Cembranoids from the Red Sea soft coral Sarcophyton glaucum protect against indomethacin-induced gastric injury

Abstract

Soft corals and their secondary metabolites represent an exceptional source of potential drugs. In this regard, Sarcophyton glaucum-derived secondary metabolites were examined for their preventive activities against indomethacin-induced gastric ulcer. Extraction and chromatographic processing of a specimen of S. glaucum collected from the Red Sea waters of Jeddah city resulted in the isolation of eight metabolites including two furanone-based cembranoids (1 and 2), two known pyran-based cembranoids (3 and 4), a known aromadendrene derivative (5), a δ-lactone fatty acid derivative (6), and two known gorgostane-type sterols (7 and 8). Compounds 1 and 6 are new chemical structures, named Δ¹²⁽²⁰⁾-sarcophine and sarcoglaucanoate, respectively. In an initial pilot experiment, compounds 1 and 2 showed significant protective activities against indomethacin-induced peptic ulcer in rats. These data were evidenced by their ability to ameliorate the elevated ulcer indices and prevent histopathological alterations observed in the untreated animals. Their effects were mediated by enhanced mucin as shown by Alcian blue and periodic acid-Schiff (PAS) staining of stomach sections. Compounds 1 and 2 exerted significant antioxidant properties as they prevent reduced glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and superoxide dismutase (SOD) exhaustion. Furthermore, immunohistochemical analyses indicated that both compounds inhibited the expression of interleukin-6 (IL-6) and tumor necrosis-α (TNF-α) as compared to indomethacin alone-treated animals. These actions were accompanied by significant enhancement of tumor growth factor-β (TGF-β) expression. In conclusion, two cembranoids exhibited protective activities against indomethacin-induced peptic ulcer. This is, at least partly, mediated by their pro-mucin, antioxidant, anti-inflammatory, and TGF-β stimulating properties.

Keywords: Anti-inflammatory; Gastric ulcer; Marine natural products; Mucin; TGF-β.