Insights into cyclooxygenase-2 inhibition by isolated bioactive compounds 3-caffeoyl-4-dihydrocaffeoyl quinic acid and isorhamnetin 3-O-β-D-glucopyranoside from Salicornia herbacea |
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| Institution: | 1. Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do 38541, South Korea;2. Nanotechnology Research and Application Center, Sabanci University, Istanbul 34956, Turkey;3. Department of Energy and Materials Engineering, Dongguk University, Seoul 04620, South Korea;4. TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, Gwal Pahari, Gurugram, Haryana 122003, India;5. College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea;6. Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Gangwon-do 25451, South Korea;7. Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon 22212, South Korea;8. Department of Analytical Chemistry and Food Science, University of Vigo - Ourense Campus, E-32004 Ourense, Spain;10. Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do 38541, South Korea;1. Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea;2. Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea;1. Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina;2. Herbario, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, 5700 San Luis, Argentina;3. Centro de Referencia de Micología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina |
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| Abstract: | BackgroundCyclooxygenase-2 (COX-2) is an important enzyme with numerous biological functions. Overexpression of COX-2 has been associated with various inflammatory-related diseases and therefore, projected as an important pharmacological target.PurposeWe aimed to investigate the inhibitory potential of isolated bioactive compounds, 3-caffeoyl-4-dihydrocaffeoyl quinic acid (CDQ) and isorhamnetin 3-O-β-d-glucopyranoside (IDG), from Salicornia herbacea against COX-2 using both computational and in vitro approaches.MethodsComputational analysis, including molecular docking, molecular dynamics (MD) simulations, and post-simulations analysis, were employed to estimate the binding affinity and stability of CDQ and IDG in the catalytic pocket of COX-2 against Celecoxib as positive control. These predictions were further evaluated using in vitro enzyme inhibition as well as gene expression mediation in macrophages cells.ResultsMolecular docking analysis revealed substantial binding energy of CDQ (-6.1 kcal/mol) and IDG (-5.9 kcal/mol) with COX-2, which are lower than Celecoxib (-8.1 kcal/mol). MD simulations (100 ns) and post simulation analysis exhibited the substantial stability and binding affinity of docked CDQ and IDG compounds with COX-2. In vitro assays indicated significant COX-2 inhibition by CDQ (IC50 = 76.91 ± 2.33 μM) and IDG (IC50 = 126.06 ± 9.44 μM). This result supported the inhibitory potential of isolated bioactive compounds against COX-2. Also, a cellular level study revealed a downregulation of COX-2 expression in tumor necrosis factor-alpha stimulated RAW 264.7 macrophages treated with CDQ and IDG.ConclusionComputational and experimental analysis of CDQ and IDG from S. herbacea established their potential in the inhibition and mediation of COX-2. Hence, CDQ and IDG can be considered for therapeutic development against COX-2 linked disorders, such as inflammation and cancer. Furthermore, CDQ and IDG structures can be served as a lead compound for the development of advanced novel anti-inflammatory drugs. |
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