Trévo abrogates Lead Acetate Neurotoxicity in Male Wistar Rats viz Antiamyloidogenesis, Antiglutaminergic, and Anticholinesterase Activities.

Background: Exposure to lead has been linked to biochemical changes similar to those patients suffering from Alzheimer's disease. Trévo is a phytonutrient-rich product with antiaging and antioxidant properties. Purpose: To investigate the neuroprotective activity of trévo against lead-induced biochemical changes in male Wistar rats. Methods: The study involves 35 animals that were randomly divided into five groups of seven rats each. Group I (Control): Orally administered distilled water; Group II (Induced): Administered 15 mg/kg of lead acetate (PbA) intraperitoneally; Group III (Treatment group): Orally administered 2 mL/kg of trévo for two days before co-administration with PbA for 12 consecutive days; Group IV (Treatment group): Orally administered 5 mL/kg of trévo for two days prior to coadministration with PbA for 12 consecutive days; Group V: Orally administered 5 mL/kg of trévo for 14 consecutive days. Animals were anesthetized with diether and the brain excised and processed for the following biochemical assays: Malonedialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GT), acetylcholinesterase (AChE), beta-amyloid, glutamate, Na+/K+ ATPase, and glutamate dehydrogenase (GD). Results: PbA caused significant oxidative stress (increased MDA concentration, decreased GSH concentration, suppressed the activity of CAT, SOD), decreased GT activity, increased activity of AChE, increased the concentration of beta-amyloid, and caused glutamate excitotoxicity (increased concentration of glutamate, decreased activity of Na+/K+ ATPase, and GD) in rat brains. Treatment with trévo at the two different doses significantly prevented oxidative damage, beta-amyloid aggregation, glutamate excitotoxicity, and acetylcholine breakdown induced by lead acetate. Conclusion: Our findings added to the reported pharmacological activity of trévo and supported the antiaging potential of trévo.

Hydroethanolic Extracts of Senna alata Leaves Possess Antimalarial Effects and Reverses Haematological and Biochemical Pertubation in Plasmodium berghei-infected Mice.

The current work investigated the chemical profile, antimalarial potential and capacity of hydroethanolic Senna alata extract (SAE) to reverse hematological and biochemical pertubation in Plasmodium berghei infected mice. Results of the phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, tannins, terpenoids, saponins, steroids and cardiac glycosides. Total phenolic and flavonoid content was estimated to be 45.29 ± 2.34 mg GAE/g and 25.22 ± 2.26 mg QE/g respectively. In vitro analysis of the extract also confirmed its antioxidant property. Results of the test for prophylaxis of P. berghei indicated that SAE suppressed parasitemia significantly in treated groups in a dose dependent manner when compared with negative control group. Similarly, SAE improved the mean survival time (MST) and packed cell volume (PCV) of infected mice. The test for curative effect showed that SAE significantly suppressed parasitemia to 4.50 ± 1.05% compared to untreated group 29.83 ± 3.49%. Results of liver and kidney functions indices of treated animals indicated that whereas infection with P. berghei caused increase in the levels of AST, ALT, ALP, urea and creatinine, treatment with SAE significantly reversed the perturbation. Similarly, infected mice were dyslipidemic with concomitant increased activity of HMG CoA reductase and decreased activity of antioxidant enzymes with increase in lipid peroxides levels. However, these alterations were significantly reversed by administration of SAE. Results of this study shows that Senna alata possess antimalarial activity and therefore justify the traditional use of plant for the treatment of malaria.

Evaluation of chemical composition, in vitro antioxidant, and antidiabetic activities of solvent extracts of Irvingia gabonensis leaves.

Irvingia gabonensis commonly referred to as wild mango or ogbono is a tropical plant with both nutritional and medicinal uses. The present study was designed to evaluate the chemical composition, in vitro antioxidant activity, and inhibitory activity of carbohydrate hydrolyzing enzymes related to diabetes by different extracts of the plant. From the results of the study, Total Phenolic Content (TPC) was highest in the aqueous and ethanol extracts (367.30 ± 00 mg/100g GAE) compared to the chloroform and n-hexane extracts whereas the Total Flavonoid Content (TFC) was highest (230.69 ± 0.18 mg/100g QE) in the ethanol extract. Analysis of the in vitro antioxidant activity showed that the ethanol extract also possessed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50: 21.42 ± 0.05 µg/ml) and hydroxyl radical scavenging activity (81.43 ± 0.11%) compared to other solvent extracts. The aqueous extract had the highest (23.91 ± 0.04 mM Fe++ equivalent) ferric antioxidant reducing power (FRAP). However, the antioxidant activity of the extracts was significantly lower than that of the reference compounds used for the study (butylated hydroxytoluene and Gallic acid). In vitro antidiabetic activity of the extracts was measured based on inhibition of α-amylase and α-glucosidase. The aqueous extract had the highest α-amylase and α-glucosidase inhibitory activity followed by the ethanol extract compared to the chloroform and n-hexane extracts. The inhibitory activity of the aqueous extract against both enzymes was higher compared to the reference compound Acarbose. Gas Chromatography-Mass Spectrometry analysis of the extracts revealed the presence of chemical constituents including fatty acids, vitamin, phytosterols, aromatic compounds, glycosides. The interaction of these compounds with α-amylase and α-glucosidase was evaluated in silico by molecular docking. Phytosterols namely, campesterol, stimasterol and γ-sitosterol had the best binding affinities to α-amylase and α-glucosidase. In conclusion, the results of this study revealed that the aqueous and ethanol extracts of Irvingia gabonensis had the highest phenolic content, antioxidant activity, and in vitro antidiabetic activity. These results offer a scientific explanation for the mode of preparation and traditional use of the plant in the treatment of diabetes.

Maternal Transmission of SARS-CoV-2: Safety of Breastfeeding in Infants Born to Infected Mothers.

Coronavirus disease 2019 (COVID-19) is a recent epidemic disease caused by severe acute respiratory syndrome virus type 2 (SARS-CoV-2). In pregnancy, SARS-Cov-2 infection creates additional alarm due to concerns regarding the potential for transmission from the mother to the baby during both the antenatal and postpartum times. In general, breastfeeding is seldom disallowed because of infection of the mother. However, there are few exceptions with regards to certain infectious organisms with established transmission evidence from mother to infant and the link of infection of a newborn with significant morbidity and mortality. It is confirmed that pregnant women can become infected with SARS-CoV-2, although the debate on the possible vertical transmission of SARS-CoV-2 infection during pregnancy is still open. In this regard, the literature is still poor. On the contrary, the information on the safety of breastfeeding even during infections seems reassuring when the mother takes the necessary precautions. However, there are still answered questions regarding the precautions to be taken during breastfeeding by COVID-19 patients. This paper reviews the existing answers to these and many other questions. This review therefore presents a summary of the present-day understanding of infection with SARS-CoV-2 and discusses the answers around the maternal transmission of COVID-19 and the potential threat of breastfeeding to babies born to infected pregnant mothers. In conclusion, intrauterine transmission of SARS-CoV-2 infection is less likely to occur during pregnancy. Most studies suggest that COVID-19 is not transmitted through breast milk. Correspondingly, COVID-19-infected neonates might acquire the infection via the respiratory route because of the postnatal contact with the mother rather than during the prenatal period. International organizations encourage breastfeeding regardless of the COVID-19 status of the mother or child as long as proper hygienic and safety measures are adhered to so as to minimize the chance of infant infection by droplets and direct contact with the infected mother. Pasteurized donor human milk or infant formula as supplemental feeding can be quite beneficial in the case of mother-infant separation till breastfeeding is safe.

Evaluation of Antimalarial Potential of Extracts from Alstonia boonei and Carica papaya in Plasmodium berghei-Infected Mice.

Extracts of Alstonia boonei and Carica papaya are used in herbal medicine for the treatment of malaria. This work investigated the phytochemical, antioxidant, and antimalarial effects of hydromethanolic extracts of Alstonia boonei and Carica papaya. A four-day chemosuppressive test was conducted to assess the ability of the extracts to prevent establishment of infection. Three doses of the extracts were administered-100, 200, and 400 mg/kg bw-prior to Plasmodium berghei challenge. Change in body weight, parasitemia, packed cell volume (PCV), and mean survival time was determined. A three-day curative test was also carried out on Plasmodium berghei-infected mice to determine the effects of the plant extracts (200 mg/kg bw) on parasitemia and biochemical indices of liver and kidney functions, lipid metabolism, and oxidative stress. The study revealed that the extracts possessed phenolic compounds (34.13 ± 1.90 mg GAE/g for Alstonia boonei and 27.99 ± 1.46 mg GAE/g for Carica papaya) and flavonoids (19.47 ± 1.89 mg QE/g for Alstonia boonei and 18.24 ± 1.36 mg QE/g for Carica papaya). In vitro antioxidant activity measured as total antioxidant power, total reducing power, and DPPH radical scavenging activity showed that the extracts possessed higher antioxidant activity than the reference compounds. The outcome of the chemosuppressive test revealed that whereas Plasmodium berghei-infected mice had high parasitemia, decreased mean survival time, exhibited loss of weight, and had low PCV, treatment with the extracts reversed the effects in a concentration-dependent manner. Similarly, the curative test revealed that the extracts significantly suppressed parasitemia compared with the malaria negative control group. This was mirrored by reversal of indices of hepatic toxicity (AST, ALT, and ALP levels), nephropathy (urea and creatinine levels), oxidative stress (SOD, CAT, GPx, GSH, and lipid peroxides), and dyslipidemia (TC, HDL, and TG levels and HMG-CoA reductase activity) in infected but treated mice compared with negative control. Put together, the results of this study demonstrate that the extracts of Alstonia boonei and Carica papaya possess antimalarial properties and are able to ameliorate metabolic dysregulations that characterize Plasmodium berghei infection. The phytoconstituents in these extracts are believed to be responsible for the pharmacological activity reported in this study.

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective.

In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking.

Postprandial hyperglycemia has orchestrated untimely death among diabetic patients over the decades and regulation of α-amylase activity is now becoming a promising management option for type 2 diabetes. The present study investigated the binding interactions of three structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase to ascertain the affinity of the ligands for α-amylase using spectroscopic and molecular docking methods. The ligands were characterized using 1H and 31P NMR spectroscopy and CHN analysis. Diselenoimidodiphosphinate ligand (DY300), dithioimidodiphosphinate ligand (DY301), and thioselenoimidodiphosphinate ligand (DY302) quenched the intrinsic fluorescence intensity of α-amylase via a static quenching mechanism with bimolecular quenching constant (Kq) values in the order of x1011 M-1s-1, indicating formation of enzyme-ligand complexes. A binding stoichiometry of n≈1 was observed for α-amylase, with high binding constants (Ka). α-Amylase inhibition was as follow: Acarbose > DY301>DY300>DY302. Values of thermodynamic parameters obtained at temperatures investigated (298, 304 and 310 K) revealed spontaneous complex formation (ΔG<0) between the ligands and α-amylase; the main driving forces were hydrophobic interactions (with DY300, DY301, except DY302). UV-visible spectroscopy and Förster resonance energy transfer (FRET) affirmed change in enzyme conformation and binding occurrence. Molecular docking revealed ligands interaction with α-amylase via some key catalytic site amino acid residues (Asp197, Glu233 and Asp300). DY301 perhaps showed highest α-amylase inhibition (IC50, 268.11 ±â€¯0.74 µM) due to its moderately high affinity and composition of two sulphide bonds unlike the others. This study might provide theoretical basis for development of novel α-amylase inhibitors from dichalcogenoimidodiphosphinate ligands for management of postprandial hyperglycemia.

A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy.

Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE(-/-) mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane ß-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.