Unexpected Antidepressant and Analgesic Activities of Chinese Medicine Puerarin and its Molecular Targets

Abstract

Pain and depression are common health problems and closely related. Current therapies have not been validated for simultaneous relief of the pain from the body and brain. We recently discovered that natural plant product, Puerarin does not only co-ordinate nerve growth factor to promote neurite outgrowth but also induces arginase-2 to protect neurons against oxidative injury. These results have stimulated us to further investigate the effects of Puerarin on depressive behaviors and pain in mice with spared nerve injury (SNI). C57BL6/N mice were divided into 8 different groups (n=6). On Day 8 after the surgery, SNI mice were treated with Puerarin, Citalopram and Ibuprofen, alone or in combination, for 8 to 14 days. Animals in Sham group and one SNI group were treated with vehicle. Depressive behaviors were assessed by forced swim test and tail suspension test. Pain responses were assessed by the von Frey filaments. It was found that Puerarin ameliorated depression and pain in SNI mice as effectively as the existing antidepressant drug, Citalopram. Anti-inflammatory drug, Ibuprofen attenuated the pain response to a lesser extent and did not show any activity against SNI-induced depression. The mechanisms were different. Collectively, our results suggested that Puerarin may ameliorate the SNI-induced depression and pain via activating ERK, CREB and BDNF pathways. These results may be translatable for the development of novel therapeutic approach for depression and pain comorbidity.