., Mohsin K., & Al-Jenoobi F. I., et al(2015). Hepatoprotective effect of commiphora myrrha against d-galn/lps-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes. Pharmaceutical biology;53(12):1759-1767. https://doi.org/10.3109/13880209.2015.1005754

27. Su S., Wang T., Duan J.-A., Zhou W., Hua Y.-Q., & Tang Y.-P., et al(2011). Anti-inflammatory and analgesic activity of different extracts of commiphora myrrha. Journal of ethnopharmacology;134(2):251-258. https://doi.org/10.1016/j.jep.2010.12.003

28. Klemm S., & Ruland J.(2006). Inflammatory signal transduction from the fcεri to nf-κb. Immunobiology;211(10):815-820. https://doi.org/10.1016/j.imbio.2006.07.001

29. Gibbs B. F., Räthling A., Zillikens D., Huber M., & Haas H.(2006). Initial fcɛri-mediated signal strength plays a key role in regulating basophil signaling and deactivation. Journal of allergy and clinical immunology;118(5):1060-1067. https://doi.org/10.1016/j.jaci.2006.07.022

30. Kinet J.-P.(1999). The high-affinity ige receptor (fcεri): From physiology to pathology. Annual review of immunology;17(1):931-972. https://doi.org/10.1146/annurev.immunol.17.1.931

31. Li Y., Leung P. S. C., Gershwin M. E., & Song J.(2022). New mechanistic advances in fcepsilonri-mast cell-mediated allergic signaling. Clin Rev Allergy Immunol;63(3):431-446. https://doi.org/10.1007/s12016-022-08955-9

32. Hu X., Li J., Fu M., Zhao X., & Wang W.(2021). The jak/stat signaling pathway: From bench to clinic. Signal Transduct Target Ther;6(1):402 https://doi.org/10.1038/s41392-021-00791-1

33. Jo B. G., & Bang I. S.(2022). Anti-inflammatory effect of morinda citrifolia on lps-induced inflammation in raw 264.7 cells through the jak/stat signaling pathway. J Life Sci;32125-134. https://doi.org/10.5352/JLS.2022.32.2.125

34. Packard K. A., & Khan M. M.(2003). Effects of histamine on th1/th2 cytokine balance. International immunopharmacology;3(7):909-920. https://doi.org/10.1016/S1567-5769(02)00235-7

35. Di Lorenzo A., Fernández-Hernando C., Cirino G., & Sessa W. C.(2009). Akt1 is critical for acute inflammation and histamine-mediated vascular leakage. Proceedings of the National Academy of Sciences;106(34):14552-14557. https://doi.org/10.1073/pnas.0904073106

36. Iorga B., Herlem D., Barré E., & Guillou C.(2006). Acetylcholine nicotinic receptors: Finding the putative binding site of allosteric modulators using the “blind docking” approach. Journal of molecular modeling;12(366–372): https://doi.org/10.1007/s00894-005-0057-z

37. Gao Y., Zhaoyu L., Xiangming F., Chunyi L., Jiayu P., & Lu S., et al(2016). Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model. Int Immunopharmacol;38261-266. https://doi.org/10.1016/j.intimp.2016.05.029

38. Park J., Kim J. E., Jin Y. J., Roh Y. J., Song H. J., & Seol A., et al(2023). Anti-atopic dermatitis effects of abietic acid isolated from rosin under condition optimized by response surface methodology in dncb-spread balb/c mice. Pharmaceuticals (Basel);16(3): https://doi.org/10.3390/ph16030407