auraptenol and Disease-Models--Animal

Depression is a major psychiatric disorder affecting nearly 21% of the world population and imposes a substantial health burden on society. Current available antidepressants are not adequate to meet the clinical needs. Here we report that auraptenol, an active component of the traditional Chinese medicine, angelicae dahuricae radix, had antidepressant-like effects in mice models of depression. In mouse forced swimming test and tail suspension test, two validated models of depression, auraptenol dose-dependently decreased the immobility duration within the dose range of 0.05-0.4 mg/kg. In addition, the antidepressant-like effects of auraptenol was significantly averted by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). These doses that affected the immobile response did not affect locomotor activity. In summary, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust antidepressant-like efficacy in mice. These data support further exploration for the possibility of developing auraptenol as a novel antidepressant agent in the treatment of major depression disorders.

Topics: Angelica; Animals; Antidepressive Agents; Behavior, Animal; Coumarins; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Hindlimb Suspension; Male; Mice; Mice, Inbred C57BL; Motor Activity; Phytotherapy; Piperazines; Pyridines; Receptors, Serotonin, 5-HT1; Serotonin 5-HT1 Receptor Antagonists; Swimming

Common chemotherapeutic agents such as vincristine often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is refractory to common analgesics and represents a challenging clinical issue. Angelicae dahuricae radix is an old traditional Chinese medicine with demonstrated analgesic efficacy in humans. However, the active component(s) that attribute to the analgesic action have not been identified. This work described the anti-hyperalgesic effect of one coumarin component, auraptenol, in a mouse model of chemotherapeutic agent vincristine-induced neuropathic pain. We reported that auraptenol dose-dependently reverted the mechanical hyperalgesia in mice within the dose range of 0.05-0.8 mg/kg. In addition, the anti-hyperalgesic effect of auraptenol was significantly blocked by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). Within the dose range studied, auraptenol did not significantly alter the general locomotor activity in mice. Taken together, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust analgesic efficacy in mice. These data support further studies to assess the potential of auraptenol as a novel analgesic for the management of neuropathic pain.

Topics: Analgesics; Animals; Coumarins; Disease Models, Animal; Herbal Medicine; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Motor Activity; Neuralgia; Phytotherapy; Receptor, Serotonin, 5-HT1A; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin 5-HT1 Receptor Antagonists; Vincristine