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Anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from barks of Litsea glutinosa in ob/ob mice.

ABSTRACT: The present study investigated the anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from Litsea glutinosa barks (CG) in ob/ob mice. CG was orally administrated (50, 100 and 200?mg/kg) to ob/ob mice for 4 weeks. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and inflammation were measured. CG was chemically characterized using UPLC-QTOF-MS. CG dose-dependently decreased body and fat weights without reducing average food intake. CG (100-200?mg/kg) significantly reduced the serum levels of fasting glucose, glycosylated hemoglobin (HbAlc) and glycosylated serum protein (GSP). CG increased insulin sensitivity as manifested by decreased fasting serum insulin, reduced homeostasis model assessment-estimated insulin resistance (HOMA-IR) and improved oral glucose tolerance. CG also alleviated dyslipidemia, ameliorated liver steatosis, increased the activity of serum lipase and alleviated inflammation. The activities of liver pyruvate kinase and glucokinase as well as liver content of glycogen were increased after CG treatment. CG was rich in alkaloids and eight main alkaloids were identified, many of which had been demonstrated to possess adequate anti-diabetic activities. These results suggest that the alkaloid-rich extract of CG possesses potential anti-hyperglycemic and anti-hyperlipidemic effects and can be utilized as an effective agent for the treatment of type 2 diabetes.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6107583 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from barks of Litsea glutinosa in ob/ob mice.

Zhang Xiaopo X Jin Yan Y Wu Younan Y Zhang Caiyun C Jin Dejun D Zheng Qingxia Q Li Youbin Y

Scientific reports 20180823 1

The present study investigated the anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from Litsea glutinosa barks (CG) in ob/ob mice. CG was orally administrated (50, 100 and 200 mg/kg) to ob/ob mice for 4 weeks. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and inflammation were measured. CG was chemically characterized using UPLC-QTOF-MS. CG dose-dependently decreased body and fat weights without reducing average food intake. CG (100-200 mg/kg) s ...[more]

PMID: 30140027

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Project description:The genus Eremophila, despite comprising more than 250 species, has scarce literature studies that could be traced concerning the chemical profile and bioactivity of Eremophila purpurascens. The current study targets the investigation of the in vitro and in vivo anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of the polyphenol-rich leaf extract of E. purpurascens (EP). EP showed promising total anti-oxidant capacity with IC50 values of 106 and 114 μg/mL in 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) and diphenyl-1-picrylhydrazyl (DPPH) assays, respectively, with total anti-oxidant capacities of 331, 245, and 1767 μmol/g in ABTS, DPPH, and ferric reducing anti-oxidant power assays, respectively. In HepG2 cells, pre-treated with CCl4, a dose of 100 μg/mL EP ameliorated the reduced superoxide dismutase and glutathione levels and total anti-oxidant capacity with values of 312.5 U/mL, 15.47 mg/dL, and 1.03 nmol/mL, respectively. In vitro anti-diabetic evaluation using 3T3-L1 adipocyte culture showed that at a dose of 30 μg/mL, the EP extract elicited a 6.3% decrease in the concentration of glucose (22.4 mmol/L), showing significant amelioration with regard to pioglitazone and insulin. EP also demonstrated elevated serum insulin by 77.78% with a marked reduction in fasting blood glucose level by 64.55% relative to the streptozotocin diabetic rats in vivo. EP also relieved the liver stress markers both in vitro in CCl4 and in vivo in tamoxifen (TAM) models. EP markedly decreased TAM toxicity, as demonstrated by the decline in the liver stress markers, ALT and AST, by 36.1 and 51.1%, respectively. It also relieved the oxidative stress triggered by TAM, as revealed by the reduction in the levels of TBARs and TNF-α by 21.4 and 40%, respectively. Liquid chromatography electrospray ionization mass spectrometry of EP revealed a total of twelve peaks belonging to phenylpropanoids, lignans, and phenolics, where verbascoside and pinoresinol-4-O-β-d-glucoside represented the most abundant secondary metabolites. The docking experiment showed that tri-O-galloyl-hexoside had the best fitting within the NADPH oxidase active sites with binding energy (ΔG = -81.12 kcal/mol). Thus, the plant can be of beneficial value in the control of hyperglycemia in diabetic patients, besides its prophylactic potential against hepatic complications.

Project description:BackgroundLitsea glutinosa (Lour.) C. B. Rob. belongs to the Litsea genus and is categorized under the family of Lauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques.MethodsExtensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from the L. glutinosa plant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques.ResultsIn the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by 1H and 13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract of L. glutinosa at doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption.ConclusionAccording to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.

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Anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from barks of Litsea glutinosa in ob/ob mice.

Publications

Anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from barks of Litsea glutinosa in ob/ob mice.

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