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  • Khan et al studied the effects

    2019-11-20

    Khan et al. studied the effects of two structurally divergent coumarins viz calipteryxin 3 and (3′S,4′S)-3′,4′-disenecioyloxy-3′,4′-dihydroseselin 4 from Seseli recinosum, in lipopolysaccharide (LPS)-stimulated murine macrophages. The study revealed that calipteryxin and (3′S,4′S)-3′,4′-disenecioyloxy-3′,4′-dihydroseselin treatment showed potent inhibitory effects on pro-inflammatory Dutasteride and cytokines associated with the molecular signaling pathways, Further both coumarins inhibited the LPS-induced protein and mRNA expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells. To explore the potential mechanisms underlying the inhibitory activity of coumarin derivatives, the protein signaling pathways for NF-κB, mitogen-activated protein kinase (MAPK) and Akt were examined. Both coumarins 3 and 4 reduced the LPS-stimulated phosphorylation of IKKα/β, p-IκBα and IκBα degradation as well as the nuclear translocation of the p65 subunit of pro-inflammatory transcription factor NF-κB also inhibiting the LPS-induced expression of ERK, c-Jun N-terminal kinase (JNK), p38 and Akt proteins. Further the study supports the therapeutic potential and molecular mechanisms of 3 and 4 for inflammatory diseases [42]. Ju et al. investigated the chemical constituents of the endophytic fungus Botryosphaeria sp. KcF6 derived from the mangrove plant Kandelia candel. A new mellein derivative, 3S-5,8-dihydroxy-3-hydroxymethyldihydroisocoumarin 5, in addition to five other known compounds monocerin 6, 3-methyl-6,8-dihydroxyisocoumarin 7, 8-methoxymellein 8. The endophytic fungal strain KcF6 was isolated from the inner fruit part of the mangrove plant K. candel and grown on a solid-rice medium. The isolated compounds were evaluated for their cytotoxic and anti-inflammatory (COX-2) activities. 5 exhibited significant COX-2 inhibitory activity with an IC50 value of 6.51μM, whereas none of the compds. exhibited cytotoxicity on the tested cancer cell lines (IC50>100μM) [43]. Ishita et al. studied the anti-inflammatory activity of 9 coumarin derivatives isolated from a 90% methanol fraction of Angelica decursiva traditional used in age old Korean medicine as an antitussive, analgesic, antipyretic, and cough remedy, it was evaluated via inhibition of production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Amongst the tested compounds, edulisin II 9, decursidin 10, Pd-C-III 11, 4-hydroxy Pd-C-III 12 inhibited COX-2 protein expression in LPS-stimulated RAW 264.7 cells. These results suggest that coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation-assocd. disorders [44]. Kim et al. studied the inhibitory effect of three chromones and a coumarin derived from plant abstracts of corydalis heterocarpa on the production of nitric oxide (NO) was evaluated in LPS-induced RAW 264.7 macrophage cells. Among the compounds tested heterocarpin a furochromone, significantly inhibited its production in a dose-dependent manner. Also it suppressed prostaglandin E2 (PGE2) production and expression of cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), however coumarin isopimpinellin was found to be moderately active [45]. Yang et al. studied anti-inflammatory and antioxidant activities of methanol extract of the fruits of Foeniculum vulgare (F. vulgare) traditionally used to treat inflammatory diseases. Four coumarins viz scopoletin 13, 8-methoxypsoralen 14, bergapten 15 and imperatorin 16 were isolated. Although four coumarins isolated from the fruits of F. vulgare provide effective anti-inflammatory and antioxidant activities, imperatorin was found to be most potent [46]. Shokoohinia et al. studied acetone extracts of Prangos ferulacea (Apiaceae), a perennial plant found in the Middle-East, where it is commonly used as an antispasmodic and anti-inflammatory agent and is a rich source of coumarins. Several coumarins from P. ferulacea were isolated and screened and isoimperatorin 17 was found to be a cyclooxygenase-2 inhibitor [47]. Hemshekhar et al. reported a significant amelioration of the upregulated non-enzymic inflammatory markers such as TNF-α, IL-1β, IL-6, COX-2 and PGE2 [48] by 4-methyl esculetin 18. Hwang et al. reported Phenylpropanoids and coumarins isolated from Ailanthus altissima were screened for COX-1/COX-2 inhibition. These findings suggested that new synthetic phenylpropanoid derivatives good activity and were potential selective COX-2 inhibitors [49].