Eun-Jung Bak1, Kyung-Chul Choi2, Sungil Jang3, Gye-Hyeong Woo4, Ho-Geun Yoon5, Younghwa Na6, Yun-Jung Yoo7, Youngseok Lee8, Yangsik Jeong9, Jeong-Heon Cha10. 1. Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea. 2. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea. 3. BK21 PLUS Project, Yonsei University College of Dentistry, South Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea. 4. Department of Clinical Laboratory Science, Semyung University, Jecheon, South Korea. 5. Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul, South Korea. 6. College of Pharmacy, CHA University, Seoul, South Korea. 7. Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea. 8. Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, South Korea. 9. Department of Biochemistry, Yonsei University Wonju College of Medicine, Wonju, South Korea. Electronic address: yjeong@yonsei.ac.kr. 10. Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea; BK21 PLUS Project, Yonsei University College of Dentistry, South Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea. Electronic address: Jcha@yuhs.ac.
Abstract
BACKGROUND & AIMS: Licochalcone (lico) F is a novel synthetic retrochalcone. In this study, we investigated the anti-inflammatory effects of lico F in vitro, and its effects on obesity-induced chronic inflammation, glucose intolerance, and fatty liver in vivo. METHODS: The inhibitory effects of lico F on TNFα-induced inflammation were investigated using NF-κB luciferase reporter assay and RT-PCR. Diet-induced obese mice were treated orally, once per day, with vehicle or lico F (10 mg/kg/day), for 3 weeks, and blood, liver, and adipose tissues were analyzed. RESULTS: Lico F inhibited TNFα-induced NF-κB activation and mRNA expression of TNFα, COX-2, IL-6, IL-1β, and NOS2. In obese mice, lico F administration significantly alleviated glucose tolerance without changes in body weight gain and food intake. Lico F reduced adipocyte size and macrophage infiltration into white adipose tissue and improved hepatic lesions, by decreasing fat droplets and glycogen deposition. The mRNA expression levels of TNFα, MCP-1, and CD68 in white adipose tissue also decreased markedly. Moreover, lico F enhanced Akt signaling, but reduced p38 MAPK signaling in white adipose tissue. CONCLUSIONS: Lico F had anti-inflammatory effects and showed beneficial effects on glucose metabolism, which could be partially caused by activation of the Akt signal pathway and obesity-induced chronic inflammation, probably by downregulating p38 signal pathway. Moreover, lico F could be used as a potential novel therapeutic compound against type 2 diabetes and obesity-induced chronic inflammation without the deleterious effects of body weight gain and fatty liver.
BACKGROUND & AIMS:Licochalcone (lico) F is a novel synthetic retrochalcone. In this study, we investigated the anti-inflammatory effects of lico F in vitro, and its effects on obesity-induced chronic inflammation, glucose intolerance, and fatty liver in vivo. METHODS: The inhibitory effects of lico F on TNFα-induced inflammation were investigated using NF-κB luciferase reporter assay and RT-PCR. Diet-induced obesemice were treated orally, once per day, with vehicle or lico F (10 mg/kg/day), for 3 weeks, and blood, liver, and adipose tissues were analyzed. RESULTS:Lico F inhibited TNFα-induced NF-κB activation and mRNA expression of TNFα, COX-2, IL-6, IL-1β, and NOS2. In obesemice, lico F administration significantly alleviated glucose tolerance without changes in body weight gain and food intake. Lico F reduced adipocyte size and macrophage infiltration into white adipose tissue and improved hepatic lesions, by decreasing fat droplets and glycogen deposition. The mRNA expression levels of TNFα, MCP-1, and CD68 in white adipose tissue also decreased markedly. Moreover, lico F enhanced Akt signaling, but reduced p38 MAPK signaling in white adipose tissue. CONCLUSIONS:Lico F had anti-inflammatory effects and showed beneficial effects on glucose metabolism, which could be partially caused by activation of the Akt signal pathway and obesity-induced chronic inflammation, probably by downregulating p38 signal pathway. Moreover, lico F could be used as a potential novel therapeutic compound against type 2 diabetes and obesity-induced chronic inflammation without the deleterious effects of body weight gain and fatty liver.
Authors: Sara Sayonara da Cruz Nascimento; Jaluza Luana Carvalho de Queiroz; Amanda Fernandes de Medeiros; Ana Clara de França Nunes; Grasiela Piuvezam; Bruna Leal Lima Maciel; Thaís Souza Passos; Ana Heloneida de Araújo Morais Journal: PLoS One Date: 2022-09-01 Impact factor: 3.752
Authors: Satyamaanasa Polubothu; Davide Zecchin; Lara Al-Olabi; Daniël A Lionarons; Mark Harland; Stuart Horswell; Anna C Thomas; Lilian Hunt; Nathan Wlodarchak; Paula Aguilera; Sarah Brand; Dale Bryant; Cristina Carrera; Hui Chen; Greg Elgar; Catherine A Harwood; Michael Howell; Lionel Larue; Sam Loughlin; Jeff MacDonald; Josep Malvehy; Sara Martin Barberan; Vanessa Martins da Silva; Miriam Molina; Deborah Morrogh; Dale Moulding; Jérémie Nsengimana; Alan Pittman; Joan-Anton Puig-Butillé; Kiran Parmar; Neil J Sebire; Stephen Scherer; Paulina Stadnik; Philip Stanier; Gemma Tell; Regula Waelchli; Mehdi Zarrei; Susana Puig; Véronique Bataille; Yongna Xing; Eugene Healy; Gudrun E Moore; Wei-Li Di; Julia Newton-Bishop; Julian Downward; Veronica A Kinsler Journal: Genet Med Date: 2021-06-18 Impact factor: 8.822