Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle

Yan, Li; Pan, Hong; Zhang, Xuetong; Wang, Hui; Liu, Shengnan; Zhang, Hui; Qian, Haifeng; Wang, Li; Ying, Hao

doi:10.1021/acs.jafc.9b00402

Cited by 26 publications

(28 citation statements)

References 41 publications

(78 reference statements)

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“…Many of these components are glycosides. For example, geniposide, a kind of bioactive iridoid glycoside, creates anti-inflammatory effects by reducing the release of inflammatory cytokines [ 20 ] and can also alleviate obesity-related cardiac injury by activating AMPK-α and the Sirt1 pathway [ 21 ]. Another glycoside of aucubin in E. ulmoides was shown to have anti-inflammatory effects, which may inhibit pulmonary inflammation and fibrosis in a mouse model established by the intratracheal injection of bleomycin [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Genomic-Wide Identification and Characterization of the Uridine Diphosphate Glycosyltransferase Family in Eucommia ulmoides Oliver

Ouyang

Wang

Tang

et al. 2021

Plants

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Eucommia ulmoides Oliver is a woody plant with great economic and medicinal value. Its dried bark has a long history of use as a traditional medicinal material in East Asia, which led to many glycosides, such as aucubin, geniposide, hyperoside, astragalin, and pinoresinol diglucoside, being recognized as pharmacologically active ingredients. Uridine diphosphate glycosyltransferases (UGTs) catalyze a glycosyl-transferring reaction from the donor molecule uridine-5′-diphosphate-glucose (UDPG) to the substrate, which plays an important role in many biological processes, such as plant growth and development, secondary metabolism, and environmental adaptation. In order to explore the biosynthetic pathways of glycosides in E. ulmoides, 91 putative EuUGT genes were identified throughout the complete genome of E. ulmoides through function annotation and an UDPGT domain search. Phylogenetic analysis categorized them into 14 groups. We also performed GO annotations on all the EuUGTs to gain insights into their functions in E. ulmoides. In addition, transcriptomic analysis indicated that most EuUGTs showed different expression patterns across diverse organs and various growing seasons. By protein–protein interaction predication, a biosynthetic routine of flavonoids and their glycosides was also proposed. Undoubtedly, these results will help in future research into the biosynthetic pathways of glycoside compounds in E. ulmoides.

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Section: Introductionmentioning

confidence: 99%

Genomic-Wide Identification and Characterization of the Uridine Diphosphate Glycosyltransferase Family in Eucommia ulmoides Oliver

Ouyang

Wang

Tang

et al. 2021

Plants

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“…Moreover, we determined the effects of sesamol on glucose oxidation. PDK4 is one of the essential rate-controlling enzymes for glucose oxidation, which can phosphorylate pyruvate dehydrogenase (PDH) to suppress the catalysis of pyruvate to acetyl-CoA, resulting in reduced glucose oxidation ( 41 ). In line with the former studies that PDK4 expression levels were increased in the obese state ( 42 ), the level of PDK4 in this study was enhanced in the obese model; however, it was noticeably down-regulated after delivering sesamol.…”

Section: Discussionmentioning

confidence: 99%

Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism

Mei

Chen

Zhang

et al. 2022

Food & Nutrition Research

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Background: Globally, obesity is a significant public problem, especially when aging. Sesamol, a phenolic lignan present in sesame seeds, might have a positive effect on high-fat diet (HFD)-induced obesity associated with aging. Objective: The purpose of current research study was to explore salutary effects and mechanisms of sesamol in treating alimentary obesity and associated metabolic syndrome in middle-aged mice. Methods: C57BL/6J mice aged 4–6 weeks and 6–8 months were assigned to the young normal diet group, middle-aged normal diet group, middle-aged HFD group, and middle-aged HFD + sesamol group. At the end of experiment, glucose tolerance test and insulin tolerance test were performed; the levels of lipids and oxidative stress-related factors in the serum and skeletal muscle were detected using chemistry reagent kits; lipid accumulation in skeletal muscle was observed by oil red O staining; the expressions of muscular glucose and lipid metabolism associated proteins were measured by Western blotting. Results: Sesamol decreased the body weight and alleviated obesity-associated metabolism syndrome in middle-aged mice, such as glucose intolerance, insulin resistance, dyslipidemia, and oxidative stress. Moreover, muscular metabolic disorders were attenuated after treatment with sesamol. It increased the expression of glucose transporter type-4 and down-regulated the protein levels of pyruvate dehydrogenase kinase isozyme 4, implying the increase of glucose uptake and oxidation. Meanwhile, sesamol decreased the expression of sterol regulatory element binding protein 1c and up-regulated the phosphorylation of hormone-sensitive lipase and the level of carnitine palmityl transferase 1α, which led to the declined lipogenesis and the increased lipolysis and lipid oxidation. In addition, the SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism. Conclusions: Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism, which might be associated with the stimulation of the SIRT1/AMPK pathway.

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“…Geniposide, which is the main component of Gardenia jasminoides Ellis, has also received specific attention [ 12 , 100 , 101 ]. It has been proven to have therapeutic potential for various diseases, including liver disease, kidney disease, cardiovascular disease, neurodegenerative diseases, tumours and various types of inflammation throughout the body [ 13 , 102 – 104 ]. Combined with modern pharmacological research, the anti-inflammatory, anti-apoptotic, and antioxidant functions of geniposide are very significant and have been reported in many studies [ 105 , 106 ].…”

Section: Discussion and Outlookmentioning

confidence: 99%

The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review

Zhang

et al. 2021

Chin Med

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With the advanced discoveries in the field of pathogenesis, a series of cerebral diseases, such as cerebral ischaemia, Alzheimer's disease, and depression, have been found to have multiple signalling targets in the microenvironment. Only a few existing agents have been shown to have curative effects due to this specific circumstance. In recent decades, active ingredients isolated from natural plants have been shown to be crucial for original drug development. Geniposide, mainly extracted from Gardenia jasminoides Ellis, is representative of these natural products. Geniposide demonstrates various biological activities in the treatment of cerebral, cardiovascular, hepatic, tumorous, and other diseases. The multiple protective effects of geniposide on the brain have especially drawn increasing attention. Thus, this article specifically reviews the characteristics of current models of cerebral ischaemia and illustrates the possible effects of geniposide and its pathogenetic mechanisms on these models. Geniposide has been shown to significantly reduce the area of cerebral infarction and alleviate neuronal damage and necrosis mainly by inhibiting inflammatory signals, including NLRP3, TNF-α, IL-6, and IL-1β. Neuronal protection was also involved in activating the PI3K/Akt and Wnt/catenin pathways. Geniposide was able to increase autophagy and inhibit apoptosis by regulating the function of mTOR in treating Alzheimer's disease. Geniposide has also been shown to act as a glucagon-like peptide-1 receptor (GLP-1R) agonist to reduce amyloid plaques and inhibit oxidative stress to alleviate memory impairment as well as synaptic loss. Moreover, geniposide has been shown to exert antidepressant effects primarily by regulating the hypothalamic–pituitary–adrenal (HPA) axis. Detailed explorations have shown that the biological activities of inhibiting inflammatory cytokine secretion, alleviating oxidative stress, and suppressing mitochondrial damage are also involved in the mechanism of action of geniposide. Therefore, geniposide is a promising agent awaiting further exploration for the treatment of cerebral diseases via various phenotypes or signalling pathways.

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Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle

Cited by 26 publications

References 41 publications

Genomic-Wide Identification and Characterization of the Uridine Diphosphate Glycosyltransferase Family in Eucommia ulmoides Oliver

Genomic-Wide Identification and Characterization of the Uridine Diphosphate Glycosyltransferase Family in Eucommia ulmoides Oliver

Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism

The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review

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