ABSTRACT
Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Subject(s)
Mice , Animals , Adipose Tissue, Brown , Sirtuin 1/pharmacology , Diabetes Mellitus, Type 2/metabolism , AMP-Activated Protein Kinases/metabolism , Morus/metabolism , Flavonoids/metabolism , Prospective Studies , Signal Transduction , Adipose Tissue, White , Plant Leaves , Uncoupling Protein 1/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolismABSTRACT
DNJ, an inhibitor of α-glucosidase, is used to suppress the elevation of postprandial hyperglycemia. In this study, we focus on screening an appropriate microorganism for performing fermentation to improve DNJ content in mulberry leaf. Results showed that Ganoderma lucidum was selected from 8 species and shown to be the most effective in improvement of DNJ production from mulberry leaves through fermentation. Based on single factor and three factor influence level tests by following the Plackett-Burman design, the optimum extraction yield was analyzed by response surface methodology (RSM). The extracted DNJ was determined by reverse-phase high performance liquid chromatograph equipped with fluorescence detector (HPLC-FD). The results of RSM showed that the optimal condition for mulberry fermentation was defined as pH 6.97, potassium nitrate content 0.81% and inoculums volume 2 mL. The extraction efficiency reached to 0.548% in maximum which is 2.74 fold of those in mulberry leaf.
Subject(s)
1-Deoxynojirimycin/isolation & purification , 1-Deoxynojirimycin/metabolism , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/metabolism , Morus/metabolism , Reishi/metabolism , Biotechnology/methods , Chromatography, High Pressure Liquid , Culture Media/chemistry , Fermentation , Hydrogen-Ion Concentration , Plant Leaves/metabolism , Reishi/growth & development , Technology, Pharmaceutical/methodsABSTRACT
A high-dose of vitamin B(3) in silkworm diet interrupts larval feeding and normal growth. High mortality of larvae occurs during molting and they cannot complete this process normally. Also the larvae exhibit nicotinamide hypervitaminosis symptoms such as immobility, dyspepsia, darkening of the skin, inability to excrete normally, exerting brownish fluid from anus and swelling of rectal muscles. Maximum larval weights in 1, 2 and 3 g/l treatments were 2.9, 1.6 and 1.2 g respectively, while maximum larval weight in the control was 5.6 g. Larval stage compared to control had increased 18, 26 and 31 days respectively. The concentration increase of uric acid in haemolymph demonstrates the hyperuricemia, while other measured biochemical compounds show significant decrease; sodium and potassium did not change significantly.