Effect of 1-Deoxynojirimycin Isolated from Mulberry Leaves on Glucose Metabolism and Gut Microbiota in a Streptozotocin-Induced Diabetic Mouse Model

Abstract

1-Deoxynojirimycin (DNJ) exerts hypoglycemic effects. However, the traditional method for DNJ extraction is inefficient, and the hypoglycemic mechanism of DNJ remains unclear. In this study, the mixed fermentation by Lactobacillus fermentum and Saccharomyces cerevisiae was used to enhance DNJ extraction efficiency. It was found that this strategy was more efficient than the traditional method as the yield improved from the original 3.24 mg/g to 5.97 mg/g. The purified DNJ significantly decreased serum glucose (P < 0.01) and insulin levels (P < 0.05), improved serum lipid levels (P < 0.05), and reversed insulin resistance (P < 0.05) in diabetic mice. These changes were caused by up-regulating the protein expression of insulin receptor and glycolysis enzymes (GK, PK, and PFK) (P < 0.05) and downregulating the protein expression of insulin receptor substrate-1 and gluconeogenesis enzymes (PCB, PEPCK, FBPase, and G-6-Pase) (P < 0.05), thus alleviating glucose tolerance. Additionally, DNJ treatment relieved gut dysbiosis in diabetic mice by promoting the growth of Lactobacillus, Lachnospiraceae NK4A136 group, Oscillibacter, norank Lachnospiraceae, Alistipes, and Bif idobacterium (P < 0.05) and suppressing the growth of Ruminococcaceae UCG-014, Weissella, Ruminococcus, Prevotellaceae Ga6A1 group, Anaerostipes, Klebsiella, Prevotellaceae UCG-001, and Bacteroidales S24-7 group (P < 0.05).

The Gut Microbiota-Produced Indole-3-Propionic Acid Confers the Antihyperlipidemic Effect of Mulberry-Derived 1-Deoxynojirimycin

“…Recently, several investigations have reported that DNJ or DNJ-enriched mulberry leaf extracts markedly altered gut microbial community to improve metabolic diseases by promoting the growth of Akkermansia spp. and SCFA-producing genera such as Bifidobacterium , Lactobacillus , and Alistipes ( 24 , 38 , 39 ). In particular, DNJ was reported to enrich the abundance of Akkermansia spp.…”

Ethanol extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in type 2 diabetic rats

“…Sheng et al found that mulberry leaf powder could alleviate the pathological conditions of streptozotocin-induced diabetic rats and modulate intestinal microflora [ 9 ]. In addition, Hu et al discovered that the compound 1-Deoxynojirimycin isolated from mulberry leaves could significantly decrease serum glucose and insulin levels while improving serum lipid levels and reversing insulin resistance in streptozotocin-induced diabetic mice [ 13 ]. The effects of mulberry leaf on blood glucose response were also tested in healthy and diabetic human subjects, which confirmed that blood glucose levels were markedly reduced by mulberry leaf ingestion [ 14 ].…”

The hypoglycemic effect of freeze‐dried fermented mulberry mixed with soybean on type 2 diabetes mellitus

“…For example, Hu et al . studied the hypoglycemic effect of 1‑deoxynojirimycin, isolated from mulberry leaves, and found that it promoted the growth of beneficial bacteria, such as lactic acid‐generating bacteria, and inhibited that of harmful bacteria, thereby improving the intestinal microbial composition and alleviating intestinal disorders in diabetic mice (Hu et al., 2019).…”

“…It plays an important role in the intake of nutrients, the growth and development of cells, and metabolism of the host (Rad et al, 2017), and accumulating data show that it may mediate some of the effects of anti-diabetic therapies (Min et al, 2009;Zhao et al, 2016). For example, Hu et al studied the hypoglycemic effect of 1-deoxynojirimycin, isolated from mulberry leaves, and found that it promoted the growth of beneficial bacteria, such as lactic acid-generating bacteria, and inhibited that of harmful bacteria, thereby improving the intestinal microbial composition and alleviating intestinal disorders in diabetic mice (Hu et al, 2019).…”