Quercetin-3-O-rutinoside from Moringa oleifera Downregulates Adipogenesis and Lipid Accumulation and Improves Glucose Uptake by Activation of AMPK/Glut-4 in 3T3-L1 Cells

Abstract

Natural product-based therapeutic alternatives have drawn immense interest to deal with growing incidence of metabolic disorders. Rutin (quercetin-3- O -rutinoside) is found in a variety of fruits, vegetables, and plant beverages. In the present study, rutin was isolated from Moringa oleifera Lam., leaves and its anti-lipidemic and anti-adipogenic activity was evaluated through inhibition of key digestive enzymes and in vitro cell culture experiments using 3T3-L1 adipocytes. Rutin treatment substantially reduced α-glucosidase and pancreatic lipase activities with IC 50 values of 40 and 35 μg/ml, respectively. MTT assay with 3T3-L1 cells demonstrated the non-toxic effect of rutin up to 160 μg/ml. Oil Red O-stained images of rutin-treated 3T3-L1 cells depicted that rutin considerably reduced lipid content and adipogenesis (79.9%), and enhanced glycerol release in 3T3-L1 cells when compared to untreated cells. Rutin significantly ( p < 0.05) enhanced glucose uptake in 3T3-L1 adipocytes and also led to reduced levels of leptin but enhanced levels of adiponectin. Western blot analysis of rutin-treated (40 µg/ml) adipocytes showed phosphorylation of AMPK, upregulated expression of Glut-4 (1.31-fold) and UCP-1 (1.47-fold), but downregulated expression of PPAR-γ by 0.73-fold. At transcriptional level, similar trends were observed in the mRNA expression of the above genes, except AMPK. Our results demonstrate that rutin isolated from M. oleifera significantly alleviates lipid content and adipogenesis, and improves glucose uptake through regulating PPAR-γ and AMPK signaling pathways; thus, rutin can be considered as a potential therapeutic agent against adiposity and glucose intolerance. Graphical Abstract

Integrated 16s RNA sequencing and network pharmacology to explore the effects of polyphenol-rich raspberry leaf extract on weight control

“…For example, Q3G inhibits the production of IL-6 and TNF-α ( 48 ), as well as quercetin inhibits the inflammatory factors IL-1β and IL-6, and stimulates the secretion of the anti-inflammatory factor ( 49 ). Quercetin-3-O-rutinoside reduces glucose uptake by modulating the PPAR-γ signaling pathway ( 50 ). Chlorogenic acid also weakens disordered lipid metabolism through PPAR-α ( 51 ).…”

Photoperiod-Dependent Effects on Blood Biochemical Markers of Phenolic-Enriched Fruit Extracts

“…Cyanidin-3- O -rutinoside could be involved in the effects of the cherry extract given this compound, the majority of which, can inhibit several enzymes in vitro , such as pancreatic cholesterol esterase and lipase, and reduce cholesterol uptake in Caco-2 cells . Similarly, rutin (quercetin-3- O -rutinoside), the main phenolic compound in the apricot extract, also inhibited pancreatic lipase in vitro and reduced the lipid content and adipogenesis of 3T3-L1 cells . Total cholesterol levels have also been shown to be modulated by ellagitanins present in the pomegranate extract when administered to rats fed a high fructose diet .…”

Positive effects of rutin on egg quality, lipid peroxidation and metabolism in post-peak laying hens

“…As the major metabolite of rutin, quercetin can increase the potential of anti-steatosis in the liver of rat by reducing the activity of hepatic lipogenic enzymes and activating the cytoplasmic lipase adipose triglyceride lipase (ATGL) activity ( 45 ). Administration of rutin in adipocytes inhibits the activity of alpha-glucosidase and pancreatic lipase and increases adiponectin levels in vitro ( 46 ). To the best of our knowledge, this is the first study on the effect of rutin on hepatic lipid metabolizing enzymes in laying hens, and the results showed that dietary rutin could reduce the activities of ACC and ME in the liver of aged laying hens.…”