ACTIVE COMPOUNDS FROM MEDICINAL PLANTS AS NOVEL APPROACHES FOR ASTHMA THERAPY: IN SILICO DOCKING ANALYSIS

Yıl 2025, Cilt: 49 Sayı: 3, 689 - 713, 19.09.2025

Muhammet Zahit Çelik , Fatma Uysal , Nuriye Hilal Taştekin , Cenk Andaç , Seyfullah Oktay Arslan

https://doi.org/10.33483/jfpau.1479879

Öz

Objective: Pharmaceutical molecules have historically drawn inspiration from natural substances.
Nowadays, research on natural compounds is escalating, particularly on phytochemicals. In this context, asthma, characterized by airway constriction and inflammation, occupies a significant place in the search for effective herbal treatments. Nonetheless, the bronchodilatory efficacy of the bioactive phytochemicals remains ambiguous. This study explores plant-derived compounds proposed for asthma treatment, focusing on their bronchodilator effects mediated through β2-adrenergic and M3-muscarinic receptors. These receptors facilitate muscle relaxation respectively by increasing intracellular cAMP levels and reducing intracellular calcium release from the endoplasmic reticulum.
Material and Method: A comprehensive literature search was performed on phytochemicals tested on asthmatic animal models. A total of 898 articles were assessed in this manner. Following the elimination of duplicates, 100 bioactive plant compounds in 3D format, demonstrating potential bronchodilator effects, were assessed in silico for their impact on β2 and M3 receptors. The receptors were obtained from the Protein Data Bank. Compounds and references were docked to specific proteins by the PyRx program to facilitate the docking, and high-scored molecules were visualized by the DSV program. Besides, in silico pharmacokinetic parameters were evaluated via SwissADME tool and toxicity parameters were determined using ADMETLab 3.0 platform.
Result and Discussion: In the docking experiments, 34 out of the 100 compounds were demonstrated to have a potentially high affinity to β2 and/or M3 receptors. Several molecules like cryptotanshinone, paeoniflorin and rottlerin were found to have high binding affinities for the β2 receptor. On the other hand, it has been demonstrated that tetrandrine, fisetin, and cryptotanshinone have strong affinities for the M3 receptor. Considering the findings, these bioactive substances could benefit bronchodilation, particularly through the β2 and M3 receptor pathways. This in silico study highlighted the potential of plant compounds for bronchodilation in respiratory diseases and suggested avenues for future research and experimental validation in asthma therapy.

Anahtar Kelimeler

Asthma , β2 adrenergic receptor , M3 muscarinic receptor , molecular docking , phytochemical

Etik Beyan

-

Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

ASTIM TEDAVİSİNDE YENİ YAKLAŞIMLAR İÇİN TIBBİ BİTKİLERDEN ELDE EDİLEN AKTİF BİLEŞİKLERİN İN SİLİKO DOCKING ANALİZİ

Öz

Amaç: İlaç molekülleri tarihsel olarak doğal maddelerden ilham alagelmektedir. Günümüzde doğal bileşikler ve özellikle fitokimyasallar üzerinde yapılan araştırmalar giderek artmaktadır. Bu bağlamda, solunum yolu daralması ve enflamasyonu ile karakterize astım hastalığı, etkili bitkisel tedavilere yönelik araştırmalarda önemli bir yer tutmaktadır. Bununla birlikte, biyoaktif fitokimyasalların bronkodilatör etkinliği belirsizliğini korumaktadır. Bu çalışmada astım tedavisi için önerilen bitkisel kaynaklı bileşiklerin, β2-adrenerjik ve M3-muskarinik reseptör aracılı bronkodilatör etkilerine odaklanılmıştır. Bu reseptörler, sırasıyla hücre içi cAMP seviyelerini artırarak ve endoplazmik retikulumdan hücre içi kalsiyum salınımını azaltarak kas gevşemesini sağlar.
Gereç ve Yöntem: Astımlı hayvan modelleri üzerinde çalışılmış bitkisel bileşikler hakkında kapsamlı bir literatür araştırması yapılmıştır. Toplamda 898 makale bu şekilde değerlendirmeye alınmıştır. Tekrar eden literatürlerin çıkarılmasının ardından, potansiyel bronkodilatör etkinlik gösteren üç boyutlu yapıdaki 100 farklı bitkisel bileşik, β2 ve M3 reseptörleri üzerindeki etkileri açısından in silico olarak değerlendirilmiştir. Reseptörler Protein Data Bank'tan elde edilmiştir. Bileşikler ve referanslar, kenetlenmeyi kolaylaştırmak için PyRx programı tarafından belirli proteinlere kenetlenmiş ve yüksek puanlı moleküller DSV programı tarafından görselleştirilmiştir. Ayrıca, in silico farmakokinetik parametreleri SwissADME aracılığıyla değerlendirilmiş ve toksisite parametreleri ADMETLab 3.0 platformu kullanılarak belirlenmiştir.
Sonuç ve Tartışma: Docking deneylerinde, 100 bileşikten 34'ünün β2 ve/veya M3 reseptörlerine potansiyel olarak yüksek afiniteye sahip olduğu gösterilmiştir. Kriptotanşinon, paeoniflorin ve rottlerin gibi birkaç molekülün β2 reseptörü için yüksek bağlanma afinitesine sahip olduğu bulunmuştur. Diğer taraftan, tetrandrin, fisetin ve kriptotanşinonun M3 reseptörü için güçlü afinitelere sahip olduğu gösterilmiştir. Bulgular göz önünde bulundurulduğunda, bu biyoaktif maddeler özellikle β2 ve M3 reseptör yolları aracılığıyla bronkodilatasyona fayda sağlayabilir. Bu in silico çalışma, solunum yolu hastalıklarında bronkodilatasyon için bitki bileşiklerinin potansiyelini göstermiştir. Astım tedavisinin gelecekteki araştırmaları ve deneysel çalışmaları için yollar göstermiştir.

Anahtar Kelimeler

Astım , β2 adrenerjik reseptör , bitkisel bileşik , M3 muskarinik reseptör , moleküler yerleştirme

Proje Numarası

-

Kaynakça

• 1. Deng, Y., Guan, M., Xie, X., Yang, X., Xiang, H., Li, H., Zou, L., Wei, J., Wang, D., Deng, X. (2013). Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. International Immunopharmacology, 17(3), 561-567. [CrossRef]
• 2. Su, X., Ren, Y., Yu, N., Kong, L., Kang, J. (2016). Thymoquinone inhibits inflammation, neoangiogenesis and vascular remodeling in asthma mice. International İmmunopharmacology, 38, 70-80. [CrossRef]
• 3. Hu, L., Li, L., Zhang, H., Li, Q., Jiang, S., Qiu, J., Sun, J., Dong, J. (2019). Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complementary and Alternative Medicine, 19(1), 316. [CrossRef]
• 4. Shaban, N.Z., Sleem, A.A., Abu-Serie, M.M., Maher, A.M., Habashy, N.H. (2022). Regulation of the NF-κB signaling pathway and IL-13 in asthmatic rats by aerosol inhalation of the combined active constituents of Punica granatum juice and peel. Biomedicine & Pharmacotherapy, 155, 113721. [CrossRef]
• 5. Cusack, R.P., Satia, I., O’Byrne, P.M. (2020). Asthma maintenance and reliever therapy: Should this be the standard of care? Annals of allergy, asthma & immunology: Official publication of the American College of Allergy. Asthma and Immunology, 125(2), 150-155. [CrossRef]
• 6. Azman, S., Sekar, M., Bonam, S.R., Gan, S.H., Wahidin, S., Lum, P.T., Dhadde, S.B. (2021). Traditional medicinal plants conferring protection against ovalbumin-induced asthma in experimental animals: A review. Journal of Asthma and Allergy, 14, 641-662. [CrossRef]
• 7. Baker, J.G. (2005). The selectivity of β-adrenoceptor antagonists at the human β1, β2 and β3 adrenoceptors. British Journal of Pharmacology, 144(3), 317-322. [CrossRef]
• 8. Katzung, B.G. (2018). Basic and Clinical Pharmacology, McGraw-Hill, p.137-140.
• 9. Pera, T., Penn, R.B. (2014). Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway. Current Opinion in Pharmacology, 16, 72-81. [CrossRef]
• 10. Marques, L., Vale, N. (2022). Salbutamol in the management of asthma: A review. International Journal of Molecular Sciences, 23(22), 14207. [CrossRef]
• 11. Papi, A., Fabbri, L.M., Kerstjens, H.A.M., Rogliani, P., Watz, H., Singh, D. (2021). Inhaled long-acting muscarinic antagonists in asthma - A narrative review. European Journal of Internal Medicine, 85, 14-22. [CrossRef]
• 12. Albertson, T.E., Chenoweth, J.A., Pearson, S.J., Murin, S. (2020). The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). Expert Opinion on Pharmacotherapy, 21(2), 213-231. [CrossRef]
• 13. Arslan, B., Cxetin, G.P., Yilmaz, I. (2023). The role of long-acting antimuscarinic agents in the treatment of asthma. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 36(4), 189-209. [CrossRef]
• 14. Pinzi, L., Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18), 4331. [CrossRef]
• 15. Stanzione, F., Giangreco, I., Cole, J.C. (2021). Use of molecular docking computational tools in drug discovery. Progress In Medicinal Chemistry, 60, 273-343. [CrossRef]
• 16. Crampon, K., Giorkallos, A., Deldossi, M., Baud, S., Steffenel, L.A. (2022). Machine-learning methods for ligand-protein molecular docking. Drug Discovery Today, 27(1), 151-164. [CrossRef]
• 17. Pirintsos, S., Panagiotopoulos, A., Bariotakis, M., Daskalakis, V., Lionis, C., Sourvinos, G., Karakasiliotis, I., Kampa, M., Castanas, E. (2022). From traditional ethnopharmacology to modern natural drug discovery: A methodology discussion and specific examples. Molecules, 27(13), 4060. [CrossRef]
• 18. PubChem Web site. (2004). Retrieved June 24, 2023, from https://pubchem.ncbi.nlm.nih.gov/. Accessed date: 04.08.2025.
• 19. RCSB PDB Web site. (1999). Retrieved June 26, 2023, from https://www.rcsb.org/. Accessed date: 04.08.2025.
• 20. PyRx – Python Prescription – Virtual Screening Tool Web site. (2010). Retrieved July 12, 2023, from https://pyrx.sourceforge.io/. Accessed date: 04.08.2025.
• 21. Prasanth, D.S.N.B.K., Murahari, M., Chandramohan, V., Panda, S.P., Atmakuri, L.R., Guntupalli, C. (2021). In silico identification of potential inhibitors from Cinnamon against main protease and spike glycoprotein of SARS CoV-2. Journal of Biomolecular Structure and Dynamics, 39(13), 4618-4632. [CrossRef]
• 22. SwissADME Web site. (2016). Retrieved December 13, 2024, from http://www.swissadme.ch/. Accessed date: 04.08.2025.
• 23. ADMETlab 3.0. Web site. (2018). Retrieved December 13, 2024, from https://admetlab3.scbdd.com/. Accessed date: 04.08.2025
• 24. Lommatzsch, M., Virchow, J.C. (2014). Severe asthma: Definition, diagnosis and treatment. Deutsches Arzteblatt international, 111(50), 847-855. [CrossRef]
• 25. Upreti, S., Prusty, J.S., Pandey, S.C., Kumar, A., Samant, M. (2021). Identification of novel inhibitors of angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19). Molecular Diversity, 25(3), 1795–1809. [CrossRef]
• 26. Nam, S.Y., Kim, M.H., Seo, Y., Choi, Y., Jang, J.B., Kang, I.C., Kim, M.J., Pak, S.C., Kim, H.M., Jeong, H.J. (2014). The (2’S,7’S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis-control agent. Life Sciences, 98(2), 103-112. [CrossRef]
• 27. Bezerra Barros, G.C., Paiva Ferreira, L.K.D., Ferreira, L.A.M.P., Mozzini Monteiro, T., Alves, A.F., Pereira, R. de A., Piuvezam, M.R. (2020). 4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis. International Immunopharmacology, 88, 106938. [CrossRef]
• 28. Yocum, G.T., Yocum, G.T., Hwang, J.J., Mikami, M., Danielsson, J., Kuforiji, A.S., Emala, C.W. (2020). Ginger and its bioactive component 6-shogaol mitigate lung inflammation in a murine asthma model. American Journal of Physiology Lung Cellular and Molecular Physiology, 318(2), L296-L303. [CrossRef]
• 29. Chang, J.H., Chuang, H.C., Hsiao, G., Hou, T.Y., Wang, C.C., Huang, S.C., Li, B.Y., Lee, Y.L. (2022). Acteoside exerts immunomodulatory effects on dendritic cells via aryl hydrocarbon receptor activation and ameliorates Th2-mediated allergic asthma by inducing Foxp3+ regulatory T cells. International Immunopharmacology, 106, 108603. [CrossRef]
• 30. Li, J., Zhang, B. (2013). Apigenin protects ovalbumin-induced asthma through the regulation of Th17 cells. Fitoterapia, 91, 298–304. [CrossRef]
• 31. Xu, T., Ge, X., Lu, C., Dai, W., Chen, H., Xiao, Z., Wu, L., Liang, G., Ying, S., Zhang, Y., Dai, Y. (2019). Baicalein attenuates OVA-induced allergic airway inflammation through the inhibition of the NF-κB signaling pathway. Aging, 11(21), 9310-9327. [CrossRef]
• 32. Liu, J., Wei, Y., Luo, Q., Xu, F., Zhao, Z., Zhang, H., Lu, L., Sun, J., Liu, F., Du, X., Li, M., Wei, K., Dong, J. (2016). Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-κB and suppressing CCR7/CCL19/CCL21. International Journal of Molecular Medicine, 38(5), 1541-1548. [CrossRef]
• 33. Li, Z., Zheng, J., Zhang, N., Li, C. (2016). Berberine improves airway inflammation and inhibits NF-κB signaling pathway in an ovalbumin-induced rat model of asthma. The Journal of Asthma, 53(10), 999-1005. [CrossRef]
• 34. Nie, Y., Yang, B., Hu, J., Zhang, L., Ma, Z. (2021). Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway. Allergologia Et Immunopathologia, 49(6), 73-79. [CrossRef]
• 35. Liao, W., Foo, H.Y.C., Tran, T.N.Q., Chai, C.L.L., Wong, W.S.F. (2023). Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function. British Journal of Pharmacology, 180(8), 1056-1071. [CrossRef]
• 36. Yuan, W.Y., Li, L.Q., Chen, Y.Y., Zhou, Y.J., Bao, K.F., Zheng, J., Hua, Y.Q., Jiang, G.R., Hong, M. (2020). Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein-coupled estrogen receptor: Probing a possible target for allergic inflammation. Journal of Leukocyte Biology, 108(1), 59–71. [CrossRef]
• 37. Boskabady, M.H., Jalali, S. (2013). Effect of carvacrol on tracheal responsiveness, inflammatory mediators, total and differential WBC count in blood of sensitized guinea pigs. Experimental Biology and Medicine, 238(2), 200-208. [CrossRef]
• 38. Liou, C.J., Cheng, C.Y., Yeh, K.W., Wu, Y.H., Huang, W.C. (2018). Protective effects of casticin from vitex trifolia alleviate eosinophilic airway inflammation and oxidative stress in a murine asthma model. Frontiers in Pharmacology, 9, 635. [CrossRef]
• 39. Chakraborty, S., Kar, N., Kumari, L., De, A., Bera, T. (2017). Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock in mice. International Journal of Nanomedicine, 12, 4849-4868. [CrossRef]
• 40. Zeng, Z., Lin, X., Zheng, R., Zhang, H., Zhang, W. (2018). Celastrol alleviates airway hyperresponsiveness and inhibits Th17 responses in obese asthmatic mice. Frontiers in Pharmacology, 9, 49. [CrossRef]
• 41. Roy, S., Manna, K., Jha, T., Saha, K. Das (2020). Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis. Nanomedicine: Nanotechnology, Biology, and Medicine, 30, 102292. [CrossRef]
• 42. Lim, H.J., Lee, J.H., Choi, J.S., Lee, S.K., Kim, Y.S., Kim, H.P. (2014). Inhibition of airway inflammation by the roots of Angelica decursiva and its constituent, columbianadin. Journal of Ethnopharmacology, 155(2), 1353-1361. [CrossRef]
• 43. Li, J., Zheng, M., Wang, C., Jiang, J., Xu, C., Li, L., Li, L., Yan, G., Jin, Y. (2020). Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Bioscience, Biotechnology, and Biochemistry, 84(2), 268-278. [CrossRef]
• 44. Zhu, X., Cao, Y., Su, M., Chen, M., Li, C., Yi, L., Qin, J., Tulake, W., Teng, F., Zhong, Y., Tang, W., Wang, S., Dong, J. (2021). Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy. Molecular Medicine Reports, 24(5), 805. [CrossRef]
• 45. Zhang, Y., Qu, L., Sun, Y., Lin, Y.P., Zeng, J., He, L.X., Li, X., Gu, W., Nie, J., Yu, X., Tong, X.Y., Huang, F. (2022). Daphnetin contributes to allergen-induced Th2 cytokine expression and type 2-immune responses in atopic dermatitis and asthma. Food and Function, 13(23), 12383-12399. [CrossRef]
• 46. Santana, F.P.R., da Silva, R.C., Ponci, V., Pinheiro, A.J.M.C.R., Olivo, C.R., Caperuto, L.C., Arantes-Costa, F.M., Claudio, S.R., Ribeiro, D.A., Tibério, I.F.L.C., Lima-Neto, L.G., Lago, J.H.G., Prado, C.M. (2020). Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways. Biochemical Pharmacology, 180, 114175. [CrossRef]
• 47. Shin, N.R., Ryu, H.W., Ko, J.W., Park, S.H., Yuk, H.J., Kim, H.J., Kim, J.C., Jeong, S.H., Shin, I.S. (2017). Artemisia argyi attenuates airway inflammation in ovalbumin-induced asthmatic animals. Journal of Ethnopharmacology, 209, 108-115. [CrossRef]
• 48. Liu, W., Wang, Y., He, D.D., Li, S.P., Zhu, Y.D., Jiang, B., Cheng, X.M., Wang, Z.T., Wang, C.H. (2015). Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L. Phytomedicine, 22(12), 1088-1095. [CrossRef]
• 49. Xu, B., Huang, S., Wang, C., Zhang, H., Fang, S., Zhang, Y. (2017). Anti inflammatory effects of dihydromyricetin in a mouse model of asthma. Molecular Medicine Reports, 15(6), 3674-3680. [CrossRef]
• 50. Junchao, Y., Zhen, W., Yuan, W., Liying, X., Libin, J., Yuanhong, Z., Wei, Z., Ruilin, C., Lu, Z. (2017). Anti-trachea inflammatory effects of diosgenin from Dioscorea nipponica through interactions with glucocorticoid receptor α. The Journal of International Medical Research, 45(1), 101-113. [CrossRef]
• 51. Poachanukoon, O., Meesuk, L., Pattanacharoenchai, N., Monthanapisut, P., Ayudhya, T.D.N., Koontongkaew, S. (2015). Zingiber cassumunar ROXb. and its active constituent inhibit MMP-9 direct activation by house dust mite allergens and MMP-9 expression in PMA-stimulated human airway epithelial cells. Asian Pacific Journal of Allergy and Immunology, 33(1), 42-51. [CrossRef]
• 52. De Freitas Alves, C., Angeli, G.N., Favarin, D.C., Lemos De Andrade, E., Lazo Chica, J.E., Faccioli, L.H., Roberto Da Silva, P., De Paula Rogerio, A. (2013). The effects of proresolution of ellagic acid in an experimental model of allergic airway inflammation. Mediators of Inflammation, 2013, 863198. [CrossRef]
• 53. Rodrigues, L.B., Oliveira Brito Pereira Bezerra Martins, A., Cesário, F.R.A.S., Ferreira e Castro, F., de Albuquerque, T.R., Martins Fernandes, M.N., Fernandes da Silva, B.A., Quintans Júnior, L.J., da Costa, J.G.M., Melo Coutinho, H.D., Barbosa, R., Alencar de Menezes, I.R. (2016). Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models. Chemico-Biological Interactions, 257, 14-25. [CrossRef]
• 54. Andarini, I., Salimo, H., Purwanto, B., Rahardjo, S.S., Wasita, B., Widyaningsih, V. (2021). Ethyl p-methoxycinnamate isolated from Kaempferia galanga L. rhizome reduces airway remodeling in asthmatic rat models. Bali Medical Journal, 10(3), 1006-1009. [CrossRef]
• 55. Kennedy-Feitosa, E., Oliveira-Melo, P., Evangelista-Costa, E., Serra, D.S., Cavalcante, F.S.Á., da Ponte, E.L., Barbosa, R., da Silva, R.E.R., Assreuy, A.M.S., Leal-Cardoso, J.H., Lima, C.C. (2020). Eucalyptol reduces airway hyperresponsiveness in rats following cigarette smoke-exposed. Pulmonary Pharmacology and Therapeutics, 61, 101887. [CrossRef]
• 56. Ku, C.M., Lin, J.Y. (2015). Farnesol, a sesquiterpene alcohol in herbal plants, exerts anti-inflammatory and antiallergic effects on ovalbumin-sensitized and -challenged asthmatic mice. Evidence-Based Complementary and Alternative Medicine, 2015, 385357. [CrossRef]
• 57. Wu, S.J., Huang, W.C., Cheng, C.Y., Wang, M.C., Cheng, S.C., Liou, C.J. (2022). Fisetin suppresses the inflammatory response and oxidative stress in bronchial epithelial cells. Nutrients, 14(9), 1841. [CrossRef]
• 58. Yuan, S., Cao, S., Jiang, R., Liu, R., Bai, J., Hou, Q. (2014). FLLL31, a derivative of curcumin, attenuates airway inflammation in a multi-allergen challenged mouse model. International Immunopharmacology, 21(1), 128–136. [CrossRef]
• 59. Yang, C., Tian, J., Ko, W., Shih, C., Chiou, Y. (2019). Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study. Experimental and Therapeutic Medicine, 17(1), 3-10. [CrossRef]
• 60. Wu, S.J., Liou, C.J., Chen, Y.L., Cheng, S.C., Huang, W.C. (2021). Fucoxanthin ameliorates oxidative stress and airway inflammation in tracheal epithelial cells and asthmatic mice. Cells, 10(6), 1311. [CrossRef]
• 61. Deng, Y., Guan, M., Xie, X., Yang, X., Xiang, H., Li, H., Zou, L., Wei, J., Wang, D., Deng, X. (2013). Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. International Immunopharmacology, 17(3), 561-567. [CrossRef]
• 62. Ahmed, Z.H., Zalzala, M.H. (2021). The anti-asthmatic activity of guggulsterone study the anti-asthmatic activity of guggulsterone in ovalbumin-induced asthma in rat. Iraqi Journal of Pharmaceutical Sciences, 30(2). [CrossRef]‬‬‬‬‬
• 63. Pina, L.T.S., Ferro, J.N.S., Rabelo, T.K., Oliveira, M.A., Scotti, L., Scotti, M.T., Walker, C.I.B., Barreto, E.O., Quintans Júnior, L.J., Guimarães, A.G. (2019). Alcoholic monoterpenes found in essential oil of aromatic spices reduce allergic inflammation by the modulation of inflammatory cytokines. Natural Product Research, 33(12), 1773-1777. [CrossRef]
• 64. Wu, W., Li, Y., Jiao, Z., Zhang, L., Wang, X., Qin, R. (2019). Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: Role of IgE, Nrf2, iNOs, TNF-α, and IL’s. Immunopharmacology and Immunotoxicology, 41(1), 55-67. [CrossRef]
• 65. Hu, L., Li, L., Zhang, H., Li, Q., Jiang, S., Qiu, J., Sun, J., Dong, J. (2019). Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complementary and Alternative Medicine, 19(1), 316. [CrossRef]
• 66. Hsieh, C.C., Ng, Y.Y., Li, W.S., Tzeng, C.Y., Hsu, T.Y., Huang, W.H., Tsai, J.C. (2022). Ameliorative effect of imperatorin on Dermatophagoides pteronyssinus-induced allergic asthma by suppressing the Th2 response in mice. Molecules, 27(20), 7028. [CrossRef]
• 67. Cao, M., Zhan, M., Wang, Z., Wang, Z., Li, X.M., Miao, M. (2020). Development of an orally bioavailable isoliquiritigenin self-nanoemulsifying drug delivery system to effectively treat ovalbumin-induced asthma. International Journal of Nanomedicine, 15, 8945-8961. [CrossRef]
• 68. Rogerio, A.P., Kanashiro, A., Fontanari, C., Da Silva, E.V.G., Lucisano-Valim, Y.M., Soares, E.G., Faccioli, L.H. (2007). Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflammation Research, 56(10), 402-408. [CrossRef]
• 69. Huang, W.C., Liu, C.Y., Shen, S.C., Chen, L.C., Yeh, K.W., Liu, S.H., Liou, C.J. (2019). Protective effects of licochalcone a improve airway hyper-responsiveness and oxidative stress in a mouse model of asthma. Cells, 8(6), 617. [CrossRef]
• 70. Ji, N.F., Xie, Y.C., Zhang, M.S., Zhao, X., Cheng, H., Wang, H., Yin, K.S., Huang, M. (2014). Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model. International Immunopharmacology, 21(1), 76-81. [CrossRef]
• 71. Kim, M.G., Kim, S.M., Min, J.H., Kwon, O.K., Park, M.H., Park, J.W., Ahn, H.I., Hwang, J.Y., Oh, S.R., Lee, J.W., Ahn, K.S. (2019). Anti-inflammatory effects of linalool on ovalbumin-induced pulmonary inflammation. International Immunopharmacology, 74, 105706. [CrossRef]
• 72. Shen, M.L., Wang, C.H., Lin, C.H., Zhou, N., Kao, S. Te, Wu, D.C. (2016). Luteolin attenuates airway mucus overproduction via inhibition of the GABAergic system. Scientific Reports, 6(6), 32756. [CrossRef]
• 73. Shin, K., Chung, H.C., Kim, D.U., Hwang, J.K., Lee, S.H. (2013). Macelignan attenuated allergic lung inflammation and airway hyper-responsiveness in murine experimental asthma. Life Sciences, 92(22), 1093-1099. [CrossRef]
• 74. Huang, Q., Han, L., Lv, R., Ling, L. (2019). Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice. The Korean Journal of Physiology and Pharmacology, 23(4), 251-261. [CrossRef]
• 75. Yun, C., Chang, M., Hou, G., Lan, T., Yuan, H., Su, Z., Zhu, D., Liang, W., Li, Q., Zhu, H., Zhang, J., Lu, Y., Deng, J., Guo, H. (2019). Mangiferin suppresses allergic asthma symptoms by decreased Th9 and Th17 responses and increased Treg response. Molecular Immunology, 114, 233-242. [CrossRef]
• 76. Su, Y.H., Lin, J.Y. (2022). Menthone inhalation alleviates local and systemic allergic inflammation in ovalbumin-sensitized and challenged asthmatic mice. International Journal of Molecular Sciences, 23(7), 4011. [CrossRef]
• 77. Franova, S., Kazimierova, I., Pappova, L., Joskova, M., Plank, L., Sutovska, M. (2016). Bronchodilatory, antitussive and anti-inflammatory effect of morin in the setting of experimentally induced allergic asthma. The Journal of Pharmacy and Pharmacology, 68(8), 1064-1072. [CrossRef]
• 78. Rajizadeh, M.A., Najafipour, H., Fekri, M.S., Rostamzadeh, F., Jafari, E., Bejeshk, M.A., Masoumi-Ardakani, Y. (2019). Anti-inflammatory and anti-oxidative effects of myrtenol in the rats with allergic asthma. Iranian Journal of Pharmaceutical Research, 18(3), 1488–1498.
• 79. Fuchs, S., Hsieh, L.T., Saarberg, W., Erdelmeier, C.A.J., Wichelhaus, T.A., Schaefer, L., Koch, E., Fürst, R. (2015). Haemanthus coccineus extract and its main bioactive component narciclasine display profound anti-inflammatory activities in vitro and in vivo. Journal of Cellular and Molecular Medicine, 19(5), 1021-1032. [CrossRef]
• 80. Lee, Y.S., Yang, W.K., Yee, S.M., Kim, S.M., Park, Y.C., Shin, H.J., Han, C.K., Lee, Y.C., Kang, H.S., Kim, S.H. (2019). KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice. Phytomedicine, 62, 152942. [CrossRef]
• 81. Lu, Y., Cai, S., Nie, J., Li, Y., Shi, G., Hao, J., Fu, W., Tan, H., Chen, S., Li, B., Xu, H. (2016). The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma. Biochemical Pharmacology, 100, 61-72. [CrossRef]
• 82. Kim, S.H., Hong, J.H., Lee, Y.C. (2014). Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factors T-bet, GATA-3, RORγt and Foxp3 in asthmatic mice. International Immunopharmacology, 18(2), 311-324. [CrossRef]
• 83. Lee, S.Y., Bae, C.S., Seo, N.S., Na, C.S., Yoo, H.Y., Oh, D.S., Bae, M.S., Kwon, M.S., Cho, S.S., Park, D.H. (2019). Camellia japonica oil suppressed asthma occurrence via GATA-3 & IL-4 pathway and its effective and major component is oleic acid. Phytomedicine, 57, 84-94. [CrossRef]
• 84. Zhou, D.G., Diao, B.Z., Zhou, W., Feng, J.L. (2016). Oroxylin a inhibits allergic airway inflammation in ovalbumin (OVA)-induced asthma murine model. Inflammation, 39(2), 867-872. [CrossRef]
• 85. Yang, Q., Kong, L., Huang, W., Mohammadtursun, N., Li, X., Wang, G., Wang, L. (2020). Osthole attenuates ovalbumin induced lung inflammation via the inhibition of IL 33/ST2 signaling in asthmatic mice. International Journal of Molecular Medicine, 46(4), 1389-1398. [CrossRef]
• 86. Wang, C.N., Lee, Y.L., Lin, Y.P., Chung, W.H., Tzeng, Y.M., Lee, C.C. (2017). Ovatodiolide suppresses allergic airway inflammation and hyperresponsiveness in a murine model of asthma. European Journal of Pharmacology, 812, 9-17. [CrossRef]
• 87. Ashraf, M.I., Shahzad, M., Shabbir, A. (2015). Oxyresveratrol ameliorates allergic airway inflammation via attenuation of IL-4, IL-5, and IL-13 expression levels. Cytokine, 76(2), 375-381. [CrossRef]
• 88. Shou, Q., Jin, L., Lang, J., Shan, Q., Ni, Z., Cheng, C., Li, Q., Fu, H., Cao, G. (2019). Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying paeoniflorin for the treatment of allergic asthma. Frontiers in Pharmacology, 9, 1531. [CrossRef]
• 89. Wu, W., Li, Y., Jiao, Z., Zhang, L., Wang, X., Qin, R. (2019). Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: Role of IgE, Nrf2, iNOs, TNF-α, and IL’s. Immunopharmacology and Immunotoxicology, 41(1), 55-67. [CrossRef]
• 90. Song, H.H., Shin, I.S., Woo, S.Y., Lee, S.U., Sung, M.H., Ryu, H.W., Kim, D.Y., Ahn, K.S., Lee, H.K., Lee, D., Oh, S.R. (2015). Piscroside C, a novel iridoid glycoside isolated from Pseudolysimachion rotundum var. subinegrum suppresses airway inflammation induced by cigarette smoke. Journal of Ethnopharmacology, 170, 20-27. [CrossRef]
• 91. Xu, R., Deng, H., Gan, L., Zhong, L., Deng, Y., Wang, Q., Lv, C., Huang, L. (2022). Chinese herbal component, Praeruptorin E, enhances anti-asthma efficacy and prevents toxicity of aminophylline by targeting the NF-κB/PXR/CYP3A4 pathway. Annals of Translational Medicine, 10(4), 225-225. [CrossRef]
• 92. Wei, M., Chu, X., Guan, M., Yang, X., Xie, X., Liu, F., Chen, C., Deng, X. (2013). Protocatechuic acid suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. International Immunopharmacology, 15(4), 780-788. [CrossRef]
• 93. Song, Y., Wu, Y., Li, X., Shen, Y., Ding, Y., Zhu, H., Liu, F., Yu, K., Sun, L., Qian, F. (2018). Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation. Biochemical Pharmacology, 155, 198-206. [CrossRef]
• 94. Yamamoto, T., Matsunami, E., Komori, K., Hayashi, S., Kadowaki, M. (2019). The isoflavone puerarin induces Foxp3+ regulatory T cells by augmenting retinoic acid production, thereby inducing mucosal immune tolerance in a murine food allergy model. Biochemical and Biophysical Research Communications, 516(3), 626-631. [CrossRef]
• 95. Min, Z., Zhou, J., Mao, R., Cui, B., Cheng, Y., Chen, Z. (2022). Pyrroloquinoline quinone administration alleviates allergic airway inflammation in mice by regulating the JAK-STAT signaling pathway. Mediators of Inflammation, 2022, 1267841. [CrossRef]
• 96. Oliveira, T.T., Campos, K.M., Cerqueira-Lima, A.T., Carneiro, T.C.B., Da Silva Velozo, E., Melo, I.C.A.R., Figueiredo, E.A., De Jesus Oliveira, E., De Vasconcelos, D.F.S.A., Pontes-De-Carvalho, L.C., Alcântara-Neves, N.M., Figueiredo, C.A. (2015). Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. DARU Journal of Pharmaceutical Sciences, 23(1), 18. [CrossRef]
• 97. Wu, X.N., Yang, Y., Zhang, H.H., Zhong, Y. Sen, Wu, F., Yu, B., Yu, C.H. (2020). Robustaflavone-4’-dimethyl ether from Selaginella uncinata attenuated lipopolysaccharide-induced acute lung injury via inhibiting FLT3-mediated neutrophil activation. International Immunopharmacology, 82, 106338. [CrossRef]
• 98. Yang, H., Sun, W., Ma, P., Yao, C., Fan, Y., Li, S., Yuan, J., Zhang, Z., Li, X., Lin, M., Hou, Q. (2020). Multiple components rapidly screened from perilla leaves attenuate asthma airway inflammation by synergistic targeting on Syk. Journal of Inflammation Research, 13, 897-911. [CrossRef]
• 99. Shakeri, F., Eftekhar, N., Roshan, N.M., Rezaee, R., Moghimi, A., Boskabady, M.H. (2019). Rosmarinic acid affects immunological and inflammatory mediator levels and restores lung pathological features in asthmatic rats. Allergologia et Immunopathologia, 47(1), 16-23. [CrossRef]
• 100. Chan, T.K., Ng, D.S.W., Cheng, C., Guan, S.P., Koh, H.M., Wong, W.S.F. (2013). Anti-allergic actions of rottlerin from Mallotus philippinensis in experimental mast cell-mediated anaphylactic models. Phytomedicine, 20(10), 853–860. [CrossRef]
• 101. Shin, N.R., Kwon, H.J., Ko, J.W., Kim, J.S., Lee, I.C., Kim, J.C., Kim, S.H., Shin, I.S. (2019). S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model. International Immunopharmacology, 68, 124-130. [CrossRef]
• 102. Lertnimitphun, P., Zhang, W., Fu, W., Yang, B., Zheng, C., Yuan, M., Zhou, H., Zhang, X., Pei, W., Lu, Y., Xu, H. (2021). Safranal alleviated OVA-induced asthma model and inhibits mast cell activation. Frontiers in Immunology, 12, 585595. [CrossRef]
• 103. Ingawale, D.K., Mandlik, S.K., Patel, S.S. (2020). Combination of Sarsasapogenin and Fluticasone attenuates ovalbumin-induced airway inflammation in a mouse asthma model. Immunopharmacology and Immunotoxicology, 42(2), 128-137. [CrossRef]
• 104. Chen, Y., Kong, Y., Wang, Q., Chen, J., Chen, H., Xie, H., Li, L. (2021). Schisandrin B attenuates airway inflammation by regulating the NF- κ B/Nrf2 signaling pathway in mouse models of asthma. Journal of Immunology Research, 2021, 8029963. [CrossRef]
• 105. Wu, Z., Jia, M., Zhao, W., Huang, X., Yang, X., Chen, D., Qiaolongbatu, X., Li, X., Wu, J., Qian, F., Lou, Y., Fan, G. (2022). Schisandrol A, the main active ingredient of Schisandrae chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-β signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification. Journal of Ethnopharmacology, 289, 115031. [CrossRef]
• 106. Liou, C.J., Chen, Y.L., Yu, M.C., Yeh, K.W., Shen, S.C., Huang, W.C. (2020). Sesamol alleviates airway hyperresponsiveness and oxidative stress in asthmatic mice. Antioxidants, 9(4), 295. [CrossRef]
• 107. Nasab, E.M., Athari, S.M., Ghafarzade, S., Nasab, A.R.M., Athari, S.S. (2020). Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergologia et Immunopathologia, 48(6), 646-653. [CrossRef]
• 108. Saeedavi, M., Goudarzi, M., Mehrzadi, S., Basir, Z., Hasanvand, A., Hosseinzadeh, A. (2022). Sinapic acid ameliorates airway inflammation in murine ovalbumin-induced allergic asthma by reducing Th2 cytokine production. Life Sciences, 307, 120858. [CrossRef]
• 109. Chu, S., Liu, W., Lu, Y., Yan, M., Guo, Y., Chang, N., Jiang, M., Bai, G. (2020). Sinigrin enhanced antiasthmatic effects of beta-adrenergic receptors agonists by regulating cAMP-mediated pathways. Frontiers in Pharmacology, 11, 723. [CrossRef]
• 110. Arora, P., Nainwal, L.M., Gupta, G., Singh, S.K., Chellappan, D.K., Oliver, B.G., Dua, K. (2022). Orally administered solasodine, a steroidal glycoalkaloid, suppresses ovalbumin-induced exaggerated Th2-immune response in rat model of bronchial asthma. Chemico-Biological Interactions, 366, 110138. [CrossRef]
• 111. Wang, M.C., Huang, W.C., Chen, L.C., Yeh, K.W., Lin, C.F., Liou, C.J. (2022). Sophoraflavanone G from sophora flavescens ameliorates allergic airway inflammation by suppressing Th2 response and oxidative stress in a murine asthma model. International Journal of Molecular Sciences, 23(11), 6104. [CrossRef]
• 112. Kim, B.H., Lee, S. (2021). Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice. Biomedicine and Pharmacotherapy, 133, 111029. [CrossRef]
• 113. Huang, W.C., Huang, C.H., Hu, S., Peng, H.L., Wu, S.J. (2019). Topical spilanthol inhibits MAPK signaling and ameliorates allergic inflammation in DNCB-induced atopic dermatitis in mice. International Journal of Molecular Sciences, 20(10), 2490. [CrossRef]
• 114. Fu, M., Zou, B., An, K., Yu, Y., Tang, D., Wu, J., Xu, Y., Ti, H. (2019). Anti-asthmatic activity of alkaloid compounds from Pericarpium Citri Reticulatae (Citrus reticulata ’Chachi’). Food and Function, 10(2), 903–911. [CrossRef]
• 115. Dai, R., Niu, M., Wang, N., Wang, Y. (2021). Syringin alleviates ovalbumin-induced lung inflammation in BALB/c mice asthma model via NF-κB signaling pathway. Environmental Toxicology, 36(3), 433-444. [CrossRef]
• 116. Lin, Y., Yao, J., Wu, M., Ying, X., Ding, M., Wei, Y., Fu, X., Feng, W., Wang, Y. (2019). Tetrandrine ameliorates airway remodeling of chronic asthma by interfering TGF- β 1/Nrf-2/HO-1 signaling pathway-mediated oxidative stress. Canadian Respiratory Journal, 2019, 7930396. [CrossRef]
• 117. Zhou, E., Fu, Y., Wei, Z., Yu, Y., Zhang, X., Yang, Z. (2014). Thymol attenuates allergic airway inflammation in ovalbumin (OVA)-induced mouse asthma. Fitoterapia, 96, 131-137. [CrossRef]
• 118. Kuo, C.Y., Huang, W.C., Liou, C.J., Chen, L.C., Shen, J.J., Kuo, M.L. (2017). Tomatidine attenuates airway hyperresponsiveness and inflammation by suppressing Th2 cytokines in a mouse model of asthma. Mediators of Inflammation, 2017, 5261803. [CrossRef]
• 119. Sung, Y.Y., Kim, S.H., Kim, D.S., Lee, J.E., Kim, H.K. (2017). Illicium verum extract and trans-anethole attenuate ovalbumin-induced airway inflammation via enhancement of Foxp3+ regulatory T cells and inhibition of Th2 cytokines in mice. Mediators of Inflammation, 2017, 7506808. [CrossRef]
• 120. Liu, W., Wang, Y., He, D.D., Li, S.P., Zhu, Y.D., Jiang, B., Cheng, X.M., Wang, Z.T., Wang, C.H. (2015). Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L. Phytomedicine, 22(12), 1088-1095. [CrossRef]
• 121. Yang, H., Sun, W., Ma, P., Yao, C., Fan, Y., Li, S., Yuan, J., Zhang, Z., Li, X., Lin, M., Hou, Q. (2020). Multiple components rapidly screened from perilla leaves attenuate asthma airway inflammation by synergistic targeting on Syk. Journal of Inflammation Research, 13, 897-911. [CrossRef]
• 122. Venturini, C.L., Macho, A., Arunachalam, K., de Almeida, D.A.T., Rosa, S.I.G., Pavan, E., Balogun, S.O., Damazo, A.S., de Oliviera Martins, D.T. (2018). Vitexin inhibits inflammation in murine ovalbumin-induced allergic asthma. Biomedicine and Pharmacotherapy, 97, 143-151. [CrossRef]
• 123. Zhao, H., Gao, Z., Xie, S., Han, X., Sun, Q. (2019). Withaferin A attenuates ovalbumin induced airway inflammation. Frontiers in Bioscience, 24(3), 576-596. [CrossRef]
• 124. Takagi, R., Kawano, M., Nakagome, K., Hashimoto, K., Higashi, T., Ohbuchi, K., Kaneko, A., Matsushita, S. (2014). Wogonin attenuates ovalbumin antigen-induced neutrophilic airway inflammation by inhibiting th17 differentiation. International Journal of Inflammation, 2014, 571508. [CrossRef]
• 125. Abohalaka, R. (2023). Bronchial epithelial and airway smooth muscle cell interactions in health and disease. Heliyon, 9(9), e19976. [CrossRef]
• 126. Li, J., Zheng, M., Wang, C., Jiang, J., Xu, C., Li, L., Li, L., Yan, G., Jin, Y. (2020). Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Bioscience, Biotechnology, and Biochemistry, 84(2), 268-278. [CrossRef]
• 127. Zhao, H., Gao, Z., Xie, S., Han, X., Sun, Q. (2019). Withaferin A attenuates ovalbumin induced airway inflammation. Frontiers in Bioscience, 24(3), 576–596. [CrossRef]
• 128. Shou, Q., Jin, L., Lang, J., Shan, Q., Ni, Z., Cheng, C., Li, Q., Fu, H., Cao, G. (2019). Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying paeoniflorin for the treatment of allergic asthma. Frontiers in Pharmacology, 9, 1531. [CrossRef]
• 129. Parlar, A., Arslan, S.O. (2019). Thymoquinone exhibits anti-inflammatory, antioxidant, and immunomodulatory effects on allergic airway inflammation. Archives of Clinical and Experimental Medicine, 4(2), 60–65. [CrossRef]
• 130. Dogan, M.F., Parlar, A., Cam, S.A., Tosun, E.M., Uysal, F., Arslan, S.O. (2020). Glabridin attenuates airway inflammation and hyperresponsiveness in a mice model of ovalbumin-induced asthma. Pulmonary Pharmacology and Therapeutics, 63, 101936. [CrossRef]
• 131. Deng, Y., Guan, M., Xie, X., Yang, X., Xiang, H., Li, H., Zou, L., Wei, J., Wang, D., Deng, X. (2013). Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. International Immunopharmacology, 17(3), 561-567. [CrossRef]
• 132. Wang, C.N., Lee, Y.L., Lin, Y.P., Chung, W.H., Tzeng, Y.M., Lee, C.C. (2017). Ovatodiolide suppresses allergic airway inflammation and hyperresponsiveness in a murine model of asthma. European Journal of Pharmacology, 812, 9-17. [CrossRef]
• 133. Li, Z., Gao, H., Li, J., Zhang, Y. (2017). Identification of bioactive compounds in Shaoyao-Gancao decoction using β2-adrenoceptor affinity chromatography. Journal of Separation Science, 40(12), 2558-2564. [CrossRef]
• 134. Wang, J., Zhao, X., Yuan, X., Hao, J., Chang, Z., Li, Q., Zhao, X. (2021). Rapid screening of bioactive compound in Sanzi Yangqin Decoction and investigating of binding mechanism by immobilized β2-adrenogic receptor chromatography coupled with molecular docking. Journal of Pharmaceutical and Biomedical Analysis, 197, 113957. [CrossRef]
• 135. Saadat, S., Naghdi, F., Ghorani, V., Rakhshandeh, H., Boskabady, M.H. (2019). Histamine (H1) receptors, cyclooxygenase pathway and nitric oxide formation involved in rat tracheal smooth muscle relaxant effect of berberine. Iranian Journal of Allergy, Asthma, and immunology, 18(3), 320-331. [CrossRef]
• 136. Sánchez-Mendoza, M.E., Castillo-Henkel, C., Navarrete, A. (2008). Relaxant action mechanism of berberine identified as the active principle of Argemone ochroleuca Sweet in guinea-pig tracheal smooth muscle. The Journal of Pharmacy and Pharmacology, 60(2), 229-236. [CrossRef]
• 137. Goldklang, M.P., Perez-Zoghbi, J.F., Trischler, J., Nkyimbeng, T., Zakharov, S.I., Shiomi, T., Zelonina, T., Marks, A.R., D’Armiento, J.M., Marx, S.O. (2013). Treatment of experimental asthma using a single small molecule with anti-inflammatory and BK channel-activating properties. FASEB Journal, 27(12), 4975-4986. [CrossRef]
• 138. Brown, A., Danielsson, J., Townsend, E.A., Zhang, Y., Perez-Zoghbi, J.F., Emala, C.W., Gallos, G. (2016). Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ. American Journal of Physiology Lung Cellular and Molecular Physiology, 310(8), L747-L758. [CrossRef]
• 139. Ko, W.C., Shih, C.M., Leu, I.J., Chen, T.T., Chang, J.P. (2005). Mechanisms of relaxant action of luteolin in isolated guinea pig trachea. Planta Medica, 71(5), 406-411. [CrossRef]
• 140. Gupta, M., Sharma, R., Kumar, A. (2018). Docking techniques in pharmacology: How much promising? Computational Biology and Chemistry, 76, 210-217. [CrossRef]