Introduction:: High glucose status can worsen the biology of neurons; therefore, diabetic neuropathy is one of the common complications of diabetes. Olfactory Ensheathing Cells (OECs) have special properties, such as reducing inflammation. Hypericin and the Hypericum perforatum L. have various pharmacological properties, including antioxidant properties. Therefore, in this study, the effects of different concentrations of hypericin and H. perforatum extract have been investigated on oxidative stress factors in OECs by an in vitro method. Materials and Methods:: OECs were extracted from neonatal rat olfactory mucosa and cultured in normal (NG: 5.5 mM) or high glucose (HG: 30 mM) conditions. Hypericin in the H. perforatum extract was isolated via Soxhlet extraction and quantified using HPLC. Cell viability (MTT assay), Reactive Oxygen Species (ROS), and Nitric Oxide (NO) production were measured after treatment with protective (0.5 and 1 μM) and toxic (25 and 50 μM) hypericin concentrations. Immunocytochemistry confirmed OEC identity. Statistical analysis used ANOVA with (P ≤ 0.05). Results:: The results of the MTT test showed that high glucose conditions significantly decrease the survival of OECs, but using lower (protective) doses of hypericin and H. perforatum extract causes an increase in cell survival rate. Also, the protective concentrations of hypericin and hypericum extract in high glucose conditions decrease the production of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) in OECs. Discussion:: Protective hypericin and H. perforatum extract concentrations mitigated HGinduced oxidative stress, aligning with prior reports of their antioxidant and anti-inflammatory effects. The dual role of hypericin and H. perforatum extract (protective at low doses, toxic at high doses) underscores their concentration-dependent therapeutic potential. These findings suggest hypericin and H. perforatum extract’s utility in diabetic neuropathy treatment when combined with OECs. Conclusion:: The results of this study showed that the protective concentrations of hypericin or hypericum extract, in high glucose conditions similar to what occurs in diabetes, positively affect reducing oxidative factors.
Jafari et al. (Fri,) studied this question.