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Mechanism of effective components of Mori Folium in alleviating insulin resistance based on JNK signaling pathway
Abstract
A stable hepatoma cell line(Hep G2 cell) insulin resistance model was established and used to analyze the effect of effective components of Mori Folium in alleviating insulin resistance,and preliminary explore the mechanism for alleviating insulin resistance. The Hep G2 insulin action concentration and the duration of action were investigated using the glucose oxidase method(GOD-POD method) to establish a stable Hep G2 insulin resistance model. Normal control group,model group,Mori Folium polysaccharide group,Mori Folium flavonoid group and rosiglitazone group were divided to determine the glucose consumption. The effect of Mori Folium effective components on Hep G2 insulin resistance was analyzed. The mRNA expressions of JNK,IRS-1 and PDX-1 in each group were detected by Real-time quantitative PCR(qRT-PCR). The protein expressions of p-JNK,IRS-1 and PDX-1 were detected by Western blot. And the mechanism of effective components of Mori Folium in alleviating insulin resistance was investigated. The results showed that the glucose consumption was significantly decreased in the insulin resistance cells after incubation with 25. 0 mg·L-1 insulin for 36 h(P<0. 01),and the model was relatively stable within 36 h. Mori Folium polysaccharides and flavonoids all alleviated insulin resistance,among which Mori Folium flavonoids had better effect in alleviating Hep G2 insulin resistance(P<0. 05). The qRT-PCR analysis showed that Mori Folium polysaccharides and flavonoids could inhibit JNK and IRS-1 mRNA expressions,while enhancing PDX-1 mRNA expression. Western blot analysis displayed that Mori Folium polysaccharides and flavonoids could inhibit p-JNK and IRS-1 protein expressions,while enhancing PDX-1 protein expression. Mori Folium polysaccharides and flavonoids can alleviate insulin resistance in Hep G2 cells,and its mechanism may be the alleviation of insulin resistance by inhibiting JNK signaling pathway.
... Modern pharmacological studies have found mulberry leaf to have a high median lethal dose (LD50 > 15.0 g·kg⁻ 1 ) and to exhibit safety across various genotoxicity assessments [15][16][17]. Moreover, mulberry leaf aqueous extracts significantly inhibit macrophage inflammatory mediator secretion and autophagic pathways, thereby alleviating obesity [18,19]. In murine models, mulberry leaf demonstrates substantial hypoglycemic effects, modulating blood lipids and gut microbiota [20]. ...
To elucidate the underlying mechanisms by which mulberry leaves, in conjunction with gut microbiota, ameliorate hyperlipidemia and identify key gut microbial taxa involved, a mulberry leaf/gut microbiota-active components-metabolites-target-pathway network was constructed.
Information on active constituents of mulberry leaves, metabolites generated by gut microbiota, and target proteins associated with hyperlipidemia were retrieved from multiple databases. Employing bioinformatics tools, relevant pathways and targets involved in the synergistic effect of mulberry leaves and gut microbiota on hyperlipidemia improvement were systematically analyzed. Through multi-level data analysis and integration of existing knowledge on the interplay between mulberry leaves, gut microbiota, and hyperlipidemia, the atherosclerosis signaling pathway was identified as the central pathway, with AKT1 as the core target protein. Based on metabolites produced by gut microbiota that act on AKT1, 29 specific gut microbial strains were found to exhibit synergistic action within the context of mulberry leaf-mediated hyperlipidemia alleviation. This culminated in the establishment of a comprehensive mulberry leaf/gut microbiota-active components-metabolites-target-pathway network. Moreover, molecular docking and visualization analyses demonstrated stable interactions between the selected gut microbiota-derived metabolites and the central target AKT1.
These findings provide a robust scientific basis for the application of mulberry leaf-based formulations combined with probiotics in the development of specialized medical foods targeting hyperlipidemia, grounded in the elucidated molecular mechanisms and identified key gut microbial players.
Species of genus Morus (family Moraceae) have been used as traditional medicinal and edible resources since ancient times. Genus Morus has been acknowledged as a promising resource for the exploration of novel compounds with various bioactivities. Phytochemical investigations of the genus have led to the discovery of more than approximately 453 natural products from 2011 to 2023, mainly including flavonoids, Diels-Alder adducts, 2-arylbenzfuran, alkaloids and stilbenes. Bioactive constituents and extracts of this genus displayed a wide range of impressive biological properties including antidiabetic, anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, renoprotective, and some other activities. Herein, the research progress of this genus Morus from 2011 to 2023 on phytochemistry and pharmacology are systematically presented and discussed for the first time. This current review provides the easiest access to the information on genus Morus for readers and researchers in view of enhancing the continuity on research done on this genus.
Cysestermerol A (1), a rare and new stilbene sestermer, was isolated from the whole herb of Cynodon dactylon. The planar and relative structures of 1 were elucidated based on HRESIMS, one- and two-dimensional NMR analyses, and its absolute configuration was further established by electronic circular dichroism calculations. Compound 1 obviously increased the glucose consumption in HepG2 cells equivalent to the positive control rosiglitazone and markedly inhibited the activity of α-glucosidase in vitro.
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