Mulberry (Morus alba L.) Leaf Extract and 1-Deoxynojirimycin Improve Skeletal Muscle Insulin Resistance via the Activation of IRS-1/PI3K/Akt Pathway in db/db Mice

Kang, Chaewon; Park, Miey; Lee, Hae‐Jeung

doi:10.3390/life12101630

Cited by 14 publications

(10 citation statements)

References 55 publications

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“…Although insulin is produced in vivo, the cells use insulin inefficiently, leading to hyperglycemia. 16,17 Hyperglycemia can induce oxidative stress and aggravate IR in surrounding tissues, leading to metabolic syndrome. This can result in retinopathy, nephropathy, and neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Taraxasterol Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Signaling Pathway

Zhao

Zeng

et al. 2023

Natural Product Communications

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Objective: Taraxasterol (TS) is the main active compound of Taraxacum, which plays a significant role in the treatment of diabetes in many classic prescriptions. However, the mechanisms of TS in the treatment of diabetes remain unclear. This study aimed to investigate the underlying mechanism of TS in hepatic gluconeogenesis and glycogen synthesis in HepG2 cells with insulin resistance (IR). Methods: Molecular docking was conducted by using Discovery Studio (DS) to predict the target of TS in the treatment of diabetes. Then we treated HepG2 cells with glucosamine for 18 h. After the cells were treated with TS, the glucose consumption was examined. Oil red O staining was used to detect the lipid accumulation of HepG2 cells, and cellular glucose uptake levels were assessed using fluorescent 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-D-glucose. The expression of the related proteins of the PI3K/Akt signaling pathway in the HepG2 cells was evaluated by western blot assay. Results: The molecular docking analysis revealed a good binding pose between the insulin receptor and TS. Furthermore, TS administration significantly enhanced glucose uptake and consumption, and reduced lipid accumulation in HepG2 cells with IR. The results of pharmacological mechanism study showed that TS up-regulated glycogenesis by PI3K/Akt/GSK3-motivated GS activation, and down-regulated gluconeogenesis by PI3K/Akt/FoxO1 expression of PEPCK and G6Pase in HepG2 cells with IR. Conclusions: Molecular docking and in vitro experimental results indicate that TS suppresses hepatic gluconeogenesis and augments glycogen synthesis by the PI3K/Akt signaling pathway, and it may have similar effects as insulin in regulating blood glucose.

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Section: Discussionmentioning

confidence: 99%

Taraxasterol Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Signaling Pathway

Zhao

Zeng

et al. 2023

Natural Product Communications

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“…Many studies have reported that dexamethasone induces thinning of muscle fibers through decreased muscle protein synthesis and increased degradation, resulting in decreased muscle strength due to a decrease in muscle mass [ 41 - 43 ]. MA attenuates insulin resistance in skeletal muscle by activating the insulin receptor substrate-1/PI3K/Akt signaling pathway [ 44 ], and flavonoids derived from MA have been associated with improvements in type 2 diabetes through enhanced mitochondrial function in the muscle [ 45 ]. According to previous studies, AK and compounds from AK inhibit muscle wasting by promoting myogenesis [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

A Mixture of Morus alba and Angelica keiskei Leaf Extracts Improves Muscle Atrophy by Activating the PI3K/Akt/mTOR Signaling Pathway and Inhibiting FoxO3a In Vitro and In Vivo

Hwangbo,

Kim,

et al. 2023

J. Microbiol. Biotechnol.

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Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors ( MyoD and myogenin ) and decreased the expression levels of E3 ubiquitin ligases ( atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

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“…The main ingredients of the formulated treatment feed were Morus alba leaves along with hydrolyzed chicken, oats, hydrolyzed dried chicken, chicken fat, powdered cellulose, oats, bit pulp, inulin, omega 3, vitamins C and E, and a mineral premix (calcium, potassium, magnesium, carbohydrate, and salt). As shown in previous mouse experiments, the amount Morus alba leaves used in this study was determined based on the amount of 1-deoxynojirimycin [ 60 ]. Unlike previous mouse experiments, this pet food used hydrolyzed Morus alba leaf powder.…”

Section: Methodsmentioning

confidence: 99%

1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity

Jaiswal,

Lee,

Chun

et al. 2024

BMC Vet Res

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Background Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. Results After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. Conclusions 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

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Mulberry (Morus alba L.) Leaf Extract and 1-Deoxynojirimycin Improve Skeletal Muscle Insulin Resistance via the Activation of IRS-1/PI3K/Akt Pathway in db/db Mice

Cited by 14 publications

References 55 publications

Taraxasterol Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Signaling Pathway

Taraxasterol Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Signaling Pathway

A Mixture of Morus alba and Angelica keiskei Leaf Extracts Improves Muscle Atrophy by Activating the PI3K/Akt/mTOR Signaling Pathway and Inhibiting FoxO3a In Vitro and In Vivo

1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity

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