Potential Role of Phytochemicals as Glucagon-like Peptide 1 Receptor (GLP-1R) Agonists in the Treatment of Diabetes Mellitus.

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

Insight into antioxidant-like activity and computational exploration of identified bioactive compounds in Talinum triangulare (Jacq.) aqueous extract as potential cholinesterase inhibitors.

BACKGROUND: Recent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities. METHODS: In vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank ( https://www.rcsb.org/ ). RESULTS: The results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses. CONCLUSION: Overall, this study offers valuable insights into the interactions and dynamics of protein-ligand complexes, offering a basis for further drug development targeting these proteins in AD.

GC-MS analysis of aqueous extract of Nymphaea lotus and ameliorative potential of its biosynthesized gold nanoparticles against cadmium-induced kidney damage in rats.

Plants possess compounds serving as reducing agents for green synthesis of gold nanoparticles (AuNPs), which is currently considered for biomedical application. Exposure to cadmium (Cd) can affect the functional integrity of the several organs such as kidney and liver. Nymphaea lotus (NL) is known for its several medicinal properties, including its protective role against tissue damages. This study investigated the bioactive compounds in NL using gas chromatography-mass spectroscopy (GC-MS) and ameliorative potential of its biosynthesized AuNPs (NL-AuNPs) against Cd-induced nephrotoxicity in rats. The presence of bioactive compounds in N. lotus was investigated by GC-MS in aqueous extract of NL. Gold nanoparticles were synthesized using aqueous extract of NL. Thirty rats were grouped into six (n = 5). Group 1 served as control, while group 2, 3, 4 and 5 received CdCl2 (10 mg/kg) orally for five days. Thereafter, groups 3, 4, and 5, respectively, received silymarin (75 mg/kg), 5 and 10 mg/kg NL-AuNPs, orally for 14 days, while group 6 received 10 mg/kg NL-AuNPs only. Rats were sacrificed after treatment, and biochemical parameters and kidney histopathology were evaluated. Bioactive compounds of pharmacological importance identified include pyrogallol, oxacyclohexadecan-2-one, 22-Desoxycarpesterol, 7,22-Ergostadienol, ß-sitosterol and Dihydro-ß-agarofuran. Cadmium caused nephrotoxicity in rats, as evidenced by significant (p < 0.05) increase in the levels of kidney function markers (serum urea and creatinine) and inflammatory markers (Interleukin-6 (IL-6) and Nuclear Factor-κB (NF-κB)) when compared with control. These changes were significantly (p < 0.05) ameliorated by the spherically-synthesized NL-AuNPs (25-30 nm) with the 5 mg/kg NL-AuNPs more potent against kidney damage induced by Cd in rats but high doses of NL-AuNPs (≥10 mg/kg) could be suggested toxic. NL possess phytochemicals capable of reducing gold salts to nanoparticle form, and doses up to 5 mg/kg could be considered safe for the treatment of renal damage occasioned by cadmium.

In vitro antioxidant and inhibitory activities of polyphenolic-rich extracts of Syzygium cumini (Linn) Skeels leaf on two important enzymes relevant to type II diabetes mellitus.

In this study, the effect of free and bound polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf on antioxidant as well as α-amylase and α-glucosidase activities were determined using in vitro model. Polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf was prepared accordingly and the capability of the extract to inhibit antioxidants as typified by ferric reducing power (FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) among other free radicals scavenging abilities were quantified spectrophotometrically, added to this, the activities of (α-amylase and α-glucosidase were also assessed. The bound phenolic extract exhibited more in vitro antioxidant properties as represented by their high radicals scavenging ability in all the free radicals evaluated. Also, the polyphenolic-rich extracts inhibited α-amylase and α-glucosidase, with bound phenolics showing significant (p<0.05) increase in a dose-dependent manner than free phenolics. Therefore, this study suggests the use of Syzygium cumini leaf as a nutraceutical in the management/ control of type II diabetes mellitus patients.

In vitro antioxidant activities and inhibitory effects of phenolic extract of Senecio biafrae (Oliv and Hiern) against key enzymes linked with type II diabetes mellitus and Alzheimer's disease.

The phenolic extract of Senecio biafrae leaves was investigated to determine the in vitro antioxidant, phenolic profiles, and inhibition of key enzymes relevant to type II diabetes mellitus (α-amylase and α-glucosidase) and Alzheimer's disease (acetylcholinesterase and butrylcholinesterase). The phenolic extract demonstrated significant scavenging abilities against all in vitro antioxidant parameters assessed. Reversed-phase HPLC of the extract revealed the presence of gallic acid, chlorogenic, caffeic acid, rutin, quercetin, and kaempferol. The extract also inhibited activities of α-amylase (IC 50 = 126.90 µg/ml), α-glucosidase (IC 50 = 139.66 µg/ml), acetylcholinesterase (IC 50 = 347.22 µg/ml), and butrylcholinesterase (IC 50 = 378.79 µg/ml), which may be attributed to the antioxidant potential of the extract and its phenolic composition. Therefore, this study suggests that the leaves of S. biafrae may be useful in the management of diabetes mellitus and Alzheimer's disease.

Anti-Hyperglycemic and Anti-Inflammatory Activities of Polyphenolic-Rich Extract of Syzygium cumini Linn Leaves in Alloxan-Induced Diabetic Rats.

In this study, anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cumini leaves in alloxan-induced diabetic rats were determined. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg body weight) in female Wistar rats. The rats were orally administered with 400 mg/kg free phenol, 400 mg/kg bound phenol, and 5 mg/kg metformin, respectively. On the 14th day of oral administration, the animals were sacrificed, anti-hyperglycemic and anti-inflammatory were assessed. Fasting blood glucose and glycated hemoglobin levels; homeostasis model assessment-insulin resistance scores, lipid peroxidation concentration, glucose-6-phosphatase activity, and all concentrations of anti-inflammatory studied in alloxan-induced diabetic rats were significantly ( P < .05) reduced with the administration of polyphenolic-rich extract of Syzygium cumini leaves. Also there was significant ( P < .05) increase in glycogen and insulin concentrations, pancreatic ß-cell scores, antioxidant enzymes and hexokinase activities, as well as glucose transporter levels in diabetic animals administered with polyphenolic-rich extract of S cumini leaves. The results indicate that S cumini leaves possess anti-hyperglycemic and anti-inflammatory activities.