Viridicatol Isolated from Deep-Sea Penicillium Griseofulvum Alleviates Anaphylaxis and Repairs the Intestinal Barrier in Mice by Suppressing Mast Cell Activation

Abstract

Viridicatol is a quinoline alkaloid isolated from the deep-sea-derived fungus Penicillium griseofulvum. The structure of viridicatol was unambiguously established by X-ray diffraction analysis. In this study, a mouse model of ovalbumin-induced food allergy and the rat basophil leukemia (RBL)-2H3 cell model were established to explore the anti-allergic properties of viridicatol. On the basis of the mouse model, we found viridicatol to alleviate the allergy symptoms; decrease the levels of specific immunoglobulin E, mast cell protease-1, histamine, and tumor necrosis factor-α; and promote the production of interleukin-10 in the serum. The treatment of viridicatol also downregulated the population of B cells and mast cells (MCs), as well as upregulated the population of regulatory T cells in the spleen. Moreover, viridicatol alleviated intestinal villi injury and inhibited the degranulation of intestinal MCs to promote intestinal barrier repair in mice. Furthermore, the accumulation of Ca2+ in RBL-2H3 cells was significantly suppressed by viridicatol, which could block the activation of MCs. Taken together, these data indicated that deep-sea viridicatol may represent a novel therapeutic for allergic diseases.

Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus

“…Its molecular formula was established as C17H18N2O4 according to the protonated molecule peak at m/z 337.1176 [M + Na] + in its (+)−HRESIMS (High Resolution Electrospray Ionization Mass Spectroscopy) spectrum, requiring ten degrees of unsaturation. The 1 H and 13 C NMR spectroscopic data (Table 1) displayed 17 carbons, characteristics of one mono-substituted aromatic unit [δH 7.24 (1H, br t, J = 7.4 Hz, H-4), 7.33 (2H, dd, J = 7.8, 7.3 Hz, H-3, 5), 7 3 Hz) confirmed the two benzene units and deduced another fragment of C-7/C-8. By the HMBC (Heteronuclear Multiple-bond Correlation) correlations of H-7 (δH 5.16) to C-1/C-2/C-6/C-9 and H-6' (δH 7.60)/7′-NMe (δH 2.89) to C-7', 1 was then assigned a phenylpropionyl moiety and a benzamide groups (Figure 2).…”

“…Its molecular formula was established as C 17 H 18 N 2 O 4 according to the protonated molecule peak at m/z 337.1176 [M + Na] + in its (+)−HRESIMS (High Resolution Electrospray Ionization Mass Spectroscopy) spectrum, requiring ten degrees of unsaturation. The 1 H and 13 C NMR spectroscopic data (Figures S1 and S2, Table 1) displayed 17 carbons, characteristics of one mono-substituted aromatic unit [δ H 7.24 (1H, br t, J = 7.4 Hz, H-4), 7.33 (2H, dd, J = 7.8, 7. 3 Hz) confirmed the two benzene units and deduced another fragment of C-7/C-8.…”

“…Its molecular formula was established as C 12 H 23 NO 4 based on the sodium adduct ionic peak at m/z 268.1526 [M + Na] + in its positive HRESIMS spectrum, requiring two degrees of unsaturation. Its 1 H and 13 C NMR spectra were very similar to those of pyroglutamylleucinmethylester (20) [15], except for a 2-hydroxy-3-methylbutanoyl unit instead of a pyroglutamyl moiety in 4. This was confirmed by the 1 H-1 H COSY correlations of H 3 -4 (δ H 1.00, d, J = 7.0 Hz) and H 3 -5 (δ H 0.84, d, J = 6.8 Hz) via H-3 (δ H 2.07 m) to H-2 (δ H 3.86, d, J = 3.7 Hz).…”

“…As our ongoing research for novel and bioactive secondary metabolites from the deep sea-derived microorganisms [8][9][10][11], the fungal strain Penicillium griseofulvum isolated from the Indian Ocean sediment was selected for a systematic chemical examination. As a result, five carotanes, four naphthalenes, and three viridicatol derivates were obtained [12,13]. A continuous study, however, led to the isolation of 10 new (Figure 1) and 26 known compounds.…”

Marine Heterocyclic Compounds That Modulate Intracellular Calcium Signals: Chemistry and Synthesis Approaches

“…Recent data suggest that, in mast cells, viridicatol may inhibit Ca 2+ signaling induced by ionophores. As a consequence, viridicatol may prevent mast cell degranulation, which could block the activation of mast cells that are involved in the inflammatory response [ 14 ]. Evidence showed that viridicatol also abolishes intracellular Ca 2+ increases in rat basophilic leukemia cells and mast cells isolated from mice treated with ovalbumin to induce food allergy, thus alleviating allergic symptoms.…”