In silico and in vitro potentials of crocin and amphotericin B on Leishmania major: Multiple synergistic mechanisms of actions
A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding beh...
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| creator | Salarkia, Ehsan Sharifi, Iraj Keyhani, Alireza Tavakoli Oliaee, Razieh Khosravi, Ahmad Sharifi, Fatemeh Bamorovat, Mehdi Babaei, Zahra |
| description | A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-[gamma], and TNF- [alpha]), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-[beta]) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings. |
| doi_str_mv | 10.1371/journal.pone.0291322 |
| format | Article |
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Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-[gamma], and TNF- [alpha]), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-[beta]) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0291322</identifier><identifier>PMID: 37682934</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Amphotericin B ; Antifungal agents ; Antioxidants ; Apoptosis ; Arginase ; Biology and Life Sciences ; c-Fos protein ; Care and treatment ; Cell cycle ; Cell death ; Complications and side effects ; Cutaneous leishmaniasis ; Cytokines ; Cytotoxicity ; Diagnosis ; Drug development ; Drug resistance ; Drugs ; G1 phase ; Leishmania major ; Leishmaniasis ; Lymphocytes T ; Medicine and Health Sciences ; Molecular docking ; Nitric oxide ; Nitric-oxide synthase ; Oxygen ; Parasites ; Parasitic diseases ; Patient compliance ; Patient outcomes ; Penicillin G ; Phenotypes ; Phosphatidylserine ; Promastigotes ; Proteins ; Reactive oxygen species ; Stat1 protein ; Transcription factors ; Transforming growth factor-b ; Tropical diseases ; Vector-borne diseases ; γ-Interferon</subject><ispartof>PloS one, 2023-09, Vol.18 (9), p.e0291322</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Salarkia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright: © 2023 Salarkia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>2023 Salarkia et al 2023 Salarkia et al</rights><rights>2023 Salarkia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.</description><subject>Amphotericin B</subject><subject>Antifungal agents</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Arginase</subject><subject>Biology and Life Sciences</subject><subject>c-Fos protein</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Complications and side effects</subject><subject>Cutaneous leishmaniasis</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Diagnosis</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Drugs</subject><subject>G1 phase</subject><subject>Leishmania major</subject><subject>Leishmaniasis</subject><subject>Lymphocytes T</subject><subject>Medicine and Health Sciences</subject><subject>Molecular docking</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Oxygen</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Patient compliance</subject><subject>Patient outcomes</subject><subject>Penicillin G</subject><subject>Phenotypes</subject><subject>Phosphatidylserine</subject><subject>Promastigotes</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Stat1 protein</subject><subject>Transcription factors</subject><subject>Transforming growth factor-b</subject><subject>Tropical diseases</subject><subject>Vector-borne 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salarkia, Ehsan</au><au>Sharifi, Iraj</au><au>Keyhani, Alireza</au><au>Tavakoli Oliaee, Razieh</au><au>Khosravi, Ahmad</au><au>Sharifi, Fatemeh</au><au>Bamorovat, Mehdi</au><au>Babaei, Zahra</au><au>Badirzadeh, Alireza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In silico and in vitro potentials of crocin and amphotericin B on Leishmania major: Multiple synergistic mechanisms of actions</atitle><jtitle>PloS one</jtitle><date>2023-09-08</date><risdate>2023</risdate><volume>18</volume><issue>9</issue><spage>e0291322</spage><pages>e0291322-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-[gamma], and TNF- [alpha]), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-[beta]) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>37682934</pmid><doi>10.1371/journal.pone.0291322</doi><tpages>e0291322</tpages><orcidid>https://orcid.org/0000-0002-6894-6834</orcidid><orcidid>https://orcid.org/0000-0001-6125-5101</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2023-09, Vol.18 (9), p.e0291322 |
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| language | eng |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amphotericin B Antifungal agents Antioxidants Apoptosis Arginase Biology and Life Sciences c-Fos protein Care and treatment Cell cycle Cell death Complications and side effects Cutaneous leishmaniasis Cytokines Cytotoxicity Diagnosis Drug development Drug resistance Drugs G1 phase Leishmania major Leishmaniasis Lymphocytes T Medicine and Health Sciences Molecular docking Nitric oxide Nitric-oxide synthase Oxygen Parasites Parasitic diseases Patient compliance Patient outcomes Penicillin G Phenotypes Phosphatidylserine Promastigotes Proteins Reactive oxygen species Stat1 protein Transcription factors Transforming growth factor-b Tropical diseases Vector-borne diseases γ-Interferon |
| title | In silico and in vitro potentials of crocin and amphotericin B on Leishmania major: Multiple synergistic mechanisms of actions |
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