We attempted to determine whether
betanin (from natural pigments) that has
antioxidant properties would be protective against
fructose-induced diabetic cardiac
fibrosis in Sprague-Dawley rats.
Fructose water
solution (30%) was accessed freely, and
betanin (25 and 100 mg/kg/d) was administered by intra-gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in
bovine serum albumin/
fructose system was also performed. In rats treated only with
fructose, levels of plasma markers:
glucose,
insulin, HOMA and
glycated hemoglobin rised, left ventricle
collagen accumulated and cross-linked, profibrotic
factor-transforming growth factor (TGF)-β1 and
connective tissue growth factor (CTGF)
protein expression increased, and soluble
collagen decreased, compared with those in normal rats, showing
fructose induces diabetic cardiac
fibrosis. Treatment with
betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of
betanin in the selected diabetic models. In further mechanistic study,
betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (
methylglyoxal),
advanced glycation end product (N(ε)-(
carboxymethyl) lysine) and receptors for
advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by
fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms.
Betanin also showed anitglycative effect in BSA/
fructose system, which supported that anitglycation was involved in
betanin's protective roles in vivo. Taken together, the potential for using
betanin as an auxillary
therapy for
diabetic cardiomyopathy deserves to be explored further.