Brominated indoles from a marine mollusc inhibit inflammation in a murine model of acute lung injury

Ahmad, Tarek B. and Rudd, David and Benkendorff, Kirsten and Mahdi, Layla K. and Pratt, Kayla-Ann and Dooley, Leanne and Wei, Chuanyu and Kotiw, Michael (2017) Brominated indoles from a marine mollusc inhibit inflammation in a murine model of acute lung injury. PLoS ONE, 12 (10).

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Abstract

New drug leads for the treatment of inflammation are urgently needed. Marine molluscs are widely used as traditional medicines for the treatment of inflammation. Here we report the positive effects of a hypobranchial gland (HBG) extract and the dominant bioactive compound 6-bromoisatin from the Muricidae mollusc Dicathais orbita, for reducing lipopolysaccharide (LPS) induced acute lung inflammation in a mouse model. Both 6-bromoisatin and the HBG extract suppressed the inflammatory response in mice that were pre-treated byoral gavage at 48, 24 and 1 h prior to LPS infusion. The inflammatory antagonists weretested at concentrations of 0.5 mg/g and 0.1 mg/g HBG extract and 0.1 mg/g and 0.05 mg/g 6-bromoisatin in carrier oil and all treatments reduced inflammation as indicated by a significant suppression of inflammatory markers present in bronchoalveolar lavage fluid (BALF), in comparison to LPS induced positive control mice administered the carrier oil alone (p <0.0001). Tumour necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) levels, in addition to total protein concentration were all significantly reduced in BALF from mice treated with the extract or 6-bromoisatin. Furthermore, all treatment groups showed significant
reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the positive control (p < 0.0001). The combined results from this study and our previous in vitro studies indicate that 6-bromoisatin in the HGB extracts inhibit the activation of inflammatory signalling pathway. The results from this study further confirm that the HBG extract from Muricidae molluscs and 6-bromoisatin are bioavailable and effective in vivo, thus have potential for development as natural therapeutic agents for inflammation.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Published version made available under Creative Commons Attribution License 4.0.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 29 Jan 2018 03:06
Last Modified: 29 Jan 2018 03:06
Uncontrolled Keywords: brominated indoles, 6-bromoisitin inflammation muricidae molluscs
Fields of Research : 11 Medical and Health Sciences > 1104 Complementary and Alternative Medicine > 110499 Complementary and Alternative Medicine not elsewhere classified
Socio-Economic Objective: C Society > 92 Health > 9299 Other Health > 929999 Health not elsewhere classified
Identification Number or DOI: 10.1371/journal.pone.0186904
URI: http://eprints.usq.edu.au/id/eprint/33619

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