NO inhibitors function as potential anti-neuroinflammatory agents for AD from the flowers of Inula japonica |
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| Institution: | 1. School of Chemistry and Chemical Engineering, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, China;2. School of Biological Science and Technology, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, China;1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China;2. School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, PR China;3. School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China;1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China;2. Tianjin Key Laboratoy of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin 300020, China;3. Research and Development Division, Korean Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210, Republic of Korea;4. Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;5. Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan;1. Aix Marseille Univ, UMR-MD3, Laboratory of Pharmacognosy and Ethnopharmacology, Faculty of Pharmacy, 27 bld Jean Moulin, CS 30064, 13385 Marseille, France;2. Aix Marseille Univ, Spectropole, FR1739, Service 511, Campus Saint-Jérome, 13397 Marseille, France.;3. Aix Marseille Univ, Laboratoire de Mutagenèse Environnementale, IMBE, IFR ECCOREV, Faculty of Pharmacy, 27 bld Jean Moulin, CS 30064, 13385 Marseille, France;4. Luberon Natural Regional Park, 60, place Jean Jaurès, 84400 Apt, France;5. Avignon University, Qualisud, UMR 95, F-84000 Avignon, France |
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| Abstract: | The extensive pathology studies revealed that Alzheimer’s disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. Inula japonica is a member of the Asteraceae plant family and its flowers have been used as a healthy tea and a traditional Chinese medicine. Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of two new sesquiterpenes and ten known terpenes from the flowers of I. japonica. Their structures were established on the basis of extensive analysis of NMR and MS spectroscopic data, as well as calculated and experimental electronic circular dichroism (ECD) spectra. Among these isolates, compound 1 is a new sesquiterpene with a rare tricyclic fused skeleton, and 2 processes a 1,10-seco-eudesmane skeleton. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein. The present study disclosed that the flowers of I. japonica as a healthy tea are potentially useful for AD and related neuroinflammatory diseases. |
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| Keywords: | Sesquiterpenes Anti-neuroinflammatory NO inhibitory effects Molecular docking iNOS |
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