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Three new sesquiterpene‐hydroquinone hybrids, saromacrophorins A–C (1–3) were isolated from the deep‐sea‐derived fungus Sarocladium terricola 494a, along with nine known compounds. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Noteworthily, compound 1 is a rare 5′,6′‐dihydroxymacrophorin and compound 3 is the first example of macrophorin possessing 4′S‐configuration. Compound 4 showed potent anti‐food allergic activity with an IC50 value of 18.9 μM. [ABSTRACT FROM AUTHOR]

(*, IBS-D FSN vs. control FSN in BDNF+/- mice; #, IBS-D FSN in BDNF+/+ mice vs. in BDNF+/- mice; †control FSN in BDNF+/+ mice vs. in BDNF+/- mice). (B) TrkB/Fc significantly suppressed the effect of IBS-D FSN at 30, 45 and 60 mmHg (*, IBS-D FSN vs. control; #, IBS-D FSN vs. [Extracted from the article]

Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity. [ABSTRACT FROM AUTHOR]