In Gyoung Ju1, Eugene Huh2, Namkwon Kim1, Seungmin Lee1, Jin Gyu Choi3, Jongki Hong4, Myung Sook Oh5. 1. Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea. 2. Department of Medical Science of Meridian, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea. 3. BK21 PLUS Integrated Education and Research Center for Nature-inspired Drug Development Targeting Healthy Aging, Kyung Hee University, Seoul 02447, Republic of Korea. 4. Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea. 5. Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: msohok@khu.ac.kr.
Abstract
BACKGROUND: Neuroinflammation plays a major role in the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The regulation of microglia is an efficient therapeutic approach to controlling neuroinflammation. PURPOSE: In this study, we aimed to determine whether Artemisiae Iwayomogii Herba (AIH), which is herbal medicine traditionally used for inflammation-related disorders, controls neuroinflammatory responses by regulating the microglia-mediated signaling pathway. METHODS: BV-2 microglial cells were treated with AIH and lipopolysaccharides (LPS), then various pro-inflammatory mediators were analyzed using griess reaction, quantitative reverse-transcription polymerase chain reaction, or western blotting. C57BL/6 J mice were orally administered by AIH for 17 days and intraperitoneally injected with LPS for the last 14 days. The brains were collected and the microglial activation and nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) expression in the cortex and hippocampus were analyzed using immunohistochemistry or western blotting. RESULTS: In BV-2 microglial cells, we found that AIH inhibited nitric oxide (NO) production induced by LPS. AIH also suppressed the expressions of pro-inflammatory mediators, including inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. The study also revealed that the effects of AIH are related to the regulation of the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we found that AIH prevented the formation of NLRP3 inflammasomes. Consistent with the results of in vitro studies on the brains of LPS-injected mice, we observed that AIH suppressed microglial activation and NLRP3 expression. CONCLUSION: Taken together, these results suggest that AIH attenuates neuroinflammation by regulating the NF-κB and MAPK pathways, and it may be used for treating neurological diseases.
BACKGROUND: Neuroinflammation plays a major role in the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The regulation of microglia is an efficient therapeutic approach to controlling neuroinflammation. PURPOSE: In this study, we aimed to determine whether Artemisiae Iwayomogii Herba (AIH), which is herbal medicine traditionally used for inflammation-related disorders, controls neuroinflammatory responses by regulating the microglia-mediated signaling pathway. METHODS:BV-2 microglial cells were treated with AIH and lipopolysaccharides (LPS), then various pro-inflammatory mediators were analyzed using griess reaction, quantitative reverse-transcription polymerase chain reaction, or western blotting. C57BL/6 J mice were orally administered by AIH for 17 days and intraperitoneally injected with LPS for the last 14 days. The brains were collected and the microglial activation and nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) expression in the cortex and hippocampus were analyzed using immunohistochemistry or western blotting. RESULTS: In BV-2 microglial cells, we found that AIH inhibited nitric oxide (NO) production induced by LPS. AIH also suppressed the expressions of pro-inflammatory mediators, including inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. The study also revealed that the effects of AIH are related to the regulation of the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we found that AIH prevented the formation of NLRP3 inflammasomes. Consistent with the results of in vitro studies on the brains of LPS-injected mice, we observed that AIH suppressed microglial activation and NLRP3 expression. CONCLUSION: Taken together, these results suggest that AIH attenuates neuroinflammation by regulating the NF-κB and MAPK pathways, and it may be used for treating neurological diseases.