Joungmin Kim1, Seong-Wook Jeong1, Hui Quan1,2, Cheol-Won Jeong1, Jeong-Il Choi1, Hong-Beom Bae3,4. 1. Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea. 2. Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. 3. Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 5 Hak dong, Gwangju, 501-746, Korea. nextphil2@jnu.ac.kr. 4. Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. nextphil2@jnu.ac.kr.
Abstract
PURPOSE: Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice. RESULTS: Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment. CONCLUSION: These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.
PURPOSE:Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice. RESULTS:Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment. CONCLUSION: These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.
Authors: Kong Yen Liew; Md Faizul Hafiz; Yi Joong Chong; Hanis Hazeera Harith; Daud Ahmad Israf; Chau Ling Tham Journal: Evid Based Complement Alternat Med Date: 2020-10-28 Impact factor: 2.629