FARELERDE OLUŞTURULAN DENEYSEL DEPRESYON MODELİNDE EPİGALLOKATEŞİN-GALLAT’IN ETKİLERİNİN İNCELENMESİ

Abstract

Depresyon, yaygın bir hastalıktır. Depresyonun patofizyolojisinde monoamin eksikliği, kortizol düzeylerinde artış, Beyin Kaynaklı Nörotrofik Faktör (BDNF) eksikliği, glutamat artışı ve inflamasyonun rol oynadığı bildirilmektedir. Epigallocatechin gallate (EGCG), yeşil çayda doğal olarak bulunan, antienflamatuvar, antioksidan ve anksiyolitik etkileri bulunan bir flavonoid türevidir. Bu çalışma, EGCG'nin anti inflamatuvar mekanizmalar yoluyla potansiyel antidepresan etkisini araştırmak amacıyla gerçekleştirilmiştir. Bu amaçla, fareler yedi gruba (n=10) ayrılmış ve EGCG'nin klasik antidepresan ilaçlar (paroksetin, venlafaksin, moklobemid) ile etkilerini karşılaştırmak için “Porsolt'un zorlu yüzme testi” uygulanmıştır. Ayrıca, etkili EGCG dozu (100 mg/kg) ile tedaviden önce ve sonra farelerde kortizol ve IL-6 düzeyleri ölçülmüştür. Geleneksel antidepresanlarla gözlenen etkilerin aksine, 25 mg/kg ve 50 mg/kg EGCG dozları önemli bir etki göstermezken, 100 mg/kg dozunda önemli bir antidepresan etki gözlenmiştir. Kontrol ve EGCG 100 mg/kg grupları arasında kortikosteron düzeylerinin karşılaştırılması (sırasıyla 9387,7 pg/ml ve 6147,0 pg/ml) EGCG 100 grubunda kortikosteron düzeylerinde önemli (p<0,05) bir azalma olduğunu ortaya koymuştur. Benzer şekilde, kontrol ve EGCG 100 grupları arasındaki IL-6 düzeylerinin karşılaştırılması (sırasıyla 159,0 pg/ml ve 128,3 pg/ml) EGCG 100 mg/kg grubunda IL-6 düzeylerinde önemli (p<0,05) bir azalma olduğunu ortaya koymuştur. Sonuç olarak, EGCG'nin Porsolt'un zorla yüzme testinde kortikosteron ve IL-6 düzeyleri üzerindeki inhibe edici etkisi, antidepresan etki olarak yorumlanabilir. Potansiyel antidepresan etki, antienflamatuvar mekanizmalar aracılığıyla ortaya çıkabilir. Bu alanda daha fazla çalışma yapılması gerekmektedir.

Keywords

• Kortikosteron
• Depresyon
• Epigallokateşin gallat (EGKG)
• Zorunlu Yüzme Testi
• IL-6

Supporting Institution

Destekleyen bir kurum yoktur.

Ethical Statement

Bu çalışma, Karadeniz Teknik Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu'nun 8 Şubat 2017 tarihli ve 53488718-162 numaralı onayı ile gerçekleştirilmiştir.

EXAMINATION OF THE EFFECTS OF EPIGALLOCATECHIN GALLATE IN EXPERIMENTAL DEPRESSION MODEL OF MICE

Abstract

Depression has a prevalence of approximately 5%. The pathophysiology of depression is reported to involve monoamine deficiency, elevated cortisol levels, Brain-Derived Neurotrophic Factor (BDNF) deficiency, increased glutamate, and inflammation. To date, no effective treatment protocol has been developed for cortisol elevation and inflammatory factors, which are proposed to play a role in the pathophysiology of depression. Epigallocatechin gallate (EGCG) is a flavonoid derivative that occurs naturally in green tea. Numerous studies have shown that the substance possesses both antiinflammatory and antioxidant properties. It has also been demonstrated to possess anxiolytic properties. The present study was conducted to investigate the potential antidepressant effect of EGCG through anti-inflammatory mechanisms. To this end, the mice were divided into seven groups (n=10) and the "Porsolt's forced swimming test" was administered to compare the effects of EGCG with those of classic antidepressant drugs (paroxetine, venlafaxine, moclobemide). Furthermore, cortisol and IL-6 levels were measured in mice before and after treatment with the effective EGCG dose (100 mg kg⁻¹). In contrast to the effects observed with conventional antidepressants, EGCG doses of 25 mg kg⁻¹ and 50 mg kg⁻¹ did not demonstrate a significant impact, while the 100 mg/kg dose exhibited a substantial antidepressant effect. A subsequent comparison of corticosterone levels between the control and EGCG 100 mg/kg groups (9387.7 pg mL⁻¹ and 6147.0 pg mL⁻¹ respectively) revealed a significant (p<0.05) decrease in corticosterone levels in the EGCG 100 mg kg⁻¹group. In a similar manner, a comparison of IL-6 levels between the control and EGCG 100 mg kg⁻¹ groups (159.0 pg mL⁻¹ and 128.3 pg mL⁻¹, respectively) revealed a significant (p<0.05) reduction in IL-6 levels in the EGCG 100 mg kg⁻¹ group. In conclusion, the inhibitory effect of EGCG on corticosterone and IL-6 levels in Porsolt's forced swimming test can be interpreted as an antidepressant effect. The potential antidepressant effect may be mediated by anti-inflammatory mechanisms. Further studies in this area are required.

Keywords

• Corticosterone
• Depression
• Epigallocathecin-gallate (EGCG)
• Forced Swimming Test
• IL-6

Supporting Institution

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.”

Ethical Statement

This study was conducted with the approval of the Local Ethics Committee for Animal Experiments at Karadeniz Technical University, dated February 8, 2017, and numbered 53488718-162.

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