Capparis spinosa L. meyvelerinin metanol ekstraktının Parkinson hastalığının in-vitro deneysel modelinde nöroprotektif etkisi

Abstract

Amaç: Parkinson hastalığı, en sık görülen ikinci nörodejeneratif hastalıktır. Bu çalışmada, önemli biyoaktif bileşenlere sahip olduğu bilinen Capparis spinosa L. meyvelerinden elde edilen metanol ekstraktının in vitro deneysel Parkinson hastalığı modeline etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Alanya/Antalya’dan Capparis spinosa L. meyveleri toplandıktan sonra kurutulup öğütülerek metanol özütü hazırlandı. Flasklarda geliştirilen SH-SY5Y hücreleri, 96 oyuklu plakalara aktarıldı ve %80 hücre yoğunluğuna ulaşılana kadar inkübe edilmiştir. Parkinson hastalığı modeli oluşturulmadan 30 dakika önce hücrelere farklı dozlarda metanol özütü uygulanmıştır. Parkinson hastalığı modeli için SH-SY5Y hücreleri, 24 saat boyunca 200 uM 6-OHDA’ya maruz bırakılmıştır. 24 saatlik sürenin sonunda SH-SY5Y hücrelerinin canlılığını değerlendirmek için MTT analizi yapılmıştır. Hücre ortamındaki TOS, TAC ve IL-17A seviyeleri ELISA yöntemi kullanılarak belirlenmiştir. TNFα ve α-sinüklein ekspresyonu, immünohistokimyasal yöntem kullanılarak tespit edilmiştir. Bulgular: Hücre canlılığının tüm tedavi gruplarında 6-OHDA grubuna göre daha yüksek olduğu bulundu. 1500 µg/ml metanol özütü grubunda orta düzeyde TNFα ve a-sinüklein pozitifliği gözlendi. TOS ve TAC düzeylerinin doza bağlı olarak değiştiği belirlendi. Düşük dozlarda IL-17A seviyesinin düştüğü bulundu. Gruplar arasında istatistiksel anlamlılık saptandı. Sonuç: Bulgular incelendiğinde Capparis spinosa L. meyvelerinden elde edilen metanol ekstraktının düşük dozlarda oksidatif stres ve IL-17A düzeylerini azalttığı ve antioksidan kapasiteyi artırarak nöroprotektif etki sağladığı belirlendi.

Keywords

• Capparis spinosa L.
• SH-SY5Y
• Parkinson hastalığı
• nöroprotektif

Neuroprotective effect of methanol extract of Capparis spinosa L. fruits in an in-vitro experimental model of Parkinson’s disease

Abstract

Aim: Parkinson’s disease (PD) is the second most widespread neurodegenerative disease. This study, it was aimed to investigate the effect of methanol extract obtained from Capparis spinosa L. fruits, which are known to have important bioactive components, on in-vitro experimental PD model. Material and Method: After collecting Capparis spinosa L. fruits from Alanya/Antalya, methanol extract was prepared by drying and grinding. SH-SY5Y cells grown in flasks were transferred to 96 well plates and were incubated until 80% cell density was reached. Different doses of methanol extract were applied to the cells 30 minutes before the PD model was formed. For the PD model, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 24 hours. MTT analysis was performed to assess the viability of SH-SY5Y cells at the end of the 24-hour period. TOS, TAC, and IL-17A levels in the cell medium were determined using the ELISA method. Expression of TNFα and α-synuclein was defined using the immunohistochemical method. Results: Cell viability was found to be higher in all treatment groups than in the 6-OHDA group. Moderate levels of TNFα and α-synuclein positivity were observed in the 1500 µg/ml methanol extract group. It was determined that TOS and TAC levels change depending on the dose. It has been determined that the level of IL-17A decreases at low doses. Statistical significance was found between the groups. Conclusion: When the findings were examined, it was determined that the methanol extract obtained from Capparis spinosa L. fruits reduced oxidative stress and IL-17A levels at low doses and provided a neuroprotective effect by increasing the antioxidant capacity.

Keywords

• Capparis spinosa L.
• SH-SY5Y
• Parkinson’s disease
• neuroprotective

References

1. De Miranda BR, Goldman SM, Miller, GW, Greenamyre JT, Dorsey ER. Preventing Parkinson’s Disease: An Environmental Agenda J Parkinsons Dis 2022; 12: 45-68.
2. Dorsey ER, Sherer T, Okun MS, Bloem BR. The emerging evidence of the parkinson pandemic. J Parkinsons Dis 2018; 8: 3-8.
3. Ó Breasail M, Smith MD, Tenison E, Henderson EJ, Lithander FE. Parkinson’s disease: the nutrition perspective. Proc Nutr Soc 2022; 81: 12-26.
4. Markulin I, Matasin M, Turk VE, Salković-Petrisic M. Challenges of repurposing tetracyclines for the treatment of Alzheimer’s and Parkinson’s disease. J Neural Transm (Vienna) 2022; 129: 773-804.
5. Hu S, Tan J, Qin L et al. Molecular chaperones and Parkinson’s disease. Neurobiol Dis 2021; 160: 105527.
6. Tamtaji OR, Taghizadeh M, Aghadavod et al. The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin Neurol Neurosurg 2019; 176: 116-21.
7. Paknahad Z, Sheklabadi E, Derakhshan Y, Bagherniya M, Chitsaz A. The effect of the Mediterranean diet on cognitive function in patients with Parkinson’s disease: A randomized clinical controlled trial. Complement Ther Med 2020; 50: 102366.
8. Pantzaris M, Loukaides G, Paraskevis D, Kostaki EG, Patrikios I. Neuroaspis PLP10™, a nutritional formula rich in omega-3 and omega-6 fatty acids with antioxidant vitamins including gamma-tocopherol in early Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin Neurol Neurosurg 2021; 210: 106954.

9. Zhang H, Ma ZF. Phytochemical and pharmacological properties of Capparis spinosa as a medicinal plant. Nutrients 2018; 10: 116.
10. Jiang HE, Li X, Ferguson DK, Wang YF, Liu CJ, Li CS. The discovery of Capparis spinosa L. (Capparidaceae) in the Yanghai Tombs (2800 years b.p.), NW China, and its medicinal implications. J Ethnopharmacol 2007; 113: 409-20.
11. Yang T, Wang C, Liu H, Chou G, Cheng X, Wang Z. A new antioxidant compound from Capparis spinosa. Pharm Biol 2010 ;48: 589-94.
12. Annaz H, Sane Y, Bitchagno et al. Caper (Capparis spinosa L.): An updated review on its phytochemistry, nutritional value, traditional uses, and therapeutic potential. Front Pharmacol 2022 ;13: 878749.
13. Çaliş I, Kuruüzüm A, Rüedi P. 1H-Indole-3 acetonitrile glycosides from Capparis spinosa fruits. Phytochemistry 1999; 50: 1205-8.
14. Aliyazicioglu R, Eyupoglu OE, Sahin H, Yildiz, O, Baltas N. Phenolic components, antioxidant activity, and mineral analysis of Capparis spinosa L. Afr J Biotechnol 2013; 12: 6643-9.
15. Jalali MT, Mohammadtaghvaei N, Larky DA. Investigating the effects of Capparis spinosa on hepatic gluconeogenesis and lipid content in streptozotocin-induced diabetic rats. Biomed Pharmacother 2016; 84: 1243-8.
16. Moutia M, El Azhary K, Elouaddari A, et al. Capparis spinosa L. promotes anti-inflammatory response in vitro through the control of cytokine gene expression in human peripheral blood mononuclear cells Capparis spinosa L. promotes anti-inflammatory response in vitro through the control of cytokine gene expression in human peripheral blood mononuclear cells. BMC Immunol 2016; 17: 26.
17. Tlili N, Feriani A, Saadoui E, Nasri N, Khaldi A. Capparis spinosa leaves extract: Source of bioantioxidants with nephroprotective and hepatoprotective effects. Biomed Pharmacother 2017; 87: 171-9.
18. Vahid H, Bonakdaran S, Khorasani ZM, et al. Effect of Capparis spinosa extract on metabolic parameters in patients with type-2 diabetes: a randomized controlled trial. Endocr Metab Immune Disord Drug Targets 2019; 19: 100-7.
19. Kdimy A, El Yadini, M, Guaadaoui A, Bourais I, El Hajjaji S, Le HV. Phytochemistry, biological activities, therapeutic potential, and socio-economic value of the caper bush (Capparis spinosa L.). Chem Biodivers 2022; 19: e202200300.
20. Agar G, Gulluce M, Aslan A, Bozari S, Karadayi M, Orhan F. Mutation preventive and antigenotoxic potential of methanol extracts of two natural lichen. J Med Plant Res 2010; 4: 2132-7.
21. Taghizadehghalehjoughi A, Sezen S, Hacimuftuoglu A, Güllüce M. Vincristine combination with Ca+2 channel blocker increase antitumor effects. Mol Biol Rep 2019; 46: 2523-8.
22. Okkay U, Okkay Ferah I. Beneficial effects of linagliptin in cell culture model of Parkinson’s disease. EuRJ 2022; 8: 242-6.
23. Ferah Okkay I, Okkay U, Cicek B, et al. Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson’s disease. Mol Biol Rep 2021; 48: 7711-7.
24. Taghizadehghalehjoughi A, Sezen S, Bayram C, Hacimuftuoglu A, Güllüce M Investigation of anti-tumor effect in neuroblastoma cell line; amlodipine & metformin, Anatol J Bio 2020; 1: 16-21.
25. Aksay O, Selli S, Kelebek H. LC-DAD-ESI-MS/MS-based assessment of the bioactive compounds in fresh and fermented caper (Capparis spinosa) buds and berries. Food Chem 2021; 337: 127959.
26. Zhu X, Yang Y, Gao W, Jiang B, Shi L. Capparis spinosa alleviates dss-induced ulcerative colitis via regulation of the gut microbiota and oxidative stress. Evid Based Complement Alternat Med 2021; 2021: 1227876.
27. Jalali MT, Mohammadtaghvaei N, Larky DA. Investigating the effects of Capparis spinosa on hepatic gluconeogenesis and lipid content in streptozotocin-induced diabetic rats. Biomed Pharmacother 2016; 84: 1243-8.
28. Mousavi SH, Hosseini A, Bakhtiari E, Rakhshandeh H. Capparis spinosa reduces Doxorubicin-induced cardio-toxicity in cardiomyoblast cells. Avicenna J Phytomed 2016; 6: 488-94.
29. Baradaran Rahimi V, Rajabian A, Rajabi H, et al. The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies. J Ethnopharmacol 2020; 256: 112706.
30. Turgut NH, Kara H, Arslanbaş E, Mert DG, Tepe B, Güngör H. Effect of Capparis spinosa L. on cognitive impairment induced by D-galactose in mice via inhibition of oxidative stress. Turk J Med Sci 2015; 45: 1127-36.
31. Mohebali N, Shahzadeh Fazeli SA, Ghafoori H, et al. Effect of flavonoids rich extract of Capparis spinosa on inflammatory involved genes in amyloid-beta peptide injected rat model of Alzheimer’s disease. Nutr Neurosci 2018; 21: 143-50.