Harmaline Improves Oxidative Stress and Inflammatory Markers in Human Lung Epithelial Cells Exposed to Elastase

Document Type : Original Research

Authors
K. Hoseinynejad 1
M. gholipour 2
F. Nejad dehbashi 2
M. radan 1
1 Department of Physiology, Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Abstract
Background: Harmaline exhibits a diverse array of pharmacological properties, including antimicrobial, antidiabetic, osteogenic, immunomodulatory, emmenagogue, and antitumor activities. The current study aimed to investigating the effect of harmaline on oxidative stress factors in lung epithelial cells exposed to elastase. Material and method: oxidative stress markers of lung epithelial cells were investigated in all cell groups including, control, H2O2, elastase and elastase plus harmaline (50, 100, 200 μm). lung epithelial cells (A549) were exposed to elastase with concentrations of 60 U/ml for 24 hours. In other groups, cells exposed to elastase were co-treated with three different doses of harmaline (50, 100 and 200 µm) for 24 hours at 37°C. Results: the results show a significant effect of harmaline's protective effect on cell viability, free radical production (ROS), malondialdehyde (MDA) and total antioxidant capacity (TAC). harmaline significantly increased the viability and TAC level in the cells exposed to elastase. Also, harmaline significantly decreased the percentage of free radicals and the MDA level in the cells exposed to elastase. Conclusion: The results obtained from this study showed a significant protective effect of harmaline on cell viability through increases in antioxidant defense system. Therefore, harmaline, can probably considered as a therapeutic strategy to prevent or treatment of lung diseases.

Keywords

Subjects

1. Barnes PJ. Oxidative stress in chronic obstructive pulmonary disease. Antioxidants. 2022 May 13;11(5):965.
2. Tanner L, Single AB. Animal models reflecting chronic obstructive pulmonary disease and related respiratory disorders: translating pre-clinical data into clinical relevance. Journal of innate immunity. 2020 May 20;12(3):203-25.
3. Voynow JA, Shinbashi M. Neutrophil elastase and chronic lung disease. Biomolecules. 2021 Jul 21;11(8):1065.
4. Zhang Y, Qi J, Yan D, Deng Y, Zhang J, Luo Q. HNE induces the hyperexpression of MUC5AC in chronic rhinosinusitis with nasal polyps by activating the TRAF6/autophagy regulatory axis. American Journal of Rhinology & Allergy. 2022 Nov;36(6):816-26.
5. Domon H, Nagai K, Maekawa T, Oda M, Yonezawa D, Takeda W, Hiyoshi T, Tamura H, Yamaguchi M, Kawabata S, Terao Y. Neutrophil elastase subverts the immune response by cleaving toll-like receptors and cytokines in pneumococcal pneumonia. Frontiers in immunology. 2018 Apr 25;9:732.
6. Krotova K, Khodayari N, Oshins R, Aslanidi G, Brantly ML. Neutrophil elastase promotes macrophage cell adhesion and cytokine production through the integrin-Src kinases pathway. Scientific reports. 2020 Sep 28;10(1):15874.
7. Saputra PB, Purwati DD, Ulhaq AU, Yolanda S, Djatioetomo YC, Rosyid AN, Bakhtiar A. Neutrophil Elastase in the Pathogenesis of Chronic Obstructive Pulmonary Disease: A Review. Current Respiratory Medicine Reviews. 2023 Feb 1;19(1):29-35.
8. Zhao J, Yang T, Qiao W, Ye Y, Zhang J, Luo Q. Human neutrophil elastase mediates MUC5AC hypersecretion via the tumour necrosis factor-α converting enzyme-epidermal growth factor receptor signalling pathway in vivo. ORL. 2021 Sep 22;83(5):310-8.
9. Barnes PJ. Oxidative stress-based therapeutics in COPD. Redox biology. 2020 Jun 1;33:101544.
10. Ou J, Wang M, Zheng J, Ou S. Positive and negative effects of polyphenol incorporation in baked foods. Food Chemistry. 2019.
11. Majid A. A review study of the chemical constituents and therapeutic effects of Peganum harmala L. Global J Pure Appl Chem Res. 2018 Oct;6(2):12-9.
12. Shahrajabian MH, Sun W, Cheng Q. Improving health benefits with considering traditional and modern health benefits of Peganum harmala. Clinical Phytoscience. 2021 Dec;7(1):1-9.
13. Liu W, Cheng X, Wang Y, Li S, Zheng T, Gao Y, Wang G, Qi S, Wang J, Ni J, Wang Z. In vivo evaluation of the antitussive, expectorant and bronchodilating effects of extract and fractions from aerial parts of Peganum harmala linn. Journal of ethnopharmacology. 2015 Mar 13;162:79-86.
14. Moradi MT, Karimi A, Fotouhi F, Kheiri S, Torabi A. In vitro and in vivo effects of Peganum harmala L. seeds extract against influenza A virus. Avicenna journal of phytomedicine. 2017 Nov;7(6):519.
15. Doskaliyev A, Seidakhmetova R, Tutai DS, Goldaeva K, Surov VK, Adekenov SM. Alkaloids of Peganum harmala L. and their Pharmacological Activity. Open Access Macedonian Journal of Medical Sciences. 2021 Sep 8;9(A):766-75.
16. Liu W, Wang Y, He DD, Li SP, Zhu YD, Jiang B, Cheng XM, Wang ZT, Wang CH. Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L. Phytomedicine. 2015 Nov 15;22(12):1088-95.
17. Jalali A, Dabaghian F, Zarshenas MM. Alkaloids of Peganum harmala: Anticancer Biomarkers with Promising Outcomes. Current Pharmaceutical Design. 2021 Jan 1;27(2):185-96.
18. Behairy A, Abd El-Rahman GI, Aly SS, Fahmy EM, Abd-Elhakim YM. Di (2-ethylhexyl) adipate plasticizer triggers hepatic, brain, and cardiac injury in rats: Mitigating effect of Peganum harmala oil. Ecotoxicology and Environmental Safety. 2021 Jan 15;208:111620.
19. Radan M, Dianat M, Badavi M, Mard SA, Bayati V, Goudarzi G. In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10): the effective role of gallic acid. Free radical research. 2019;53(2):210-25.
20. Hou HH, Wang HC, Cheng SL, Chen YF, Lu KZ, Yu CJ. MMP-12 activates protease-activated receptor-1, upregulates placenta growth factor, and leads to pulmonary emphysema. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2018 Sep 1;315(3):L432-42.
21. Habib MZ, Tadros MG, Abd-Alkhalek HA, Mohamad MI, Eid DM, Hassan FE, Elhelaly H, El Faramawy Y, Aboul-Fotouh S. Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK. European Journal of Pharmacology. 2022 Jul 15;927:175046.
22. Hogg JC, Paré PD, Hackett TL. The contribution of small airway obstruction to the pathogenesis of chronic obstructive pulmonary disease. Physiological reviews. 2017 Apr;97(2):529-52.
23. Ono H, Sakamoto A, Sakura N. Plasma total glutathione concentrations in healthy pediatric and adult subjects. Clinica chimica acta. 2001;312(1):227-9.
24. Pomatto LC, Davies KJ. Adaptive homeostasis and the free radical theory of ageing. Free Radical Biology and Medicine. 2018 Aug 20;124:420-30.
25. Aghadavod E, Nasri H. What are the molecular mechanisms of oxidant and antioxidant compounds? Annals of Research in Antioxidants. 2016;1(1).
26. Salmaninejad A KP, Shakoori A. Oxidative stress: development and progression of breast cancer. Tehran University Medical Journal. 2017;75:1-9.
27. Bensalem S, Soubhye J, Aldib I, Bournine L, Nguyen AT, Vanhaeverbeek M, et al. Inhibition of myeloperoxidase activity by the alkaloids of Peganum harmala L. (Zygophyllaceae). J Ethnopharmacol 2014; 154(2): 361-69.
28. El Gendy MA, Somayaji V, El-Kadi AO. Peganum harmala L. is a candidate herbal plant for preventing dioxin mediated effects. Planta Med 2010; 76(7): 671-77.
29. Doskaliyev A, Seidakhmetova R, Tutai DS, Goldaeva K, Surov VK, Adekenov SM. Alkaloids of Peganum harmala L. and their Pharmacological Activity. Open Access Macedonian Journal of Medical Sciences. 2021 Sep 8;9(A):766-75.
30. Sharma A, Sharma A, Wahengbam S, Cooper R, Singh H, Bhardwaj G. Overview of Traditional Uses, Phytochemistry and Pharmacology of Peganum Harmala L. Frontiers in Natural Product Chemistry: Volume 9. 2022 Mar 11;9:95-124.
31. Sharifi-Rad J, Quispe C, Herrera-Bravo J, Semwal P, Painuli S, Özçelik B, Hacıhasanoğlu FE, Shaheen S, Sen S, Acharya K, Amirian M. Peganum spp.: A Comprehensive Review on Bioactivities and Health‐Enhancing Effects and Their Potential for the Formulation of Functional Foods and Pharmaceutical Drugs. Oxidative Medicine and Cellular Longevity. 2021;2021(1):5900422.
32. Liang GB, He ZH. Animal models of emphysema. Chinese medical journal. 2019 Oct 20;132(20):2465-75.
33. Lalmanach G, Saidi A, Bigot P, Chazeirat T, Lecaille F, Wartenberg M. Regulation of the proteolytic activity of cysteine cathepsins by oxidants. International journal of molecular sciences. 2020 Mar 12;21(6):1944.
34. Tovar A, Smith GJ, Nalesnik MB, Thomas JM, McFadden KM, Harkema JR, Kelada SN. A locus on chromosome 15 contributes to acute ozone-induced lung injury in collaborative cross mice. American Journal of Respiratory Cell and Molecular Biology. 2022 Nov;67(5):528-38.
35. Kowsari Moghadam T, Jafary H, Yaghmaei P. Evaluation of the Effect of Harmaline on the Serum Level of Liver Index Enzymes in a Model of Non-alcoholic Fatty Liver of Male NMRI Mice. Journal of Animal Biology. 2021 Sep 23;14(1):143-52.
36. Wang C, Zhang Z, Wang Y, He X. Cytotoxic Constituents and Mechanism from Peganum harmala. Chem Biodivers 2016; 13(7): 961-68.
37. Sreelatha S, Inbavalli R. Antioxidant, antihyperglycemic, and antihyperlipidemic effects of Coriandrum sativum leaf and stem in alloxaninduced diabetic rats. J Food Sci 2012; 77(7): 119- 23.
Pathobiology Reserach
Volume 27, Issue 2
November 2024
Pages 23-32