Tingli Qu1, Erbing Wang2, Baofen Jin1,3, Weiping Li4, Ruiling Liu1, Zheng-Bao Zhao1. 1. a School of Pharmaceutical Science of Shanxi Medical University , Taiyuan , Shanxi , People's Republic of China. 2. b Chemical and Biological Engineering College of Taiyuan University of Science and Technology , Taiyuan , Shanxi , People's Republic of China. 3. c Fuyong People's Hospital , Shenzhen , Guangdong , People's Republic of China. 4. d Department of Pharmacology , Fenyang College Shanxi Medical University , Fenyang , Shanxi , People's Republic of China.
Abstract
CONTEXT: 5-Aminosalicylic acid (5-ASA), as an anti-inflammatory drug, has been extensively used for the treatment of mild to moderate active ulcerative colitis (UC), but the possible mechanisms of action remain unclear. OBJECTIVE: To investigate the effects of 5-ASA on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS), and determine the underlying pharmacological mechanism of action. MATERIALS AND METHODS: The levels of nitric oxide (NO) and interleukin-6 (IL-6) were measured by Varioskan Flash and IL-6 Enzyme-Linked Immunosorbent Assay sets. Real time quantitative polymerase chain reaction was used to determine the level of induced nitric oxide synthase (iNOS). The effects of 5-ASA on iNOS, the c-Jun N-terminal kinases (JNKs), p38 and nuclear factor (NF)-κB signaling pathways were examined using western blotting. RESULTS: 5-ASA suppressed the production of NO and IL-6, and also decreased the expression of iNOS in LPS-induced RAW264.7 cells. 5-ASA inhibited the phosphorylation of JNKs and p38, but did not block NF-κB activation at all doses tested. DISCUSSION AND CONCLUSION: The results indicated that the anti-inflammatory effect of 5-ASA was mainly regulated by the inhibition of the JNKs, p38 pathways rather than NF-κB pathway. Further research is required to clarify the detailed mechanism of the action.
CONTEXT: 5-Aminosalicylic acid (5-ASA), as an anti-inflammatory drug, has been extensively used for the treatment of mild to moderate active ulcerative colitis (UC), but the possible mechanisms of action remain unclear. OBJECTIVE: To investigate the effects of 5-ASA on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS), and determine the underlying pharmacological mechanism of action. MATERIALS AND METHODS: The levels of nitric oxide (NO) and interleukin-6 (IL-6) were measured by Varioskan Flash and IL-6 Enzyme-Linked Immunosorbent Assay sets. Real time quantitative polymerase chain reaction was used to determine the level of induced nitric oxide synthase (iNOS). The effects of 5-ASA on iNOS, the c-Jun N-terminal kinases (JNKs), p38 and nuclear factor (NF)-κB signaling pathways were examined using western blotting. RESULTS:5-ASA suppressed the production of NO and IL-6, and also decreased the expression of iNOS in LPS-induced RAW264.7 cells. 5-ASA inhibited the phosphorylation of JNKs and p38, but did not block NF-κB activation at all doses tested. DISCUSSION AND CONCLUSION: The results indicated that the anti-inflammatory effect of 5-ASA was mainly regulated by the inhibition of the JNKs, p38 pathways rather than NF-κB pathway. Further research is required to clarify the detailed mechanism of the action.
Authors: Jolanta Artym; Maja Kocięba; Ewa Zaczyńska; Michał Zimecki; Wojciech Kałas; Leon Strządała; Alicja Pawlak; Małgorzata Jeleń; Beata Morak-Młodawska; Krystian Pluta; Katarzyna Kaleta-Kuratewicz; Jan P Madej; Piotr Kuropka; Jan Kuryszko Journal: Histol Histopathol Date: 2019-12-13 Impact factor: 2.303
Authors: Javier Pinel Ríos; Carlos Javier Madrid Navarro; María José Pérez Navarro; María José Cabello Tapia; María José Piña Vera; Víctor Campos Arillo; María Rosario Gómez García; Adolfo Mínguez Castellanos; Francisco Escamilla Sevilla Journal: BMJ Open Date: 2019-06-19 Impact factor: 2.692