Facilitating effects of Buyang Huanwu decoction on axonal regeneration after peripheral nerve transection

Ethnopharmacological relevance: In traditional Asian medicine, Buyang Huanwu decoction (BYHWD) has been used for the treatment of cardiovascular and neurological disorders. Recent experimental studies have begun to provide evidence on the protective effects of BYHWD on injured peripheral nerves. Aim of the study: To examine whether BYHWD was effective in inducing axonal regeneration after peripheral nerve transection, and if so, how it acted on the nerve. Materials and methods: The sciatic nerve in rats was transected and resutured 0, 1, or 4 weeks later. BYHWD was orally administered daily into the animals with nerve transection and coaptation (NTC). Axonal regeneration was measured by immunofluorescence staining of NF-200 and superior cervical ganglion 10 (SCG10) and by retrograde tracing method. Changes of protein levels in the sciatic nerve were analyzed by western blot analysis. Effects of BYHWD and its constituents on neurite outgrowth were analyzed in cultured dorsal root ganglion (DRG) neurons. Hot plate and treadmill training tests were performed to assess the levels of functional recovery after nerve injury. Results: The rate of axonal regeneration was attenuated by delayed coaptation after transection, but improved by BYHWD treatment. Levels of phospho-Erk1/2 and Cdc2 phosphorylation of vimentin, measured as indicators of the activation of regenerating axons and supportive Schwann cells, were increased in the sciatic nerve of NTC animals, and their distribution in the proximal and distal nerves were affected by BYHWD treatment. Treatment of BYHWD during the period of chronic denervation significantly increased axonal regeneration when analyzed by immunofluorescence staining and retrograde tracing methods. Neurite outgrowth of DRG neurons cocultured with Schwann cells from the chronically transected sciatic nerves was enhanced by BYHWD treatment. Radix Paeoniae Rubra induced neurite outgrowth most efficiently among all herbal constituents of BYHWD. Finally, hot plate and treadmill training tests demonstrated that BYHWD administration significantly improved the sensorimotor nerve function in NTC animals. Conclusions: Our data suggest that BYHWD treatment may contribute to the timely interaction between regenerating axons and distal Schwann cells in the transected nerve and facilitate axonal regeneration.