1,7‑Bis(4‑hydroxy‑3‑methoxyphenyl)‑1,4,6‑heptatrien‑3‑one alleviates lipopolysaccharide‑induced inflammation by targeting NF‑κB translocation in murine macrophages and it interacts with MD2 in silico
| Autor: | Apichart Suksamrarn, Poonsit Hiransai, Tanyarath Utaipan, Pathumwadee Yotmanee, Apsorn Sattayakhom, Wanatsanan Chulrik, Waraluck Chaichompoo, Chutima Jansakun, Wilanee Chunglok, Kanokporn Lehboon, Warangkana Chunglok, Kornyok Kamdee |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Cancer Research Curcumin Lipopolysaccharide Lymphocyte Antigen 96 Pharmacology Biochemistry Nitric oxide Mice chemistry.chemical_compound Genetics Animals Curcuminoid Molecular Biology Inflammation biology Macrophages Transcription Factor RelA NF-κB Nitric oxide synthase RAW 264.7 Cells Oncology chemistry Apoptosis biology.protein Molecular Medicine Cytokine secretion |
| Zdroj: | Molecular Medicine Reports. 23 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2021.11848 |
| Popis: | Trienones are curcuminoid analogues and are minor constituents in the rhizomes of numerous Curcuma plant species. Studies investigating the biological activities of trienones, particularly their anti‑inflammatory activities, are limited. In the present study, the trienone 1,7‑bis(4‑hydroxy‑3‑methoxyphenyl)‑1,4,6‑heptatrien‑3‑one (HMPH) was structurally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential anti‑inflammatory effects on lipopolysaccharide (LPS)‑activated RAW264.7 macrophages. Furthermore, LPS‑induced nitric oxide secretion in RAW264.7 cells was markedly and dose‑dependently inhibited by HMPH; in addition, HMPH had a greater efficacy compared with curcumin. This inhibition was accompanied by the suppression of inducible nitric oxide synthase and cyclooxygenase‑2 expression, as well as pro‑inflammatory cytokine secretion. To elucidate the molecular mechanism underlying the anti‑inflammatory effects of HMPH, the effects of this compound on nuclear factor‑κB (NF‑κB) translocation were assessed. HMPH significantly inhibited the translocation of p65 NF‑κB into the nucleus to a greater extent than curcumin, thus indicating that HMPH has more potent anti‑inflammatory activity than curcumin. In addition, an in silico modelling study revealed that HMPH possessed stronger binding energy to myeloid differentiation factor 2 (MD2) compared with that of curcumin, and indicated that the anti‑inflammatory effects of HMPH may be through upstream inhibition of the inflammatory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NF‑κB translocation and interfering with MD2 binding. |
| Databáze: | OpenAIRE |
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