Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites.

The discovery of a relict plastid, also known as an apicoplast (apicomplexan plastid), that houses housekeeping processes and metabolic pathways critical to Plasmodium parasites' survival has prompted increased research on identifying potent inhibitors that can impinge on apicoplast-localised processes. The apicoplast is absent in humans, yet it is proposed to originate from the eukaryote's secondary endosymbiosis of a primary symbiont. This symbiotic relationship provides a favourable microenvironment for metabolic processes such as haem biosynthesis, Fe-S cluster synthesis, isoprenoid biosynthesis, fatty acid synthesis, and housekeeping processes such as DNA replication, transcription, and translation, distinct from analogous mammalian processes. Recent advancements in comprehending the biology of the apicoplast reveal it as a vulnerable organelle for malaria parasites, offering numerous potential targets for effective antimalarial therapies. We provide an overview of the metabolic processes occurring in the apicoplast and discuss the organelle as a viable antimalarial target in light of current advances in drug discovery. We further highlighted the relevance of these metabolic processes to Plasmodium falciparum during the different stages of the lifecycle.

Changes in nutritional, health benefits, and pharmaceutical potential of raw and roasted tropical almond (Terminalia catappa Linn.) nuts from Nigeria.

Tropical almond (Terminalia catappa Linn.) is highly distributed within the tropics, but appears rather underutilized in developing countries like Nigeria. Specifically, relevant information regards the nutritional, health benefits, and pharmaceutical potential of roasted T. catappa nuts remains scanty. Comparing both raw and roasted T. catappa nuts should provide additional information especially from product development and potential commercial prospect standpoints. The changes in nutritional, health benefits, and pharmaceutical potentials of raw and roasted T. catappa nuts were, therefore, investigated. Whereas the raw T. catappa nuts obtained significantly (p < 0.05) higher protein, ash, moisture, crude fiber, as well as vitamins C, and B1-3 compared to the roasted ones, some contents like carbohydrates, energy, vitamin A, calcium, manganese, zinc, hydrogen cyanide, as well as oxalate would noticeably change (p < 0.05) after the roasting process. Twenty phytochemicals were identified in both raw and roasted samples with the concentrations of quinine, ribalinidine, sapogenin, flavan-3-ol and tannin significantly reduced, while catechin seemed enhanced upon roasting. Promising drug-likeness, pharmacokinetic properties, and safety profiles could be predicted among the phytochemicals. Overall, roasting T. catappa nuts should enhance the nutritional contents, which could aid both absorption and palatability.

Corrigendum to "Toxicopathological, proinflammatory and stress response evaluation of Terminalia catappa extract in male Wistar rats" [Toxicol. Rep. 8 (2021) 1769-1776].

[This corrects the article DOI: 10.1016/j.toxrep.2021.10.005.].

Counteractive role of Terminalia catappa leaf extract on hematological and coagulation disturbance in Type 2 diabetic rats.

Background and Aim: Diabetes mellitus is a leading cause of mortality worldwide associated with hyperglycemia-induced hematological aberrations and thromboembolic complications. This study aimed to explore the modulatory effect of Terminalia catappa leaf aqueous crude extract (TCLE) on hematological and coagulation disturbances in a Type 2 diabetic rat model. Materials and Methods: High-fat diet streptozotocin-induced diabetic rats were treated orally with 400 and 800 mg/kg body weight TCLE daily for 28 days. Full blood count, coagulation parameters, plasma calcium (Ca), and erythrocyte glycogen (GLYC) levels were assessed using standard procedures. Results: Terminalia catappa leaf aqueous crude extract treatment had a significant (p < 0.05) prolonging effect on clotting and bleeding times while increasing Ca, GLYC and mean corpuscular volume in diabetic rats. On the other hand, lymphocytes (LYM), platelet (PLT) count, mean PLT volume, neutrophil-LYM ratio (NLR), and PLT-LYM ratio (PLR) of TCLE-treated diabetic animals were significantly reduced (p < 0.05) compared with untreated diabetic animals. Lymphocyte, PLT count, NLR, and PLR correlated positively (p < 0.05) with plasma glucose, while a significant positive association was observed between Ca and GLYC. On the other hand, a strong negative association (p < 0.05) was observed between clotting time and fasting plasma glucose. Conclusion: These findings suggest that T. catappa leaf extract may be useful in reversing diabetic-mediated hematological anomalies due to its anticoagulant and anti-anemic activities.

Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats.

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 ß-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.

Stage 2 Hypertension and Electrocardiogram Abnormality: Evaluating the Risk Factors of Cardiovascular Diseases in Nigeria.

INTRODUCTION: This study evaluated the status of stage 2 hypertension, abnormal ECG and their co-occurrence as possible risk factors of cardiovascular disease and their predictors in a Nigerian University population. METHODS: A total of 717 subjects participated in this study. Blood pressure (BP), resting electrocardiogram (ECG) and other clinical parameters were measured and categorised according to standard organisational guidelines. Bivariate correlation and multivariate logistic regression model were used to determine covariates and clinical parameter association at a 95 % significant level. RESULTS: Stage 2 hypertension and abnormal ECG respectively occurred in 264 (37 %) and 217 (39.2 %) subjects, with co-occurrence and abnormal BMI in 85 (11.8 %) and 459 (64.8%) subjects, respectively. Sex (p = 0.001) and occupation (p = 0.022) were independently associated with abnormal BP and ECG, respectively, while age was independently associated (p < 0.001) with abnormal BP, ECG and co-occurrence of these conditions. Predictors of stage 2 hypertension and abnormal ECG were sex (adjusted odds ratio [aOR] = 1.652, 95 % CI 1.097-2.488) and occupation (aOR = 0.411, 95 % CI 0.217-0.779), respectively, while age was a predictor for stage 2 hypertension (aOR = 0.065, 95 % CI 0.015-0.283), abnormal ECG (aOR = 0.137, 95 % CI 0.053-0.351) and their co-occurrence (aOR = 0.039, 95 % CI 0.014-0.113). CONCLUSIONS: This study shows prevalence rates of these risk factors are on the increase. It also suggests that ECG abnormality is a public health issue among stage 2 hypertensive patients that must be monitored. Therefore, appropriate interventions that prevent and control hypertension and identified risk factors should be put in place in addition to lifestyle changes, regular screening and surveillance.

Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene.

This study aims at evaluating the ameliorative role of Terminalia catappa aqueous leaf extract (TCA) on hyperglycaemia-induced oxidative stress and inflammation in a high-fat, low dose streptozotocin-induced type 2 diabetic rat model. Experimental rats were treated orally with 400 and 800 mg/kg bw TCA daily for four weeks. Antioxidant enzyme activities, plasma glucose concentration, protein concentration, oxidative stress, and inflammation biomarkers were assayed using standard methods. Hepatic relative expressions of tumour necrosis factor-alpha (TNF-α), interleukin-six (IL-6), and nuclear factor-erythroid 2 related factor 2 (Nrf-2) were also assessed. Molecular docking and prediction of major TCA phytoconstituents' biological activity related to T2DM-induced oxidative stress were evaluated in silico. Induction of diabetes significantly (p < 0.05) reduced superoxide dismutase, glutathione-S-transferase, and peroxidase activities. Glutathione and protein stores were significantly (p < 0.05) depleted, while glucose, MDA, interleukin-six (IL-6), and tumour necrosis factor-α (TNF-α) concentrations were significantly (p < 0.05) increased. A significant (p < 0.05) upregulation of hepatic TNF-α and IL-6 expression and downregulation (p < 0.05) of Nrf-2 expression were observed during diabetes onset. TCA treatment significantly (p < 0.05) modulated systemic diabetic-induced oxidative stress and inflammation, mRNA expression dysregulation, and dysregulated macromolecule metabolism. However, only 800 mg/kg TCA treatment significantly (p < 0.05) downregulated hepatic TNF-α expression. 9-Oxabicyclo[3.3.1]nonane-2,6-diol and 1,2,3-Benzenetriol bound comparably to glibenclamide in Nrf-2, IL-6, and TNF-α binding pockets. They were predicted to be GST A and M substrate, JAK2 expression, ribulose-phosphate 3-epimerase, NADPH peroxidase, and glucose oxidase inhibitors. These results suggest that TCA ameliorates hyperglycaemia-induced oxidative stress and inflammation by activating Nrf-2 gene.

Type 2 Diabetes Mellitus Mediation by the Disruptive Activity of Environmental Toxicants on Sex Hormone Receptors: In Silico Evaluation.

This study investigates the disruptive activity of environmental toxicants on sex hormone receptors mediating type 2 diabetes mellitus (T2DM). Toxicokinetics, gene target prediction, molecular docking, molecular dynamics, and gene network analysis were applied in silico techniques. From the results, permethrin, perfluorooctanoic acid, dichlorodiphenyltrichloroethane, O-phenylphenol, bisphenol A, and diethylstilbestrol were the active toxic compounds that could modulate androgen (AR) and estrogen-α and -ß receptors (ER) to induce T2DM. Early growth response 1 (EGR1), estrogen receptor 1 (ESR1), and tumour protein 63 (TP63) were the major transcription factors, while mitogen-activated protein kinases (MAPK) and cyclin-dependent kinases (CDK) were the major kinases upregulated by these toxicants via interactions with intermediary proteins such as PTEN, AKT1, NfKß1, SMAD3 and others in the gene network analysis to mediate T2DM. These toxicants pose a major challenge to public health; hence, monitoring their manufacture, use, and disposal should be enforced. This would ensure reduced interaction between people and these toxic chemicals, thereby reducing the incidence and prevalence of T2DM.

Toxicopathological, proinflammatory and stress response evaluation of Terminalia catappa extract in male Wistar rats.

The present study was carried out to assess the oral safety, proinflammatory and stress response effect of Terminalia catappa aqueous leaf extract (TCA) in male Wistar rats. The acute and sub-acute oral toxicity of TCA was assessed using guidelines 423 and 407 of the Organisation for Economic Co-operation and Development (OECD), respectively. Signs of clinical toxicity, morbidity and mortality were observed. The biochemical, haematological, proinflammatory, stress response and histopathological indices were assessed. In the acute toxicity study, no sign of clinical toxicity, morbidity, and mortality was observed for TCA treatment, up to 5000 mg/kg bwt. However, in the sub-acute toxicity study, repeated daily TCA treatment significantly (p<0.05) altered the body weight gain, plasma alkaline phosphatase activity and albumin concentration. There were no obvious morphological and macroscopic alterations in the organs investigated. TCA appear not to elicit any proinflammatory, stress, systemic and organ toxic effect when utilised at the reported dose and time frame.

Protective Role of Picralima nitida Seed Extract in High-Fat High-Fructose-Fed Rats.

Picralima nitida is a therapeutic herb used in ethnomedicine for the management of several disease conditions including diabetes. This study examined the potential palliative effect of aqueous seed extract of Picralima nitida (APN) on dyslipidemia, hyperglycemia, oxidative stress, insulin resistance, and the expression of some metabolic genes in high-fat high-fructose-fed rats. Experimental rats (2 months old) were fed a control diet or a high-fat diet with 25% fructose (HFHF diet) in their drinking water for nine weeks. APN was administered orally during the last four weeks. Anthropometric and antioxidant parameters, lipid profile, plasma glucose, and insulin levels and the relative expression of some metabolic genes were assessed. APN caused a significant decrease (P < 0.05) in weight gained, body mass index, insulin resistance, plasma glucose, and insulin levels. High-density lipoprotein cholesterol level was significantly increased (P < 0.05), while triacylglycerol, cholesterol, low-density lipoprotein, cardiac index, atherogenic index, coronary artery index, and malondialdehyde levels in plasma and liver samples were also significantly decreased (P < 0.05) by APN at all experimental doses when compared to the group fed with an HFHF diet only. APN also significantly (P < 0.05) upregulated the relative expression of glucokinase, carnitine palmitoyltransferase-1 (CPT-1), and leptin at 400 mg/kg body weight when compared to the group fed with an HFHF diet only. This study showed that APN alleviated dyslipidemia, hyperglycemia, and oxidant effect associated with the intake of a high-fat high-fructose diet.

Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants.

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.

Nauclea latifolia Sm. Leaf Extracts Extenuates Free Radicals, Inflammation, and Diabetes-Linked Enzymes.

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.

Model Optimization and In Silico Analysis of Potential Dipeptidyl Peptidase IV Antagonists from GC-MS Identified Compounds in Nauclea latifolia Leaf Extracts.

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-ß-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.

GC-MS Analysis and Inhibitory Evaluation of Terminalia catappa Leaf Extracts on Major Enzymes Linked to Diabetes.

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.

Potential Anti-Cancer Flavonoids Isolated From Caesalpinia bonduc Young Twigs and Leaves: Molecular Docking and In Silico Studies.

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-ß-d-xylopyranoside and kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-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.

Data on in vivo antioxidant, hypolipidemic and hepatoprotective potential of Thaumatococcus daniellii (Benn.) Benth leaves.

This data article reports on the in vivo biochemical activity of ethanolic extract of Thaumatococcus daniellii (Benn.) Benth leaves (ETD) in male Wistar rats at an oral dose of 500-1500 mg/kg daily for 14 days. Control groups were administered distilled water and Vitamin C (10 mg/kg; b.wt). Indices of oxidative stress, dyslipidemia, liver injury and liver pathology were estimated in the plasma and organs after the investigation period. Oral treatment with ETD increased organ superoxide dismutase (SOD) activity, renal reduced glutathione (GSH) and plasma high density lipoprotein (HDL) concentrations while reducing plasma alanine transaminase (ALT) activity, plasma cholesterol (CHOL), bilirubin (DBIL) and organ malondialdehyde (MDA) concentrations (P<0.05). Data was supported by histological report showing no pathologic abnormality. This data indicate ethanolic extract of T. daniellii leaves shows antioxidant, hypolipidemic and hepatoprotective potential.