Effects of Royal Jelly on Gut Dysbiosis and NAFLD in db/db Mice

Abstract

Royal jelly (RJ) is a naturally occurring substance synthesized by honeybees and has various health benefits. Herein, we focused on the medium-chain fatty acids (MCFAs) unique to RJ and evaluated their therapeutic efficacy in treating non-alcoholic fatty liver disease (NAFLD). We examined db/m mice that were exclusively fed a normal diet, db/db mice exclusively fed a normal diet, and db/db mice fed varying RJ quantities (0.2, 1, and 5%). RJ improved NAFLD activity scores and decreased gene expression related to fatty acid metabolism, fibrosis, and inflammation in the liver. RJ regulated innate immunity-related inflammatory responses in the small intestine and decreased the expression of genes associated with inflammation and nutrient absorption transporters. RJ increased the number of operational taxonomic units, the abundance of Bacteroides, and seven taxa, including bacteria that produce short-chain fatty acids. RJ increased the concentrations of RJ-related MCFAs (10-hidroxy-2-decenoic acid, 10-hydroxydecanoic acid, 2-decenedioic acid, and sebacic acid) in the serum and liver. These RJ-related MCFAs decreased saturated fatty acid deposition in HepG2 cells and decreased the gene expression associated with fibrosis and fatty acid metabolism. RJ and RJ-related MCFAs improved dysbiosis and regulated the expression of inflammation-, fibrosis-, and nutrient absorption transporter-related genes, thereby preventing NAFLD.

Royal Jelly: Biological Action and Health Benefits

“…In addition to increasing mucus production and strengthening the tight junctions between the intestinal epithelial cells, SCFAs also cause an increase in mucin expression in goblet cells. Furthermore, SCFAs bind to the free fatty acid receptor and inhibit the activation of NF-κB [77], suppressing the secretion of pro-inflammatory cytokines like IL-1, IL-12, and TNF-α [78][79][80]. These cytokines further impact innate lymphoid cells (ILC1 and ILC3) and the production of their cytokines, including NF-α, IFN-γ, IL-17, and IL-22, leading to inflammation and cytotoxicity.…”

“…According to Kobayashy et al [80], RJ can help in non-alcoholic fatty liver disease (NAFLD). Besides improving gut dysbiosis and inflammation, RJ increases the excretion of saturated palmitic acid in the feces, thus decreasing its content in the blood and liver, and increases the content MCFAs in the liver.…”

“…In RJ, four main MCFAs have been identified: 10-HDA, 10 HDAA, 2-decenedioic acid (2-DA), and sebacic acid (SA). This finding is important as it is recognized that a high content of saturated fatty acids in a diet may increase the secretion of IL-12 from macrophages, induce mitochondrial damage, and sustain chronic low-grade inflammation, contributing to the pathogenesis of metabolic disorders, muscular atrophy, progressive liver inflammation, and cardiovascular diseases [77][78][79][80]. NAFLD pathogenesis is related to the "two-hits" hypothesis, which suggests that steatosis develops into nonalcoholic steatohepatitis (NASH) through excessive free fatty acids (FFAs), hyperinsulinemia, and lipid peroxidation [81].…”

10‐hydroxy decanoic acid, trans‐10‐hydroxy‐2‐decanoic acid, and sebacic acid: Source, metabolism, and potential health functionalities and nutraceutical applications

“…If taken for a long time, 10-H2DA can also effectively enhance the antioxidant capacity of the liver (Niu et al, 2020). For chronic excessive drinkers, 10-H2DA is expected to maintain their liver's health, improve fat metabolism, and lower blood lipids (Kobayashi et al, 2023).…”