scholarly journals Maca against Echinococcosis?—A Reverse Approach from Patient to In Vitro Testing

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1335
Author(s):  
Tanja Karpstein ◽  
Sheena Chaudhry ◽  
Solange Bresson-Hadni ◽  
Michael Hayoz ◽  
Ghalia Boubaker ◽  
...  

Drug-based treatment of alveolar echinococcosis (AE) with benzimidazoles is in most cases non-curative, thus has to be taken lifelong. Here, we report on a 56-year-old male AE patient who received standard benzimidazole treatment and biliary plastic stents, and additionally self-medicated himself with the Peruvian plant extract Maca (Lepidium meyenii). After 42 months, viable parasite tissue had disappeared. Based on this striking observation, the anti-echinococcal activity of Maca was investigated in vitro and in mice experimentally infected with Echinococcus multilocularis metacestodes. Albendazole (ABZ)-treated mice and mice treated with an ABZ+Maca combination exhibited a significantly reduced parasite burden compared to untreated or Maca-treated mice. As shown by a newly established UHPLC-MS/MS-based measurement of ABZ-metabolites, the presence of Maca during the treatment did not alter ABZ plasma levels. In vitro assays corroborated these findings, as exposure to Maca had no notable effect on E. multilocularis metacestodes, and in cultures of germinal layer cells, possibly unspecific, cytotoxic effects of Maca were observed. However, in the combined treatments, Maca inhibited the activity of ABZ in vitro. While Maca had no direct anti-parasitic activity, it induced in vitro proliferation of murine spleen cells, suggesting that immunomodulatory properties could have contributed to the curative effect seen in the patient.

2021 ◽  
Vol 11 (13) ◽  
pp. 5823
Author(s):  
Alexia Barbarossa ◽  
Alessia Catalano ◽  
Jessica Ceramella ◽  
Alessia Carocci ◽  
Domenico Iacopetta ◽  
...  

Thalidomide is an old well-known drug that is still of clinical interest, despite its teratogenic activities, due to its antiangiogenic and immunomodulatory properties. Therefore, efforts to design safer and effective thalidomide analogs are continually ongoing. Research studies on thalidomide analogs have revealed that the phthalimide ring system is an essential pharmacophoric fragment; thus, many phthalimidic compounds have been synthesized and evaluated as anticancer drug candidates. In this study, a panel of selected in vitro assays, performed on a small series of phthalimide derivatives, allowed us to characterize compound 2k as a good anticancer agent, acting on A2058 melanoma cell line, which causes cell death by apoptosis due to its capability to inhibit tubulin polymerization. The obtained data were confirmed by in silico assays. No cytotoxic effects on normal cells have been detected for this compound that proves to be a valid candidate for further investigations to achieve new insights on possible mechanism of action of this class of compounds as anticancer drugs.


Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 525
Author(s):  
Laerte Marlon Conceição dos Santos ◽  
Eduardo Santos da Silva ◽  
Fabricia Oliveira Oliveira ◽  
Leticia de Alencar Pereira Rodrigues ◽  
Paulo Roberto Freitas Neves ◽  
...  

O3 dissolved in water (or ozonized water) has been considered a potent antimicrobial agent, and this study aimed to test this through microbiological and in vitro assays. The stability of O3 was accessed following modifications of the physicochemical parameters of water, such as the temperature and pH, with or without buffering. Three concentrations of O3 (0.4, 0.6, and 0.8 ppm) dissolved in water were tested against different microorganisms, and an analysis of the cytotoxic effects was also conducted using the human ear fibroblast cell line (Hfib). Under the physicochemical conditions of 4 °C and pH 5, O3 remained the most stable and concentrated compared to pH 7 and water at 25 °C. Exposure to ozonized water resulted in high mortality rates for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, and Candida albicans. Scanning electron micrograph images indicate that the effects on osmotic stability due to cell wall lysis might be one of the killing mechanisms of ozonized water. The biocidal agent was biocompatible and presented no cytotoxic effect against Hfib cells. Therefore, due to its cytocompatibility and biocidal action, ozonized water can be considered a viable alternative for microbial control, being possible, for example, its use in disinfection processes.


1989 ◽  
Vol 18 (8) ◽  
pp. 1007-1017 ◽  
Author(s):  
W. K. Dowjat ◽  
P. Zhou ◽  
L. J. Quackenbush ◽  
T. Gorzynski ◽  
M. B. Zoleski

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 7-15
Author(s):  
M Bala ◽  
◽  
M. Kumar ◽  
M. Chandel ◽  
N. Sharma ◽  
...  

The present work deals with evaluation of bioactivities of Anthocephalus cadamba unripe fruits and their phytochemical analysis. The 80% methanol extract of unripe fruits (MACF) was tested for antioxidant potential using various in vitro assays, antimutagenicity using TA98 and TA100 tester strains of Salmonella typhimurium in Ames assay and cytotoxicity using MTT assay. MACF scavenged DPPH and nitric oxide radicals with an IC50 of 313.18 and 512.08 μg/mL, respectively. MACF extract inhibited the mutagenicity of sodium azide more effectively than that of 4-nitro-o-phenylenediamine (NPD) and was found to be desmutagenic in nature. MACF extract dose-dependently inhibited the growth of colon (COLO 205) cancer cells. HPLC analysis revealed the presence of copious amounts of catechin, gallic acid and kaempferol in the MACF extract. Overall, MACF extract of A. cadamba fruits demonstrated potent antioxidant, antimutagenic and anticancer properties which can be exploited as functional foods because of their health benefits.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4942-4942
Author(s):  
Pablo E Morande ◽  
Samanta Zanetti ◽  
Mercedes Borge ◽  
Paula Nannini ◽  
Carolina Jancic ◽  
...  

Abstract Abstract 4942 Plitidepsin (Aplidin®) is a marine-derived cyclic depsipeptide with strong cytotoxic effects against a variety of cancer cell types. It is currently in Phase II/III clinical trials for solid and hematologic malignancies. We evaluated the cytotoxic effects of Plitidepsin on lymphoid and monocyte cells from healthy donors and analysed the mechanisms involved. We found that monocyte cells showed a markedly higher sensitivity to Plitidepsin compared to lymphoid subsets as determined by incorporation of 7-AAD and flow cytometry analysis. Plitidepsin induced a dose- and time-dependent cell death on freshly isolated monocytes (7-AAD+ cells at 24 h: control: 3±1% versus Plitidepsin 10 nM: 47±5%, mean±SEM, n=6) and on macrophages (5±2 vs 49±3, n=5) and dendritic cells (4±1 vs 21±4, n=5) differentiated in vitro. By contrast, resting or mitogen-activated lymphocytes were not affected by Plitidepsin at 10 nM. The mechanisms of induced cell death in monocytes involved the early exposure of phosphatidylserine to the outer leaflet of plasma membrane, activation of caspase-3 and subsequent PARP fragmentation, indicative of death via apoptosis. Incubation of monocytes with Plitidepsin (10 or 100 nM) for 30 minuntes induced ROS production. On the other hand, the cytotoxic effect of Plitidepsin was significantly diminished when monocytes were pre-incubated with the antioxidant reagent Ebselen, which acts as an scavenger of peroxynitrite. We also determined Plitidepsin activity on malignant cells from chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL) patients. Monocyte-like cells obtained from 3 CMML samples resulted sensitive to Plitidepsin, though to a different extent (viable CD14+ cells at 24 h: control 100%, incubated with Plitidepsin 10 nM: sample 1: 79%, sample 2: 82%, sample 3: 29%). Finally we evaluated the effects of Plitidepsin on nurse-like cells (NLC) from CLL patients. These cells represent a subset differentiated from monocytes that favours leukemic cell progression through pro-survival signals. NLC were very sensitive to Plitidepsin and, more importantly, their death indirectly decreased neoplasic clone viability (7-AAD+ leukemic B cells co-cultured with control NLC: 36±10 versus 7-AAD+ leukemic B cells co-cultured with NLC exposed to Plitidepsin 100 nM for 24 h: 47±6, n=5, p<0.05). Myeloid cells are present in tumor microenvironment and actively affect the malignant cells, both directly and indirectly via the suppression of host immunity. Given their relevance in supporting tumor growth, the sensitivity of monocyte-like cells to Plitidepsin may contribute to its antitumoral effects. Disclosures: Galmarini: PharmaMar: Employment, Equity Ownership. Giordano: PharmaMar: Research Funding.


1989 ◽  
Vol 90 (2) ◽  
pp. 162-168 ◽  
Author(s):  
P. Zhou ◽  
L.J. Quackenbush ◽  
M.B. Zaleski

2003 ◽  
Vol 17 (5-6) ◽  
pp. 731-736 ◽  
Author(s):  
F.I. Abdullaev ◽  
L. Riverón-Negrete ◽  
H. Caballero-Ortega ◽  
J. Manuel Hernández ◽  
I. Pérez-López ◽  
...  

2021 ◽  
Vol 14 (3) ◽  
Author(s):  
Fatemeh Ghaffarifar ◽  
Soheila Molaei ◽  
Zuhair Mohammad Hassan ◽  
Mohammad Saaid Dayer ◽  
Abdolhossein Dalimi ◽  
...  

Background: The adverse effects and increased resistance of drugs necessities the discovery of novel combination therapy. Objectives: This study aimed to examine the effects of Artemisinin plus glucantime or shark cartilage extract on the Iranian strain of Leishmania major (MRHO/IR/75/ER) in vitro and in vivo. Methods: In in vitro experiments, the effects of drugs and their combination in different concentrations (3.12 - 400 µg/mL) on the promastigotes, amastigotes, and un-infected macrophage cells were evaluated. In in vivo experiments, infected BALB/c mice were used as a cutaneous leishmaniasis model to evaluate the effects of the drugs and their combinations with different routes of administrations (namely Artemisinin: oral, ointment, and intraperitoneal; glucantime: intraperitoneal, intramuscular, intralesional, and subcutaneous; shark cartilage extract: oral) on parasite burden, lesion size, and immune system modulation. Results: The results revealed that Artemisinin and glucantime in combination with shark cartilage extract had greater effects on promastigotes than either Artemisinin or glucantime (P < 0.05), and that the combinations also had high cytotoxic effects on promastigotes and uninfected macrophages (P = 0.001). These combinations had more inhibitory effects on amastigotes and infected macrophages than promastigotes. The lesion sizes and parasite burden in the spleen decreased against the combinations of the drugs in different administrations. It was also noticed that the best combination administration route of Artemisinin and glucantime, as strong inducers of INF-γ and Th1 immune response, were ointment and IM, respectively (P < 0.05). Conclusions: The findings indicate that Artemisinin- glucantime or Artemisinin- Shark cartilage combinations are effective inhibitors of L. major. However, further clinical trials are recommended to evaluate the effects of these combinations in human subjects.


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