Antioxidative and anti-diabetic effects of Tapinanthus cordifolius leaf extract on high-fat diet and streptozotocin-induced type 2 diabetic rats.

Type 2 diabetes mellitus (T2DM) remains a global health concern despite current treatment options. This study investigated the potential of Tapinanthus cordifolius (TC) leaf extract as a therapeutic agent for T2DM. T2DM was induced in rats using a high-fat diet and streptozotocin. Diabetic rats received daily oral administration of TC extract (200, 400, or 800 mg/kg) and metformin (400 mg/kg) or remained untreated for 21 days. Blood glucose levels, body weight, diabetic symptoms, oxidative stress markers, and gene expression of metabolic regulators were assessed. TC treatment significantly reduced blood glucose levels and restored body weight in diabetic rats, comparable to the effects of metformin. TC also increased antioxidant enzyme activities (SOD, GST, and CAT) and decreased lipid peroxidation in various tissues. Furthermore, TC upregulated gene expression of glucose transporter type 4 (GLUT-4) and adiponectin receptor 2 (ADIPOR-2) while downregulating pro-inflammatory cytokines TNF-α and IL-6. This study provides the first in vivo evidence supporting TC leaf extract's anti-diabetic and antioxidant efficacy. The findings suggest that TC holds promise as a natural therapeutic agent for managing T2DM through multiple mechanisms, including improved glycemic control, enhanced insulin sensitivity, and protection against oxidative stress and tissue damage. In conclusion, this study validates the ethnobotanical use of TC as an anti-diabetic agent. Further research is warranted to isolate the bioactive compounds responsible for these effects.

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.

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.].

In vitro and in silico inhibitory validation of Tapinanthus cordifolius leaf extract on alpha-glucosidase in the management of type 2 diabetes.

The anti-diabetic properties of medicinal plants are becoming more widely recognized. To identify potential anti-diabetic agents for diabetes drug discovery, the current study used in vitro and in silico approaches to assess the alpha glucosidase inhibitory activities of Tapinanthus cordifolius (TC) leaf extracts and its bioactive components respectively. In vitro alpha glucosidase inhibitory assay was carried out on TC extract and fractions at various concentrations (50-1600 µg/mL), and the compounds with alpha glucosidase inhibitory potentials were identified using molecular docking, pharmacophore modelling, and molecular dynamics simulation. The crude extract exhibited the highest activity with an IC50 value of 248 µg/mL. Out of the 42 phytocompounds of the extract, α-Tocopherol-ß-d-mannoside gave the lowest binding energy of -6.20 Kcal/mol followed by, 5-Ergosterol (-5.46 kcal/mol), Acetosyringone (-4.76 kcal/mol), and Benzaldehyde, 4-(Ethylthio)-2,5-Dimethoxy-(-4.67 kcal/mol). The selected compounds interacted with critical active site amino acid residues of alpha-glucosidase, just like the reference ligand. Molecular dynamics simulation revealed the formation of a stable complex between α-glucosidase and α-Tocopherol-ß-d-mannoside, with ASP 564 sustaining two hydrogen bond connections for 99.9 and 75.0% of the simulation duration, respectively. Therefore, the selected TC compounds, especially α-Tocopherol-ß-d-mannoside might be explored for future research and development as diabetic medicines.Communicated by Ramaswamy H. Sarma.

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.

Anopheles gambiae Trehalase Inhibitors for Malaria Vector Control: A Molecular Docking and Molecular Dynamics Study.

Trehalase inhibitors are considered safe alternatives for insecticides and fungicides. However, there are no studies testing these compounds on Anopheles gambiae, a major vector of human malaria. This study predicted the three-dimensional structure of Anopheles gambiae trehalase (AgTre) and identified potential inhibitors using molecular docking and molecular dynamics methods. Robetta server, C-I-TASSER, and I-TASSER were used to predict the protein structure, while the structural assessment was carried out using SWISS-MODEL, ERRAT, and VERIFY3D. Molecular docking and screening of 3022 compounds was carried out using AutoDock Vina in PyRx, and MD simulation was carried out using NAMD. The Robetta model outperformed all other models and was used for docking and simulation studies. After a post-screening analysis and ADMET studies, uniflorine, 67837201, 10406567, and Compound 2 were considered the best hits with binding energies of -6.9, -8.9, -9, and -8.4 kcal/mol, respectively, better than validamycin A standard (-5.4 kcal/mol). These four compounds were predicted to have no eco-toxicity, Brenk, or PAINS alerts. Similarly, they were predicted to be non-mutagenic, carcinogenic, or hepatoxic. 67837201, 10406567, and Compound 2 showed excellent stability during simulation. The study highlights uniflorine, 67837201, 10406567, and Compound 2 as good inhibitors of AgTre and possible compounds for malaria vector control.

Ficus exasperata Attenuates Acetaminophen-Induced Hepatic Damage via NF-κB Signaling Mechanism in Experimental Rat Model.

Ficus exasperata has been used to treat ulcer, diabetes, fever, and a variety of stress-related disorders. Acetaminophen (APAP) overdose is the most common cause of drug-induced acute liver injury. In this study, we evaluated the hepatoprotective effect and antioxidant capacity of ethanolic extract of F. exasperata (EFE) on acetaminophen-induced hepatotoxicity in albino rats. Rats were pretreated with EFE (150, 250, 500 mg/kg) and thereafter received 250 mg/kg APA intraperitoneally (i.p.). The normal control group received distilled water, while the negative control group received 250 mg/kg APAP, respectively. Hepatotoxicity and oxidative stress-antioxidant parameters were then assessed. Flavonoids, saponins, steroids, and glycosides, but not phenolics were detected by EFE phytochemical analysis. No mortality was recorded on acute exposure of rats to varying concentrations of APAP after 24 h; however, a dose-dependent increase in severity of convulsion, urination, and hyperactivity was observed. APAP overdose induced high AST, ALT, ALP, and total bilirubin levels in the serum, invoked lipid peroxidation, depleted GSH, decreased CAT, SOD, and GST levels, respectively. Nitric oxide (NO) level, myeloperoxidase activity, TNF-α, IL-1ß, NF-κB, COX-2, MCP-1, and IL-6 were also increased. Importantly, pretreatment of rats with EFE before acetaminophen ameliorated and restored cellular antioxidant status to levels comparable to the control group. Our results show and suggest the hepatoprotective effect of F. exasperata and its ability to modulate cellular antioxidant status supports its use in traditional medicine and renders it safe in treating an oxidative stress-induced hepatic injury.

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.

In Vitro Experimental Assessment of Ethanolic Extract of Moringa oleifera Leaves as an α-Amylase and α-Lipase Inhibitor.

Methods: Phytochemical screening, antioxidant activity, α-amylase, and α-lipase inhibitory assessment were carried out on Moringa oleifera extract. Results: The result of the phytochemical screening revealed the presence of total phenolic, flavonoid, tannin, and alkaloid contents of values 0.070 ± 0.005 mg gallic acid equivalent/g, 0.180 ± 0.020 mg rutin equivalent/g, 0.042 ± 0.001 mg tannic equivalent/g, and 12.17 ± 0.001%, respectively, while the total protein analysis was 0.475 ± 0.001 mg bovine serum albumin equivalent/g. Ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) values were 0.534 ± 0.001 mg gallic acid equivalent/g and 0.022 ± 0.00008 mg rutin equivalent/g, respectively. Diphenyl-2-picrylhydrazyl (DPPH), ABTS (2,2'-azino-bis (ethylbenzothiazoline-6-sulfonic acid)), and nitric oxide (NO) assays showed the extract to have a strong free radical scavenging activity. The 50% inhibitory concentration (IC50) values of the lipase and amylase activities of the extract are 1.0877 mg/mL and 0.1802 mg/mL, respectively. Conclusion: However, α-lipase and α-amylase inhibiting activity of M. oleifera could be related to the phytochemicals in the extract. This research validates the ethnobotanical use of M. oleifera leaves as an effective plant-based therapeutic agent for diabetes and obesity.

Polygenic Risk Score in African populations: progress and challenges.

Polygenic Risk Score (PRS) analysis is a method that predicts the genetic risk of an individual towards targeted traits. Even when there are no significant markers, it gives evidence of a genetic effect beyond the results of Genome-Wide Association Studies (GWAS). Moreover, it selects  single nucleotide polymorphisms (SNPs) that  contribute to the disease with low effect size  making it more precise at individual level risk prediction. PRS  analysis addresses the shortfall of GWAS by taking into account the SNPs/alleles with  low effect size but play an indispensable role to the observed phenotypic/trait variance.  PRS analysis has  applications that investigate the genetic basis of several traits, which includes rare diseases. However, the accuracy of PRS analysis depends on the genomic data of the underlying population. For instance, several studies  show   that obtaining higher prediction power of PRS analysis is challenging for non-Europeans. In this manuscript, we review the conventional PRS methods and their application to sub-Saharan African communities. We conclude that  lack of sufficient GWAS data and tools is  the limiting factor of applying PRS analysis to sub-Saharan populations.   We recommend developing Africa-specific PRS methods and tools for estimating and analyzing  African population data   for clinical  evaluation of PRSs of interest and predicting  rare diseases.

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.

Structural Transformation and Creativity Induced by Biological Agents during Fermentation of Edible Nuts from Terminalia catappa.

Terminalia catappa L. (tropical almond) is a nutritious fruit found mainly in the tropics. This study is aimed to establish the naturally biotransformed molecules and identify the probiotic agents facilitating the fermentation. The aqueous extracts from both the unfermented and fermented T. catappa nuts were subjected to gas chromatography/mass spectrometry (GC/MS) analysis. Syringol (6.03%), glutamine (1.71%), methyl laurate (1.79%), methyl palmitate (1.53%), palmitic acid (5.20%), palmitoleic acid (2.80%), and methyl oleate (2.97%) were detected in the unfermented nuts of the T. catappa. Additionally, two of these natural compounds (palmitic acid (4.19%) and palmitoleic acid (1.48%)) survived the fermentation process to emerge in the fermented seeds. The other natural compounds were biotransformed into 2,3-butanediol (1.81%), butyric acid (16.20%), propane-1,3-diol (19.66%), neoheptanol (2.89%), 2-piperidinone (6.63%), palmitoleic acid (1.18%), formamide, n-(p-hydroxyphenethyl)- (2.80%), and cis-vaccenic acid (1.69%) that newly emerged in the fermented seeds. The phytochemical compounds are likely carbon sources for the organisms facilitating the biotransformed molecules and product production. Four (4) potential probiotic bacteria strains, namely, Probt B1a, Probt B2a, Probt B4a, and Probt B4b, were isolated from the fermented nut. Enterococcus faecum, and Enterococcus faecalis were the organisms identified as driving the fermentation of the seeds. All strains were gram-positive, catalase-negative, and non-hemolytic, which suggests their harmless nature. N-(p-hydroxyphenethyl)-) was associated with fermentation for the first time, and neoheptanol was discovered as the main alcoholic molecule formed during the fermentation of the seeds. This fermentation is a handy tool for bio-transforming compounds in raw food sources into compounds with nutritious and therapeutic potentials.

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.

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum.

Chrysophyllum albidum Linn (African star apple) is a fruit with extensive nutritional and medicinal benefits. The fruit and kernel in the seed are both edible. Strains of lactic acid bacteria (LAB) were isolated from fermented seeds and assessed for probiotic characteristics. The extracts in both the unfermented and the fermented aqueous extracts from the kernels obtained from the seeds of C. albidum were subjected to analysis using the gas chromatography/mass spectrometry (GC-MS) method. This analysis identified the bioactive compounds present as possible substrate(s) for the associated organisms inducing the fermentation and the resultant biotransformed products formed. Three potential probiotic LAB strains identified as Lactococcus raffinolactis (ProbtA1), Lactococcus lactis (ProbtA2a), and Pediococcus pentosaceus (ProbtA2b) were isolated from the fermented C. albidum seeds. All strains were non hemolytic, which indicated their safety, Probt (A1, A2a, and A2b) grew in an acidic environment (pH 3.5) during the 48-h incubation time, and all three strains grew in 1% bile, and exhibited good hydrophobicity and auto-aggregation properties. Mucin binding proteins was not detected in any strain, and bile salt hydrolase was detected in all the strains. l-lactic acid (28.57%), norharman (5.07%), formyl 7E-hexadecenoate (1.73%), and indole (1.51%) were the four major constituents of the fermented kernel of the C. albidum, while 2,5-dimethylpyrazine (C1, 1.27%), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (C2, 2.90%), indole (C3, 1.31%), norharman (C4, 3.01%), and methyl petroselinate (C5, 4.33%) were the five major constituents of the unfermented kernels. The isolated LAB are safe for consumption. The fermenting process metabolized C1, C2, and C5, which are possible starter cultures for the growth of probiotics. Fermentation is an essential tool for bioengineering molecules in foods into safe and health beneficial products.

Anopheles metabolic proteins in malaria transmission, prevention and control: a review.

The increasing resistance to currently available insecticides in the malaria vector, Anopheles mosquitoes, hampers their use as an effective vector control strategy for the prevention of malaria transmission. Therefore, there is need for new insecticides and/or alternative vector control strategies, the development of which relies on the identification of possible targets in Anopheles. Some known and promising targets for the prevention or control of malaria transmission exist among Anopheles metabolic proteins. This review aims to elucidate the current and potential contribution of Anopheles metabolic proteins to malaria transmission and control. Highlighted are the roles of metabolic proteins as insecticide targets, in blood digestion and immune response as well as their contribution to insecticide resistance and Plasmodium parasite development. Furthermore, strategies by which these metabolic proteins can be utilized for vector control are described. Inhibitors of Anopheles metabolic proteins that are designed based on target specificity can yield insecticides with no significant toxicity to non-target species. These metabolic modulators combined with each other or with synergists, sterilants, and transmission-blocking agents in a single product, can yield potent malaria intervention strategies. These combinations can provide multiple means of controlling the vector. Also, they can help to slow down the development of insecticide resistance. Moreover, some metabolic proteins can be modulated for mosquito population replacement or suppression strategies, which will significantly help to curb malaria transmission.

Ganoderma Lucidum from Red Mushroom Attenuates Formaldehyde-Induced Liver Damage in Experimental Male Rat Model.

The majority of liver-related illnesses are caused by occupational and domestic exposure to toxic chemicals like formaldehyde (FA), which is widely common in Africa and the world at large. Hence, measures should be taken to protect humans from its hazardous effects. This study, therefore, examines the protective potential of Ganoderma lucidum (100 mg/kg body weight) on formaldehyde-induced (40%) liver oxido-inflammation in male rats. Male Wistar rats, 150-200 g, were allotted into four groups of 10 animals as follows: Group 1 was orally treated with 1 mg/mL distilled water, Group 2 was exposed to a 40% formaldehyde vapor environment for 30 min per day, Group 3 was orally treated with 100 mg/kg ethanol extract of Ganoderma lucidum, and Group 4 was co-administered formaldehyde and 100 mg/kg ethanol extract of Ganoderma lucidum. Rats were then sacrificed 24 h after administering the last dose of treatment, and the livers were excised. Ganoderma lucidum significantly reversed the formaldehyde-mediated reduction in body and organ weight. Ganoderma lucidum administration significantly prevented oxido-inflammation by reducing the levels of hydrogen peroxide and malondialdehyde and increasing the activity of antioxidant enzymes and glutathione contents, as well as the normal level of nitrite and myeloperoxidase production in FA-treated rats. Additionally, Ganoderma lucidum reversed a large decline in proinflammatory markers in formaldehyde. Furthermore, Ganoderma lucidum restores formaldehyde-induced histological alterations in the liver. Collectively, our results provide valuable information on the protective potential of Ganoderma lucidum in protecting formaldehyde-induced liver oxido-inflammation in male rats.

Anti-inflammatory Mechanism of Ruzu Bitters on Diet-Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats.

Nonalcoholic fatty liver disease (NAFLD) has become notorious globally. Increasingly emerging evidence shows that NAFLD is strongly associated with inflammation, with proinflammatory cytokines such as interleukin-2 (IL-2), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) playing a vital role in its progression. In this work, an attempt was made to verify the anti-inflammatory activity of Ruzu herbal bitters (RHB), an antiobesity medicinal concoction, on NAFLD induced by a high-fat diet (HFD) in albino Wistar rats. Twenty-five (25) rats were divided into five groups as follows: Group 1, the normal control, was maintained on standard rat chow and received normal saline (1 ml/kg body weight (BW)/day) for twelve weeks. The other groups were maintained on HFD for twelve weeks. Thereafter, groups 2-5 were treated with pioglitazone (4 mg/kg BW/day), RHB (0.6 ml/kg BW/day), normal saline (1 ml/kg BW/day), and fenofibrate (10 mg/kg BW/day), respectively. The animals were sacrificed after the experimental period. Biochemical indicators of oxidative stress and inflammation were assayed in the liver according to standard methods. The histological features of the liver were also compared to assess liver damage. RHB significantly (p < 0.05) reduced body weight and liver index, inhibited oxidative stress, boosted antioxidant enzymes by increasing the activity and level of SOD and GSH, reduced proinflammatory markers (IL-2, IL-6, TNF-α), and reversed histological alterations induced by NAFLD in rat liver. In conclusion, the anti-inflammatory activity of RHB in the prevention of NAFLD in rats has been confirmed.

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.