Evaluation of potential antidiabetic activity of abelmoschus esculentus and evidence of possible pharmacokinetic interaction with metformin

The study is aimed at the evaluation of potential activity of and possible interaction with metformin in animal Models of Diabetes Mellitus. Study objectives include study the anti-diabetic effect of for Diabetes Mellitus in animal models and also to study the effect of Abelmoschus esculentus with metformin and explore any interaction. Plant material was collected () followed by extraction of plant materials () Exudate collection of and activity test study was done (acute toxicity study, according to standard OECD guidelines) Experimental animals were divided into groups. Dosing was done for 28 days. Biochemical parameters were studied. Histopathology studies are done. Results showed that in this study administrations of Abelmoschus esculentus extract (2000mg/kg body weight) Metformin with extract (5mg/kg b.w. and 2000mg/kg body weight and Metformin 5mg/kg body weight decreased elevated blood glucose levels significantly from first to fourth week compared to diabetic control rats and showed minimal safety concerns.

Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells

Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β2-adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic β2-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.

Glucose oxidase as a model enzyme for antidiabetic activity evaluation of medicinal plants: In vitro and in silico evidence

Diabetes mellitus is a major public health problem in the world. In Africa, more than 80% of patients use plants for their treatment. However, the methods of validation of endogenous knowledge usually used are costly. The alternative method developed in this study aims at creating hyperglycemia <i>in vitro</i> and exploiting the metabolic pathway involving glucose oxidase for UV-visible spectrophotometric screening of medicinal plants’ antidiabetic activity. The evolution of glucose oxidation as a function of drug concentration is followed by UV-visible spectrophotometry. The formation of the stable complex between the enzyme and the inhibitor is studied using molecular docking. Drugs used (Gliben) and plant extracts exhibited an <i>in vitro</i> hypoglycemic effect by reducing exponentially, <i>in vitro</i>, the level of free glucose. The results also showed that <i>L. multiflora</i> is more active than <i>V. amygdalina</i> (IC₅₀: 1.36 ± 0.09 mg/mL Vs IC₅₀: 3.00 ± 0.54 mg/mL). Gliben (0.5 mg/mL) and <i>L. multiflora</i> (2 mg/mL) reduced both the rate of oxidation of glucose by glucose oxidase (catalytic power V_max: 0.84 ± 0.11 mg*mL^-1*min^-1 for Gliben and 1.72 ± 0.13 mg*mL^-1*min^-1 for ^{L. multiflora}); and the affinity of this enzyme for its substrate-glucose (K_M: 15.11 ± 2.72 mg*mL^-1 for Gliben and 9.17 ± 1.56 mg*mL^-1 for <i>L. multiflora</i>) when these results are compared to enzyme catalysis in the absence of inhibitor (V_max: 2.86 ± 0.44 mg*mL^-1*min-1; K_M: 8.07 ± 1.96 mg*mL^-1). The binding of GOX (1GAL) to selected phytocompounds derived from <i>L. multiflora</i> was confirmed by molecular docking. The most stable complexes were obtained for four compounds; <b>8</b> (-10.1±0.0 Kcal/mol), <b>6</b> (-9.5±0.1 Kcal/mol), <b>3</b> (-8.3±0.0 Kcal/mol) and <b>9</b> (-8.2±0.1 Kcal/mol). Among these, compounds <b>8</b> and <b>6</b> formed complexes with the enzyme stabilized by hydrogen bonds, the compound <b>8</b> forms 5 hydrogen bonds (<b>ASN514</b>, <b>ASP424</b>, <b>ARG95</b>, <b>TYP68</b>, <b>LEU65</b>) while compound <b>6</b> forms 2 hydrogen bonds (<b>ASN514</b> and <b>SER422</b>). However, no H-bonding interaction occurs in the complex that involves ligands <b>9</b> and <b>3</b> despite their high binding energy (-8.2±0.1 Kcal/mol and -8.3±0.0 Kcal/mol respectively). Glucose oxidase can serve as a marker enzyme for<i> in vitro</i> antidiabetic activity evaluation of medicinal plants.

Some Common Medicinal Plants with Antidiabetic Activity, Known and Available in Europe (A Mini-Review)

Diabetes is a metabolic disease that affected 9.3% of adults worldwide in 2019. Its co-occurrence is suspected to increase mortality from COVID-19. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycaemic raw plant materials that are present in the consciousness of Europeans and relatively easily accessible to them on the market and sometimes even grown on European plantations. The following raw materials are discussed in this mini-review: Morus alba L., Cinnamomum zeylanicum J.Presl, Trigonella foenum-graecum L., Phaseolus vulgaris L., Zingiber officinale Rosc., and Panax ginseng C.A.Meyer in terms of scientifically tested antidiabetic activity and the presence of characteristic biologically active compounds and their specific properties, including antioxidant properties. The characteristics of these raw materials are based on in vitro as well as in vivo studies: on animals and in clinical studies. In addition, for each plant, the possibility to use certain morphological elements in the light of EFSA legislation is given.