Honeysuckle Berry (Lonicera caerulea L.) Inhibits Lipase Activity and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice

Abstract

Honeysuckle berry (HB, Lonicera caerulea L.) is an oriental herbal medicine reported to have beneficial effects on metabolic disorders, such as obesity and non-alcoholic fatty liver disease. The fruit part of HB is rich in anthocyanin, a type of polyphenol. Most studies credit the antioxidant and anti-inflammatory properties of HB as the mechanisms of its effectiveness. This study investigated the inhibitory effects of HB on lipase using an in vitro assay and the modulatory effect of HB on gut microbiota in high-fat diet (HFD)-fed mice. HB inhibited pancreatic lipase activity with IC₅₀ values of approximately 0.47 mg/mL. The fecal triglyceride (TG) levels were higher from the HFD of the HB-fed mice than they were for the control mice. Moreover, the fecal microbiota from the HFD of the HB-fed mice had relatively lower Firmicutes and higher Bacteroidetes than that from the HFD-only mice. These results suggest that HB modulates gut microbiota composition, which may contribute to body fat reduction. Hence, HB could present a useful agent for treating metabolic diseases through lower TG uptake and the regulation of gut microflora.

Keywords: Lonicera caerulea L.; gut microbiota; obesity; pancreatic lipase inhibition.

Figure 1

Effects of HB on pancreatic lipase inhibition and TG contents in the feces for HFD-fed mice. (A) Pancreatic lipase inhibition of HB; (B) fecal TG contents, NC–normal diet control; HC–high-fat diet (HFD) control; PC–HFD with orlistat at 20 mg/kg; HB100–HFD with HB 100 mg/kg; HB200–HFD with HB 200 mg/kg; and HB400–HFD with HB 400 mg/kg. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests.

Figure 2

Effects of HB on the epididymal fat weight and adipocyte size in HFD-fed mice. (A) Photography of epididymal fat and hematoxylin and eosin (H&E) staining of epididymal fat tissue; (B) epididymal fat weight; and (C) average adipocyte cell size. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests.

Figure 3

Effects of HB on the expression levels of genes related to the lipid metabolism in epididymal fat tissue of HFD-fed mice. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests.

Figure 4

Effects of HB on the expression levels of genes related to thermogenesis in the epididymal fat tissue of HFD-fed mice. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests.

Figure 5

Fecal microbial relative abundance of phyla. (A) Bar plot represent the relative bacterial phylum abundance. Colors are used to distinguish each taxon. From the bottom, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Tenericutes, Deferribacteres, Verrucomicrobia, Cyanobacteria, Saccharibacteria, Euryarchaeota, Deinococcus-Thermus, and Fusobacteria are shown. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests. * p < 0.05, ** p < 0.01 versus HC group. The group means were compared by Student’s t-test.

Figure 6

Fecal microbial relative abundance of family. (A) Bar plot of relative bacterial family abundance. All data are mean ± SD. Significant differences among six groups are expressed as different letters based on one-way ANOVA (p < 0.05), followed by Duncan’s multiple range tests. * p < 0.05, ** p < 0.01, *** p < 0.001 versus HC group. The group means were compared by Student’s t-test.

Figure 7

(A) Taxonomic cladogram and (B) linear discriminant analysis (LDA), obtained from LEfSe analysis of the gut microbiota in HC and HB200 groups. The only taxa meeting an LDA-significant threshold of >3 are shown.