Acta Pharmacologica Sinica (2009) 30: 1081-1091; doi: 10.1038/aps.2009.95; published online 13 July 2009

Aim: To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo.

Methods: Cultured neonatal cardiomyocytes were divided into i) control; ii) high glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high glucose+breviscapine; or v) high glucose+NF-κB inhibitor BAY11-7082.  Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-κB, TNF-α, and c-fos were assessed by Western blot or reverse transcription-polymerase chain reaction (RT-PCR).  Diabetic rats were induced by a single intraperitoneal injection of streptozotocin, and randomly divided into i) control rats; ii) diabetic rats; or iii) diabetic rats administered with breviscapine (10 or 25 mg·kg^-1·d^-1).  After treatment with breviscapine for six weeks, the echocardiographic parameters were measured.  All rats were then sacrificed and heart tissue was obtained for microscopy.  The expression patterns of PKC , NF -κB, TNF-α, and c-fos were measured by Western blot or RT-PCR.  

Results: Cardiomyocytes cultured in a high concentration of glucose showed an increased pulsatile frequency and cellular volume, as well as a higher expression of PKC , NF -κB, TNF-α, and c-fos compared with the control group.  Breviscapine could partly prevent these changes.  Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC , NF -κB, TNF-α, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy.

Conclusion: Breviscapine prevented cardiac hypertrophy in diabetic rats by inhibiting the expression of PKC, which may have a protective effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-κB/c-fos signal transduction pathway.

Keywords: diabetic cardiomyopathy; protein kinase C; cardiomegaly; breviscapine