Effects of colocynth alkaloids and glycosides on Wistar rats fed high-fat diet. A biochemical and morphological study

Introduction. In traditional medicine, Citrullus colocynthis is used to treat diabetes, hyperlipidemia, cardiovascular diseases, inflammation, and oxidative stress, all of which can appear when a diet rich in vegetable fats, such as palm oil, is continuously consumed. Such high-fat diets are chronic stressors of the hypothalamic–pituitary–adrenal axis. The objective of our study was to analyze and evaluate the effects of colocynth total alkaloids and glycosides on metabolic, hormonal, and structural disorders of the adrenal medulla in Wistar rats fed a high-fat diet. Material and methods. Twenty six Wistar rats were distributed as follows: six control animals received a standard laboratory diet; twenty experimental rats received the standard laboratory diet supplemented with palm oil — the high-fat diet (HFD). After seven months of this diet, the HFD group was subdivided into rats treated for the next 2 months with either alkaloid extract (HFD-ALk group) or ethanol extract of glycosides (HFD-GLc) or animals on HFD only. Plasma metabolites and ACTH concentrations were measured by standard methods. Sections of adrenal medulla were stained by Heidenhain-Azan method and Sudan Black. Results. The adrenal medulla of the HFD rats showed prominent structural changes, such as hypertrophy of chromaffin and ganglion cells, vacuolation, inflammatory foci, and fibrosis. The biochemical and hormonal parameters were significantly improved in the HFD rats treated with alkaloid and glycoside extracts of Citrullus colocynthis. Moreover, the morphological changes of the adrenal medulla were attenuated in HFD-ALk and HFD-Glc rats. Conclusions. The results of the study indicate that phytotherapy using Citrullus colocynthis alkaloids may correct metabolic and hormonal perturbations as well as adrenal medulla structure of rats maintained on HFD.

Effet hypolipémiant des alcaloïdes de la coloquinte chez le rat Wistar soumis à un régime hyperlipidique [Hypolipidemic effect of colocynth alkaloids in Wistar rat fed high-fat diet]

Introduction. Animals fed high-fat diet have been shown to develop hyperglycemia, insulin resistance, hyperlipidemia, and moderate obesity, which resemble to human metabolic syndrome Many plant extracts have been recommended worldwide for metabolic disorders treatment. Objective. The purpose of this study was to examine the effects of alkaloids colocynth extract in rats fed high-fat diet. Material and methods. Male rats (n=18), were divided into three groups: a control group (LT) (n = 6) fed a standard diet (1.3 MJ/100 g), and an experimental group (LE) (n=12) received a standard diet enriched with palm oil (2.3 MJ/100 g). After four months of high-fat diet feeding, LE animals received intraperitoneally administration of alkaloids during five weeks (LTr). Results. Treated animals with bitter apple compared to experimental animals, showed significant reduction in serum triacylglycerols (-73%), total cholesterol (-30%), and low density lipoprotein (LDL) (-47%). Whereas, a significant increase was noted in high density lipoprotein (HDL)(+57%).Enzymatic activities of aspartate, alanine amino transaminase and alkaline phosphatase were lowered by 37, 20 and 34%, respectively. Conclusion. Our results suggest that alkaloids have positive effects on metabolic disorders caused by high-fat diet in rat

Effects of colocynth alkaloids and glycosides on Wistar rats fed high-fat diet. A biochemical and morphological study

Introduction. In traditional medicine, Citrullus colocynthis is used to treat diabetes, hyperlipidemia, cardiovascular diseases, inflammation, and oxidative stress, all of which can appear when a diet rich in vegetable fats, such as palm oil, is continuously consumed. Such high-fat diets are chronic stressors of the hypothalamic–pituitary–adrenal axis. The objective of our study was to analyze and evaluate the effects of colocynth total alkaloids and glycosides on metabolic, hormonal, and structural disorders of the adrenal medulla in Wistar rats fed a high-fat diet. Material and methods. Twenty six Wistar rats were distributed as follows: six control animals received a standard laboratory diet; twenty experimental rats received the standard laboratory diet supplemented with palm oil — the high-fat diet (HFD). After seven months of this diet, the HFD group was subdivided into rats treated for the next 2 months with either alkaloid extract (HFD-ALk group) or ethanol extract of glycosides (HFD-GLc) or animals on HFD only. Plasma metabolites and ACTH concentrations were measured by standard methods. Sections of adrenal medulla were stained by Heidenhain-Azan method and Sudan Black. Results. The adrenal medulla of the HFD rats showed prominent structural changes, such as hypertrophy of chromaffin and ganglion cells, vacuolation, inflammatory foci, and fibrosis. The biochemical and hormonal parameters were significantly improved in the HFD rats treated with alkaloid and glycoside extracts of Citrullus colocynthis. Moreover, the morphological changes of the adrenal medulla were attenuated in HFD-ALk and HFD-Glc rats. Conclusions. The results of the study indicate that phytotherapy using Citrullus colocynthis alkaloids may correct metabolic and hormonal perturbations as well as adrenal medulla structure of rats maintained on HFD. (Folia Histochemica et Cytobiologica 2017, Vol. 55, No. 2, 74–85

A Citrullus colocynthis fruit extract acutely enhances insulin-induced GLUT4 translocation and glucose uptake in adipocytes by increasing PKB phosphorylation

International audienceEthnopharmacological relevance: Citrullus colocynthis (L.) Schrad is a common fruit in traditional medicine and used as remedy against various diseases, especially diabetes. Up to now, its anti-diabetic effects have been fully attributed to its enhancement of pancreatic insulin secretion. Whether C. colocynthis also ameliorates insulin action in peripheral tissues has not been investigated.Aim of the study: In the present study, using 3T3-L1 adipocytes as cell model, we have investigated whether colocynth fruit extracts affect insulin action.Materials and methods: Various extracts were prepared from the C. colocynthis fruit and screened using a cell-based 96 well plate GLUT4 translocation assay. Promising extracts were further studied for their effects on glucose uptake and cell viability. The effect on insulin signal transduction was determined by Western blot and the molecular composition was established by LC-MS.Results: The ethyl acetate fractions of aqueous non-defatted extracts of seed and pulp, designated Sna1 and Pna1, acutely enhanced insulin-induced GLUT4 translocation. In accordance, both extracts increased insulin-stimulated cellular glucose uptake. Pna1, which displayed greater effects on GLUT4 and glucose uptake than Snal, was further investigated and was demonstrated to increase GLUT4 translocation without changing the half-maximum dose (ED50) of insulin, nor changing GLUT4 translocation kinetics. At the molecular level, Pna1 was found to enhance insulin-induced PKB phosphorylation without changing phosphorylation of the insulin receptor. Pna1 appeared not to be toxic to cells and, like insulin, restored cell viability during serum starvation. By investigating the molecular composition of Pna1, nine compounds were identified that made up 87% of the mass of the extract, one of which is likely to be responsible for the insulin-enhancing effects of Pna1.Conclusions: The C. colocynthis fruit possesses insulin-enhancing activity. This activity may explain in part its antidiabetic effects in traditional medicine. It also identifies the C. colocynthis as a source of a potential novel insulin enhancer that may prove to be useful to reduce hyperglycemia in type 2 diabetes

Carob leaf polyphenols trigger intrinsic apoptotic pathway and induce cell cycle arrest in colon cancer cells

IF 3.973International audienceChemoprevention of Colorectal cancer (CRC) is the major concern for improving public health. We investigated the protective effects of carob, Ceratonia siliqua L, leaf polyphenols (CLP) against CRC. Phenolic content analysis showed that CLP is enriched with gallic acid and m-coumaric acid. We observed that CLP exerted a dose dependent cytotoxic effect through the induction of apoptosis on CRC cell lines, with an IC50 around 20 mu g/mL CLP induced intrinsic apoptotic pathway through the caspase-9 activation and PARP cleavage in HCT-116 and CT-26 cells. Moreover, CLP induced cell cycle arrest in the G1 phase through p53 activation. Gallic acid and m-coumaric acid exerted similar effect of CLP but at higher concentration to that expected to be present in CLP, suggesting the synergistic effect between polyphenols in CLP activity. Interestingly, the carob leaf infusion reduced CT-26 tumour growth in BALB/c mice. This study suggests that CLP can be used for the prevention of CRC. (C) 2017 Elsevier Ltd. All rights reserved