Role of GLP-1 receptors in the effect of hypericin on mouse neuroblastoma cell line (NB2a)
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
Kaynakça
- Agnello L, Gambino CM, Lo Sasso B, Bivona G, Milano S, Ciaccio AM et al. Neurogranin as a novel biomarker in Alzheimer’s disease. Lab Med. 2021;52:188-96.
- Cheng YJ, Lin CH, Lane HY. From menopause to neurodegeneration: molecular basis and potential therapy. Int J Mol Sci. 2021;22:8654.
- Fonseca Cabral G, Schaan AP, Cavalcante GC, Sena-Dos-Santos C, de Souza TP, Souza Port's NM et al. Nuclear and mitochondrial genome, epigenome, and gut microbiome: emerging molecular biomarkers for Parkinson’s disease. Int J Mol Sci. 2021;22:9839.
- Kholghi G, Arjmandi-Rad S, Zarrindast MR, Vaseghi S. St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems. Naunyn Schmiedebergs Arch Pharmacol, 2022;395:629-42.
- Chen H, Muhammad I, Zhang Y, Ren Y, Zhang R, Huang X et al. Antiviral activity against infectious bronchitis virus and bioactive components of Hypericum perforatum L. Front Pharmacol. 2019;10:1272.
- Matos ADR, Caetano BC, de Almeida Filho JL, Martins JSCC, de Oliveira MGP, Sousa TDC et al. Identification of Hypericin as a candidate repurposed therapeutic agent for COVID-19 and its potential anti-SARS-CoV-2 activity. Front Microbiol. 2022;13:828984.
- Majerník M, Jendželovský R, Babinčák M, Košuth J, Ševc J, Tonelli Gombalová Z et al. Novel insights into the effect of Hyperforin and photodynamic therapy with Hypericin on chosen angiogenic factors in colorectal micro-tumors created on the chorioallantoic membrane. Int J Mol Sci. 2019;20:3004.
- Luo L, Sun Q, Mao YY, Lu YH, Tan RX. Inhibitory effects of flavonoids from Hypericum perforatum on nitric oxide synthase. J Ethnopharmacol. 2004;93:221-5.
- Yuan X, Yan F, Gao LH, Ma QH, Wang J. Hypericin as a potential drug for treating Alzheimer’s disease and type 2 diabetes with a view to drug repositioning. CNS Neurosci Ther. 2023;29:3307-21.
- Novelli M, Masiello P, Beffy P, Menegazzi M. Protective role of St. John’s Wort and its components Hyperforin and Hypericin against diabetes through inhibition of inflammatory signaling: evidence from in vitro and in vivo studies. Int J Mol Sci. 2020;21:8108.
