Limonene-carvacrol: A combination of monoterpenes with enhanced antileishmanial activity
Leishmaniasis is a parasitosis with a wide incidence in developing countries. The drugs which are indicated for the treatment of this infection usually are able to promote high toxicity. A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitut...
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| Veröffentlicht in: | Toxicology in vitro 2021-08, Vol.74, p.105158, Article 105158 |
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| creator | Carvalho, Rita de Cássia Viana de Sousa, Valéria Carlos de Santos, Laíz Pinheiro Santos, Ingredy Lopes dos Diniz, Roseane Costa Rodrigues, Raiza Raianne Luz Medeiros, Maria das Graças Freire de Rodrigues, Klinger Antonio da Franca Alves, Michel Muálem de Moraes Arcanjo, Daniel Dias Rufino Carvalho, Fernando Aécio de Amorim |
| description | Leishmaniasis is a parasitosis with a wide incidence in developing countries. The drugs which are indicated for the treatment of this infection usually are able to promote high toxicity.
A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitute an alternative for the treatment of these diseases.
In this study, the antileishmania activity against Leishmania major, cytotoxicity tests, assessment of synergism, parasite membrane damage tests as well as molecular docking and immunomodulatory activity of limonene–carvacrol (Lim–Car) combination were evaluated.
The Lim–Car combination (5:0; 1:1; 1:4; 2:3; 3:2; 4:1 and 0:5) showed potential antileishmania activity, with mean inhibitory concentration (IC50) ranging from 5.8 to 19.0 μg.mL−1. They demonstrated mean cytotoxic concentration (CC50) ranging from 94.1 to 176.0 μg.mL−1, and did not show significant hemolytic effect. In the investigation of synergistic interaction, the 4:1 Lim–Car combination showed better fractional inhibitory concentration (FIC) index as well as better activity on amastigotes and IS. The samples caused considerable damage to the parasite membrane this monoterpene activity seems to be more related to Trypanothione Reductase (TryR) enzyme interaction, demonstrated in the molecular docking assay. In addition, the 4:1 Lim–Car combination stimulated macrophage activation, and showed at was the best association, with reduction of infection and infectivity of parasitized macrophages.
The 4:1 Lim–Car combination appears to be a promising candidate as a monotherapeutic antileishmania agent.
[Display omitted]
•Lim–Car-based associations showed antileishmanial activity in vitro against L. major promastigote and amastigote forms.•4:1 Lim–Car association showed a higher selectivity index than the reference drug.•4:1 Lim–Car association has been shown to act on parasite membrane enzymes.•4:1 Lim–Car association to induce macrophages activation. |
| doi_str_mv | 10.1016/j.tiv.2021.105158 |
| format | Article |
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A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitute an alternative for the treatment of these diseases.
In this study, the antileishmania activity against Leishmania major, cytotoxicity tests, assessment of synergism, parasite membrane damage tests as well as molecular docking and immunomodulatory activity of limonene–carvacrol (Lim–Car) combination were evaluated.
The Lim–Car combination (5:0; 1:1; 1:4; 2:3; 3:2; 4:1 and 0:5) showed potential antileishmania activity, with mean inhibitory concentration (IC50) ranging from 5.8 to 19.0 μg.mL−1. They demonstrated mean cytotoxic concentration (CC50) ranging from 94.1 to 176.0 μg.mL−1, and did not show significant hemolytic effect. In the investigation of synergistic interaction, the 4:1 Lim–Car combination showed better fractional inhibitory concentration (FIC) index as well as better activity on amastigotes and IS. The samples caused considerable damage to the parasite membrane this monoterpene activity seems to be more related to Trypanothione Reductase (TryR) enzyme interaction, demonstrated in the molecular docking assay. In addition, the 4:1 Lim–Car combination stimulated macrophage activation, and showed at was the best association, with reduction of infection and infectivity of parasitized macrophages.
The 4:1 Lim–Car combination appears to be a promising candidate as a monotherapeutic antileishmania agent.
[Display omitted]
•Lim–Car-based associations showed antileishmanial activity in vitro against L. major promastigote and amastigote forms.•4:1 Lim–Car association showed a higher selectivity index than the reference drug.•4:1 Lim–Car association has been shown to act on parasite membrane enzymes.•4:1 Lim–Car association to induce macrophages activation.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2021.105158</identifier><identifier>PMID: 33823240</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amastigotes ; Antiparasitic agents ; Carvacrol ; Cell activation ; Cytotoxicity ; Damage ; Developing countries ; Immunomodulation ; Imunomodulation ; Infections ; Infectivity ; LDCs ; Leishmania major ; Leishmaniasis ; Limonene ; Macrophages ; Medical treatment ; Membranes ; Molecular docking ; Monoterpenes ; Natural products ; Parasites ; Parasitic diseases ; Reductases ; Synergism ; Toxicity ; Trypanothione ; Trypanothione reductase ; Vector-borne diseases</subject><ispartof>Toxicology in vitro, 2021-08, Vol.74, p.105158, Article 105158</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Aug 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-5326bdecc6bfc14e06582f61a7f978dedeeec84d355875a62e80b0c1093f9603</citedby><cites>FETCH-LOGICAL-c429t-5326bdecc6bfc14e06582f61a7f978dedeeec84d355875a62e80b0c1093f9603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tiv.2021.105158$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33823240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carvalho, Rita de Cássia Viana de</creatorcontrib><creatorcontrib>Sousa, Valéria Carlos de</creatorcontrib><creatorcontrib>Santos, Laíz Pinheiro</creatorcontrib><creatorcontrib>Santos, Ingredy Lopes dos</creatorcontrib><creatorcontrib>Diniz, Roseane Costa</creatorcontrib><creatorcontrib>Rodrigues, Raiza Raianne Luz</creatorcontrib><creatorcontrib>Medeiros, Maria das Graças Freire de</creatorcontrib><creatorcontrib>Rodrigues, Klinger Antonio da Franca</creatorcontrib><creatorcontrib>Alves, Michel Muálem de Moraes</creatorcontrib><creatorcontrib>Arcanjo, Daniel Dias Rufino</creatorcontrib><creatorcontrib>Carvalho, Fernando Aécio de Amorim</creatorcontrib><title>Limonene-carvacrol: A combination of monoterpenes with enhanced antileishmanial activity</title><title>Toxicology in vitro</title><addtitle>Toxicol In Vitro</addtitle><description>Leishmaniasis is a parasitosis with a wide incidence in developing countries. The drugs which are indicated for the treatment of this infection usually are able to promote high toxicity.
A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitute an alternative for the treatment of these diseases.
In this study, the antileishmania activity against Leishmania major, cytotoxicity tests, assessment of synergism, parasite membrane damage tests as well as molecular docking and immunomodulatory activity of limonene–carvacrol (Lim–Car) combination were evaluated.
The Lim–Car combination (5:0; 1:1; 1:4; 2:3; 3:2; 4:1 and 0:5) showed potential antileishmania activity, with mean inhibitory concentration (IC50) ranging from 5.8 to 19.0 μg.mL−1. They demonstrated mean cytotoxic concentration (CC50) ranging from 94.1 to 176.0 μg.mL−1, and did not show significant hemolytic effect. In the investigation of synergistic interaction, the 4:1 Lim–Car combination showed better fractional inhibitory concentration (FIC) index as well as better activity on amastigotes and IS. The samples caused considerable damage to the parasite membrane this monoterpene activity seems to be more related to Trypanothione Reductase (TryR) enzyme interaction, demonstrated in the molecular docking assay. In addition, the 4:1 Lim–Car combination stimulated macrophage activation, and showed at was the best association, with reduction of infection and infectivity of parasitized macrophages.
The 4:1 Lim–Car combination appears to be a promising candidate as a monotherapeutic antileishmania agent.
[Display omitted]
•Lim–Car-based associations showed antileishmanial activity in vitro against L. major promastigote and amastigote forms.•4:1 Lim–Car association showed a higher selectivity index than the reference drug.•4:1 Lim–Car association has been shown to act on parasite membrane enzymes.•4:1 Lim–Car association to induce macrophages activation.</description><subject>Amastigotes</subject><subject>Antiparasitic agents</subject><subject>Carvacrol</subject><subject>Cell activation</subject><subject>Cytotoxicity</subject><subject>Damage</subject><subject>Developing countries</subject><subject>Immunomodulation</subject><subject>Imunomodulation</subject><subject>Infections</subject><subject>Infectivity</subject><subject>LDCs</subject><subject>Leishmania major</subject><subject>Leishmaniasis</subject><subject>Limonene</subject><subject>Macrophages</subject><subject>Medical treatment</subject><subject>Membranes</subject><subject>Molecular docking</subject><subject>Monoterpenes</subject><subject>Natural products</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Reductases</subject><subject>Synergism</subject><subject>Toxicity</subject><subject>Trypanothione</subject><subject>Trypanothione reductase</subject><subject>Vector-borne diseases</subject><issn>0887-2333</issn><issn>1879-3177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEURYMotlZ_gBsZcD01H5OZjK5K8QsKbrpwFzKZNzSlk9QkrfTfmzLVpavw4Lyb-w5CtwRPCSblw3oazX5KMSVp5oSLMzQmoqpzRqrqHI2xEFVOGWMjdBXCGmPMBcWXaMSYoIwWeIw-F6Z3FizkWvm90t5tHrNZpl3fGKuicTZzXZYQF8FvExeybxNXGdiVshraTNloNmDCqlfWqE2mdOpk4uEaXXRqE-Dm9E7Q8uV5OX_LFx-v7_PZItcFrWPOGS2bFrQum06TAnCZKnYlUVVXV6KFFgC0KFrGuai4KikI3GBNcM26usRsgu6H2K13XzsIUa7dztv0o6SclZzVBaOJIgOV7gvBQye33vTKHyTB8qhSrmWqLY8q5aAy7dydkndND-3fxq-7BDwNAKTz9ga8DNrAUYrxoKNsnfkn_geTcoUY</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Carvalho, Rita de Cássia Viana de</creator><creator>Sousa, Valéria Carlos de</creator><creator>Santos, Laíz Pinheiro</creator><creator>Santos, Ingredy Lopes dos</creator><creator>Diniz, Roseane Costa</creator><creator>Rodrigues, Raiza Raianne Luz</creator><creator>Medeiros, Maria das Graças Freire de</creator><creator>Rodrigues, Klinger Antonio da Franca</creator><creator>Alves, Michel Muálem de Moraes</creator><creator>Arcanjo, Daniel Dias Rufino</creator><creator>Carvalho, Fernando Aécio de Amorim</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>202108</creationdate><title>Limonene-carvacrol: A combination of monoterpenes with enhanced antileishmanial activity</title><author>Carvalho, Rita de Cássia Viana de ; Sousa, Valéria Carlos de ; Santos, Laíz Pinheiro ; Santos, Ingredy Lopes dos ; Diniz, Roseane Costa ; Rodrigues, Raiza Raianne Luz ; Medeiros, Maria das Graças Freire de ; Rodrigues, Klinger Antonio da Franca ; Alves, Michel Muálem de Moraes ; Arcanjo, Daniel Dias Rufino ; Carvalho, Fernando Aécio de Amorim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-5326bdecc6bfc14e06582f61a7f978dedeeec84d355875a62e80b0c1093f9603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amastigotes</topic><topic>Antiparasitic agents</topic><topic>Carvacrol</topic><topic>Cell activation</topic><topic>Cytotoxicity</topic><topic>Damage</topic><topic>Developing countries</topic><topic>Immunomodulation</topic><topic>Imunomodulation</topic><topic>Infections</topic><topic>Infectivity</topic><topic>LDCs</topic><topic>Leishmania major</topic><topic>Leishmaniasis</topic><topic>Limonene</topic><topic>Macrophages</topic><topic>Medical treatment</topic><topic>Membranes</topic><topic>Molecular docking</topic><topic>Monoterpenes</topic><topic>Natural products</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Reductases</topic><topic>Synergism</topic><topic>Toxicity</topic><topic>Trypanothione</topic><topic>Trypanothione reductase</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carvalho, Rita de Cássia Viana de</creatorcontrib><creatorcontrib>Sousa, Valéria Carlos de</creatorcontrib><creatorcontrib>Santos, Laíz Pinheiro</creatorcontrib><creatorcontrib>Santos, Ingredy Lopes dos</creatorcontrib><creatorcontrib>Diniz, Roseane Costa</creatorcontrib><creatorcontrib>Rodrigues, Raiza Raianne Luz</creatorcontrib><creatorcontrib>Medeiros, Maria das Graças Freire de</creatorcontrib><creatorcontrib>Rodrigues, Klinger Antonio da Franca</creatorcontrib><creatorcontrib>Alves, Michel Muálem de Moraes</creatorcontrib><creatorcontrib>Arcanjo, Daniel Dias Rufino</creatorcontrib><creatorcontrib>Carvalho, Fernando Aécio de Amorim</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology in vitro</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carvalho, Rita de Cássia Viana de</au><au>Sousa, Valéria Carlos de</au><au>Santos, Laíz Pinheiro</au><au>Santos, Ingredy Lopes dos</au><au>Diniz, Roseane Costa</au><au>Rodrigues, Raiza Raianne Luz</au><au>Medeiros, Maria das Graças Freire de</au><au>Rodrigues, Klinger Antonio da Franca</au><au>Alves, Michel Muálem de Moraes</au><au>Arcanjo, Daniel Dias Rufino</au><au>Carvalho, Fernando Aécio de Amorim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Limonene-carvacrol: A combination of monoterpenes with enhanced antileishmanial activity</atitle><jtitle>Toxicology in vitro</jtitle><addtitle>Toxicol In Vitro</addtitle><date>2021-08</date><risdate>2021</risdate><volume>74</volume><spage>105158</spage><pages>105158-</pages><artnum>105158</artnum><issn>0887-2333</issn><eissn>1879-3177</eissn><abstract>Leishmaniasis is a parasitosis with a wide incidence in developing countries. The drugs which are indicated for the treatment of this infection usually are able to promote high toxicity.
A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitute an alternative for the treatment of these diseases.
In this study, the antileishmania activity against Leishmania major, cytotoxicity tests, assessment of synergism, parasite membrane damage tests as well as molecular docking and immunomodulatory activity of limonene–carvacrol (Lim–Car) combination were evaluated.
The Lim–Car combination (5:0; 1:1; 1:4; 2:3; 3:2; 4:1 and 0:5) showed potential antileishmania activity, with mean inhibitory concentration (IC50) ranging from 5.8 to 19.0 μg.mL−1. They demonstrated mean cytotoxic concentration (CC50) ranging from 94.1 to 176.0 μg.mL−1, and did not show significant hemolytic effect. In the investigation of synergistic interaction, the 4:1 Lim–Car combination showed better fractional inhibitory concentration (FIC) index as well as better activity on amastigotes and IS. The samples caused considerable damage to the parasite membrane this monoterpene activity seems to be more related to Trypanothione Reductase (TryR) enzyme interaction, demonstrated in the molecular docking assay. In addition, the 4:1 Lim–Car combination stimulated macrophage activation, and showed at was the best association, with reduction of infection and infectivity of parasitized macrophages.
The 4:1 Lim–Car combination appears to be a promising candidate as a monotherapeutic antileishmania agent.
[Display omitted]
•Lim–Car-based associations showed antileishmanial activity in vitro against L. major promastigote and amastigote forms.•4:1 Lim–Car association showed a higher selectivity index than the reference drug.•4:1 Lim–Car association has been shown to act on parasite membrane enzymes.•4:1 Lim–Car association to induce macrophages activation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33823240</pmid><doi>10.1016/j.tiv.2021.105158</doi></addata></record> |
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| subjects | Amastigotes Antiparasitic agents Carvacrol Cell activation Cytotoxicity Damage Developing countries Immunomodulation Imunomodulation Infections Infectivity LDCs Leishmania major Leishmaniasis Limonene Macrophages Medical treatment Membranes Molecular docking Monoterpenes Natural products Parasites Parasitic diseases Reductases Synergism Toxicity Trypanothione Trypanothione reductase Vector-borne diseases |
| title | Limonene-carvacrol: A combination of monoterpenes with enhanced antileishmanial activity |
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