ÇUHA ÇİÇEĞİ VE SARI KANTARON YAĞLARININ MULTİPLE SKLEROZ MODELİ OLUŞTURULMUŞ FARELERDEKİ JAK/STAT SİNYAL YOLAKLARI ÜZERİNE ETKİSİ

Year 2022, , 225 - 235, 31.08.2022

Huri Bulut , Emine Şeyda Teloğlu , Hilal Şentürk , Savaş Üstünova , Zozan Güleken , Şahabettin Selek

https://doi.org/10.24938/kutfd.986098

Abstract

Amaç: Multipl Skleroz, merkezi sinir sisteminde inflamatuar infiltrasyonlarla ilerleyen otoimmün demiyelinizan bir hastalıktır. JAK-STAT sinyal yolunun düzensizliği, otoimmün ensefalomiyelit ile indüklenmiş Multipl Skleroz modellerinin patogenezinde önemli bir rol oynar. Bu çalışmanın amacı, sarı kantaron ve çuha çiçeği yağlarının tüketiminin, JAK-STAT sinyal yolu üzerindeki terapötik etkilerini ortaya çıkarmaktır.

Gereç ve Yöntemler: Çalışmamızda 42 adet dokuz haftalık C57bl/6 J fareler kullanıldı. Fareler, Multipl Skleroz (MS) (n=32) ve kontrol grubu (n=10) olmak üzere iki ana gruba ayrıldıktan sonra MS grubundaki tüm farelere deneysel otoimmün ensefalomiyelit yöntemi ile Multipl Skleroz hastalığı oluşturuldu. Multipl Skleroz grubu kendi içinde MS (n=7), MS + Çuha çiçeği (n=10) ve MS + Sarı Kantaron (n=15) olacak şekilde üç gruba ayrıldı. Tedavi grupları, 6 hafta boyunca sarı kantaron (20 g/kg) ve çuha çiçeği (20 g/kg) yağları içeren özel üretim yemler ile beslendi. Multipl Skleroz indüksiyonundan iki hafta sonra, hastalığın klinik belirtileri her fare için günlük olarak puanlandı. Çalışmamızın sonunda beyin dokusu örneklerini elde etmek için tüm gruplardaki fareler sakrifiye edildi. Beyin doku homojenatlarında Western Blot yöntemi ile JAK2, p-JAK2, STAT1 ve p-STAT1 protein ekspresyon seviyeleri ölçüldü.

Bulgular: Çalışmamızda Multipl Skleroz hastalığı patogenezi ile ilişkili JAK/STAT yolağındaki p-JAK2, JAK2, p-STAT1 ve STAT1 ekspresyon düzeylerinin MS grubunda kontrollere göre anlamlı olarak arttığını, sarı kantaron ve çuha çiçeği yağı ile beslenen gruplarda ise anlamlı olarak azaldığını gösterdik (p<0.05).

Sonuç: Bu çalışmada elde ettiğimiz veriler ışığında, özellikle çuha çiçeği ve sarı kantaron yağlarının besin takviyesi olarak tüketilmesinin, Multipl Skleroz hastalığının moleküler patogenezinin iyileşmesine katkı sağlayacağı söylenebilir.

Keywords

Multipl Skleroz, çuha çiçeği (oenothera biennis),, sarı kantaron (hypericum perforatum),, JAK/STAT sinyal yolağı

Supporting Institution

Bezmialem Vakıf Üniversitesi

The Effect of Evening Primrose and St. John's Wort Oils on Jak/STAT Signaling Pathways in Mice with Multiple Sclerosis Modeled

Abstract

Objective: Multiple Sclerosis is an autoimmune demyelinating disease that progresses with inflammatory infiltrates in the central nervous system. Dysregulation of the JAK-STAT signaling pathway plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis-induced Multiple Sclerosis models. The aim of this study was to reveal the therapeutic effects of the consumption of St. John's Wort and evening primrose oils on the JAK-STAT signaling pathway.

Material and Methods: In our study, 42 nine-week-old C57bl/6 J mice were used and divided into two groups as Multiple Sclerosis (MS) (n = 32) and control group (n = 10). MS group was divided into three groups as MS (n=7), MS + evening primrose oil (n=10) and MS + St. John's Wort oil (n= 15). All groups except the control group were immunized by experimental autoimmune encephalomyelitis methods. Treatment groups were fed special feeds containing 20 g/kg St. John's Wort and 20 g/kg evening primrose oils for 6 weeks. Two weeks after Multiple Sclerosis induction, clinical signs of disease were scored daily for each mouse. Brain tissue samples were collected for measurement of JAK2, p-JAK2, STAT1 and p-STAT1 protein expression level by Western blot method.

Results: We showed that the expression levels of p-JAK2, JAK2, p-STAT1 and STAT1 in the JAK/STAT pathway associated with the pathogenesis of Multiple Sclerosis disease increased significantly in the Multiple Sclerosis group compared to the controls and decreased significantly in the groups fed with St. John's wort and evening primrose oil (p<0.05).

Conclusion: In the light of the data, consumption of evening primrose and alternatively St. John's wort oils as nutritional supplements may contribute to the improvement of the molecular pathogenesis of Multiple Sclerosis disease.

Keywords

Multiple Sclerosis,, Evening Primrose (Oenothera biennis),, St. John's Wort (Hypericum perforatum),, JAK/STAT signalling pathway

References

• 1. Przybek J, Gniatkowska I, Mirowska-Guzel D, Członkowska A. Evolution of diagnostic criteria for multiple sclerosis. Neurol Neurochir Pol. 2015;49(5):313-21. 2. Gelfand JM. Multiple sclerosis: diagnosis, differential diagnosis, and clinical presentation. Handbook of Clinical Neurology. 2014;122(3):269-90.
• 3. Ferrazzano G, Crisafulli SG, Baione V, Tartaglia M, Cortese A, Frontoni M et al. Early diagnosis of secondary progressive multiple sclerosis: focus on fluid and neurophysiological biomarkers. Journal of Neurology. 2021;268(10):3626-45.
• 4. Hohlfeld R, Wekerle H. Immunological update on multiple sclerosis. Current Opinion in Neurology. 2001;14(3):299-304.
• 5. Robinson AP, Harp CT, Noronha A, Miller SD. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment. Handbook of Clinical Neurology. 2014;122(1):173-89.
• 6. Rezapour-Firouzi S, Arefhosseini SR, Farhoudi M, Ebrahimi-Mamaghani M, Rashidi M-R, Torbati M-A et al. Association of expanded disability status scale and cytokines after intervention with co-supplemented hemp seed, evening primrose oils and hot-natured diet in multiple sclerosis patients. BioImpacts. 2013;3(7):43-7.
• 7. Denic A, Johnson AJ, Bieber AJ, Warrington AE, Rodriguez M, Pirko I. The relevance of animal models in multiple sclerosis research. Pathophysiology. 2011;18(1):21-9.
• 8. Xin J, Feinstein DL, Hejna MJ, Lorens SA, McGuire SO. Beneficial effects of blueberries in experimental autoimmune encephalomyelitis. Journal of Agricultural and Food Chemistry. 2012;60(23):5743-8.
• 9. Tian J, Zhang F, Cheng J, Guo S, Liu P, Wang H. Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L. Scientific Reports. 2014;4(1):1-6.
• 10. Oliveira AI, Pinho C, Sarmento B, Dias ACP. Neuroprotective activity of Hypericum perforatum and its major components. Frontiers in plant science. 2016;7(1):1004.
• 11. Lu YH, Du CB, Liu JW, Hong W, Wei DZ. Neuroprotective effects of Hypericum perforatum on trauma induced by hydrogen peroxide in PC12 cells. The American Journal of Chinese Medicine. 2004;32(3):397-405.
• 12. Sasaki N, Toda T, Kaneko T, Baba N, Matsuo M. Protective effects of flavonoids on the cytotoxicity of linoleic acid hydroperoxide toward rat pheochromocytoma PC12 cells. Chem Biol Interact. 2003;145(2):101-16.
• 13. Zou YP, Lu YH, Wei DZ. Protective effects of a flavonoid-rich extract of Hypericum perforatum L. against hydrogen peroxide-induced apoptosis in PC12 cells. Phytother Res. 2010;24(1):6-10.
• 14. Rebas E, Rzajew J, Radzik T, Zylinska L. Neuroprotective Polyphenols: A Modulatory Action on Neurotransmitter Pathways. Current Neuropharmacology. 2020;18(5):431-45.
• 15. Timoszuk M, Bielawska K, Skrzydlewska E. Evening primrose (Oenothera biennis) biological activity dependent on chemical composition. Antioxidants. 2018;7(8):108.
• 16. Liu Y, Holdbrooks AT, De Sarno P, Rowse AL, Yanagisawa LL, McFarland BC et al. Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of experimental autoimmune encephalomyelitis. The Journal of Immunology. 2014;192(1):59-72.
• 17. Dujmovic I. Cerebrospinal fluid and blood biomarkers of neuroaxonal damage in multiple sclerosis. Multiple sclerosis international. 2011;2011(1):1-18.
• 18. Kotelnikova E, Bernardo-Faura M, Silberberg G, Kiani NA, Messinis D, Melas IN et al. Signaling networks in MS: a systems-based approach to developing new pharmacological therapies. Multiple Sclerosis Journal. 2015;21(2):138-46.
• 19. Selek S, Esrefoglu M, Meral I, Bulut H, Caglar HG, Sonuc G et al. Effects of Oenothera biennis L. and Hypericum perforatum L. extracts on some central nervous system myelin proteins, brain histopathology and oxidative stress in mice with experimental autoimmune encephalomyelitis. Biotechnic & Histochemistry. 2019;94(2):75-83.
• 20. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British Journal of Pharmacology. 2011;164(4):1079-106.
• 21. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. Journal of Cell Science. 2004;117(8):1281-3.
• 22. Mojaverrostami S, Bojnordi MN, Ghasemi-Kasman M, Ebrahimzadeh MA, Hamidabadi HG. A review of herbal therapy in multiple sclerosis. Advanced Pharmaceutical Bulletin. 2018;8(4):575-90.
• 23. Yan Z, Gibson SA, Buckley JA, Qin H, Benveniste EN. Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clinical Immunology. 2018;189(1):4-13.
• 24. Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. International Immunopharmacology. 2020;80(1):106210.
• 25. Benveniste EN, Liu Y, McFarland BC, Qin H. Involvement of the janus kinase/signal transducer and activator of transcription signaling pathway in multiple sclerosis and the animal model of experimental autoimmune encephalomyelitis. Journal of Interferon & Cytokine Research. 2014; 34(8):577-88.
• 26. Hammer KDP, Yum M-Y, Dixon PM, Birt DF. Identification of JAK–STAT pathways as important for the anti-inflammatory activity of a Hypericum perforatum fraction and bioactive constituents in RAW 264.7 mouse macrophages. Phytochemistry. 2010;71(7):716-25.
• 27. Naziroglu M, Kutluhan S, Övey İS, Aykur M, Yurekli VA. Modulation of oxidative stress, apoptosis, and calcium entry in leukocytes of patients with multiple sclerosis by Hypericum perforatum. Nutritional Neuroscience. 2014;17(5):214-21.
• 28. Shamsizadeh A, Roohbakhsh A, Ayoobi F, Moghaddamahmadi A. The role of natural products in the prevention and treatment of multiple sclerosis. In: Watson RR, Killgore WDS, eds. Nutrition and Lifestyle in Neurological Autoimmune Diseases.1th ed. United Kingdom. Elsevier Inc, 2017:249-260.
• 29. Rezapour-Firouzi S, Arefhosseini SR, Mehdi F, Mehrangiz E-M, Baradaran B, Sadeghihokmabad E et al. Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. Complementary Therapies in Medicine. 2013;21(5):473-80.
• 30. Majdinasab N, Namjoyan F, Taghizadeh M, Saki H. The effect of evening primrose oil on fatigue and quality of life in patients with multiple sclerosis. Neuropsychiatric Disease and Treatment. 2018;14(1):1505-12.