Meliasanines A-L, tirucallane-type triterpenoids from Melia toosendan with anti-inflammatory properties via NF-κB signaling pathway.

Publisher: Elsevier Country of Publication: England NLM ID: 0151434 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3700 (Electronic) Linking ISSN: 00319422 NLM ISO Abbreviation: Phytochemistry Subsets: MEDLINE

Publication: 2003- : London : Elsevier
Original Publication: 1961-2003: Oxford : Pergamon Press.

Triterpenes*/pharmacology ; Triterpenes*/chemistry ; Triterpenes*/isolation & purification ; NF-kappa B*/metabolism ; NF-kappa B*/antagonists & inhibitors ; Signal Transduction*/drug effects ; Anti-Inflammatory Agents*/pharmacology ; Anti-Inflammatory Agents*/chemistry ; Anti-Inflammatory Agents*/isolation & purification ; Nitric Oxide*/biosynthesis ; Nitric Oxide*/antagonists & inhibitors ; Nitric Oxide*/metabolism ; Lipopolysaccharides*/pharmacology ; Lipopolysaccharides*/antagonists & inhibitors ; Melia*/chemistry; Mice ; Animals ; RAW 264.7 Cells ; Molecular Structure ; Nitric Oxide Synthase Type II/metabolism ; Nitric Oxide Synthase Type II/antagonists & inhibitors ; Plant Bark/chemistry ; Cyclooxygenase 2/metabolism ; Dose-Response Relationship, Drug ; Structure-Activity Relationship

Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC 50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC 50  = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)

Keywords: Anti-inflammatory activity; Melia toosendan; Meliaceae; NF-κB signaling pathway; Tirucallane-type triterpenoids

0 (Triterpenes)
0 (NF-kappa B)
0 (Anti-Inflammatory Agents)
31C4KY9ESH (Nitric Oxide)
0 (Lipopolysaccharides)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
0 (tirucallane)
EC 1.14.99.1 (Cyclooxygenase 2)

Date Created: 20240620 Date Completed: 20240711 Latest Revision: 20240807

20240807

10.1016/j.phytochem.2024.114192

38901624