Watermelon produces many byproducts (watermelon rind and skin) even though those components contain various bioactive compounds, including citrulline. This study evaluated the citrulline concentration, total phenolic content, and antioxidant activity (DPPH and FRAP assays) of different parts of watermelon and investigated the bioavailability of citrulline from different parts of watermelon using an in vitro human intestinal epithelial Caco-2 cell monolayer model. Solid-phase extracted watermelon flesh, rind, and skin samples were treated on a Caco-2 cell monolayer for 1, 2, and 4 h. The collected basolateral solution at each time point was analyzed for the percentage of citrulline transport. Watermelon flesh had the highest citrulline content, but the watermelon skin had the highest total phenolic content and antioxidant activity compared to other watermelon parts. The citrulline bioavailability showed greater % transport in watermelon skin than in watermelon flesh, rind, and L-citrulline standard. It may be due to the different food matrices of watermelon parts. This suggests that the utilization of watermelon by-products such as skin would help develop value-added products with better bioavailability of citrulline. However, since this study was conducted with an in vitro cell model, more extensive research with in vivo studies will be needed.

Background: Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect. Methods: Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured. Results: OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1. Conclusions: It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts.

Hindering the absorption of glucose through inhibition of intestinal carbohydrate-hydrolyzing enzymes is an efficient strategy for reducing hyperglycemia. The purpose of this study was to examine the effect of watermelon flesh extracts (WFE), rind extract (WRE), skin extract (WSE), and citrulline on intestinal carbohydrate-hydrolyzing enzymes and to identify their bioactive compounds. WSE showed higher bioactive compounds and total phenolic content than WFE and WRE. WFE, WRE, and WSE demonstrated dose-dependent inhibition against carbohydrate-hydrolyzing enzymes. WFE, WRE, and WSE inhibited α-glucosidase by 40~45% at a concentration of 60 mg/mL whereas 80 mg/mL citrulline showed a similar inhibitory effect. WRE and citrulline showed IC₅₀ values of 0.02 and 0.01 mg/mL for maltase and sucrase, respectively. Citrulline at 20 mg/mL exhibited higher glucoamylase and pancreatic α-amylase inhibition than WFE, WRE, and WSE at the same concentration. Citrulline and WRE showed similar IC₅₀ values for glucoamylase and α-amylase compared to 1 mg/mL acarbose. This study suggests that watermelon, including its byproduct parts possibly due to citrulline, has the potential for carbohydrate-hydrolyzing enzyme inhibition that is beneficial to reducing postprandial hyperglycemia.