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.

Nephroprotective Effects of Caffeine, Vanillin, and Their Combination against Experimental AlCl3-Induced Renal Toxicity in Adult Male Wistar Rats.

Aluminum (Al) is known to be a nephrotoxic metal that can cause renal toxicity in both humans and animals. The use of functional foods has been reported to have significance in managing the toxic effects associated with such metals. This study aimed to assess the potential protective effects of caffeine, vanillin, and their combination in mitigating AlCl3-induced renal toxicity in adult male Wistar rats. A total of thirty (30) adult male Wistar rats weighing between 150 and 200 g were randomly divided into five groups, each consisting of six rats (n = 6). Group 1 served as the control, while the remaining treatment groups received a daily oral dose of 100 mg/kg AlCl3 for a duration of 21 days. In addition, groups 3-5 were coadministered 50 mg/kg body weight (bw) of caffeine, vanillin, and a combination (50/50 mg/kg bw) of both substances, respectively. In the results, AlCl3-treated showed a significant (p < 0.05) increase in serum biomarkers such as ALT, ALP, urea, and creatinine, and a significant (p < 0.05) decrease in serum total proteins (TPs). The renal tissue's antioxidant system, including SOD, CAT, GPx, and GSH, exhibited a significant (p < 0.05) reduction, accompanied by an elevated MDA level. However, the administration of caffeine, vanillin, and their combination resulted in a significant (p < 0.05) decrease in serum ALT, ALP, urea, and creatinine, and a significant (p < 0.05) increase in serum TP. Furthermore, following the treatment, there was a significant (p < 0.05) increase in renal SOD, CAT, GPx, and GSH levels, along with a reduction in the MDA level. In addition, the treatment for 21 days caused a significant (p < 0.05) reversal to the altered histomorphological architecture. These findings suggest that caffeine, vanillin, and their combination could potentially be an effective regimen in managing AlCl3-induced renal toxicity.

Antioxidant evaluation and computational prediction of prospective drug-like compounds from polyphenolic-rich extract of Hibiscus cannabinus L. seed as antidiabetic and neuroprotective targets: assessment through in vitro and in silico studies.

BACKGROUND: Reports have implicated diabetes mellitus (DM) and Alzheimer's disease (AD) as some of the global persistent health challenges with no lasting solutions, despite of significant inputs of modern-day pharmaceutical firms. This study therefore, aimed to appraise the in vitro antioxidant potential, enzymes inhibitory activities, and as well carry out in silico study on bioactive compounds from polyphenolic-rich extract of Hibiscus cannabinus seed (PEHc). METHODS: In vitro antioxidant assays were performed on PEHc using standard methods while the identification of phytoconstituents was carried out with high performance liquid chromatography (HPLC). For the in silico molecular docking using Schrodinger's Grid-based ligand docking with energetics software, seven target proteins were retrieved from the database ( https://www.rcsb.org/ ). RESULTS: HPLC technique identified twelve chemical compounds in PEHc, while antioxidant quantification revealed higher total phenolic contents (243.5 ± 0.71 mg GAE/g) than total flavonoid contents (54.06 ± 0.09 mg QE/g) with a significant (p < 0.05) inhibition of ABTS (IC50 = 218.30 ± 0.87 µg/ml) and 1, 1-diphenyl-2-picrylhydrazyl free radicals (IC50 = 227.79 ± 0.74 µg/ml). In a similar manner, the extract demonstrated a significant (p < 0.05) inhibitory activity against α-amylase (IC50 = 256.88 ± 6.15 µg/ml) and α-glucosidase (IC50 = 183.19 ± 0.23 µg/ml) as well as acetylcholinesterase (IC50 = 262.95 ± 1.47 µg/ml) and butyrylcholinesterase (IC50 = 189.97 ± 0.82 µg/ml), respectively. Furthermore, In silico study showed that hibiscetin (a lead) revealed a very strong binding affinity energies for DPP-4, (PDB ID: 1RWQ) and α-amylase (PDB ID: 1SMD), gamma-tocopherol ( for peptide-1 receptor; PDB ID: 3C59, AChE; PDB ID: 4EY7 and BChE; PDB ID: 7B04), cianidanol for α-glucosidase; PDB ID: 7KBJ and kaempferol for Poly [ADP-ribose] polymerase 1 (PARP-1); PDB ID: 6BHV, respectively. More so, ADMET scores revealed drug-like potentials of the lead compounds identified in PEHc. CONCLUSION: As a result, the findings of this study point to potential drug-able compounds in PEHc that could be useful for the management of DM and AD.

In-silico nucleotide and protein analyses of S-gene region in selected zoonotic coronaviruses reveal conserved domains and evolutionary emergence with trajectory course of viral entry from SARS-CoV-2 genomic data.

INTRODUCTION: the recent zoonotic coronavirus virus outbreak of a novel type (COVID-19) has necessitated the adequate understanding of the evolutionary pathway of zoonotic viruses which adversely affects human populations for therapeutic constructs to combat the pandemic now and in the future. METHODS: we analyzed conserved domains of the severe acute respiratory coronavirus 2 (SARS-CoV-2) for possible targets of viral entry inhibition in host cells, evolutionary relationship of human coronavirus (229E) and zoonotic coronaviruses with SARS-CoV-2 as well as evolutionary relationship between selected SARS-CoV-2 genomic data. RESULTS: conserved domains with antagonistic action on host innate antiviral cellular mechanisms in SARS-CoV-2 include nsp 11, nsp 13 etc. Also, multiple sequence alignments of the spike (S) gene protein of selected candidate zoonotic coronaviruses alongside the S gene protein of the SARS-CoV-2 revealed closest evolutionary relationship (95.6%) with pangolin coronaviruses (S) gene. Clades formed between Wuhan SARS-CoV-2 phylogeny data and five others suggests viral entry trajectory while revealing genomic and protein SARS-CoV-2 data from Philippines as early ancestors. CONCLUSION: phylogeny of SARS-CoV-2 genomic data suggests profiling in diverse populations with and without the outbreak alongside migration history and racial background for mutation tracking and dating of viral subtype divergence which is essential for effective management of present and future zoonotic coronavirus outbreaks.

Polyphenolic-rich extracts of Andrographis paniculata mitigate hyperglycemia via attenuating ß-cell dysfunction, pro-inflammatory cytokines and oxidative stress in alloxan-induced diabetic Wistar albino rat.

BACKGROUND: This study sought to investigate anti-hyperglycemic potentials of free and bound phenolic-rich extracts of Andrographis paniculata (A. paniculata) leaves, commonly called "king of the bitter", a plant locally employed in folkloric alternative medicine. METHOD: In vitro antioxidant potentials such as total phenolic and flavonoid contents were evaluated in addition to phosphomolybdenum reducing total antioxidant activity in bound and free polyphenol-rich extracts of A. paniculata. Also, following induction of diabetes through a single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg body weight, b.w), diabetic rats were divided into seven (7) treatment groups with six rats each (n = 6) i.e. group 1 (normal control), 2 (diabetic untreated), 3 (5 mg/kg glibenclamide -treated control), while 4-7 were administered 50 and 100 mg/kg b.w of free and bound phenolic extracts of A. paniculata, respectively for twenty-one (21) days. RESULTS: There was a significant (p < 0.05) difference in hematological indices, hepatic biomarkers, total protein, antioxidant enzymes activities, total thiol and fasting blood glucose levels of diabetic groups administered polyphenolic-rich extracts of A. paniculata compared to diabetic untreated control. Similarly, serum insulin levels, hexokinase and glucose-6-phoshatase activities were significantly (p < 0.05) improved in phenolic-rich extracts of A. paniculata-treated diabetic groups compared to diabetic untreated control. A significant (p < 0.05) reduction was as well observed in the levels of inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα) among extract of A. paniculata administered diabetic groups compared diabetic untreated group. CONCLUSIONS: Anti-hyperglycemic activities demonstrated by polyphenolic-rich extracts of A. paniculata when compared to glibenclamide and normal control, could possibly have been occasioned by ß-cell protection, restoration of glycolytic enzymes as well as mitigation of inflammatory markers via antioxidant defensive/protective properties of the extracts.

Inhibitory potentials of phenolic-rich extracts from Bridelia ferruginea on two key carbohydrate-metabolizing enzymes and Fe2+-induced pancreatic oxidative stress.

OBJECTIVE: The current study was designed to evaluate the various antioxidant potentials and inhibitory effects of phenolic-rich leaf extracts of Bridelia ferruginea (BF) on the in vitro activities of some key enzymes involved in the metabolism of carbohydrates. METHODS: In this study, BF leaf free and bound phenolic-rich extracts were used. We quantified total phenolic and flavonoid contents, and evaluated several antioxidant activities using assays for ferric reducing antioxidant power, total antioxidant activity (phosphomolybdenum reducing ability), 1,1-diphenyl-2-picrylhydrazyl and thiobarbituric acid reactive species. Also, extracts were tested for their ability to inhibit α-amylase and α-glucosidase activity. RESULTS: The total phenolic and total flavonoid contents in the free phenolic extract of BF were significantly greater than in the bound phenolic extract. Also, all the antioxidant activities considered were significantly greater in the free phenolic extract than in the bound phenolic extract. In the same vein, the free phenolic-rich extract had a significantly higher percentage inhibition against α-glucosidase activity (IC50 = 28.5 µg/mL) than the bound phenolic extract (IC50 = 340.0 µg/mL). On the contrary, the free phenolic extract (IC50 = 210.0 µg/mL) had significantly lower inhibition against α-amylase than the bound phenolic-rich extract (IC50 = 190.0 µg/mL). CONCLUSION: The phenolic-rich extracts of BF leaves showed antioxidant potentials and inhibited two key carbohydrate-metabolizing enzymes in vitro.

Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase gene expression, exploratory and motor coordination-linked behaviour in male rats.

Humans in modern society are exposed to an ever-increasing number of electromagnetic fields (EMFs) and some studies have demonstrated that these waves can alter brain function but the mechanism still remains unclear. Hence, this study sought to investigate the effect of 2.5 Ghz band radio-frequency electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA expression level as well as locomotor function and anxiety-linked behaviour in male rats. Animals were divided into four groups namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8 weeks respectively. The results revealed that WiFi exposure caused a significant increase in anxiety level and affect locomotor function. Furthermore, there was a significant decrease in AChE activity with a concomitant increase in AChE mRNA expression level in WiFi exposed rats when compared with control. In conclusions, these data showed that long term exposure to WiFi may lead to adverse effects such as neurodegenerative diseases as observed by a significant alteration on AChE gene expression and some neurobehavioral parameters associated with brain damage.

Antioxidant Properties of the Extracts of Talinum Triangulare and its Effect on Antioxidant enzymes in Tissue Homogenate of Swiss Albino Rat.

OBJECTIVES: This study was designed to put into consideration both the in vitro and in vivo investigations on Talinum triangulare (Tt), an herbaceous perennial plant that is a native of tropical America and one of the most important vegetables in Nigeria. METHODS: Total phenolic contents in (mg GAE/100 g), flavonoid contents, the ferric reducing antioxidant properties (FRAP), 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl free radical scavenging ability (OH-) and iron chelating ability were carried out in vivo using standard described methods while GSH, GPx, catalase and SOD were determined in vivo using standard described methods. RESULTS: In the three different solvents extraction of T. triangulare that were studied in vitro, it was noted that ethyl acetate and ethanolic fractions of T. triangulare showed potent antioxidant activity against DPPH and iron chelating property with high phenolic content except Hydroxyl free radical scavenging ability that showed highest value in the aqueous extract, while the Reduced GSH indicated the highest in the parameter determined in vivo. CONCLUSION: The antioxidant properties showed in this solvent extractable component probably could have been the basis for the enhanced activities of antioxidant enzymes at very lower dose in the examined tissue homogenates. Therefore, T. triangulare can thereby serve as a means of Preventing some of major degenerative diseases challenging Humans.