Screening of potential antidiabetic phytochemicals from Gongronema latifolium leaf against therapeutic targets of type 2 diabetes mellitus: multi-targets drug design

Diabetes mellitus (DM) is the most predominant group of metabolic disorders wreaking havoc on the wellbeing of man, with type 2 diabetes mellitus (type 2 DM) accounting for most DM related cases. This study, hence, investigated the antidiabetic potential of Gongronema latifolium leaf fractionated compounds against proteins implicated in different molecular pathways related to the onset and progression of type 2 DM. A total of fifteen proteins that can act as type 2 DM therapeutic targets were identified from the literature and downloaded/modelled using respective repositories. After docking the compounds with the fifteen proteins, glycogen synthase kinase 3 beta (GSK 3β), glucagon-like peptide-1 receptor (GLP-1R) and human aldose reductase were chosen as the ideal targets due to their high binding affinities with the compounds. Subsequent in silico analysis like binding free energy, ADMET predictions using different servers, and machine-learning predictive models (QSAR) using kernel partial least square regression were employed to identify promising compounds against the three targets. The eleven identified compounds (Luteonin, Kampferol, Robinetin, Gallocatechin, Baicalin, Apigenin, Genistein, Rosmaric acid, Chicoric acid and Naringenin) formed stable complexes with the proteins, showed moderation for toxicity, drugability, GI absorptions and drug-drug interactions, though structure modifications may be needed for lead optimization. The predictive QSAR models with reliable correlation coefficient (R2) showed the potency of the compounds to act as inhibitors (pIC50) of aldose reductase and GSK 3β, and act as agonists (pEC50) of GLP-1R. Thus, this study experimental framework can be used to design compounds that can modulate proteins related to type 2 DM without inducing off-target effects.

Effects of Gongronema latifolium Benth and Celosia argentea Linn supplemented diet on the hepatic and cardiac functions of high-fat diet-induced hyperlipidemic rats

Purpose The purpose of this study is to assess the effects of two green leafy vegetables (Gongronema latifolium and Celosia argentea) on the hepatic biomarkers [Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)], cardiac biomarkers [Creatine Kinase (CK) and Lactate Dehydrogenase (LDH)] and histopathology of the heart of high-fat diet-induced hyperlipidemic rats, with the aim of evaluating the vegetables as functional foods. Design/methodology/approach Experimental diets consisted of Control Diet (CD), High-Fat Diet (HFD), High-Fat Diet with Blanched Celosia argentea (HCB), High-Fat Diet with Unblanched Celosia argentea (HCU), High-Fat diet with Blanched Gongronema latifolium (HGB) and High-Fat Diet with Unblanched Gongronema latifolium (HGU). Seventy-five albino male rats (weighing 180–200 g) were used. The animals were divided into 15 groups of five albino rats each. Animals in Groups 1, 2 and 3 were fed with CD, HFD only and HFD with Atorvastin (5 mg/kg b.w), respectively. Animals in Groups 4, 5 and 6 were fed with 5, 10 and 15% HCB, respectively. Animals in Groups 7, 8 and 9 were fed with 5, 10 and 15% HCU, respectively, whereas animals in Groups 10, 11 and 12 were fed with 5, 10 and 15% HGB, respectively, and animals in Groups 13, 14 and 15 were fed with 5, 10 and 15% diet-inclusion of HGU, respectively. Findings The incorporation of the vegetal matter into the diet brought about a significant reduction (p = 0.05) in the activities of ALT, AST, CK and LDH when compared with HFD. However, the histological examination showed no pathological lesion, only at 15% inclusion of the vegetables. Originality/value The paper established that the incorporation of Celosia argentea and Gongronema latifolium into diet, most especially at 15% inclusion, may serve as functional food in the management of hyperlipidemia and associated complications.

Ethanolic Extracts of the Gongronema latifolium Stem and Leaves Caused Mild Renal Injury and Modulated Serum Triglycerides in Rats

Gongronema latifolium is a tropical plant with verse traditionally and medicinal uses in mostly Africa and Asia. In this work, we determined the biochemical effects of G. latifolium ethanolic extracts in male Wistar rats. The G. latifolium stem and leaves were air-dried separately, macerated, and extracted in 80 % ethanol. The Wistar rats were assigned into three groups randomly; control was administered distilled water, the treatment groups respectively were given 200 mg/kg bw of the extracts of leaves or stem for twenty-eight (28) days. Data showed that the rat serum ALT and ALP activities were lower in the extract-treated group than in the control group administered distilled water. In the rat liver, there were significant differences (p<0.05) in biochemical parameters compared to the control group as the extract-treated group showed a reduction in ALT, AST, and ALP activities. Meanwhile, the oral administration of the G. latifolium extracts led to the elevated (p<0.05) level of serum urea, while the serum triglycerides and creatinine levels were reduced compared with the control. Together, the data suggest that G. latifolium extracts at the doses tested had minimal renal toxicity.

Evaluation of hepatotoxicity effect of methanol leave extract of Gongronema latifolium in Albino rats

Gongronema latifolium is highly medicinal in nature. The fundamental ingredients used for medicinal purposes are stored in the various parts of the plant such as the fruits, seeds, leaves, root and stem. This present study is aimed to evaluate the hepatotoxicity effect of methanolic leaf extract of Gongronema latifolium on albino rats. This study was divided into five groups normal control groups: received commercial rat feed and water, group 2: received 1000 mg/kg b.w. of leaf extract of Gongronema latifolium, group 3: received 500 mg/kg b.w of leaf extract of G. latifolium, group 4; received 250 mg/kg of leaf extract of Gongronema latifolium, and group 5: received 125mg/kg of leaf extract of Gongronema latifolium. The result shows a significant (p<0.05) increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and conjugate bilirubin when compared to the normal control not giving the extract. Administration graded dosage of 1000mg/kg and 500mg/kg body weight significantly (p<0.05) increased the liver damage marker enzymes when compared with groups that received low dosage of 250mg/kg and 125mg/kg body weight and the normal control groups. The histopathological study revealed severe portal inflammation without steatosis and moderate portal inflammation in groups that received 1000mg/kg and 500mg/kg. Therefore, these results suggested that methanol leaf extracts of Gongronema latifolium possess hepatotoxic properties and strict caution must be observed when using the plant extract as a natural remedy of any disease.

GROWTH RESPONSE OF GONGRONEMA LATIFOLIUM (AMARANTH GLOBE) TO SOURCES AND RATES OF ORGANIC MANURES IN AN ACID SOIL ENVIRONMENT OF TROPICAL REGIONS

A field potted experiment was carried out in Asaba area of Delta State, Nigeria to evaluate sources and rates of organic manures (poultry and farmyard) on growth responses of Gongronema latifolium in an acid soil environment. It was a factorial experiment laid out in a randomized complete block design replicated 3 times. Data on plant height, number of leaves/branches, leaf area and stem girth were collected at 3, 5, 7, 9, 11 and 13 Weeks after sowing (WAS) and subjected to analysis of variance. The results that the effects on growth parameters of the crop were not significant and that higher application rates significantly increased plant height, number of leaves/branches and stem girth of G. latifolium. Application rates of 15 and 20 t/ha of both poultry and farm yard manures increased plant height from 10.45 cm to 12.52 cm and 8.12 cm and 10.68 cm respectively. The overall result indicated that the higher rate of organic manure, the better the response of growth indices of G. latifolium, though interaction effect was not significant. Poultry manure produced higher values of growth indices than farm yards manure, hence was recommended for increased productivity of G.latifolium in the study area.