**1. Introduction**

Inflammatory bowel disease (IBD) is a life-long condition of chronic and relapsing inflammation of the gastrointestinal tract associated with immune-mediated disorders [1]. It has two major phenotypes: Crohn's disease, which can severely a ffect any part of the bowel, and ulcerative colitis (UC), which involves damage in the superficial mucosa of the colon, starting always from the anus [1,2]. IBD patients are at major risk of developing gastrointestinal and extra-intestinal carcinomas, especially those carrying UC whose probability for developing colitis-associated colorectal cancer (CACC) increases with the length and severity of inflammatory manifestation [3]. The increasing incidence of UC, especially at a younger age, has raised a global concern considering the detrimental consequences in terms of quality of life, economic loss associated with lower productivity and increased medical expenses, and the imminent risk of development of CACC [2,4]. Hence, alternative ways to manage inflammation are needed, and plant origin compounds may prevent, ameliorate and alleviate chronic inflammation, and consequently the risk of IBD and associated diseases.

*Momordica charantia*, commonly known as bitter gourd, is a member of the Cucurbitaceae family mainly cultivated in Asia, Africa, and South America [5]. It is traditionally consumed as a vegetable and with medicinal purposes such as treatment of inflammation, fever, rheumatism, as well as antidiabetic and anti-helmitic [6]. Several studies have addressed in vitro and/or in vivo effects of the whole edible parts or extracts with demonstrated anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer and metabolic regulatory properties [7–12].

BG-4 is a novel 4 kDa peptide isolated from bitter gourd seeds with trypsin inhibitory and in vitro anti-colon cancer and anti-inflammatory properties [13,14]. BG-4 was isolated from the seeds of *Momordica charantia* by 70% ethanol extraction. It showed very strong trypsin inhibitory activity which is at least 8x more potent than purified soybean Kunitz trypsin inhibitor [13]. Moreover, mass spectrometric analysis showed the following peptide sequence matches: SWPQLVGSTGAAAK, VGSPVTADFR, GIVARPPAIG and DSDCLAQCICVDGHCG [13]. However, the potential bioactive properties of BG-4 in animal models remain unexplored. Herein, we made a comparative in vitro and in vivo anti-inflammatory study of BG-4, by measuring the expression of pro-inflammatory markers in lipopolysaccharide (LPS)-activated mouse-derived macrophages, and in dextran sodium sulfate (DSS)-induced colitis in mice. Our results indicate that BG-4 has differential effects in inflammation within in vitro and in vivo settings.
