Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile

2021 ◽  
Vol 70 (6) ◽  
Author(s):  
Fatemeh Sharifi ◽  
Fariba Sharififar ◽  
Mostafa Pournamdari ◽  
Mehdi Ansari ◽  
Razieh Tavakoli Oliaee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gossypium Hirsutum ◽  
Murine Model ◽  
Complex Disease ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Control Group ◽  
Standard Drug ◽  
Soxhlet Apparatus

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species. Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development. Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action. Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure. Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major. Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

scholarly journals MicroRNAs Expression Induces Apoptosis of Macrophages in Response to Leishmania major (MRHO/IR/75/ER): An In-Vitro and In-Vivo Study

2020 ◽  
Author(s):  
Mostafa GHOLAMREZAEI ◽  
Soheila ROUHANI ◽  
Mehdi MOHEBALI ◽  
Samira MOHAMMADI-YEGANEH ◽  
Mostafa HAJI MOLLA HOSEINI ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Parasite Load ◽  
Lesion Size ◽  
In Vivo Studies ◽  
Raw 264.7 Cells ◽  
Control Group

Background: We aimed to investigate the effect of miR-15a mimic and inhibitor of miR-155 expression on apoptosis induction in macrophages infected with Iranian strain of Leishmania major in-vitro and in-vivo. Methods: RAW 264.7 cells were infected with L. major promastigotes (MRHO/IR/75/ER), and then were treated with miRNAs. For in-vivo experiment, BALB/c mice were inoculated with L. major promastigotes, and then they were treated with miRNAs. For evaluation of miRNA therapeutic effect, in-vitro and in-vivo studies were performed using quantitative Real-time PCR, Flow cytometry, lesion size measurement, and Limiting Dilution Assay (LDA). This study was performed in Shahid Beheshti University of Medical Sciences in 2019. Results: In-vitro results of flow cytometry showed that using miR-15a mimic, miR-155 inhibitor or both of them increased apoptosis of macrophages. In in-vivo, size of lesion increased during experiment in control groups (P<0.05) while application of both miR-155 inhibitor and miR-15a mimic inhibited the increase in the size of lesions within 6 wk of experiment (P=0.85). LDA results showed that microRNA therapy could significantly decrease parasite load in mimic or inhibitor receiving groups compared to the control group (P<0.05). Conclusion: miR-155 inhibitor and miR-15a mimic in L. major infected macrophages can induce apoptosis and reduce parasite burden. Therefore, miRNA-based therapy can be proposed as new treatment for cutaneous leishmaniasis.

scholarly journals In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  
Keyword(s):  
Survival Rate ◽  
Murine Model ◽  
Histopathological Examination ◽  
Healing Process ◽  
Bacterial Count ◽  
Treated Group ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

scholarly journals Effects of topical gel formulation of Ficus carica latex on cutaneous leishmaniasis induced by Leishmania major in BALB/c mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ali Pouryousef ◽  
Erfan Eslami ◽  
Sepehr Shahriarirad ◽  
Sina Zoghi ◽  
Mehdi Emami ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Murine Model ◽  
Leishmania Major ◽  
Considerable Effect ◽  
Ficus Carica ◽  
Control Group ◽  
Topical Gel ◽  
The Third ◽  
Mean Size ◽  
The Mean

Abstract Objectives The current study aimed to evaluate the effects of Ficus carica latex on the treatment of cutaneous leishmaniasis (CL), induced by Leishmania major. A 5% topical gel with F. carica latex was prepared. BALB/c mice were infected by inoculation of amastigotes form of L. major. Thirty BALB/c mice were divided into five groups, where the first group was treated daily, the second group twice per day, and the third group every other day with the 5% topical gel, for 3 weeks. The sizes of the lesions were measured before and during the course of treatment. Results Although the mean size of lesions in the mice group treated with the 5% F. carica gel, especially in the group receiving daily treatment, was less than the mean size of the lesions in the control group, yet, the differences was not statistically significant (p > 0.05). The findings of the current study demonstrated that the 5% F. carica latex with a 3-week course of treatment had no considerable effect in recovery or control of CL induced by L. major in the murine model. Using higher concentration of F. carica latex and with longer treatment lengths may increase its efficacy in the treatment of CL.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

scholarly journals Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Survival Rates ◽  
Control Group ◽  
P Value ◽  
Transcriptome Profile ◽  
Embryo Viability ◽  
The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

scholarly journals Phlebotomus papatasi Antimicrobial Peptides in Larvae and Females and a Gut-Specific Defensin Upregulated by Leishmania major Infection

2021 ◽  
Vol 9 (11) ◽  
pp. 2307
Author(s):  
Barbora Kykalová ◽  
Lucie Tichá ◽  
Petr Volf ◽  
Erich Loza Telleria
Keyword(s):  
Gene Expression ◽  
Antimicrobial Peptides ◽  
Leishmania Major ◽  
Larval Instar ◽  
Gut Bacteria ◽  
Sand Fly ◽  
Control Group ◽  
Phlebotomus Papatasi ◽  
Major Infection ◽  
Defensin Gene

Phlebotomus papatasi is the vector of Leishmania major, causing cutaneous leishmaniasis in the Old World. We investigated whether P. papatasi immunity genes were expressed toward L. major, commensal gut microbes, or a combination of both. We focused on sand fly transcription factors dorsal and relish and antimicrobial peptides (AMPs) attacin and defensin and assessed their relative gene expression by qPCR. Sand fly larvae were fed food with different bacterial loads. Relish and AMPs gene expressions were higher in L3 and early L4 larval instars, while bacteria 16S rRNA increased in late L4 larval instar, all fed rich-microbe food compared to the control group fed autoclaved food. Sand fly females were treated with an antibiotic cocktail to deplete gut bacteria and were experimentally infected by Leishmania. Compared to non-infected females, dorsal and defensin were upregulated at early and late infection stages, respectively. An earlier increase of defensin was observed in infected females when bacteria recolonized the gut after the removal of antibiotics. Interestingly, this defensin gene expression occurred specifically in midguts but not in other tissues of females and larvae. A gut-specific defensin gene upregulated by L. major infection, in combination with gut-bacteria, is a promising molecular target for parasite control strategies.

scholarly journals EVALUATION OF ANALGESIC ACTIVITY OF MURRAYA KOENIGII AND CORIANDRUM SATIVUM LEAVES EXTRACT IN ANIMAL MODEL.

2018 ◽  
Vol 11 (1) ◽  
pp. 328
Author(s):  
Kartik Salwe J ◽  
Mirunalini R ◽  
Jervin Mano ◽  
Manimekalai K
Keyword(s):  
Analgesic Activity ◽  
Analgesic Effect ◽  
Coriandrum Sativum ◽  
Control Group ◽  
Tail Flick ◽  
Murraya Koenigii ◽  
Hot Plate ◽  
Plate Method ◽  
Standard Drug ◽  
Soxhlet Apparatus

 Objective: The objective of the study was to investigate the analgesic activity of hydroalcoholic extract of Murraya koenigii and Coriandrum sativum leaves and compared it with standard drug in an animal model.Methods: Hydroalcoholic extracts of M. koenigii and C. sativum leaves were obtained using Soxhlet apparatus. The central analgesic property was screened by hot plate method in mice and tail flick method in rats. The pain reaction time (PRT) was measured at 30, 60, and 120 min. The peripheral analgesic activity was evaluated by acetic acid induced writhing in mice.Results: In hot plate method M. koenigii leaves extract at both doses and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. C. sativum leaves extract showed significant increase in PRT only at 60 and 120 min compared to control group. In tail flick method M. koenigii leaves extract at both doses, higher dose of C. sativum leaves extract and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. Higher dose of M. koenigii leaves extract (200 mg/kg) was comparable with standard drug tramadol in both the methods. M. koenigii leaves extract at both dose showed significant reduction in the number of writhing but C. sativum leaves extract failed to show any significant reduction in the number of writhing compared with control. Higher dose of M. koenigii leaves extract was comparable with standard drug tramadol.Conclusion: M. koenigii leaves extract showed both peripheral and central analgesic effect while C. sativum leaves extract showed only peripheral analgesic effect.

scholarly journals Expression of Inducible Nitric Oxide Synthase in Skin Lesions of Patients with American Cutaneous Leishmaniasis

2002 ◽  
Vol 70 (8) ◽  
pp. 4638-4642 ◽  
Author(s):  
Muna Qadoumi ◽  
Inge Becker ◽  
Norbert Donhauser ◽  
Martin Röllinghoff ◽  
Christian Bogdan
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Skin Lesions ◽  
And Function ◽  
Oxide Synthase

ABSTRACT Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis that the expression of iNOS was most prominent in LCL lesions with small numbers of parasites whereas lesions with a high parasite burden (LCL or DCL) contained considerably fewer iNOS-positive cells. This is the first study to suggest an antileishmanial function of iNOS in human Leishmania infections in vivo.

scholarly journals Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

2009 ◽  
Vol 53 (6) ◽  
pp. 2259-2265 ◽  
Author(s):  
Mahmoud R. Jaafari ◽  
Neda Bavarsad ◽  
Bibi Sedigheh Fazly Bazzaz ◽  
Afshin Samiei ◽  
Dina Soroush ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Mouse Skin ◽  
Parasite Burden ◽  
Lesion Size ◽  
Control Group ◽  
In Vitro Permeation ◽  
Significant Difference ◽  
Pm 10 ◽  
Franz Diffusion Cells

ABSTRACT The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 μg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 μg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.

scholarly journals In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hélène Guegan ◽  
Kevin Ory ◽  
Sorya Belaz ◽  
Aurélien Jan ◽  
Sarah Dion ◽  
...  
Keyword(s):  
Immune Response ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
Human Monocyte ◽  
Fold Increase ◽  
Control Group ◽  
End Of Treatment ◽  
Immunosuppressed Patients

Abstract Background The chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses. Methods Here, immunostimulating and leishmanicidal properties of octyl-β-d-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations. Results Both treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1β and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1β, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment. Conclusions Overall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.

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