Yuting Lin1, Danping Qiu1, Lili Huang2, Sangsang Zhang1, Chenjian Song1, Beibei Wang1, Jianzhang Wu3, Chengshui Chen4. 1. Department of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325006, China. 2. Department of Pharmacy, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang 315041, China. 3. Department of Pharmacy, Pharmacy School, Wenzhou Medical University, Wenzhou, Zhejiang 325006, China. Electronic address: wjzwzmu@163.com. 4. Department of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325006, China. Electronic address: chenchengshui@wmu.edu.cn.
Abstract
BACKGROUND: Chalcone, a natural product, has a wide range of biological activities. L2H17, a chalcone derivative, was synthesized and screened in our previous study and exhibited excellent anti-inflammatory property in vitro. This study investigated the therapeutic potential of L2H17 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of heme oxygenase-1 (HO-1). MATERIALS AND METHODS: An ALI animal model was induced by LPS (10 mg/kg) intratracheal instillation. The effect of L2H17 on LPS-induced structural damage was determined using hematoxylin and eosin (HE) staining, and tissue edema extent was examined. Bronchoalveolar lavage fluid (BALF) was harvested to assess the levels of related cytokines by enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity was also assessed. HO-1 expression was determined using immunohistochemistry and western blotting. The effects of L2H17 on LPS stimulation in RAW 264.7 and the involvement of the HO-1 pathway were investigated. RESULTS: L2H17 alleviated the histopathological manifestations and tissue edema. Moreover, L2H17 decreased the production of pro-inflammatory factors in BALF and increased SOD activity. In vitro, L2H17 significantly reduced pro-inflammatory cytokine production. Additionally, L2H17 improved the expression of HO-1 in LPS-treated lung tissue and RAW 264.7. We also found that the inhibitory effect of L2H17 on the inflammatory responses was attenuated by an inhibitor of HO-1 activity, Tin protoporphyrin IX (SnPP). CONCLUSION: Our data confirmed that L2H17 can exert protective effect on ALI in vitro and in vivo by inhibiting inflammatory responses and modulating the HO-1 pathway.
BACKGROUND:Chalcone, a natural product, has a wide range of biological activities. L2H17, a chalcone derivative, was synthesized and screened in our previous study and exhibited excellent anti-inflammatory property in vitro. This study investigated the therapeutic potential of L2H17 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of heme oxygenase-1 (HO-1). MATERIALS AND METHODS: An ALI animal model was induced by LPS (10 mg/kg) intratracheal instillation. The effect of L2H17 on LPS-induced structural damage was determined using hematoxylin and eosin (HE) staining, and tissue edema extent was examined. Bronchoalveolar lavage fluid (BALF) was harvested to assess the levels of related cytokines by enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity was also assessed. HO-1 expression was determined using immunohistochemistry and western blotting. The effects of L2H17 on LPS stimulation in RAW 264.7 and the involvement of the HO-1 pathway were investigated. RESULTS:L2H17 alleviated the histopathological manifestations and tissue edema. Moreover, L2H17 decreased the production of pro-inflammatory factors in BALF and increased SOD activity. In vitro, L2H17 significantly reduced pro-inflammatory cytokine production. Additionally, L2H17 improved the expression of HO-1 in LPS-treated lung tissue and RAW 264.7. We also found that the inhibitory effect of L2H17 on the inflammatory responses was attenuated by an inhibitor of HO-1 activity, Tin protoporphyrin IX (SnPP). CONCLUSION: Our data confirmed that L2H17 can exert protective effect on ALI in vitro and in vivo by inhibiting inflammatory responses and modulating the HO-1 pathway.
Authors: Laura L Bassel; Carmon Co; Alaina Macdonald; Laurel Sly; Erin E McCandless; Joanne Hewson; Raksha Tiwari; Shayan Sharif; Laura Siracusa; Mary Ellen Clark; Jeff L Caswell Journal: BMC Vet Res Date: 2020-05-29 Impact factor: 2.741