Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance

In silico prediction of new antimicrobial peptides and proteins as druggable targets towards alternative anti-schistosomal therapy

Schistosomiasis is a debilitating disease caused by a parasitic flatworm found in fresh- water. With the exponential increase in prevalence, Praziquantel (PZQ) remains the only effective treatment drug, however, resistance to PZQ has been reported recently. There- fore, it is imperative to develop effective alternative anti-schistosomal compounds using bioinformatics-based tools utilizing the broad-spectrum therapeutic capabilities of antimi- crobial peptides (AMPs). AMPs are essential components of the innate immune system and are responsible for complete destruction and immunomodulatory effects in the host defence against pathogens. Here, Hidden Markov model was used to identify six anti- microbial peptides (TAK1–TAK6) with potential anti-schistosomal capabilities. Also, glyco- syltransferase and axonemal dynein intermediate chain protein were identified as impor- tant druggable Schistosome proteins. The 3-D structures of the AMPs and proteins were modelled using I-TASSER and it was shown that the six putative anti-schistosomal AMPs and the two proteins had low C-score, possibly due to lack of available templates for their modelling. Finally, PatchDock was employed to ascertain the interaction between the schis- tosome proteins and the putative AMPs

POTENTIALS OF SOME PLANT-DERIVED FOODS IN THE MANAGEMENT OF DIABETES AND ASSOCIATED COMPLICATIONS.

Background and Objective: Diabetes is an insidious as well as a debilitating metabolic disease with variety of causes that could lead to severe complications in multiple organs within the body system. There has been no documented scientific evidence as regards total cure of this complex chronic disease; therefore, it demands a lifelong management. This has necessitated the recent evaluation of several plant derived foods as costeffective alternatives in the management of diabetes and its associated complication. Materials and Methods: This review is based on integration of information from multi-databases after a comprehensive literature search on the various plant derived foods that have been reported to have shown a certain degree of amelioration in the management of diabetes and diabetic complications. Result and Discussion: Published reports suggest that oxidative stress primarily mediated by uncontrolled hyperglycemia play a pivotal role in the pathogenesis of diabetes and its associated complications. Therefore, various plant-derived foods are believed to delay, prevent or manage diabetes and its associated complications using different mechanisms which could be established through their potential to increase insulin sensitivity, free radicals scavenging abilities, hypolipidemic, hypoglycaemic, hypocholesterolemic, antioxidative, anti-inflammatory and inhibition of α-amylase and α-glucosidase activities. Conclusion: Based on the evidence presented in this review, plant-derived foods possess bioactive constituents believed to be rich in antioxidants and proteins which may be responsible for their mode of actions; we propose that Cucuma longa (curcumin), Garcinia kola (kolaviron), Telfairia occidentalis and Parkia biglobosa be explored in the management of diabetes and its associated complications due to their outstanding beneficial effects

Comparative Analyses And Structural Insights Of The Novel Cytochrome P450 Fusion Protein Family CYP5619 In Oomycetes

Published ArticlePhylogenetic and structural analysis of P450 proteins fused to peroxidase/dioxygenase has not been reported yet. We present phylogenetic and in silico structural analysis of the novel P450 fusion family CYP5619 from the deadliest fish pathogenic oomycete, Saprolegnia diclina. Data-mining and annotation of CYP5619 members revealed their unique presence in oomycetes. CYP5619 members have the highest number of conserved amino acids among eukaryotic P450s. The highest number of conserved amino acids (78%) occurred in the peroxidase/dioxygenase domain compared to the P450 domain (22%). In silico structural analysis using a high-quality CYP5619A1 model revealed that CYP5619A1 has characteristic P450 structural motifs including EXXR and CXG. However, the heme-binding domain (CXG) in CYP5619 members was found to be highly degenerated. The in silico substrate binding pattern revealed that CYP5619A1 have a high affinity to medium chain fatty acids. Interestingly, the controlling agent of S. diclina malachite green was predicted to have the highest binding affinity, along with linoleic acid. However, unlike fatty acids, none of the active site amino acids formed hydrogen bonds with malachite green. The study’s results will pave the way for assessing CYP5619A1’s role in S. diclina physiology, including the nature of malachite green binding

In vitro and in vivo hepatotoxicity study of Afriplex™ GRT through an inflammatory response

BACKGROUND : The focus on traditional and complementary medicine for supplementation and treatment of diseases is high. Aspalathus linearis commonly known as Rooibos showed several beneficial effects, this led to the standardized production of a pharmaceutical grade green rooibos extract (Afriplex TM GRT) with enhanced polyphenolic content. The aim of this study was to assess toxicity of Afriplex TM GRT in HepG2/C3A cells and Sprague Dawley rats. METHODS : Afriplex GRT TM (0.1, 1, 10, 100, or 1000 μg/mL) in DMSO was added to the media to the final 0.01% DMSO for treatment of HepG2/C3A for 1, 24 and 48 hrs followed by MTT and ATP assays. Sprague Dawley rats were grouped to Control, Afriplex TM GRT treated (10, 100 and 300 mg/kg); and acute (24hrs tetrachloromethane (CCl 4) injected hepatotoxicity control). Serum biochemistry, histology and Western blot analysis on liver were performed. RESULTS : Afriplex TM GRT significantly reduced cell viability at 100 and 1000μg/mL after 48 hrs. Acute CCl 4 treatment significantly increased serum alanine aminotransferase in rats. The highest extract treatment of 300 mg/kg significantly elevated aspartate amino transferase. There was severe macro vesicular in the CCl 4 group whereas mild to moderate micro vesicular steatosis was seen in the 300 mg/kg Afriplex TM GRT treated group. Highest extract treatment significantly reduced NFkB expression on Western blot analysis. CONCLUSION : The beneficial effects of pharmaceutical grade Afriplex GRT TM are concentration and dosage based. Afriplex GRT TM exerts its beneficial effects via NFkB as demonstrated by the dose dependent reduction of NFkB on Western blot analysis. More work need to be done to explore the exact mechanism that occurs in the NFkB pathway.The SAMRC Research Capacity Development and the National Research Foundation for the Thuthuka Grant.https://www.elsevier.com/locate/toxrephj2022BiochemistryGeneticsMicrobiology and Plant Patholog

Synthesis and cytotoxic evaluation of gum arabic surface modified cadmium telluride quantum dots

Water-soluble cadmium telluride (CdTe) quantum dots (QDs) were capped with gum Arabic (GA) is a non-toxic, water-soluble glycoprotein polymer commonly used in the food and pharmaceutical industries. The GA was used to stabilise cadmium telluride quantum dots (GA-QDs) and provides functional groups for other molecules such as nucleic acids, peptides and antibodies to be attached to the QDs for biological and biomedical applications. In this study, the GA was used to cap and stabilise QDs using two different methods. These QDs were characterised using Ultraviolet-visible (UV-vis) and Photoluminescence (PL) spectroscopy, X-powder ray diffraction (XRD), High-resolution transmission electron microscopy, zeta potential and particle size distributions. Cytotoxicity of these QDs was also investigated using four different human cell lines; HeLa, MCF-7, PC-3 and U87 cancer cells

Ocimum gratissimumLinn. Leaves reducethe key enzymes activities relevant toerectile dysfunction in isolated penile andtesticular tissues of rats

Background:Ocimum gratissimumL. is a medicinal plant widely grown in tropical and subtropical regions with theleafdecoctionusuallytakeninfolkmedicinetoenhanceerectileperformanceinmenalthoughtheprobablemechanism of actions remains undetermined. This study examined the inhibitory potentials ofOcimum gratissimumleaves on some key enzymes associated with erectile dysfunction in penile and testicular tissues of the rat.Methods:Inhibitory effect of aqueous extract (1:10w/v)ofO. gratissimumleaves on the activities of phosphodiesterase-5(PDE-5), arginase, angiotensin I–converting enzyme (ACE), and acetylcholinesterase (AChE) in penile and testicular tissueswere assessed. Also, the extract was investigated for ferric reducing antioxidant property(FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging abilities.Results:The extract showed higher PDE-5 (IC50=43.19μg/mL), ACE (IC50= 44.23μg/mL), AChE (IC50= 55.51μg/mL) andarginase (IC50= 46.12μg/mL) inhibitory activity in thepeniletissuethanPDE-5(IC50= 44.67μg/mL), ACE (IC50= 53.99μg/mL), AChE (IC50= 60.03μg/mL) and arginase (IC50=49.12μg/mL) inhibitory activity in the testicular tissue homogenate.Furthermore, the extract scavenged free radicals and in a dose-dependent manner.Conclusion:Theenzymeactivitiesdisplayedmightbeassociatedwiththebioactivecompoundspresentintheextractwhich could possibly explain its use in the management of erectile dysfunction (ED)

Immunological and Biochemical Interplay between Cytokines, Oxidative Stress and Schistosomiasis

The host–parasite schistosome relationship relies heavily on the interplay between the strategies imposed by the schistosome worm and the defense mechanisms the host uses to counter the line of attack of the parasite. The ultimate goal of the schistosome parasite entails five important steps: evade elimination tactics, survive within the human host, develop into adult forms, propagate in large numbers, and transmit from one host to the next. The aim of the parasitized host on the other hand is either to cure or limit infection. Therefore, it is a battle between two conflicting aspirations. From the host’s standpoint, infection accompanies a plethora of immunological consequences; some are set in place to defend the host, while most end up promoting chronic disease, which ultimately crosses paths with oxidative stress and cancer. Understanding these networks provides attractive opportunities for anti-schistosome therapeutic development. Hence, this review discusses the mechanisms by which schistosomes modulate the human immune response with ultimate links to oxidative stress and genetic instability

Parasite Survival and Disease Persistence in Cystic Fibrosis, Schistosomiasis and Pathogenic Bacterial Diseases: A Role for Universal Stress Proteins?

Universal stress proteins (USPs) were originally discovered in Escherichia coli over two decades ago and since then their presence has been detected in various organisms that include plants, archaea, metazoans, and bacteria. As their name suggests, they function in a series of various cellular responses in both abiotic and biotic stressful conditions such as oxidative stress, exposure to DNA damaging agents, nutrient starvation, high temperature and acidic stress, among others. Although a highly conserved group of proteins, the molecular and biochemical aspects of their functions are largely evasive. This is concerning, as it was observed that USPs act as essential contributors to the survival/persistence of various infectious pathogens. Their ubiquitous nature in various organisms, as well as their augmentation during conditions of stress, is a clear indication of their direct or indirect importance in providing resilience against such conditions. This paper seeks to clarify what has already been reported in the literature on the proposed mechanism of action of USPs in pathogenic organisms

Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer

Heat shock proteins (HSPs) play cytoprotective activities under pathological conditions through the initiation of protein folding, repair, refolding of misfolded peptides, and possible degradation of irreparable proteins. Excessive apoptosis, resulting from increased reactive oxygen species (ROS) cellular levels and subsequent amplified inflammatory reactions, is well known in the pathogenesis and progression of several human inflammatory diseases (HIDs) and cancer. Under normal physiological conditions, ROS levels and inflammatory reactions are kept in check for the cellular benefits of fighting off infectious agents through antioxidant mechanisms; however, this balance can be disrupted under pathological conditions, thus leading to oxidative stress and massive cellular destruction. Therefore, it becomes apparent that the interplay between oxidant-apoptosis-inflammation is critical in the dysfunction of the antioxidant system and, most importantly, in the progression of HIDs. Hence, there is a need to maintain careful balance between the oxidant-antioxidant inflammatory status in the human body. HSPs are known to modulate the effects of inflammation cascades leading to the endogenous generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of HIDs and cancer. We propose that careful induction of HSPs in HIDs and cancer, especially prior to inflammation, will provide good therapeutics in the management and treatment of HIDs and cancer