Hypoglycemic effects of esculeoside A are mediated via activation of AMPK and upregulation of IRS-1

Yang, Ziming; Zhang, Li; Liu, Jinglei; Lu, Fushen; Wang, Lei; Chen, Yueyuan; Li, Dianpeng

doi:10.1186/s12906-019-2543-3

Cited by 17 publications

(19 citation statements)

References 38 publications

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“…The liver is the major organ for gluconeogenesis. PEPCK and G6Pase are two crucial rate-limiting enzymes in the gluconeogenesis pathway, and their transcription levels of them determine the rate of gluconeogenesis ( 41 ). Previous studies have demonstrated that inhibiting FOXO1 reduced the expression of PEPCK and G6Pase ( 42 ).…”

Section: Resultsmentioning

confidence: 99%

Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice

Lin

Pan²,

Liu³

et al. 2023

Front. Nutr.

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IntroductionDrug monotherapy was inadequate in controlling blood glucose levels and other comorbidities. An agent that selectively tunes multiple targets was regarded as a new therapeutic strategy for type 2 diabetes. Acanthopanax trifoliatus (L.) Merr polysaccharide (ATMP) is a bio-macromolecule isolated from Acanthopanax trifoliatus (L.) Merr and has therapeutic potential for diabetes management due to its anti-hyperglycemia activity.MethodsType 2 diabetes mellitus was induced in mice using streptozotocin, and 40 and 80 mg/kg ATMP was administered daily via the intragastric route for 8 weeks. Food intake, water intake, and body weight were recorded. The fasting blood glucose (FBG), fasting insulin (FINS) and an oral glucose tolerance test (OGTT) were performed. Histological changes in the liver and pancreas were analyzed by H&E staining. The mRNA and the protein levels of key factors involved in glycogen synthesis, glycogenolysis, and gluconeogenesis were measured by quantitative real time PCR and Western blotting.ResultsIn this study, we found that ATMP could effectively improve glucose tolerance and alleviate insulin resistance by promoting insulin secretion and inhibiting glucagon secretion. In addition, ATMP decreases glycogen synthesis by inhibiting PI3K/Akt/GSK3β signaling, reduces glycogenolysis via suppressing cAMP/PKA signaling, and suppresses liver gluconeogenesis by activating AMPK signaling.ConclusionTogether, ATMP has the potential to be developed as a new multitargets therapeutics for type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice

Lin

Pan²,

Liu³

et al. 2023

Front. Nutr.

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“…Relative to the MG mice, mice in treatment group presented receded senescence characteristics. Body weight changes are capable of reflecting animal development and growth, and the adverse effects of drugs on the body [ 20 ]. The body weight data are shown in Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Chemical Constituents of Litchi Pericarp Extracts and Its Antioxidant Activity in Mice

Yang

Zhang

et al. 2022

Foods

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Litchi pericarp is the main byproduct of litchi processing and contains several polyphenols. However, the chemical constituents and the antioxidant effect in litchi pericarp extracts (LPE) have been rarely studied. The result of the quantitative analyses of the major monomers in LPE indicated that procyanidin A2, procyanidin B2, epicatechin, rutin, and catechin were the major polyphenol compounds of LPE. The LPE exhibited high radical scavenging activity, as indicated by the results of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ascorbic acid, 2,2′-Azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) tests. Moreover, administrating D-galactose in mice led to the reduced activity of antioxidant enzymes, aggravated lipid peroxidation, and induced protein oxidation. The results were improved in the aging mice after the LPE treatment was performed. The above results suggest that LPE has an excellent antioxidant effect. Accordingly, litchi pericarp can serve as a promising source of dietary antioxidants.

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“…Esculeoside A also inhibited hyaluronidase activity and ameliorated dermatitis in 2,4-dinitro-chlorobenzen-treated mice [ 24 ]. Tomato saponin, including esculeoside A ameliorated collagen-induced arthritis in vivo through Th1 inhibition and Th2 activation [ 24 ], and it exhibited a hypoglycemic effect in db/db mice through the AMP-activated protein kinase/insulin receptor substrate-1 pathway [ 27 ]. Thus, the top 10 mutant lines with the highest esculeoside A content among the mature fruits were selected and designated 13-6, 13-8, 16-7, 17-3, 17-8, 18-2, 22-1, 22-6, 23-1, and 25-2.…”

Section: Resultsmentioning

confidence: 99%

“…Esculeoside A was isolated and identified as the major constituent in ripe red tomatoes by Fujiwara et al [ 6 , 7 ]. Esculeoside A also has various pharmacological effects including anti-atherosclerosis [ 23 ], anti-hyaluronidase [ 24 , 25 ], anti-arthritis [ 26 ], and hypoglycemic [ 27 ] activity.…”

Section: Introductionmentioning

confidence: 99%

Content of Two Major Steroidal Glycoalkaloids in Tomato (Solanum lycopersicum cv. Micro-Tom) Mutant Lines at Different Ripening Stages

Ngo

Park

et al. 2022

Plants

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Esculeoside A and tomatine are two major steroidal alkaloids in tomato fruit (Solanum lycopersicum) that exhibit anti-inflammatory, anticancer, and anti-hyperlipidemia activities. Tomatine contained in immature tomato fruit is converted to esculeoside A as the fruit matures. To develop new tomato varieties based on the content analysis of functional secondary metabolites, 184 mutant lines were generated from the original cultivar (S. lycopersicum cv. Micro-Tom) by radiation breeding. Ultra-performance liquid chromatography coupled with evaporative light scattering detector was used to identify the mutant lines with good traits by analyzing tomatine and esculeoside A content. Compared with the original cultivar, candidates for highly functional cultivars with high esculeoside A content were identified in the mature fruit of the mutant lines. The mutant lines with low and high tomatine content at an immature stage were selected as edible cultivars due to toxicity reduction and as a source of tomatine with various pharmacological activities, respectively. During the process of ripening from green to red tomatoes, the rate of conversion of tomatine to esculeoside A was high in the green tomatoes with a low tomatine content, whereas green tomatoes with a high tomatine content exhibited a low conversion rate. Using methanol extracts prepared from unripe and ripe fruits of the original cultivar and its mutant lines and two major compounds, we examined their cytotoxicity against FaDu human hypopharynx squamous carcinoma cells. Only tomatine exhibited cytotoxicity with an IC50 value of 5.589 μM, whereas the other samples did not exhibit cytotoxicity. Therefore, radiation breeding represents a useful tool for developing new cultivars with high quality, and metabolite analysis is applicable for the rapid and objective selection of potential mutant lines.

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Hypoglycemic effects of esculeoside A are mediated via activation of AMPK and upregulation of IRS-1

Cited by 17 publications

References 38 publications

Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice

Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice

Evaluation of Chemical Constituents of Litchi Pericarp Extracts and Its Antioxidant Activity in Mice

Content of Two Major Steroidal Glycoalkaloids in Tomato (Solanum lycopersicum cv. Micro-Tom) Mutant Lines at Different Ripening Stages

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