Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound
INTRODUCTION: Since the synthesis of acetylsalicylic acid by Hoffmann in 1897, new classes of NSAIDs have been introduced; however, their side effects have limited their clinical applications. Consequently, our team has recently synthesized a novel bipyrazole compound that showed a satisfactory efficacy and safety profile. The aim of the current study was to elucidate the molecular mechanism of this bipyrazole compound.
METHOD: The anti-inflammatory efficacy of the compound was assessed using formalin-induced paw edema test. Computer-assisted simulation docking experiments were carried out. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), tumor necrosis factor-alpha (TNFα), interleukin-1 (IL1) and interleukin-10 (IL10) gene expression were quantified with real-time polymerase chain reaction (RT-PCR) using SYBR Green technology. The samples were taken from the plantar paw of mice after formalin local injection.
RESULTS: The efficacy of the bipyrazole compound was similar to that of indomethacin, diclofenac, and celecoxib, as proven by the formalin-induced paw edema. Docking study indicated a superior binding score for the studied compound relative to celecoxib, indomethacin, and diclofenac. RT-PCR assessment revealed a significant decrease in iNOS, COX-2, and TNFα gene expression in the bipyrazole-treated group. Moreover, a reduction in IL1 and nNOS gene expression levels and an increase in IL10 level were detected despite being insignificant compared to the control group.
CONCLUSION: These findings revealed the superiority of the newly synthesized bipyrazole compound not only on the binding site, but also by inhibiting most of the inflammatory mediators including TNF-α.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 68(2019), 5 vom: 01. Mai, Seite 379-386 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Domiati, S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.08.2019 Date Revised 25.02.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00011-019-01225-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294979212 |
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| 245 | 1 | 0 | |a Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound |
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| 500 | |a Date Completed 26.08.2019 | ||
| 500 | |a Date Revised 25.02.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: Since the synthesis of acetylsalicylic acid by Hoffmann in 1897, new classes of NSAIDs have been introduced; however, their side effects have limited their clinical applications. Consequently, our team has recently synthesized a novel bipyrazole compound that showed a satisfactory efficacy and safety profile. The aim of the current study was to elucidate the molecular mechanism of this bipyrazole compound | ||
| 520 | |a METHOD: The anti-inflammatory efficacy of the compound was assessed using formalin-induced paw edema test. Computer-assisted simulation docking experiments were carried out. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), tumor necrosis factor-alpha (TNFα), interleukin-1 (IL1) and interleukin-10 (IL10) gene expression were quantified with real-time polymerase chain reaction (RT-PCR) using SYBR Green technology. The samples were taken from the plantar paw of mice after formalin local injection | ||
| 520 | |a RESULTS: The efficacy of the bipyrazole compound was similar to that of indomethacin, diclofenac, and celecoxib, as proven by the formalin-induced paw edema. Docking study indicated a superior binding score for the studied compound relative to celecoxib, indomethacin, and diclofenac. RT-PCR assessment revealed a significant decrease in iNOS, COX-2, and TNFα gene expression in the bipyrazole-treated group. Moreover, a reduction in IL1 and nNOS gene expression levels and an increase in IL10 level were detected despite being insignificant compared to the control group | ||
| 520 | |a CONCLUSION: These findings revealed the superiority of the newly synthesized bipyrazole compound not only on the binding site, but also by inhibiting most of the inflammatory mediators including TNF-α | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bipyrazole | |
| 650 | 4 | |a Cyclooxygenase-2 (COX-2) | |
| 650 | 4 | |a Inducible nitric oxide synthase (iNOS) | |
| 650 | 4 | |a Neuronal nitric oxide synthase (nNOS) | |
| 650 | 4 | |a Non-steroidal anti-inflammatory drugs | |
| 650 | 4 | |a Tumor necrosis factor-alpha (TNF-α) | |
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| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Formaldehyde |2 NLM | |
| 650 | 7 | |a 1HG84L3525 |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type I |2 NLM | |
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| 700 | 1 | |a Mehanna, M |e verfasserin |4 aut | |
| 700 | 1 | |a Ragab, H |e verfasserin |4 aut | |
| 700 | 1 | |a El Galil, K H Abd |e verfasserin |4 aut | |
| 700 | 1 | |a Nakkash-Chmaisse, H |e verfasserin |4 aut | |
| 700 | 1 | |a El Mallah, A |e verfasserin |4 aut | |
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