Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD‐Induced Insulin Resistance by Modulating IRS‐1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways

Abstract

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.

Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress

“…Glucose uptake via GLUT4 in skeletal muscle is dependent on insulin or AMP-activated kinase (AMPK) signaling pathways [ 18 , 19 ]. To identify the signaling pathways involved in TRDI-mediated glucose uptake, immunoblotting was performed.…”

“…A major characteristic of T2DM is decreased GLUT4 intracellular trafficking into the PM [ 18 ]. The other major signaling pathway is the insulin-independent route, which is controlled by 5′-adenosine monophosphate-activated protein kinase (AMPK), a heterotrimeric functional enzyme complex regulating energy balance in the cell [ 19 ].…”

Total Sesquiterpenoids of Loquat Leaves Alleviated High-Fat Diet-Induced Obesity by Targeting Fecal Metabolic Profiling and Gut Microbiota Composition

“…TSs were prepared and identified according to our previous study . Briefly, TSs were extracted with 80% ethanol, prepared, and purified by macroporous resin XAD16 and polyamide columns with a two-phase gradient system.…”

“…Briefly, TSs were extracted with 80% ethanol, prepared, and purified by macroporous resin XAD16 and polyamide columns with a two-phase gradient system. After drying under vacuum, four sesquiterpene glycosides’ standard compounds in TSs of loquat leaves were purified and identified using Dionex Ultimate 3000 HPLC systems (Thermo Fisher Scientific Inc., Germany) as previously described. , Concisely, the column Inertsil ODS-SP (4.6 mm × 250 mm, 5 μm) was kept at 35 °C while using. The mobile phase was composed of methanol and 0.1% formic acid-water with gradient elution.…”

“…Before that, loquat leaves have already been widely used as a tea drink in Japan and China. , As an essential component in loquat leaves, the therapeutic role of sesquiterpenoids in metabolic diseases has been gradually discovered. In our previous studies, the total sesquiterpenoids (TSs) isolated from loquat leaves were found to improve glucose and lipid metabolism disorders in HFD-treated mice, displaying antiobesity-like effects. , Among that, several active monomers had the ability to prevent diabetes in db/db mice, which increased the diversity and richness of gut microbiota and effectively reshaped the microbial structure. , Nevertheless, the effect of sesquiterpenoids on gut microbiota and gut metabolites in HFD-induced obesity remains unknown.…”