scholarly journals Apoptosis-Like Cell Death in Leishmania major Treated with HESA-A: An Herbal Marine Compound

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Jasem Saki ◽  
Khalil Saki ◽  
Reza Arjmand

Background: The first drug for the treatment of leishmaniasis is pentavalent antimony compounds which have great side effects. Objectives: This study aimed to assess apoptosis induction by HESA-A, an herbal marine compound in Leishmania major promastigotes. Methods: Leishmania major promastigotes were treated with HESA-A in different increasing concentrations ranged 1.625 - 120 µg/mL, and amphotericin B and the phenomenon of apoptosis in the parasite were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and DNA fragmentation tests. Results: The IC50 value of the compound and amphotericin B at 72 h were estimated at 2.81 µg/mL and 40 µg/mL, respectively. After 72 h of the adjacency of Leishmania major promastigotes with IC50 dose (2.81 µg/mL), the percentage of promastigotes in early and late apoptosis phases in the treated group was 5.4% and 60.4%, respectively. DNA fragmentation of Leishmania major promastigotes treated with 2.81 µg/mL for 72 h was observed. Conclusions: HESA-A, with significant induction of apoptosis in Leishmania major promastigotes, can be plausible in the treatment of cutaneous Leishmaniasis.

Author(s):  
FIROZ HM ◽  
NANJUNDAIAH S ◽  
SADASHIVA CT

Objective: In the current study, an extract of turmeric rhizome (Turmesac®) was evaluated for possible anticancer activity in human cervical adenocarcinoma (HeLa) cells. Methods: Turmesac®’s ability to elicit cytotoxicity in cancer cells was evaluated by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (MTT) assay, where the IC50 value was determined. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry post-Turmesac® IC50 value treatment for 24 h. Results: The determined IC50 value of Turmesac® in HeLa cells was 115.12 μg/ml. This concentration was able to induce apoptosis 2 times greater than the apoptotic standard, camptothecin, treated cells. Cell cycle arrest was observed at the G0/G1 and S phases in Turmesac® treated HeLa cells. Conclusion: Turmesac® shows the potential of being a promising anticancer agent that may be incorporated into chemotherapies, but further study is required to elucidate the exact mechanisms involved with longer treatment duration, as would be the case in clinical trial phases.


Author(s):  
Nastaran Fallahi ◽  
Delavar Shahbazzadeh ◽  
Fatemeh Maleki ◽  
Marjaneh Aghdasi ◽  
Fatemeh Tabatabaie ◽  
...  

Background: Although a majority of patients with cutaneous leishmaniasis (CL) are healed with Glucantime chemotherapy, the increased drug resistance rate following its consumption is a concern. In this study , Naja naja oxiana crude venom of cobra snakes was used for the first time as an assembled combination of bioactive pharmaceutical components on Leishmania major (L. major) standard strain . Objective: To evaluate the efficacy of the Naja naja oxiana crude venom of Iranian cobra snakes on Leishmania major standard strain in vitro. Methods: Five concentrations (1.25, 2.5, 5, 10 and 20 µg/mL) of venom were added to Leishmania major cultures at 24, 48 and 72 h. The viability of the parasites and venom toxicity were assessed by MTT test. The apoptosis was determined by flowcytometry, while IC50 was determined by counting parasites compared to that of glucantime. Each test was conducted in triplicate. Results: After exposure the venom at 2.5 µg/mL for 72 h, IC50 value was 0.36 µg/mL and 14.12 µg/mL for promastigotes and amastigotes, respectively. MTT valuation clarified 1.01% promastigotes viability. Furthermore, the results indicated that the venom of Naja naja oxiana induced early and late apoptosis in parasites. Conclusions: The venom of Naja naja oxiana revealed remarkable anti-leishmanial effects as a novel anti-parasitic alternative. Thus the bioactive and effective fractions of this venom may be considered as anti-leishmanial candidates in future studies.


2019 ◽  
Vol 7 (4) ◽  
pp. 126-129
Author(s):  
Kaveh Eskandari ◽  
Shahram Khademvatan ◽  
Batool Sadeghi Nejad ◽  
Sedigheh Yusef Naanaie ◽  
Kobra kohansal

Background: Leishmaniasis is a major global health problem which affects millions of people, especially in the developing countries. The incidence of leishmaniasis has increased and there is no vaccination for Leishmania infections and standard drugs for treatment of the disease have many side effects; therefore, it is necessary to find new effective alternatives. Objectives: The purpose of this study was to evaluate the in vitro antileishmanial activity of Ixora brachiata root extract against Leishmania major and Leishmania infantum promastigotes. Materials and Methods: Different doses of the selected plant extract was tested against L. major and L. infantum promastigotes using colorimetric MTT [3-(4, 5-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay. Glucantime was used as the positive control. Results: Anti-parasitic activity was revealed for I. brachiata root on L. major and L. infantum with 50% inhibitory concentration (IC50) values of 0.91 and 2.63 µg/mL, respectively compared to the standard drugs, glucantime, which had an IC50 value of 40.2 µg/mL for L. major and 18.5 µg/ mL for L. infantum after 72 hours. Conclusion: The results of this study created a new background on the development of drug against leishmania parasite.


Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 234 ◽  
Author(s):  
Yea Seong Ryu ◽  
Pincha Devage Sameera Madushan Fernando ◽  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Ao Xuan Zhen ◽  
...  

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H2O2- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.


Nanomedicine ◽  
2018 ◽  
Vol 13 (24) ◽  
pp. 3129-3147 ◽  
Author(s):  
Tahereh Zadeh Mehrizi ◽  
Mehdi Shafiee Ardestani ◽  
Mostafa Haji Molla Hoseini ◽  
Ali Khamesipour ◽  
Nariman Mosaffa ◽  
...  

2018 ◽  
Vol 63 (2) ◽  
pp. e00904-18 ◽  
Author(s):  
Celia Fernández-Rubio ◽  
Esther Larrea ◽  
José Peña Guerrero ◽  
Eduardo Sesma Herrero ◽  
Iñigo Gamboa ◽  
...  

ABSTRACTConventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug resistance are not uncommon. Thus, safe and effective therapies are urgently needed. Isoselenocyanate compounds have recently been identified with potential antitumor activity. It is well known that some antitumor agents demonstrate effects againstLeishmania. In this study, thein vitroleishmanicidal activities of several organo-selenium and organo-sulfur compounds were tested againstLeishmania majorandLeishmania amazonensisparasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, the isoselenocyanate derivative NISC-6, showed selectivity indexes 2- and 10-fold higher than those of the reference drug amphotericin B when evaluated inL. amazonensisandL. major, respectively. The American strain (L. amazonensis) was less sensitive to NISC-6 thanL. major, showing a trend similar to that observed previously for amphotericin B. In addition, we also observed that NISC-6 significantly reduced the number of amastigotes per infected macrophage. On the other hand, we showed that NISC-6 decreases expression levels ofLeishmaniagenes involved in the cell cycle, such astopoisomerase-2(TOP-2),PCNA, andMCM4, therefore contributing to its leishmanicidal activity. The effect of this compound on cell cycle progression was confirmed by flow cytometry. We observed a significant increase of cells in the G1phase and a dramatic reduction of cells in the S phase compared to untreated cells. Altogether, our data suggest that the isoselenocyanate NISC-6 may be a promising candidate for new drug development against leishmaniasis.


Author(s):  
Janet Herrada ◽  
Ahmed Gamal ◽  
Lisa Long ◽  
Sonia P. Sanchez ◽  
Thomas S. McCormick ◽  
...  

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/mL, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg -treated group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data shows that AmBisome shows significant antifungal activity against C. auris in vitro as well as in vivo.


Author(s):  
Meirizky Zulharini S. ◽  
Amalia Miranda ◽  
Lina Permatasari ◽  
Hilyatul Fadliyah ◽  
Riris Istighfari Jenie

NF-κB is a transcription factor and if activated, it induces apoptosis inhibition. Phalerin from Phaleria macrocarpa fruits expected to inhibit NF-κB activation. This research is to investigate anticancer mechanism of Phaleria macrocarpa fruits extracts (EBMD) in NF-κB pathway. Molecular docking assay was performed to determine phalerin affinity to IKK. Cytotoxic activity was observed by MTT assay. Double staining was performed to determine the apoptotic cells. Docking score of phalerin to IKK is -60. The IC50 value of EBMD is 629 μg/mL. Apoptosis profile shows (shown that) many cells undergoing apoptosis after treatment. Thus, EBMD potentially inhibits activation of NF-κB pathway and triggers apoptosis on HeLa cells.Keywords : NF-κB, Phaleria macrocarpa, sel HeLa, Bcl-2, IKK, molecular docking


2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Seyedmojtaba Seyedmousavi ◽  
Johan W. Mouton ◽  
Willem J. G. Melchers ◽  
Paul E. Verweij

ABSTRACT Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Antimicrob Agents Chemother 57:1866–1871, 2013, https://doi.org/10.1128/AAC.02226-12 ). We here investigated the role of immune suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus harboring a TR34/L98H mutation in the cyp-51A gene. Survival of treated animals at day 14 in both immunosuppressed models was significantly better than that of nontreated controls. A dose-response relationship was observed that was independent of the azole-resistant mechanism and the immunosuppression method used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16 mg/kg of body weight for the WT strain and the TR34/L98H isolate. In the steroid-treated group, 90.9% survival and 100% survival were achieved for the WT isolate and the TR34/L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50% effective dose (ED50) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00 mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the TR34/L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to 2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for the TR34/L98H isolate in the steroid-treated group. Overall, there were no significant differences between the two different immunosuppressed conditions in the efficacy of L-AmB against the wild-type and azole-resistant isolates (P > 0.9). However, the required L-AmB exposure was significantly higher than that seen in the immunocompetent model.


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