Dual antidepressant-like and antinociceptive effects of Hypericum olympicum extract in mice: preclinical behavioral evidence

Hypericum Tourn. ex L. species exhibit well-documented neuropsychopharmacological activities, yet the central effects of Hypericum olympicum L. remain unknown. Given the frequent comorbidity of depressive symptoms and pain, this study aimed to characterize, for the first time, the antidepressant-like and antinociceptive profile of H. olympicum in mice. A methanolic extract of the aerial parts (HoE) was prepared, and its major phenolic constituents were identified by LC-MS/MS. At behaviorally active doses, HoE (2.5 and 5 mg/kg, i.p.) did not impair motor coordination in the Rota-rod test, in contrast to diazepam (2 mg/kg, p.o.), indicating the absence of neuromotor confounding effects. In both the tail suspension test (TST) and the modified forced swim test (MFST), HoE significantly reduced immobility, with effects comparable to those of fluoxetine (30 mg/kg, p.o.). In the MFST, increased swimming behavior without changes in climbing suggested a predominantly serotonergic component. HoE also produced marked antinociceptive effects in multiple nociceptive models. It increased response latencies in the hot-plate, tail-immersion, and tail-clip tests, reflecting activity in supraspinal and spinal thermal and mechanical nociceptive processing. In addition, HoE significantly reduced acetic acid-induced writhing, indicating visceral antinociceptive activity. Morphine (10 mg/kg, i.p.) served as the positive control in pain assays. LC-MS/MS analysis indicated the presence of major phenolic constituents, including hyperoside, myricetin derivatives, caffeoylquinic acid derivatives, a luteolin/kaempferol-type glucoside, and a biflavone of the biapigenin/amentoflavone type. These findings suggest that HoE possesses dual antidepressant-like and antinociceptive properties and support its further evaluation for disorders at the affect–pain interface.