Antidepressant-like effects of auraptenol in mice

Depression is a major psychiatric disorder affecting nearly 21% of the world population and imposes a substantial health burden on society1,2. There are three main kinds of classical antidepressants in clinical practice, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). Most of these drugs, however, have undesirable side effects and their mechanisms of action have not been satisfactorily resolved. A growing number of herbal medicines are being introduced into psychiatric practice, many of which have comparable efficacy to prescription medications with lower side effects. This makes herbal therapies as desirable alternative treatment for severe depression3. Angelicae dahuricae radix is a perennial plant that grows naturally in broad areas of China. Angelicae dahuricae radix has a strong scent and its leaves are used to make incense. In addition, the roots of angelicae dahuricae radix (also known as Bai Zhi) are used in traditional Chinese medicine to treat harmful external influences on the skin, such as cold, heat, dampness and dryness4. Modern pharmacological studies on angelicae dahuricae radix have reported that crude extracts of angelicae dahuricae radix possesses anti-inflammatory, analgesic and antipyretic actions and acute toxicity as a guideline for clinic application4. Essential oil of angelicae dahuricae radix has analgesic effect in rat models of pain, and the antinociceptive effects have been linked to the facilitated release of endogenous opioids such as beta-endorphin5. More importantly, angelicae dahuricae radix has been used clinically to treat depressive symptoms6. However, the crude extract and essential oil of angelicae dahuricae radix include multiple potentially active chemical compounds and the active ingredient(s) of angelicae dahuricae radix that are responsible for its antidepressant-like activity are currently unknown. Recent phytochemical research has purified and identified several active coumarin components of angelicae dahuricae radix7, and further pharmacological studies are needed to identify the active coumarin component underlying the antidepressant-like actions of angelicae dahuricae radix. This study reported the potent antidepressant-like effects of an active coumarin component of angelicae dahuricae radix, auraptenol (8-(2-hydroxy-3-methylbut-3-en-1-yl)-7-methoxy-2H-chromen-2-one, in mice models of depression. Receptor mechanism underlying the antidepressant-like effects of auraptenol was also studied.