Role of GLP-1 receptors in the effect of hypericin on mouse neuroblastoma cell line (NB2a)

Yıl 2025, Cilt: 50 Sayı: 4, 1163 - 1174, 22.12.2025

Furkan Öztekin , Ertan Darıverenli , Ercüment Ölmez , Sedef Gidener

https://doi.org/10.17826/cumj.1786639

Öz

Purpose: This study aimed to evaluate the possible neurotoxic effects of hypericin in mouse neuroblastoma cell culture, the potential neuroprotective effects against chlorpyrifos-induced neurotoxicity, and the role of the Glucagon-like peptide-1 (GLP-1) receptor in these effects.
Materials and Methods: The toxic effects of hypericin and the GLP-1 receptor antagonist exendin 9-39 were evaluated using the neurotoxicity screening test (NTT), Annexin V method, and Luminoskan test. The role of the GLP-1 receptor was assessed in the absence and presence of exendin 9-39.
Results: Hypericin significantly decreased cell viability at high concentrations of 30 and 100 µM to 70,47% and 93,30% respectively. The addition of 30 µM exendin 9-39 slightly but significantly increased viability for a 100 µM concentration of hypericin. Although hypericin increased total apoptosis at these doses, the increase was not significant. According to NTT results, hypericin showed a significant dose-dependent neurotoxic effect, starting at 0.1 µM, by inhibiting neurite outgrowth by up to 77,89%. Addition of exendin 9-39 significantly reversed this neurotoxic effect at high hypericin doses.
Conclusions: Hypericin decreased cell viability at high concentrations, which is likely related to its anticancer activity. The reversal of this effect by exendin 9-39 was interpreted as a possible contribution of GLP-1 receptors. The fact that hypericin inhibited neurite outgrowth even at low concentrations suggests it may have neurotoxic activity. Given the widespread use of St. John's Wort, whose active ingredient is hypericin, in the treatment of central nervous system disorders, further research is warranted, and its use is recommended with caution.

Anahtar Kelimeler

Hypericin , Exendin 9-39 , NB2a , Neurotoxicity

Destekleyen Kurum

Manisa Celal Bayar University Scientific Research Projects

Proje Numarası

2024-011

Hiperisinin fare nöroblastoma hücre hattı (NB2a) üzerindeki etkisinde GLP-1 reseptörlerinin rolü

Öz

Amaç: Bu çalışmanın amacı, hiperisin'in fare nöroblastoma hücre kültürü üzerindeki olası nörotoksik etkilerini ve klorpirifos kaynaklı nörotoksisite üzerindeki olası nöroprotektif etkilerini değerlendirmek ve bu etkilerde Glukagon benzeri peptid-1 (GLP-1) reseptörünün rolünü araştırmaktır.
Gereç ve Yöntem: Hiperisin ve GLP-1 reseptör antagonisti eksendin 9-39'un toksik etkileri nörotoksisite tarama testi (NTT), Annexin V yöntemi ve Luminoskan testi kullanılarak değerlendirildi. GLP-1 reseptörünün rolü, eksendin 9-39'un yokluğunda ve varlığında değerlendirildi.
Bulgular: Hiperisin, 30 ve 100 µM gibi yüksek konsantrasyonlarda hücre canlılığını sırasıyla %70,47 ve %93,30 oranında önemli ölçüde azalttı. 30 µM eksendin 9-39 ilavesi, 100 µM hiperisin konsantrasyonunda canlılığı hafif ancak anlamlı bir şekilde artırdı. Hiperisin bu dozlarda toplam apoptozu artırmasına rağmen, artış anlamlı değildi. NTT sonuçlarına göre, hiperisin 0,1 µM'den başlayarak nörit büyümesini %77,89'a kadar inhibe ederek anlamlı doz bağımlı nörotoksik etki gösterdi. Eksendin 9-39 ilavesi, yüksek hiperisin dozlarında bu nörotoksik etkiyi önemli ölçüde tersine çevirdi.
Sonuç: Hiperisin, yüksek konsantrasyonlarda hücre canlılığını azaltmıştır ve bu durum muhtemelen antikanser aktivitesiyle ilişkilidir. Bu etkinin eksendin 9-39 tarafından tersine çevrilmesi, GLP-1 reseptörlerinin olası bir katkısı olarak yorumlanmıştır. Hiperisin'in düşük konsantrasyonlarda bile nörit büyümesini engellemesi, hiperisin'in potansiyel nörotoksik aktiviteye sahip olabileceğini düşündürmektedir. Etken maddesi hiperisin olan Sarı Kantaron'un merkezi sinir sistemi bozukluklarında yaygın kullanımı göz önüne alındığında, bu madde üzerinde daha fazla araştırma yapılması ve dikkatli kullanılması gerektiği ortaya çıkmaktadır.

Anahtar Kelimeler

Hiperisin , Eksendin 9-39 , NB2a , Nörotoksisite

Destekleyen Kurum

Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri

Proje Numarası

2024-011

Kaynakça

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