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