This study explores the potential of polymethoxyflavones (PMFs) and polyacetylated flavones (PAFs) as novel analgesic and anti-inflammatory agents. Eight derivatives, isolated from Gardenia oudiepe bud exudate or semi-synthesized from commercial kaempferol, underwent evaluations in various in vivo, in vitro, and in silico models. Acetic acid-, formalin-induced pain, and hot-plate tests were conducted in mice (n = 6). Cell viability assay, ELISA, NO measurement and protein expression by western blot were determined on RAW264.7 macrophage cells before and after exposure to LPS. Molecular docking was performed in order to putatively corroborate the affinity of the compound library to the most promising targets. Despite closely-related chemical structures, subtle modifications significantly influenced anti-nociceptive activity and affinity on diverse cellular or enzymatic targets. The library of compounds exhibited noticeable inhibitory effects on nociception in acetic acid- and formalin-induced pain assays in mice. Biochemical assays on RAW264.7 cells elucidated anti-inflammatory properties, highlighting PAFs 7 and 8 as the most active. The study indicates a peripheral anti-nociceptive profile, suggesting interferences with the production of inflammatory mediators implicated in pain disorders (e.g., COX-2, Tnf-α, IL-6 and MAPK pathway proteins). Molecular docking analyses strongly suggested interactions between PMFs/PAFs chemical library and pre-selected targets. PAFs 7 and 8 demonstrated the best binding energies, showing potential in tackling inflammation, possibly by binding to MAPK, ERK, JNK and p38. These data provide insights for lead optimization through further pharmacomodulation, paving the way for the development of innovative multi-target analgesic and anti-inflammatory drugs.
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http://dx.doi.org/10.1016/j.biopha.2024.117742 | DOI Listing |
Biomed Pharmacother
January 2025
UMR CNRS 8038 CiTCoM, Université Paris Cité, Paris 75006, France. Electronic address:
This study explores the potential of polymethoxyflavones (PMFs) and polyacetylated flavones (PAFs) as novel analgesic and anti-inflammatory agents. Eight derivatives, isolated from Gardenia oudiepe bud exudate or semi-synthesized from commercial kaempferol, underwent evaluations in various in vivo, in vitro, and in silico models. Acetic acid-, formalin-induced pain, and hot-plate tests were conducted in mice (n = 6).
View Article and Find Full Text PDFChem Biol Interact
July 2020
LIENSs UMRi CNRS 7266, La Rochelle Université, 17042, La Rochelle, France.
A series of 10 natural and semisynthetic flavonoids (1 to 10) were obtained from Gardenia oudiepe (Rubiaceae), an endemic plant from New Caledonia. Most of them were polymethoxylated flavones (PMFs) of rare occurrence. After a cell viability screening test, PMFs 2 and 3 showed significant cytotoxic activity against A2058 human melanoma cells (IC = 3.
View Article and Find Full Text PDFBioorg Chem
February 2019
Farmacognosia, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la torre y Medina Allende, Edificio Ciencias II, X5000HUA Córdoba, Argentina; Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Ciudad Universitaria, X5000HUA Córdoba, Argentina. Electronic address:
Hyperpigmentation disorders are difficult to treat without causing permanent depigmentation or irritation. The most effective hypopigmenting agents are tyrosinase inhibitors, however some of those currently used have shown serious side effects. As several classes of flavonoids have already demonstrated ability to inhibit tyrosinase, a library of natural polymethoxyflavones isolated (1-7) from the bud exudate of Gardenia oudiepe and semi-synthetic derivatives (8,9) were evaluated.
View Article and Find Full Text PDFEur J Med Chem
January 2018
Farmacognosia, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de La Torre y Medina Allende, Edificio Ciencias II, X5000HUA Córdoba, Argentina; Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Ciudad Universitaria, X5000HUA Córdoba, Argentina. Electronic address:
Xanthine oxidase (XO), an enzyme widely distributed among mammalian tissues, is associated with the oxidation of xanthine and hypoxanthine to form uric acid. Reactive oxygen species are also released during this process, leading to oxidative damages and to the pathology called gout. Available treatments mainly based on allopurinol cause serious side effects.
View Article and Find Full Text PDFEur J Med Chem
March 2015
Laboratoire de Pharmacognosie, UMR/CNRS 8638, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Sorbonne Paris Cité, 4, Avenue de l'Observatoire, 75006 Paris, France. Electronic address:
A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar concentration.
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