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Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from Corni fructus: possible involvement of the PI3K-Akt/PKB signaling pathway.

ABSTRACT: Iridoid glycosides (CIG) are the major component of Corni fructus. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected. The results showed that CIG significantly improved oral glucose tolerance in diabetic mice. Biochemical indices also revealed that CIG had a positive effect on lipid metabolism and oxidative stress. In addition, CIG can significantly enhance the expression level of the PI3K-Akt/PKB pathway related proteins in skeletal muscle, which is the key pathway of insulin metabolism. These findings show that CIG can improve the hyperglycemia and hyperlipidemia of HFD-STZ-induced diabetic mice through the PI3K-Akt/PKB signaling pathway, and CIG might be a potential medicine or functional food for type 2 diabetes mellitus remedies.

SUBMITTER: Kang J

PROVIDER: S-EPMC9085420 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from <i>Corni fructus</i>: possible involvement of the PI3K-Akt/PKB signaling pathway.

Kang Jiefang J Guo Chen C Thome Rodolfo R Yang Ning N Zhang Yuan Y Li Xing X Cao Xiaoyan X

RSC advances 20180829 53

Iridoid glycosides (CIG) are the major component of <i>Corni fructus</i>. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transp ...[more]

PMID: 35546813

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Project description:Leaves of Passiflora suberosa L. (Family: Passifloraceae; common name: wild passion fruit, devil's pumpkin) are used in Sri Lankan traditional medicine for treating diabetes. The present study investigated the in vivo ability of P. suberosa leaves to manage blood sugar status and associated cholesterol levels. Mechanisms of action and toxicity were also determined. Phytochemical screening of aqueous extracts of P. suberosa leaves and carbohydrate content of the leaves were determined according to previously published methods. In two group of male mice (n = 9), effects on fasting and random blood glucose levels (BGLs) of different acute doses (0, 25, 50, 100 and 200 mg/kg) of the aqueous leaf extract (ALE) were evaluated at 1, 3, and 5 h post-treatment. In another set of mice, the fasting BGL was evaluated following treatment of 0 or 50 mg/kg ALE (dose prescribed in traditional medicine) for 30 consecutive days. The lipid profile, some mechanism of ALE action (diaphragm glucose uptake, glycogen content in the liver and skeletal muscles) and its toxicity (behavioural observation, food and water intake, hepatoxicity) were also assessed following 30-day treatment. However, sucrose and glucose tolerance tests and intestinal glucose uptake were conducted to determine portion of mechanisms of action following single dose of 50 mg/kg ALE. Phytochemical screening revealed the presence of alkaloids, unsaturated sterols, triterpenes, saponins, flavonoids, tannins and proanthocyanidins. Carbohydrate content of the leaves was 12.97%. The maximum hypoglycemic effect was observed after 4 h of 50 and 100 mg/kg ALE administration. The extract decreased fasting BGL (18%) following an oral sucrose challenge and inhibited (79%) glucose absorption from the intestine. Correspondingly, the levels of glycogen in the liver (61%) and in the skeletal muscles (57%) were found be higher than that of the control group. The levels of total cholesterol (17%) and tri-glyceraldehyde levels (12%) found to be reduced in treated groups. Furthermore, no significant toxic effects were observed in treated groups. The present results suggest that the leaves of P. suberosa can be used to manage blood glucose and cholesterol levels. Isolation of active compounds are recommended for further analysis.

Project description:Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein-protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson-Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

Dataset Information

Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from Corni fructus: possible involvement of the PI3K-Akt/PKB signaling pathway.

Publications

Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from <i>Corni fructus</i>: possible involvement of the PI3K-Akt/PKB signaling pathway.

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