Terminalia catappa leaves are used in managing both diabetes mellitus and its complications in Southwest Nigeria. However, its inhibitory activity on enzymes implicated in diabetes is not very clear. This study investigated the in vitro inhibitory properties and mode of inhibition of T. catappa leaf extracts on enzymes associated with diabetes. The study also identified some bioactive compounds as well as their molecular interaction in the binding pocket of these enzymes. Standard enzyme inhibition and kinetics assays were performed to determine the inhibitory effects of aqueous extract (TCA) and ethanol extract (TCE) of T. catappa leaves on α-glucosidase and α-amylase activities. The phytoconstituents of TCA and TCE were determined using GC-MS. Molecular docking of the phytocompounds was performed using Autodock Vina. TCA and TCE were the most potent inhibitors of α-glucosidase (IC50 = 3.28 ± 0.47 mg/mL) and α-amylase (IC50 = 0.24 ± 0.08 mg/mL), respectively. Both extracts displayed a mixed mode of inhibition on α-amylase activity, while mixed and noncompetitive modes of inhibition were demonstrated by TCA and TCE, respectively, on α-glucosidase activity. The GC-MS analytic chromatogram revealed the presence of 24 and 22 compounds in TCE and TCA, respectively, which were identified mainly as phenolic compounds, terpenes/terpenoids, fatty acids, and other phytochemicals. The selected compounds exhibited favourable interactions with the enzymes compared with acarbose. Overall, the inhibitory effect of T. catappa on α-amylase and α-glucosidase may be ascribed to the synergistic action of its rich phenolic and terpene composition giving credence to the hypoglycaemic nature of T. catappa leaves.

Tyrosine kinase (TK), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are important cancer therapeutic target proteins. Based on reported anti-cancer and cytotoxic activities of Caesalpinia bonduc, this study isolated phytochemicals from young twigs and leaves of C bonduc and identified the interaction between them and cancer target proteins (TK, VEGF, and MMP) in silico. AutoDock Vina, iGEMDOCK, and analysis of pharmacokinetic and pharmacodynamic properties of the isolated bioactives as therapeutic molecules were performed. Seven phytochemicals (7-hydroxy-4′-methoxy-3,11-dehydrohomoisoflavanone, 4,4′-dihydroxy-2’-methoxy-chalcone, 7,4′-dihydroxy-3,11-dehydrohomoisoflavanone, luteolin, quercetin-3-methyl, kaempferol-3-O-β-d-xylopyranoside and kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside) were isolated. Molecular docking analysis showed that the phytochemicals displayed strong interactions with the proteins compared with their respective drug inhibitors. Pharmacokinetic and pharmacodynamic properties of the compounds were promising suggesting that they can be developed as putative lead compounds for developing new anti-cancer drugs.

The COVID-19 pandemic, which started in Wuhan, China, has spread rapidly over the world with no known antiviral therapy or vaccine. Interestingly, traditional Chinese medicine helped in flattening the pandemic curve in China. In this study, molecules from African medicinal plants were analysed as potential candidates against multiple SARS-CoV-2 therapeutic targets. Sixty-five molecules from the ZINC database subset (AfroDb Natural Products) were virtually screened with some reported repurposed therapeutics against six SARS-CoV-2 and two human targets. Molecular docking, druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the best hits were further simulated. Of the 65 compounds, only three, namely, 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside found in almond (Terminalia catappa), grape (Vitis vinifera), and common verbena (Verbena officinalis), were able to bind to all eight targets better than the reported repurposed drugs. The findings suggest these molecules may play a role as therapeutic leads in tackling this pandemic due to their multitarget activity.

Dipeptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes. Inhibitors of this enzyme constitute a new class of drugs used in the treatment and management of type 2 diabetes. In this study, phytocompounds in Nauclea latifolia (NL) leaf extracts, identified using gas chromatography–mass spectroscopy (GC-MS), were tested for potential antagonists of DPP-IV via in silico techniques. Phytocompounds present in N. latifolia aqueous (NLA) and ethanol (NLE) leaf extracts were identified using GC–MS. DPP-IV model optimization and molecular docking of the identified compounds/standard inhibitors in the binding pocket was simulated. Drug-likeness, pharmacokinetic and pharmacodynamic properties of promising docked leads were also predicted. Results showed the presence of 50 phytocompounds in NL extracts of which only 2-O-p-methylphenyl-1-thio-β-d-glucoside, 3-tosylsedoheptulose, 4-benzyloxy-6-hydroxymethyl-tetrahydropyran-2,3,5-triol and vitamin E exhibited comparable or better binding iGEMDOCK and AutoDock Vina scores than the clinically prescribed standards. These four compounds exhibited promising drug-likeness as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties suggesting their candidature as novel leads for developing DPP-IV inhibitors.

This study was carried out to assess the in vitro antioxidant, anti-inflammatory and antidiabetic effects of Nauclea latifolia (Sm.) leaf extracts. Ethanolic (NLE) and aqueous (NLA) extract of N. latifolia leaves were prepared and assessed for their anti-inflammatory activity, antioxidant potential, α-amylase and α-glucosidase inhibitory activities, and the mechanism of enzyme inhibition in vitro using standard established methods. From the results, phytochemicals such as flavonoids, phenolics, glycosides, and tannins were detected in both extracts of N. latifolia with NLE having a significantly (p<0.05) higher phytochemical content. NLE displayed significantly (p<0.05) better total antioxidant capacity, reducing power, 2,2-diphenyl-2-picrylhydrazyl, and hydrogen peroxide radical scavenging activities. For anti-inflammatory activities, 70.54±2.45% albumin denaturation inhibition was observed for NLE while 68.05±1.03% was recorded for NLA. Likewise, 16.07±1.60 and 14.08±1.76% were obtained against hypotonic solution and heat-induced erythrocyte haemolysis, respectively, for NLE while 20.59±4.60 and 24.07±1.60% were respective NLA values. NLE (IC50: 4.20±0.18 and 1.19±0.11 mg/mL) and NLA (IC50: 11.21±0.35 and 2.64±0.48 mg/mL) α-glucosidase and α-amylase inhibitory activities were dose-dependent with uncompetitive and competitive inhibition elicited, respectively, by the extracts. A significant positive association (p<0.01 and 0.05) was identified between antioxidant activity and carbohydrate-metabolising enzyme inhibitory activity. The obtained result suggests N. latifolia leaf could serve as an alternative candidate for managing diabetes mellitus due to its antioxidant and anti-inflammatory association with diabetes-linked enzymes.

This study evaluated the safety of sub-acute administration of Terminalia catappa L. aqueous leaf extract (TCA) on cardiac biochemical parameters. Graded concentrations (200, 400 and 800 mg/kg) of TCA wereorally administered daily for 28 days. Cardiac biochemical parameters of toxicity were thereafter accessedusing standard methods forsuperoxide dismutase, peroxidase, glutathione-S-transferase, reduced glutathione, lipid peroxidation, protein levels, cholesterol, triglyceride, lactate dehydrogenase and creatinine kinase. TCA treatment did not alter the heart weight and cardiac biochemical parameters. Nonetheless, at 800 mg/kg, the antioxidant profile was significantly improved after TCA treatment. There was no mediated sign of treatment toxicityas well asa change in cardiac histological architecture. T. catappaaqueous leaf extract is relatively non-toxic to the heart at the experimental doses and also within the test period.

The phytochemical constituents and antioxidant properties of Nauclea latifolia leaf decoction were investigated. Dried leaves were extracted in ethanol. Qualitative and quantitative phytochemical analysis was determined spectrometrically. The antioxidant activities were examined in vitro using 2,2-diphenyl-1-picrylhydrazyl radical, total antioxidant capacity and ferric reducing antioxidant power assays. Phytochemical screening confirmed the presence of flavonoids, alkaloids, anthocyanins, betacyanins, phenols, saponins, terpenoids, cardiac glycosides and quinones. The total lycopene, β-carotene, phenolics, flavonoid and alkaloid content were found to be 0.038 ± 0.01 mg CAE/g, 0.120 ± 0.04 mg CAE/g, 58.08 ± 0.58 mg GAE/g, 10.75 ± 0.17 mg RE/g and 0.32 ± 0.08% respectively. N. latifolia ethanol leaf extract demonstrated effective antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl with an IC50 of 2.58 ± 0.08 mg/mL compared to 0.86 ± 0.02 mg/mL and < 0.01 ± 0.01 mg/mL for butylated hydroxytoluene and ascorbic acid respectively. Total antioxidant capacity and ferric reducing antioxidant power of the extract were 73.81 ± 2.27 and 1314.45 ± 197.64 mg AAE/g respectively. Excellent positive correlations between the phenolic content and antioxidant activities of the extract were observed. The leaf of N. latifolia is of therapeutic value and may be exploited for its rich antioxidant components.

Rising prevalence of type 2 diabetes mellitus (T2DM) in sub-Saharan Africa has necessitated surveys of antidiabetic medicinal plants. This study assessed the antidiabetic mechanism of Terminalia catappa aqueous leaf extract (TCA) in high fat/low dose streptozotocin-induced type 2 diabetic rats. T2DM was induced by a combination of high-fat diet and low dose STZ (30 mg/kg bw) and the animals were administered with TCA (400 and 800 mg/kg bw) orally daily for 28 days. Biochemical parameters and indices for diabetes including renal function tests and pancreatic histology were evaluated. Relative expression of hepatic insulin resistance, signalling and glucose transport genes were also assessed. Induction of T2DM resulted in significant (p < 0.05) weight loss, dysregulated glucose level and clearance, electrolyte imbalance and disrupted diabetic biochemical parameters. Diabetes onset also perturbed β-cell function and insulin resistance indices, damaged pancreas microanatomy, while disrupting the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and glucose transporter isoform 4 (GLUT-4) mRNA. Oral treatment of diabetic animals with TCA significantly (p < 0.05) ameliorated alterations due to T2DM induction in a manner comparable with glibenclamide. These results suggest TCA exerts its antidiabetic action by reversing insulin resistance, improving glucose transport and activating PI3K/AKT signalling.