Hong Li1, Yali Zhang2, Jie Min3, Long Gao3, Ren Zhang3, Yucheng Yang3. 1. Department of Endocrinology, Shanghai University of Traditional Chinese Medicine Longhua Affiliated Hospital, 725 South Wanpin Road, Shanghai, 200032, People's Republic of China. shanhongli@126.com. 2. Institute of Spleen and Stomach Disease, Shanghai University of Traditional Chinese Medicine Longhua Affiliated Hospital, 725 South Wanpin Road, Shanghai, 200032, People's Republic of China. 3. Department of Endocrinology, Shanghai University of Traditional Chinese Medicine Longhua Affiliated Hospital, 725 South Wanpin Road, Shanghai, 200032, People's Republic of China.
Abstract
INTRODUCTION: Graves' orbitopathy (GO) is an autoimmune inflammatory disorder affecting the orbit around the eye. Astragaloside IV (AS-VI) is the main active ingredient of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV exhibits antioxidant and anti-inflammatory properties, and shows therapeutic potential in a number of ischemic and inflammatory diseases; however, its pharmaceutical activities in GO remain undefined. MATERIALS AND METHODS: In this study, we investigated the effects of AS-IV on interleukin (IL)-1β-induced orbital fibroblast inflammation in vitro and GO orbital inflammation and ocular histopathological changes in vivo, as well as the underlying mechanisms responsible for these effects. RESULTS AND CONCLUSION: The results show that IL-1β increased mRNA expression of the inflammatory cytokines IL-6, IL-8, TNF-α, and MCP-1 in cultured orbital fibroblasts. This IL-1β-induced inflammation was accompanied by increased autophagic activity as reflected in increased Beclin-1 and Agt-5 expression, as well as LC3-I to LC3-II conversion. Pretreatment with the autophagy inhibitors 3-MA and bafilomycin A1, or silencing of autophagy-related proteins Beclin-1 and Atg-5, prevented IL-1β-induced orbital fibroblast inflammation, while pretreatment with the autophagy activator rapamycin had the opposite effects. These data suggested that autophagy was involved in GO orbital inflammation. AS-IV treatment significantly decreased IL-1β-induced inflammatory cytokine production in orbital fibroblasts in vitro and attenuated GO orbital inflammation, fat accumulation, collagen deposition, and macrophage infiltration in vivo. These in vitro and in vivo protective effects of AS-IV against GO were accompanied by decreased autophagic activities in orbital fibroblasts and GO orbital tissues, respectively. Collectively, our findings suggested that AS-IV protects against GO through suppression of autophagy. Thus, AS-IV may have preventive benefits for GO.
INTRODUCTION:Graves' orbitopathy (GO) is an autoimmune inflammatory disorder affecting the orbit around the eye. Astragaloside IV (AS-VI) is the main active ingredient of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV exhibits antioxidant and anti-inflammatory properties, and shows therapeutic potential in a number of ischemic and inflammatory diseases; however, its pharmaceutical activities in GO remain undefined. MATERIALS AND METHODS: In this study, we investigated the effects of AS-IV on interleukin (IL)-1β-induced orbital fibroblast inflammation in vitro and GO orbital inflammation and ocular histopathological changes in vivo, as well as the underlying mechanisms responsible for these effects. RESULTS AND CONCLUSION: The results show that IL-1β increased mRNA expression of the inflammatory cytokines IL-6, IL-8, TNF-α, and MCP-1 in cultured orbital fibroblasts. This IL-1β-induced inflammation was accompanied by increased autophagic activity as reflected in increased Beclin-1 and Agt-5 expression, as well as LC3-I to LC3-II conversion. Pretreatment with the autophagy inhibitors 3-MA and bafilomycin A1, or silencing of autophagy-related proteins Beclin-1 and Atg-5, prevented IL-1β-induced orbital fibroblast inflammation, while pretreatment with the autophagy activator rapamycin had the opposite effects. These data suggested that autophagy was involved in GO orbital inflammation. AS-IV treatment significantly decreased IL-1β-induced inflammatory cytokine production in orbital fibroblasts in vitro and attenuated GO orbital inflammation, fat accumulation, collagen deposition, and macrophage infiltration in vivo. These in vitro and in vivo protective effects of AS-IV against GO were accompanied by decreased autophagic activities in orbital fibroblasts and GO orbital tissues, respectively. Collectively, our findings suggested that AS-IV protects against GO through suppression of autophagy. Thus, AS-IV may have preventive benefits for GO.
Authors: Ran Wei; Limin Mao; Ping Xu; Xinghai Zheng; Robert M Hackman; Gerardo G Mackenzie; Yuefei Wang Journal: Food Funct Date: 2018-11-14 Impact factor: 5.396