scholarly journals Aqueous extract of Phyllanthus niruri protects against severe malaria by blocking erythrocyte invasion and modulating the host immune response

2021 ◽  
Author(s):  
Jeje Temitope Olawale ◽  
Hironori Bando ◽  
Yasuhiro Fukuda ◽  
Ibukun Emmanuel Oluwafemi ◽  
Kentaro Kato
Keyword(s):  
Aqueous Extract ◽  
Host Cells ◽  
Parasite Development ◽  
Immunomodulatory Activity ◽  
Phyllanthus Niruri ◽  
Experimental Cerebral Malaria ◽  
Erythrocyte Invasion ◽  
The Central Nervous System ◽  
Cns Dysfunction

Plasmodium falciparum parasites are the major cause of malaria across Africa. Due to the appearance of multi-drug resistant parasites, new antimalarial drugs are needed. The medicinal plant Phyllanthus niruri is being used to treat fever and other symptoms of malaria in Nigeria; however, little is known about its antimalarial mechanisms. Here, we show that aqueous extract of P. niruri (PE) has multiple antimalarial effects, including anti-parasitic and host immunomodulatory activity. We found that co-culture of P. falciparum with PE drastically reduced parasite number, but PE did not inhibit parasite development or rupture; rather, it blocked erythrocytes invasion. In addition, we identified Astragalin as one of the antimalarial compounds which are contained in PE. Moreover, we found that PE suppresses the inflammatory activity and apoptosis of immune cells (T cells) and astrocytes and neurons in the central nervous system (CNS). Furthermore, we confirmed that oral administration of PE to mice suppressed parasite growth, excessive inflammation, CNS dysfunction, and the development of experimental cerebral malaria in an in vivo murine malaria model. Our findings demonstrate that PE has multiple effects on malaria progression, targeting both parasite and host cells.

scholarly journals Sequestration of cholesterol within the host late endocytic pathway restricts liver-stage Plasmodium development

2017 ◽  
Vol 28 (6) ◽  
pp. 726-735 ◽  
Author(s):  
Wiebke Petersen ◽  
Werner Stenzel ◽  
Olivier Silvie ◽  
Judith Blanz ◽  
Paul Saftig ◽  
...  
Keyword(s):  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Parasite Development ◽  
Liver Stage ◽  
Niemann Pick ◽  
Development Analysis ◽  
Endocytic Compartments

While lysosomes are degradative compartments and one of the defenses against invading pathogens, they are also hubs of metabolic activity. Late endocytic compartments accumulate around Plasmodium berghei liver-stage parasites during development, and whether this is a host defense strategy or active recruitment by the parasites is unknown. In support of the latter hypothesis, we observed that the recruitment of host late endosomes (LEs) and lysosomes is reduced in uis4− parasites, which lack a parasitophorous vacuole membrane protein and arrest during liver-stage development. Analysis of parasite development in host cells deficient for late endosomal or lysosomal proteins revealed that the Niemann–Pick type C (NPC) proteins, which are involved in cholesterol export from LEs, and the lysosome-associated membrane proteins (LAMP) 1 and 2 are important for robust liver-stage P. berghei growth. Using the compound U18666A, which leads to cholesterol sequestration in LEs similar to that seen in NPC- and LAMP-deficient cells, we show that the restriction of parasite growth depends on cholesterol sequestration and that targeting this process can reduce parasite burden in vivo. Taken together, these data reveal that proper LE and lysosome function positively contributes to liver-stage Plasmodium development.

scholarly journals Neurons Are Host Cells for Mycobacterium tuberculosis

2014 ◽  
Vol 82 (5) ◽  
pp. 1880-1890 ◽  
Author(s):  
Philippa J. Randall ◽  
Nai-Jen Hsu ◽  
Dirk Lang ◽  
Susan Cooper ◽  
Boipelo Sebesho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mycobacterium Tuberculosis ◽  
Host Cells ◽  
Productive Infection ◽  
Target Cells ◽  
Dependent Manner ◽  
Content Type ◽  
The Central Nervous System

ABSTRACTMycobacterium tuberculosisinfection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions ofM. tuberculosiswith neuronsin vitroandin vivowere investigated. The data obtained demonstrate that neurons can act as host cells forM. tuberculosis.M. tuberculosisbacilli were internalized by murine neuronal cultured cells in a time-dependent manner after exposure, with superior uptake by HT22 cells compared to Neuro-2a cells (17.7% versus 9.8%). Internalization ofM. tuberculosisbacilli by human SK-N-SH cultured neurons suggested the clinical relevance of the findings. Moreover, primary murine hippocampus-derived neuronal cultures could similarly internalizeM. tuberculosis. InternalizedM. tuberculosisbacilli represented a productive infection with retention of bacterial viability and replicative potential, increasing 2- to 4-fold within 48 h.M. tuberculosisbacillus infection of neurons was confirmedin vivoin the brains of C57BL/6 mice after intracerebral challenge. This study, therefore, demonstrates neurons as potential new target cells forM. tuberculosiswithin the central nervous system.

scholarly journals Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy M. OʼShea ◽  
Alexander L. Wollenberg ◽  
Jae H. Kim ◽  
Yan Ao ◽  
Timothy J. Deming ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Foreign Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Peripheral Tissues ◽  
Molecular Delivery ◽  
Wound Responses ◽  
The Central Nervous System

AbstractBiomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.

scholarly journals Modulation of the Host Immune Response by Schistosome Egg-Secreted Proteins Is a Critical Avenue of Host–Parasite Communication

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 863
Author(s):  
Jack P. Carson ◽  
Geoffrey N. Gobert
Keyword(s):  
Immune Response ◽  
Current Knowledge ◽  
Host Immune Response ◽  
Egg Laying ◽  
Host Cells ◽  
Future Application ◽  
Mammalian Host ◽  
Immunomodulatory Activity ◽  
Host Immune System

During a schistosome infection, the interactions that occur between the mammalian host and the parasite change rapidly once egg laying begins. Both juvenile and adult schistosomes adapt to indefinitely avoid the host immune system. In contrast, the survival of eggs relies on quickly traversing from the host. Following the commencement of egg laying, the host immune response undergoes a shift from a type 1 helper (Th1) inflammatory response to a type 2 helper (Th2) granulomatous response. This change is driven by immunomodulatory proteins within the egg excretory/secretory products (ESPs), which interact with host cells and alter their behaviour to promote egg translocation. However, in parallel, these ESPs also provoke the development of chronic schistosomiasis pathology. Recent studies using high-throughput proteomics have begun to characterise the components of schistosome egg ESPs, particularly those of Schistosoma mansoni, S. japonicum and S. haematobium. Future application of this knowledge may lead to the identification of proteins with novel immunomodulatory activity or pathological importance. However, efforts in this area are limited by a lack of in situ or in vivo functional characterisation of these proteins. This review will highlight the current knowledge of the content and demonstrated functions of schistosome egg ESPs.

In vivo curative antimalarial effects of the aqueous extract of Entandrophragma angolense bark on Plasmodium berghei infection in mice

2019 ◽  
Author(s):  
Raceline Gounoue Kamkumo ◽  
Abel Narcisse Messi Betene ◽  
Patrick Valère Tsouh Fokou ◽  
Jean Hubert Donfack ◽  
Marius Jaures Tsakem Nangap ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Malaria Control ◽  
Plasmodium Berghei ◽  
Venous Blood ◽  
Parasite Development ◽  
Distilled Water ◽  
Biochemical Tests

Abstract Background Research for new antimalarial drugs remains a permanent quest for the control of malaria disease due to the emerging parasite resistances. The present study investigates the effects of the aqueous extract of Entandrophragma angolense (E. angolense) bark on Plasmodium. berghei-induced malaria in mice. Methods Eight weeks old female mice, were intraperitoneally infested with 200 μL of mouse blood, containing 1x106 P. berghei-infected-erythrocytes. Parasitaemia was determined using a 10% giemsa stained blood smear read under optical microscope (x100). The infected animals were randomized into 5 groups of 10 animals each and daily treated for 5 days with the plant extract at 125, 250 and 500 mg / kg. The malaria control received distilled water (10 mL / kg) while the chloroquine control was treated with 10 mg / kg of chloroquine. A group of healthy mice was used as the normal control and received distilled water. Body weight, parasitaemia and survival time were monitored daily during treatment and follow up periods. Five animals from each group were sacrificed under anaesthesia at the end of treatment (d8) and after the follow up period (d28). Venous blood was used for haematological and biochemical tests. Organs (liver, kidneys and spleen) were also collected for biochemical and histological analyses. Results Administration of the aqueous extract of E. angolense bark to infected mice significantly inhibited parasite development (p < 0.001) with ED50 estimated at 25.32 mg / kg. The extract prevented animal from death, body weight loss, anaemia, leucocytosis, high transaminases (ALT and AST), high bilirubin, creatinine and MDA levels, oxidative stress and anatomical alteration in organs as compared to the malaria control. Conclusions The E. angolense bark possesses antimalarial properties, supporting its use in traditional medicine to treat malaria.

scholarly journals Foreign body responses in central nervous system mimic natural wound responses and alter biomaterial functions

2019 ◽  
Author(s):  
Timothy M. O’Shea ◽  
Alexander L. Wollenberg ◽  
Jae H. Kim ◽  
Yan Ao ◽  
Timothy J. Deming ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Foreign Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Peripheral Tissues ◽  
Physiochemical Properties ◽  
Wound Responses ◽  
The Central Nervous System

AbstractBiomaterials hold promise for diverse therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs)in vivo, or about how such responses influence biomaterial function. Here, we probed these factors using a platform of injectable hydrogels readily modified to present interfaces with different representative physiochemical properties to host cells. We show that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. Moreover, we found that the nature and intensity of CNS FBRs are determined by definable properties. For example, cationic, anionic or nonionic interfaces with CNS cells elicit quantifiably different levels of stromal cell infiltration, inflammation, neural damage and amyloid production. The nature and intensity of FBRs significantly influenced hydrogel resorption and molecular delivery functions. These results characterize specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.

In vitro and in vivo immunomodulatory activity of aqueous extract of Clerodendrum serratum L. roots

Planta Medica ◽  
2006 ◽  
Vol 72 (11) ◽  
Author(s):  
AR Juvekar ◽  
RS Nachankar ◽  
RC Hole ◽  
AS Wakade ◽  
MP Kulkarni ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Immunomodulatory Activity

Anti-tumor and immunomodulatory activity of the aqueous extract of Sarcodon imbricatus in vitro and in vivo

2020 ◽  
Vol 11 (1) ◽  
pp. 1110-1121 ◽  
Author(s):  
Xupeng Tan ◽  
Wang Chen ◽  
Chunwei Jiao ◽  
Huijia Liang ◽  
Hao Yun ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Nutritional Value ◽  
Edible Mushroom ◽  
Immunomodulatory Activity ◽  
Wild Mushrooms

Sarcodon imbricatus (S. imbricatus), a well-known edible mushroom, is one of the most commonly consumed wild mushrooms in China because of its nutritional value.

scholarly journals Potential immunomodulatory activity of Phyllanthus niruri aqueous extract on macrophage infected with Streptococcus sanguinis

2018 ◽  
Vol 51 (3) ◽  
pp. 124
Author(s):  
Suryani Hutomo ◽  
Denise Uatami Putri ◽  
Yanti Ivana Suryanto ◽  
Heni Susilowati
Keyword(s):  
Cell Proliferation ◽  
Aqueous Extract ◽  
Anaerobic Bacteria ◽  
Bacterial Suspension ◽  
Immunomodulatory Activity ◽  
No Production ◽  
Phyllanthus Niruri ◽  
Streptococcus Sanguinis ◽  
Nitric Oxide Release ◽  
Significant Difference

Background: Streptococcus sanguinis is an oral commensal bacterium commonly found in periodontal lesions and deep abscesses that are usually dominated by anaerobic bacteria. As an important causative agent of systemic diseases, and with the increasingly numerous cases of antimicrobial resistance, some means of modulating the immune response to bacterial infection is thus necessary. Phyllanthus niruri Linn is widely used as a medicinal herb to both prevent and treat disease and demonstrates immunomodulatory properties. Purpose: This study aimed to observe the potential for aqueous extract of Phylanthus niruri to induce macrophage proliferation and NO production following S. sanguinis infection. Methods: Macrophages were isolated from the peripheral blood of healthy subjects, stimulated with P. niruri aqueous extract in graded doses and infected with S. sanguinis ATCC 10556 bacterial suspension. Cell proliferation and nitric oxide release was observed at 24 and 48 hours to determine macrophage activities. Results: NO production and cell proliferation started to increase upon 50 and 100µg/ml P niruri respective stimulation. Statistical analysis using One-way Anova demonstrated a significant difference of cell proliferation after stimulation with P. niruri aqueous extract at various doses (p<0.05). Conclusion: P. niruri aqueous extract induced macrophage proliferation and NO secretion upon S sanguinis infection, showing potential antibacterial and immunomodulatory activities. At the same concentrations, NO production and macrophage were higher at 48 hours than at 24 hours.

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