Does hypericin have GLP-1 agonistic effect? Investigation of its role in neuroprotective effect in mouse neuroblastoma cell line (NB2a)

Objective: This study aimed to evaluate the possible neurotoxic effects of hypericin in mouse neuroblastoma cell culture and the possible neuroprotective effects in chlorpyrifos-induced neurotoxicity on neurite outgrowth, cell viability and apoptosis, and to investigate the possible effect of GLP-1 receptor in these effects. Materials and Methods: The toxic effects of hypericin and GLP-1 receptor antagonist exendin 9-39 were examined with the neurotoxicity screening test (NTT), apoptotic effects with the Annexin V method, and cell viability and proliferation with the luminoscan test. The possible effect of the GLP-1 receptor on these effects of hypericin was evaluated with the combined applications of hypericin and GLP-1 receptor antagonist exendin 9-39. Results: Hypericin significantly reduces cell viability at high concentrations (30 and 100 μM) (p<0.001). When 30 μM exendin 9-39 was added to these groups, it was observed that exendin 9-39 increased cell viability in these groups, although it was not statistically significant. In apoptosis analyses, 30 and 100 μM hypericin increased the total amount of apoptosis, but this increase was not found to be statistically significant. According to NTT data, hypericin showed a dose-dependent neurotoxic effect in mouse neuroblastoma cells starting from the lowest applied concentration of 0.1 μM, and inhibited neurite extension. When 30 μM exendin 9-39 was added to the groups that received high doses of hypericin (30 and 100 μM), it was observed that exendin 9-39 inhibited the neurotoxic effect of hypericin at a statistically significant level (p<0.005). Hypericin did not show any effect on neurotoxicity in the form of inhibition of neurite extension induced by chlorpyrifos. Conclusions: In this study, it was shown that high concentrations of hypericin in mouse neuroblastoma cell culture significantly reduced cell viability, and this effect is thought to be related to the anticancer activity of hypericin. The fact that the GLP-1 antagonist exendin 9-39 reversed the decrease in cell viability suggests that GLP-1 may contribute to the anticancer activity. The fact that hypericin inhibits neurite extension even at low concentrations that do not change cell viability suggests that hypericin may have a neurotoxic activity of its own. Since St. John's wort, whose active ingredient is considered to be hypericin, is widely used in central nervous system diseases such as depression and anxiety, new studies are needed, and careful use is recommended. Keywords: Hypericin, Exendin 9-39, NB2a, Neurotoxicity