scholarly journals Potent Enhancement of the Sensitivity of Plasmodium falciparum to Chloroquine by the Bisbenzylisoquinoline Alkaloid Cepharanthin

2000 ◽  
Vol 44 (10) ◽  
pp. 2706-2708 ◽  
Author(s):  
Kosuke Haruki ◽  
Patrick G. Bray ◽  
Minoru Ono ◽  
Stephen A. Ward
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Utility ◽  
Inflammatory Diseases ◽  
Baseline Activity ◽  
Bisbenzylisoquinoline Alkaloid ◽  
Low Toxicity

ABSTRACT Cepharanthin is a proprietary extract of Stephania cepharantha, widely used in Japan for the treatment of inflammatory diseases. Cephranthin, its component alkaloids, and the standard resistance modulator verapamil were tested againstPlasmodium falciparum for capacity to modulate sensitivity to chloroquine. Cepharanthin enhanced the activity of chloroquine against resistant clones by a factor of 15 at a concentration of only 200 nM (1.2 ng/ml). It is 50 times more potent than verapamil and 3 times more potent than the sum of its individual alkaloids. Combinations of component alkaloids acted synergistically to sensitize the parasite to chloroquine, possibly explaining the enhanced potency of Cepharanthin. Cepharanthin differed from verapamil in that it further sensitized clones that are considered to be fully susceptible, improving the baseline activity of chloroquine. Potent sensitization of parasites to chloroquine in vitro coupled with low toxicity suggests that coadministration of Cepharanthin might extend the clinical utility of chloroquine.

scholarly journals Enhanced Antiobesity Efficacy of Tryptophan Using the Nanoformulation of Dendropanax morbifera Extract Mediated with ZnO Nanoparticle

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 824
Author(s):  
Wenying You ◽  
Jong Chan Ahn ◽  
Vinothini Boopathi ◽  
Lakshminarayanan Arunkumar ◽  
Esrat Jahan Rupa ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Substantial Reduction ◽  
Synergetic Effect ◽  
Zno Nanoparticle ◽  
Zno Nps ◽  
Dendropanax Morbifera ◽  
Low Toxicity ◽  
Vitro Analysis ◽  
Oil Red O Staining

Green synthesis of metal nanoparticles from medicinal plants has provided a broad scope in biomedical research and functional food formulations due to low toxicity. Dendropanax morbifera (DM) is a versatile traditional medicine used for various inflammatory diseases due to its extensive antioxidant activity. We investigated DM as a natural capping agent for Zn2+ ions and coloaded it with tryptophan for its penetration and antiobesity behavior. DM zinc oxide nanoparticles (DM-ZnO NPs) were prepared and then entrapped with tryptophan (DM-ZnO-Try nanoemulsion (NE)) for stable formulation using the O/W nanoemulsion method. The hydrodynamic sizes measured by dynamic light scattering for DM-ZnO NPs and DM-ZnO-Try NE are about 146.26 ± 3.31 and 151.16 ± 3.59 nm, respectively. TEM and SEM reveal its morphology. In vitro analysis on both NPs and NE was non-toxic to RAW 264.7 and 3T3-L1 preadipocyte cell line. It significantly reduced the accumulated lipids through lipolysis performed at 10 ug/mL in 3T3-L1 preadipocyte cells. NE suppresses the differentiation of 3T3-L1 adipocytes and lowers triglycerides. Further, the substantial reduction of lipid content is evident with Oil Red O staining and OD measurement. In this present study, the synergetic effect of DM-ZnO NPs and tryptophan is reported, which provides a way for more detailed research on its efficacy for obesity and obesity-associated disorders.

scholarly journals Antiplasmodial Activity of Aryltetralone Lignans from Holostylis reniformis

2007 ◽  
Vol 51 (7) ◽  
pp. 2346-2350 ◽  
Author(s):  
Valter F. de Andrade-Neto ◽  
Tito da Silva ◽  
Lucia M. Xavier Lopes ◽  
Virgílio E. do Rosário ◽  
Fernando de Pilla Varotti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Line ◽  
Plasmodium Berghei ◽  
Resistant Strain ◽  
Lethal Dose ◽  
Hepatic Cell ◽  
Low Toxicity ◽  
Minimum Lethal Dose

ABSTRACT Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7′R,8S,8′S)-3′,4′-methylenedioxy-4,5-dimethoxy-2,7′-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of ≤0.32 μM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mechanism Of Action ◽  
Ribonucleotide Reductase ◽  
Antimalarial Activity ◽  
Iron Chelators ◽  
Resistant Clone ◽  
Iron Deprivation ◽  
Level Of Activity ◽  
Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

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