Hypoglycaemic activity of Smilax canellifolia Mill. rhizomes: a bioassay-guided isolation and identification of synergistic compounds

Background Smilax canellifolia Mill. is a native shrub used in commercial root tonics as an aphrodisiac, stimulant, and pain reliever. Traditional medicine incorporates the rhizomes of S. canellifolia for the treatment of anaemia, rheumatoid arthritis, and diabetes in Jamaica and its diaspora. In particular, the use of this plant in the management of diabetes has yet to receive any scientific evaluation. In this study, the hexane crude extract of S. canellifolia rhizomes (SCH) was investigated to determine its hypoglycaemic activity in normal Sprague-Dawley rats and to identify the compounds contributing to this activity. Methods The hypoglycaemic compounds were isolated using bioactivity-guided purification which involved hypoglycaemic screening using an Oral Glucose Tolerance Test (via intravenous administration of SCH and its fractions). Purification was performed using column chromatography, and the bioactive fractions were elucidated using spectroscopic techniques (IR; GC-MS; 1H NMR and 13C NMR). Results Administration of SCH at 50 mg/kg body weight (BW) to normal S-D rats produced a reduced glycaemic response, notably from the 90 to the 150-min intervals when compared with the control, dimethyl sulfoxide (p < 0.05). Purification of this extract yielded four main fractions, SCH1 – SCH4, of which SCH3 and SCH4 displayed significant hypoglycaemia. Further purification of both SCH3 and SCH4 led to the isolation of sub-fractions SCH3.6 and SCH4.2, respectively. Using spectroscopic techniques stigmasterol (1) and β-sitosterol (2) from SCH3.6; and the fatty acids palmitic acid (3), oleic acid (4), and stearic acid (5) from SCH4.2 were identified as the major compounds with significant hypoglycaemic activities comparable to that of glibenclamide. Conclusion This study demonstrates that the rhizomes of Smilax canellifolia contain several bioactive constituents that are responsible for its hypoglycaemic activity and may be beneficial in the management of hyperglycaemia and complications associated with diabetes.

Epistemological Assumption: Understanding Protein Polysaccharide Complexes in Improving Diabetes Treatment

Embracing the philosophical condition of epistemology in research has led to identifying and understanding the meaning and nature of diabetes and the use of protein-polysaccharides complexes in the treatment of diabetes. The research approach is purely qualitative; thereby, postmodern epistemological assumptions were made from the theory of knowledge on diabetes, its conditions and symptoms, effects, protein and polysaccharides characteristics. The research develops knowledge on using protein-polysaccharides obtained mainly from plant species like mushrooms and pumpkins generated from credible and valid knowledge connected from observable justification, beliefs and truths from scholarly material. In the process, knowledge has been created identifying that protein-polysaccharides complexes contain polysaccharides that have proven to possess hypoglycaemic activity that reduces hyperglycaemia leading to an increase in insulin secretion and reduction of blood glucose.

COMPUTATIONAL MOLECULAR MODELLING OF 2-AMINOBENZIMIDAZOLE DERIVATIVES: STRONG SUCCESSOR OF HYPOGLYCAEMIC AGENT

Objective: The present study was aimed to design different analogues of 2-aminobenzimidazole and find the binding ability by Insilico method. Methods: Various soft wares like Chemsketch, Molinspiration, PASS, and Discovery studio were used to design the proposed derivatives. Evaluation of binding activity against different receptors was detected and checked their physicochemical properties for binding. Results: In this study, we designed different analogs of 2-aminobenzimidazole into a ligand having a binding affinity with alpha-glucosidase, Dipeptidyl–peptidase 4(DPP4), Peroximase proliferator-activated receptor gamma (PPARγ), and Insulin-like growth factor 1(IGF-1) receptor. The designed ten derivatives showed a significant binding capacity to the concerned receptors. Conclusion: These results pointed that the designed proposed derivatives promising hypoglycaemic activity.

The Isolation of Hypoglycaemic Compounds from Desmodium canum and Their Synergistic Effect on Blood Glucose Levels in Euglycaemic Sprague Dawley Rats

Desmodium canum (Strong back) commonly consumed as a tea or tonic is believed to possess hypoglycaemic activity. This paper sets out to isolate potential hypoglycaemic compounds present within the plant and investigate their synergistic effects on blood glucose levels in euglycaemic Sprague Dawley rats. The milled plant was sequentially extracted using hexane, ethyl acetate and methanol. The ethyl acetate extract was subjected to column chromatography yielding seven major fractions and were subsequently bioassayed using the Oral Glucose Tolerance Test (OGTT). Further chromatographic separation and analysis using Gas Chromatography–Mass Spectroscopy and Fourier Transform Infrared Spectroscopy enabled the identification of two hypoglycaemic compounds, oleic acid (OA) and succinic acid (SA). These were bioassayed individually and as a cocktail to determine the synergistic effects using OGTT. Intravenous administration of these compounds individually indicated both are very potent in retarding blood glucose levels. However, the most significant activity was observed on synergistic administration. The cocktail (1 : 1) displayed significant hypoglycaemic activity throughout the entire study. It also significantly differed from OA at the 120 min interval (3.43 ± 0.22 mmol/L vs. 4.98 ± 0.19 mmol/L, resp., p = 4.29 × 10 − 7 ) and significantly differed from SA at 30 min (3.95 ± 0.43 mmol/L vs. 5.17 ± 0.32 mmol/L, resp., p = 0.003 ), 90 min (4.35 ± 0.36 mmol/L vs. 5.49 ± 0.69 mmol/L, resp., p = 0.04 ), and 120 min intervals (3.43 ± 0.22 mmol/L vs. 4.94 ± 0.31, resp., p = 1.54 × 10 − 5 ). Oral administration of the cocktail showed comparable potency to that of metformin ( p > 0.05 ) throughout the OGTT curve. The synergistic effects of the naturally isolated compounds yielded higher potency levels than individual administration and when administered orally, the hypoglycaemic effect was similar to that of metformin. This may assist in paving a way to attempt a novel method in approaching antidiabetic therapy.

Comparative Hypoglycaemic Activity of Fixed Dose Combination Anti-Diabetic Formulations Versus Respective Monotherapies in Diabetic Rabbits

Type 2 diabetes mellitus is a disease of impaired glucose homeostasis and chronic hyperglycemia. Current approaches for the treatment frequently involving the use of combination therapy. The aim of the present study was to evaluate and compare the hypoglycaemic activity of fixed-dose combination anti-diabetic formulations and respective individual agents using rabbits as an animal model. Experimental diabetes was induced by a single intravenous injection of alloxan monohydrate at a dose of 150 mg/kg. Individual drugs and combination tablets were administered to experimental groups. Fasting blood glucose level was estimated at 0, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours using glucometer. Data were statistically analyzed using student t-test and p less than 0.05 considered as statistically significant. The reduction in fasting blood glucose level in diabetes-induced rabbits was significantly higher with combination products compared to individual drugs. Fixed-dose combination products had shown improved glycaemic control than individual agents. Fixed-dose combination therapy can be used as a suitable option for selected patients requiring multiple glucose-lowering therapies for use as an adjunct to diet and exercise to improve glycaemic control in type 2 diabetes mellitus.

In Vitro Investigations of Acetohexamide Binding to Glycated Serum Albumin in the Presence of Fatty Acid

The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.

Contribution of Flavonoids and Iridoids to the Hypoglycaemic, Antioxidant, and Nitric Oxide (NO) Inhibitory Activities of Arbutus unedo L.

This study aims at investigating the contribution of two classes of compounds, flavonoids and iridoids, to the bioactivity of Arbutus unedo L. leaves and fruits. The impact of different extraction procedures on phytochemicals content and hypoglycemic, antioxidant, and nitric oxide (NO) inhibitory activities of A. unedo fresh and dried plant materials was investigated. Ellagic acid 4-O-β-D-glucopyranoside, kaempferol 3-O-glucoside, and norbergenin were identified for the first time in this genus by using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). Three iridoids (gardenoside, geniposide, unedoside) are specifically identified in the leaves. Interestingly, asperuloside was extracted only from dried fruits by ethanol with Soxhlet apparatus. Extracts were screened for their potential antioxidant activities by using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Activity Power (FRAP), and β-carotene bleaching tests. Based on the Global Antioxidant Score (GAS) calculation, the most promising antioxidant extract was obtained by hydroalcoholic maceration of dried leaves that showed half maximal inhibitory concentration (IC50) of 0.42 and 0.98 μg/mL in ABTS and DPPH assays, respectively. The hypoglycaemic activity was investigated by α-amylase and α-glucosidase inhibition tests. Extracts obtained by ethanol ultrasound extraction of fresh leaves and hydroalcoholic maceration of fresh fruits (IC50 of 19.56 and 28.42 μg/mL, respectively) are more active against α-glucosidase than the positive control acarbose (IC50 of 35.50 μg/mL). Fruit extracts exhibited the highest anti-inflammatory activity.