It has been proposed that the inducible
isoform of
heme oxygenase (HO) protects cells against
oxidant-mediated injury. Although components of Agastache rugosa showed
antioxidant effect, it is unclear this effect is related with HO-1 activity. Thus, we investigated the effects of Agastache rugosa leaf extract (ALE) on HO-1
protein expression and
enzyme activity, and its protective effect against H(2)O(2)-induced oxidative damage was also investigated using RAW264.7 macrophage cells. Results showed that ALE concentration dependently increased HO-1
protein and
enzyme activity, and protected cells from H(2)O(2)-induced cytotoxicity, with an IC(50) of 0.526 mg/ml.
Hemin, a HO-1 inducer, also showed similar effect to ALE. Furthermore, the protective effect of both ALE and
hemin was inhibited by a HO inhibitor,
zinc protoporphyrin IX. The expression of HO-1
protein by ALE was reduced by pretreatment with
LY83583 and ODQ, specific inhibitors of
guanylate cyclase, but not by PKA inhibitors,
H89 and
KT5720, indicating that PKG signaling pathway regulates HO-1 induction by ALE. Taken together, it is concluded that PKG-dependent HO-1 induction is one of the important
antioxidant mechanisms by which ALE protects RAW264.7 cells from H(2)O(2). Thus, ALE along with other actions may be beneficial for the treatment of
oxidant-induced cellular
injuries.