Materials and Methods: In this experimental study, 60 adult male rats were studied in five groups (n = 12/each). The sham group (without nerve injury and treatment), the control group (with untreated nerve injury), and three experimental groups with injured sciatic nerve received oral hesperetin (100, 200, and 400 mg/kg, respectively) by gavage. All rats were euthanized on second and fourth post-treatment weeks for histopathological assessment of the sciatic nerve.

Results: The results showed increased perineurium formation in the experimental group treated with 400 mg/kg hesperetin and a decrease in leukocyte infiltration in the experimental groups treated with 200 and 400 mg/kg hesperetin compared with the controls on second and fourth post-treatment weeks (P < 0.05). At the end of the second week, axon swelling significantly decreased in the group treated with 400 mg/kg hesperetin than the control group (P < 0.05). In addition, a decrease in the axonal count was observed in hesperetin-treated groups (200 and 400 mg/kg) after two weeks compared with the controls (P < 0.05).

Conclusions: The expression of the S100 gene in groups treated with 100 and 400 mg/kg hesperetin showed a significant decrease compared with the control group on days 14 and 28. Our findings indicated that hesperetin positively affects sciatic nerve repair in the rat model.