scholarly journals The effect of conocarpan on susceptibility of Candida albicans to phagocytosis and digestion by macrophages

2019 ◽  
Vol 6 (14) ◽  
pp. 505-513
Author(s):  
Dhébora Mozena Dall'Igna ◽  
Ana Angélica Steil ◽  
Rosi Zanoni da Silva ◽  
Valdir Cechinel Filho ◽  
Alexandre Bella-Cruz

Piper solmsianum C. DC. compounds exhibit several properties, including antimicrobial activity. The aim of the present study was to investigate whether conocarpan alters Candida albicans growth or killing of the yeast by macrophages. Conocarpan showed strong activity against the yeast with minimal inhibitory concentration (MIC) of 20 µg/mL and minimal fungicidal concentration (MFC) of 30 µg/mL. Mice peritoneal cells (macrophages) were cultured for 24 and 48 hours in supplemented RPMI 1640 medium. Cellular activation was assessed by determining MTT reduction and nitric oxide production. Standardized tests were conducted to select the optimal parameters for the subsequent killing test. Results showed that conocarpan exhibited antifungal activity and that C. albicans cultivated in the presence of the compound had greater susceptibility to death by macrophages. These findings suggest that conocarpan may have potential as an antimicrobial agent for C. albicans infections, promoting macrophagic immune support by altering growth of the yeast.

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098522
Author(s):  
Xian Zhang ◽  
Fa-Lei Zhang ◽  
Xing Wu ◽  
Ke Ye ◽  
Xiao Lv ◽  
...  

A previously undescribed polyketide (1) and 3 known analogs (2-4) were obtained from cultures of the potato endophytic fungus Aspergillus carneus. The structures were elucidated on the basis of extensive nuclear magnetic resonance spectroscopic data. The absolute configuration of 1 was further determined by electronic circular dichroism and optical rotation calculations. Compounds 1-4 showed moderate antifungal activity against plant pathogens. Compounds 1, 2, and 4 inhibited nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells, with half-maximal inhibitory concentration values of 13.36, 30.16, and 51.47 µM, respectively. Compound 4 showed effective antioxidant activity.


mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jeanette Wagener ◽  
Donna M. MacCallum ◽  
Gordon D. Brown ◽  
Neil A. R. Gow

ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l -arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l -arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans -induced arginase activity with the arginase-specific substrate inhibitor N ω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l -arginine metabolism in macrophages during an infection, potentiating its own survival. IMPORTANCE The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the “conditionally essential” amino acid l -arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen Candida albicans influences l -arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of l -arginine metabolism in fungal diseases.


2017 ◽  
Vol 3 (6) ◽  
pp. 93
Author(s):  
Bayyinatul Muchtaromah ◽  
Mujahidin Ahmad ◽  
Emy Koestanti S ◽  
Yuni Ma’rifatul A ◽  
Velayati Labone A

The purpose of this study to determine the content of phytochemicals, antioxidant and antifungal properties of the combination of Acorus calamus, Curcuma mangga, and Allium sativum. This research was descriptive qualitative, extractions were done by maceration method with ethanol with 3 different combinations (C1, C2 and C3). Phytochemical test reagent included 4 kinds of test, namely: alkaloids, flavonoids, triterpenoids, saponins and tannins. As for the antioxidant test, the method used was DPPH. The concentration used at 25, 50, 100, 200, and 400 ppm. As for the antifungal test conducted on Candida albicans with Kirby-Bauer disc methods with a concentration of 100%, followed by the MIC and MBC test with a concentration of 50%, 25%, 12.5%, 6.25%, 3.13%, 1.56%, 0.78% and 0.39%. Phytochemical test results indicated the presence of the alkaloids, flavonoids and triterpenoids compounds in 3 different combinations (C1, C2 and C3). The highest antioxidant levels founded in C1 (61.75) followed by C3 (47.94) and the lowest levels founded in C2 (42.76). The antifungal test showed the inhibitory zone against C.  albicans. The highest inhibitory zone was found in C1 at 5.44 ± 1.78 mm (medium category), followed by C2 at  4.08 ± 0.86 mm (medium category), and C3 at 3.05 ± 0.23 mm (medium category). As for the minimum inhibitory concentration (MIC) value got on the concentration of 0:39% and minimum fungisidal concentration (MFC) values were at a concentration of 0.78%.    Key word: Acorus calamu, Allium sativum, Curcuma manga, Antioxidant, antifungal, Candida albicans


2009 ◽  
Vol 41 ◽  
pp. S23
Author(s):  
C. Cirillo ◽  
G. Sarnelli ◽  
A. Mango ◽  
I. Esposito ◽  
S. Masone ◽  
...  

1998 ◽  
Vol 42 (9) ◽  
pp. 2342-2346 ◽  
Author(s):  
Gail E. McElhaney-Feser ◽  
Robert E. Raulli ◽  
Ronald L. Cihlar

ABSTRACT The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was active against six species of Candida for which the MICs necessary to inhibit 50% growth (MIC50s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. kruseiwere the most susceptible to the compound. In addition to a determination of NO effects alone, the complex was utilized to investigate the synergistic potential of released NO in combination with ketoconazole, fluconazole, and miconazole. Activity was investigated in vitro against representative strains of Candida albicans, C. krusei, C. parapsilosis,C. tropicalis, C. glabrata, and C. dubliniensis. Determination of MIC50, MIC80 and MICs indicated that DETA-NO inhibits all strains tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of DETA-NO with each azole was synergistic against all strains tested as measured by fractional inhibitory concentration indices that ranged from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with similar properties may be useful in the development of new therapeutic strategies for treatment of Candida infections.


2009 ◽  
Vol 136 (5) ◽  
pp. A-4
Author(s):  
Carla Cirillo ◽  
Giovanni Sarnelli ◽  
Annamaria Mango ◽  
Ida Esposito ◽  
Rosario Cuomo

2005 ◽  
Vol 173 (4S) ◽  
pp. 137-137
Author(s):  
Michael M. Ohebshalom ◽  
Stella K. Maeng ◽  
Jie Chen ◽  
Dix P. Poppas ◽  
Diane Felsen

Sign in / Sign up

Export Citation Format

Share Document