Protein kinase G-dependent heme oxygenase-1 induction by Agastache rugosa leaf extract protects RAW264.7 cells from hydrogen peroxide-induced injury

• Published in: Journal of ethnopharmacology Vol. 103; no. 2; pp. 229 - 235
• Main Authors: Oh, Hwa Min, Kang, Young Jin, Lee, Young Soo, Park, Min Kyu, Kim, Sun Hee, Kim, Hye Jung, Seo, Han Geuk, Lee, Jae Heun, Chang, Ki Churl
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 16.01.2006; Elsevier
• Subjects: Agastache; Agastache rugosa; Animals; Antioxidant effect; Antioxidants - isolation & purification; Antioxidants - pharmacology; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Cyclic GMP-Dependent Protein Kinases - metabolism; Enzyme Induction - drug effects; General pharmacology; Heme oxygenase-1; Heme Oxygenase-1 - biosynthesis; Hydrogen Peroxide - antagonists & inhibitors; Hydrogen Peroxide - toxicity; Macrophages - drug effects; Macrophages - enzymology; Macrophages - metabolism; Medical sciences; Mice; Oxidative Stress - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves; Protein kinase G; ZnPPIX; Agastache rugosa; Protein kinase G; HO; PKA; Heme oxygenase-1; cGMP; Antioxidant effect; ALE; cAMP; ODQ; PKG; Hydrogen peroxide; Enzyme; Induction; Pharmacognosy; Toxicity; Transferases; Heme oxygenase (decyclizing); Extract; Plant leaf; Antioxidant; In vitro; Medicinal plant; Prevention; Protein kinase; Plant origin; Oxidoreductases; G protein
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2005.08.030

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 2O 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 2O 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 2O 2. Thus, ALE along with other actions may be beneficial for the treatment of oxidant-induced cellular injuries.