Novel Herbal Medicine C-KOK Suppresses the Inflammatory Gene iNOS via the Inhibition of p-STAT-1 and NF-κB

• Published in: Biotechnology and bioprocess engineering Vol. 25; no. 4; pp. 536 - 542
• Main Authors: Lee, In-Chul, Ryu, Chang-Woo, Bae, Jong-Sup
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society for Biotechnology and Bioengineering 01.08.2020; Springer Nature B.V; 한국생물공학회
• Subjects: animal models; anti-inflammatory activity; Antioxidants; Biotechnology; Chemistry; Chemistry and Materials Science; Cyclooxygenase-2; Cytokines; Cytosol; Endothelial cells; enzyme inhibition; genes; Heme; heme oxygenase (biliverdin-producing); Heme oxygenase (decyclizing); Herbal medicine; herbal medicines; humans; IL-1β; inducible nitric oxide synthase; Industrial and Production Engineering; interleukin-1beta; Lipopolysaccharides; Lung diseases; lungs; mice; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oriental traditional medicine; Oxygenase; prostaglandin synthase; Pulmonary arteries; Pulmonary artery; Regulatory sequences; Research Paper; respiratory tract diseases; response elements; RNA interference; RNA-mediated interference; Stat1 protein; transcription factor NF-kappa B; Translocation; tumor necrosis factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; 생물공학; C-KOK; endothelium; iNOS; p-STAT-1
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-020-0126-2

Cheong-Pye-Ko (CPK) and Kyung-Ok-Ko (KOK) are traditional herbal medicine prescriptions that have been used in oriental medicine as tonics for pulmonary-related diseases for centuries. However, the effects of a mixture of CPK and KOK (C-KOK) on cytokine-mediated pulmonary damage have not yet been elucidated. This study used lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs) to examine the effects of C-KOK on the induction of heme oxygenase-1 (HO-1) and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, a mouse model was used to determine if C-KOK affected the expression of tumor necrosis factor (TNF)-α and iNOS in the lung tissues of LPS-treated mice. The results showed that C-KOK induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-antioxidant response elements (ARE) activity, increased the expression of HO-1, and decreased IL-1β and iNOS/NO production in the LPS-activated HPAECs. Specifically, the suppression of iNOS/NO expression from the administration of C-KOK was reversed by the RNAi knockdown of HO-1. In conclusion, these findings indicated that C-KOK produced a critical anti-inflammatory effect due to its HO-1 dependent downregulation of p-STAT-1 and NF-κB and the resultant inhibition of iNOS and also suggested that TNF-α was a potential target for HO-1. Therefore, the administration of C-KOK showed efficacy and might be a novel approach for the treatment of inflammatory pulmonary disease.