New Coumarins and Anti-Inflammatory Constituents from the Fruits of Cnidium monnieri

Abstract

The fruit of Cnidium monnieri is commercially used as healthcare products for the improvement of impotence and skin diseases. Three new coumarins, 3'-O-methylmurraol (1), rel-(1'S,2'S)-1'-O-methylphlojodicarpin (2), and (1'S,2'S)-1'-O-methylvaginol (3), have been isolated from the fruits of C. monnieri, together with 14 known compounds (4–17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4–12, and 14–17 exhibited inhibition (IC50 ≤ 7.31 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 7, 9–11, 15, and 17 inhibited fMLP/CB-induced elastase release with IC50 values ≤7.83 µg/mL. This investigation reveals that bioactive isolates (especially 6, 7, 14, and 17) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.

Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections

“…In our case, the SIs ranged from 295 to 1021, making our compounds better potential antivirals for this virus in relation to those that were previously reported. The anti-inflammatory activity of coumarins has been described [49], and considering that the CHIKV induces a disease that is also inflammatory [50], the possible effects of the coumarins in vivo could go beyond the antiviral effect. Subsequent studies in animal models should focus on both fronts.…”

Antagonism of human formyl peptide receptor 1 with natural compounds and their synthetic derivatives

“…A natural chromone, cnidimol A (Table 1), which was isolated from Cnidium monnieri was found to inhibit f MLF-induced O 2 −· production and HNE release [94]. Likewise, the isoprenylated flavonoid ugonin 3 (Table 1) isolated from Helminthostachys zeylanica and several related ugonins potently inhibited similar f MLF-induced functional responses [95, 96].…”

“…Some coumarins have been used in the clinic because of their anticoagulant and antineurodegenerative properties (reviewed in [101, 102]). Several coumarins, including isoheraclenin, imperatorin, osthenol, bergapten, xanthyletin, alloxanthoxyletin, and demethylauraptenol were found to be inhibitors of O 2 −· production and HNE release by f MLF-stimulated human neutrophils [94, 103–106]. Chemical structures of selected coumarins are shown in Table 1.…”

“…It should be noted that osthol is a known plant-derived compound with anti-inflammatory activity and a broad spectrum of molecular targets [109, 110]. Osthol had a weak inhibitory effect on f MLF-induced HNE release [94]. Although a related coumarin, osthenol, had potent inhibitory activity on f MLF-induced O 2 −· production and HNE release [94], this compound was previously found to inhibit 5α-reductase type I, 5-lipoxygenase, and cyclooxygenase [111, 112], suggesting FPR-independent effects on cellular responses.…”

“…Osthol had a weak inhibitory effect on f MLF-induced HNE release [94]. Although a related coumarin, osthenol, had potent inhibitory activity on f MLF-induced O 2 −· production and HNE release [94], this compound was previously found to inhibit 5α-reductase type I, 5-lipoxygenase, and cyclooxygenase [111, 112], suggesting FPR-independent effects on cellular responses. Indeed, other cyclooxygenase inhibitors, such as celecoxib and indomethacin, have been reported to interfere with f MLF-induced functional responses, such as chemotaxis [113].…”