Effect Of Palm Oil (Elias Guinensis) Leaf Standardized Extract On Progression Of Renal Dysfunction And Arterial Stiffness In Normal And High Fat Diet Fed Sprague Dawley Rats With Induced Nephrotoxicity

Saturated free fatty acids (SAFFAs) trigger their deleterious effects through inducing the intracellular inflammatory pathway related to insulin resistance. This results in a constellation of biomedical disorders known as metabolic syndrome. Gentamicin is a widely used aminoglycoside antibiotic. Its nephrotoxic action is characterized by both proximal convoluted tubules and glomerular membrane damage. The mechanism of nephrotoxicity is closely related to oxidative stress and free radicals generation

Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes

Objective: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs. Methods: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay. Results: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations. Conclusions: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions

IL35 modulation altered survival, cytokine environment and histopathological consequences during malaria infection in mice

Background: The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. Methods: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.Results: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice. Conclusion: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection

In vitro antiplasmodium and chloroquine resistance reversal effects of mangostin

Aim/Background: Chloroquine (CQ) resistance that appeared among different strains of Plasmodium falciparum is considered as the worst catastrophe in the realm of malaria chemotherapy. CQ is still the most favorable drug among other antimalarials especially in the poor endemic areas due to its high potency and cost-effectiveness. This urged the scientists to explore for other alternatives or sensitizers for CQ. Materials and Methods: In this experiment, the antiplasmodium and the CQ resistance reversing effects of mangostin were tested using the in vitro SYBRE green-1-based drug sensitivity assay and the isobologram technique, respectively. Furthermore, its safety level toward two types of mammalian cells, namely Vero cells and red blood cells (RBCs), was screened using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based drug sensitivity and the RBCs hemolysis assays, respectively. On the other hand, its effect against hemozoin formation was screened using β-hematin formation. Meanwhile, its molecular characters were determined the in silico on-line free chemi-informatic Molinspiration software for the molecular characterization as well as the standard testes for the measurement of the antioxidant effect. Results: Mangostin was moderately effective and selective toward the plasmodium so it is unsuitable to be a substituent for CQ. But it improved the sensitivity of the parasite to CQ. The molecular elucidation suggests that its CQ resistance reversal effect can be ascribed to its ability to interfere with hemozoin formation or the intravacuolar accumulation of CQ. Conclusion: Overall, the study suggests mangostin as a possible pharmacophore to develop new CQ resistance reversing agents but further studies are recommended to confirm this notion

Antiplasmodium and chloroquin resistance reversing effects of selected pure phytochemicals

Malaria is a devastating parasitic multi-organ disease afflicting millions and killing thousands of people annually. Emergence of drug resistant strains of the parasite has worsened the catastrophe of its dissemination. This urged the scientists to search for safe alternatives or drugs resistance reversing agents. This study was comprised of two sections which studied the antiplasmodium and chloroquine resistance reversing effects of eleven selected phytochemicals, namely; andrographolide, embelin, mangostin, mangoferin, harmalol, harmol, harmaline, 3-aminocoumarin, scopoletin, esculetin and umbelliferone, both in vivo and in vitro. In the in vitrostudy, Plasmodium falciparum K1 and 3D7; the chloroquine resistant and sensitive strains, were used. The compounds safety was screened through comparing their potency against the mentioned parasite with that against Vero cells (mammalian cells) or intact RBCs. SYBRE-Green -1 based drug sensitivity, MTT and RBCS stability assays were used for this purpose. Isobologram technique was used to find their effect against chloroquine resistance in Plasmodium falciparum K1. Their impact on hemozoin formation was assessed through running β-haematin formation and haem fractionation assay to elucidate their molecular mechanism. Meanwhile, RBCs osmotic fragility and merozoites invasion assays were performed to assess their impact on RBCs membrane. Finally, the in vivo anti-plasmodium and chloroquine resistance reversing effects of those; which succeeded to give a safe and productive effect, in vitrowas screened using chloroquine resistant and sensitive Plasmodium berghei infected ICR mice model. The in vitrostudy showed that all the test compounds had weak to moderate anti-plasmodium effect which turned them illegible to be implemented as conventional anti-malaria drugs. Hemozoin formation was affected only by embelin, mangostin, mangoferin and 3-aminocoumarin. Unlike the others; embelin has affected the RBCs stability profoundly so it was considered to be unsuitable for this purpose while mangostin exerted milder effect. On the other hands, simple coumarins (umbeliferon, scopoletine and esculetine) produced weak antiplasmodium effect and failed to reverse chloroquine resistance. Only andrographolide, mangostin and harmaline were chosen for the in vivo study as they were the only drugs that showed optimistic outcomes in the in vitrostudy. Their effect was tested against a chloroquine resistant clone of Plasmodium berghei that was experimentally prepared through continuous exposure of the sensitive parasite to chloroquine. The study showed that mangostin and harmaline were lethal to the plasmodium infected mice in spite of their safety against the uninfected ones and in the in vitromammalian cells culture. Meanwhile andrographolide was more potent in vivo and could have reduced the extent of the disease induced damage. In conclusion, caution should be exercised while administration of herbal products in malaria patients without complete reliance on reports generated by the in vvo studies and suggests co-administration of andrographolide with chloroquine to get an additive effec

RAGE modulatory effects on cytokines network and histopathological conditions in malarial mice

This study was aimed at investigating the involvement of Receptor for Advanced Glycation End Products (RAGE) during malaria infection and the effects of modulating RAGE on the inflammatory cytokines release and histopathological conditions of affected organs in malarial animal model. Plasmodium berghei (P. berghei) ANKA-infected ICR mice were treated with mRAGE/pAb and rmRAGE/Fc Chimera drugs from day 1 to day 4 post infection. Survival and parasitaemia levels were monitored daily. On day 5 post infection, mice were sacrificed, blood were drawn for cytokines analysis and major organs including kidney, spleen, liver, brain and lungs were extracted for histopathological analysis. RAGE levels were increased systemically during malaria infection. Positive correlation between RAGE plasma concentration and parasitaemia development was observed. Treatment with RAGE related drugs did not improve survival of malaria-infected mice. However, significant reduction on the parasitaemia levels were recorded. On the other hand, inhibition and neutralization of RAGE production during the infection significantly increased the plasma levels of interleukin (IL-4, IL-17A, IL-10 and IL-2) and reduced interferon (IFN)-γ secretion. Histopathological analysis revealed that all treated malarial mice showed a better outcome in histological assessment of affected organs (brain, liver, spleen, lungs and kidney). RAGE is involved in malaria pathogenesis and targeting RAGE could be beneficial in malaria infected host in which RAGE inhibition or neutralization increased the release of anti-inflammatory cytokines (IL-10 and IL-4) and reduce pro-inflammatory cytokine (IFNγ) which may help alleviate tissue injury and improve histopathological conditions of affected organs during the infection

Quantification of C-type lectin gene expression during hyperinfection in strongyloidiasis

Strongyloides stercoralis is the intestinal nematode in humans, and it infects millions of people worldwide but thrives in warm countries with poor sanitation conditions. Clinical manifestations of the infection may range from asymptomatic to chronic. Strongyloides cause hyperinfection syndrome and dissemination in individuals with impaired cell-mediated immunity due to its ability to proliferate within the host that may increase the mortality rate up to 87%. The diagnosis of hyperinfection syndrome is difficult to establish and entails a high level of suspicion. The objective of the present study was to measure the expression level of C-type lectin gene coding to protein biomarker candidates from the excretory/secretory (ES) products of the infective filariform larva that can be used as diagnostic indicators for early hyperinfection syndrome in strongyloidiasis. An experimental study was carried out to induce hyperinfection of L3 larvae of S. ratti in experimentally immunosuppressed Wistar rats using prednisolone, a corticosteroid immunosuppressive drug. Prednisolone treatment resulted in a significant increase in the parasitic intensities. Relative semi-quantitative real-time PCR was performed to compare the expression level of the C-type lectin’s gene between treated and nontreated groups with this drug. C-type lectin gene showed significantly higher expression levels in the treated samples. The study concluded that C-type lectin expression level was successfully measured and could be used as a diagnostic biomarker during early hyperinfection syndrome in strongyloidiasis

In vitro antiplasmodium and chloroquine resistance reversal effects of andrographolide

The emergence of drug-resistant strains of Plasmodium falciparum is the worst catastrophe that has ever confronted the dedicated efforts to eradicate malaria. This urged for searching other alternatives or sensitizers that reverse chloroquine resistance. In this experiment, the potential of andrographolide to inhibit plasmodial growth and reverse CQ resistance was tested in vitro using the SYBRE green-1-based drug sensitivity assay and isobologram technique, respectively. Its safety level toward mammalian cells was screened as well against Vero cells and RBCs using MTT-based drug sensitivity and RBC hemolysis assays, respectively. Its effect against hemozoin formation was screened using β-hematin formation and heme fractionation assays. Its molecular characters were determined using the conventional tests for the antioxidant effect measurement and the in silico molecular characterization using the online free chemi-informatic Molinspiration software. Results showed that andrographolide has a moderate antiplasmodium effect that does not entitle it to be a substituent for chloroquine. Furthermore, andrographolide ameliorated the sensitivity of the parasite to chloroquine. Besides, it showed an indirect inhibitory effect against hemozoin formation within the parasite and augmented the chloroquine-induced inhibition of hemozoin formation. The study suggests that its chloroquine resistance reversal effect may be due to inhibition of chloroquine accumulation or due to its impact on the biological activity of the parasite. Overall, this in vitro study is a clue for the reliability of andrographolide to be added with chloroquine for reversal of chloroquine resistance and tolerance, but further in vivo studies are recommended to confirm this notion. In spite of its prominent and safe in vitro and in vivo growth inhibitory effect and its in vitro chloroquine resistance reversing effect, it is inapplicable to implement it in malaria chemotherapy to substitute chloroquine or to reverse its resistance

Critical roles of IL-33/ST2 pathway in neurological disorders

Interleukin-33 (IL-33) is an IL-1 family member, which exhibits both pro- and anti-inflammatory properties solely based on the type of the disease itself. Generally, IL-33 is expressed by both endothelial and epithelial cells and mediates its function based on the interaction with various receptors, mainly with ST2 variants. IL-33 is a potent inducer for the Th2 immune response which includes defence mechanism in brain diseases. Thus, in this paper, we review the biological features of IL-33 and the critical roles of IL-33/ST2 pathway in selected neurological disorders including Alzheimer’s disease, multiple sclerosis, and malaria infection to discuss the involvement of IL-33/ST2 pathway during these brain diseases and its potential as future immunotherapeutic agents or for intervention purposes