High sucrose content in traditional hawthorn leathers limits the potential consumption, particularly for elders and diabetics. In this study, sucrose-free hawthorn leathers were formulated with 75% fructooligosaccharides (FOS) and 25% xylooligosaccharides (XOS) (HLF75), which exhibited comparable morphology and sensory properties to the traditional ones. Then, the anti-obesity activity of HLF75 was investigated using high-fat diet (HFD) fed C57BL/6J mice. Comparing with traditional hawthorn leathers, HLF75 supplementation in HFD significantly decreased the levels of blood glucose and serum lipid. The histomorphologies of liver and subcutaneous fat tissues were ameliorated by HLF75, as well as the down-regulated mRNA expression levels of IL-1β, Nos2 and Cox-2 in the liver. Moreover, the protein levels of MyD88 and NF-κB in the liver were suppressed by HLF75 treatment with decreased F4/80-positive macrophage number. However, the expression levels of PI3K, phosphorylated-AKT (Thr308), and phosphorylated-mTOR (Ser2448) proteins related to glucose metabolism were increased in the liver. Moreover, fat synthesis-related gene expression in HLF75-fed mice was suppressed while expressions of lipolysis genes were improved. Thus, HLF75 supplementation alleviated HFD-induced obesity through the alleviation of inflammation and restoration of the disturbed glucose and lipid metabolism. Functional oligosaccharides could be effective sucrose substitutes in hawthorn leathers and enable their potential utilization as functional foods.

Innate immunity, particularly macrophages, is critical for intestinal homeostasis. Sulforaphane, a dietary isothiocyanate from cruciferous vegetables, has been reported to protect against intestinal inflammation. However, the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet. In this study, sulforaphane effectively attenuated dextran sodium sulphate (DSS) induced intestinal inflammation in murine model. Of note, sulforaphane skewed the switching from classically (M1) to alternatively (M2) activated phenotype both in intestinal and bone marrow-derived macrophages (BMDMs). The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide (LPS) plus interferon gamma-γ (IFN-γ) were suppressed by sulforaphane while M2 marker gene expression levels were improved. This resulted in alteration of inflammatory mediators, particularly interleukin-10 (IL-10), both in colon tissues and culture medium of BMDMs. Subsequently, IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling. This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections. Moreover, anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation. Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.