Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives

•Leishmaniasis is among the leading infectious tropical diseases, affecting about 350 million population worldwide.•Every year about 1–1.5 million cases of Cutaneous leishmaniasis and 0.5 million cases of Visceral leishmaniasis are reported.•Unfortunately, only a limited number of drugs are availabl...

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Veröffentlicht in:Steroids 2023-05, Vol.193, p.109196-109196, Article 109196
Hauptverfasser: Elawad, Mohammed Ahmed, Elkhalifa, Modawy Elnour Modawy, Hamdoon, Alashary Adam Eisa, Salim, Liga Hasan Mohammed, Ahmad, Zeeshan, Ayaz, Muhammad
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container_end_page 109196
container_issue
container_start_page 109196
container_title Steroids
container_volume 193
creator Elawad, Mohammed Ahmed
Elkhalifa, Modawy Elnour Modawy
Hamdoon, Alashary Adam Eisa
Salim, Liga Hasan Mohammed
Ahmad, Zeeshan
Ayaz, Muhammad
description •Leishmaniasis is among the leading infectious tropical diseases, affecting about 350 million population worldwide.•Every year about 1–1.5 million cases of Cutaneous leishmaniasis and 0.5 million cases of Visceral leishmaniasis are reported.•Unfortunately, only a limited number of drugs are available against leishmaniasis.•Medicinal plants-derived steroidal moieties including steroidal saponins, steroidal alkaloids and phytosterols like β-sitosterol, stigmasterol and pentalinosterol have revealed considerable efficacy.•These steroids mediate their anti-leishmanial effects via liberation of ROS and initiation of apoptotic processes. Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 → 4)-α-rhamnopyranosyl-(1 → 4)-[a-rhamnopyranosyl-(1 → 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL−1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95–8.03 µg mL−1 and even better activity against amastigotes exhibiting an IC50 of 4.50–9.29 µg mL−1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K,
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Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 → 4)-α-rhamnopyranosyl-(1 → 4)-[a-rhamnopyranosyl-(1 → 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL−1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95–8.03 µg mL−1 and even better activity against amastigotes exhibiting an IC50 of 4.50–9.29 µg mL−1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K, dehydrosarsalignone, vagenine-A, sarcovagine-C, holaphylline, saracodine, holamine, 15-α hydroxyholamine, holacurtin, N-desmethyl holacurtine and elasticine has exhibited time and dose-dependent efficacy against various strains of leishmania. β-sitosterol was found active against multiple strains of leishmania. These compounds mainly exhibit their therapeutic efficacy via liberation of ROS, mitochondrial depolarization, morphological and ultra-structural changes, accumulation of lipid droplets, depletion of non-protein thiols and triggering apoptotic pathways. In conclusion, leishmaniasis is a major health problem in many countries. Plants-derived steroids moieties have reveled efficacy against leishmaniasis and is a source of lead compounds. Further detailed molecular studies are warranted for the discovery of more effective and safe anti-leishmanial drugs.</description><identifier>ISSN: 0039-128X</identifier><identifier>EISSN: 1878-5867</identifier><identifier>DOI: 10.1016/j.steroids.2023.109196</identifier><identifier>PMID: 36764565</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alkaloids ; Amastigotes ; Antiprotozoal Agents - chemistry ; Antiprotozoal Agents - pharmacology ; Biological Products - pharmacology ; Cutanious leishmaniasis ; Humans ; Leishmaniasis ; Leishmaniasis - drug therapy ; Phytosterols ; Prevalence ; Promastigotes ; Saponins - therapeutic use ; Steroids - pharmacology ; Steroids - therapeutic use ; Visceral leishmaniasis</subject><ispartof>Steroids, 2023-05, Vol.193, p.109196-109196, Article 109196</ispartof><rights>2023 Elsevier Inc.</rights><rights>Copyright © 2023 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-4475867c5b76d0b99ef58afee4b1553bb01082b5412d9471cbd74fdd12369f5b3</citedby><cites>FETCH-LOGICAL-c368t-4475867c5b76d0b99ef58afee4b1553bb01082b5412d9471cbd74fdd12369f5b3</cites><orcidid>0000-0002-4299-2445</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0039128X23000247$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36764565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elawad, Mohammed Ahmed</creatorcontrib><creatorcontrib>Elkhalifa, Modawy Elnour Modawy</creatorcontrib><creatorcontrib>Hamdoon, Alashary Adam Eisa</creatorcontrib><creatorcontrib>Salim, Liga Hasan Mohammed</creatorcontrib><creatorcontrib>Ahmad, Zeeshan</creatorcontrib><creatorcontrib>Ayaz, Muhammad</creatorcontrib><title>Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives</title><title>Steroids</title><addtitle>Steroids</addtitle><description>•Leishmaniasis is among the leading infectious tropical diseases, affecting about 350 million population worldwide.•Every year about 1–1.5 million cases of Cutaneous leishmaniasis and 0.5 million cases of Visceral leishmaniasis are reported.•Unfortunately, only a limited number of drugs are available against leishmaniasis.•Medicinal plants-derived steroidal moieties including steroidal saponins, steroidal alkaloids and phytosterols like β-sitosterol, stigmasterol and pentalinosterol have revealed considerable efficacy.•These steroids mediate their anti-leishmanial effects via liberation of ROS and initiation of apoptotic processes. Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 → 4)-α-rhamnopyranosyl-(1 → 4)-[a-rhamnopyranosyl-(1 → 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL−1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95–8.03 µg mL−1 and even better activity against amastigotes exhibiting an IC50 of 4.50–9.29 µg mL−1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K, dehydrosarsalignone, vagenine-A, sarcovagine-C, holaphylline, saracodine, holamine, 15-α hydroxyholamine, holacurtin, N-desmethyl holacurtine and elasticine has exhibited time and dose-dependent efficacy against various strains of leishmania. β-sitosterol was found active against multiple strains of leishmania. These compounds mainly exhibit their therapeutic efficacy via liberation of ROS, mitochondrial depolarization, morphological and ultra-structural changes, accumulation of lipid droplets, depletion of non-protein thiols and triggering apoptotic pathways. In conclusion, leishmaniasis is a major health problem in many countries. Plants-derived steroids moieties have reveled efficacy against leishmaniasis and is a source of lead compounds. Further detailed molecular studies are warranted for the discovery of more effective and safe anti-leishmanial drugs.</description><subject>Alkaloids</subject><subject>Amastigotes</subject><subject>Antiprotozoal Agents - chemistry</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Biological Products - pharmacology</subject><subject>Cutanious leishmaniasis</subject><subject>Humans</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis - drug therapy</subject><subject>Phytosterols</subject><subject>Prevalence</subject><subject>Promastigotes</subject><subject>Saponins - therapeutic use</subject><subject>Steroids - pharmacology</subject><subject>Steroids - therapeutic use</subject><subject>Visceral leishmaniasis</subject><issn>0039-128X</issn><issn>1878-5867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUclqHDEQFcEhnjj5BaNjDu6J1N2SusnFxmQDk1xi8E1oqbY19DJWdQ_4E_zXqcl4fM2poOotvFeMnUuxlkLqz5s1zpCnFHFdirKiZStb_YatZGOaQjXanLCVEFVbyLK5O2XvETdCCF215Tt2Wmmja6XVij3_cvOSXc-3eYpLmJFHyGkHkR_1uUO-nWYY50QwR6PoIeHD4MZ_i3u64BceE4JDIB3YuR7GABd8GUmsf0rjPR8gPBABB9IbI-8WciUwZNxCmMkQP7C3nesRPr7MM3b77euf6x_Fze_vP6-vbopQ6WYu6trs0wXljY7Cty10qnEdQO2lUpX3Qoqm9KqWZWxrI4OPpu5ilGWl20756ox9OuhS4scFcLZDwgB970aYFrSlMUpLKrUhqD5AQ54QM3R2m9Pg8pOVwu7fYDf2WJPdv8Ee3kDE8xePxQ8QX2nH3glweQAAJd0lyBZD2pcWU6Y-bJzS_zz-AuWwoM0</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Elawad, Mohammed Ahmed</creator><creator>Elkhalifa, Modawy Elnour Modawy</creator><creator>Hamdoon, Alashary Adam Eisa</creator><creator>Salim, Liga Hasan Mohammed</creator><creator>Ahmad, Zeeshan</creator><creator>Ayaz, Muhammad</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4299-2445</orcidid></search><sort><creationdate>202305</creationdate><title>Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives</title><author>Elawad, Mohammed Ahmed ; Elkhalifa, Modawy Elnour Modawy ; Hamdoon, Alashary Adam Eisa ; Salim, Liga Hasan Mohammed ; Ahmad, Zeeshan ; Ayaz, Muhammad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-4475867c5b76d0b99ef58afee4b1553bb01082b5412d9471cbd74fdd12369f5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alkaloids</topic><topic>Amastigotes</topic><topic>Antiprotozoal Agents - chemistry</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Biological Products - pharmacology</topic><topic>Cutanious leishmaniasis</topic><topic>Humans</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis - drug therapy</topic><topic>Phytosterols</topic><topic>Prevalence</topic><topic>Promastigotes</topic><topic>Saponins - therapeutic use</topic><topic>Steroids - pharmacology</topic><topic>Steroids - therapeutic use</topic><topic>Visceral leishmaniasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elawad, Mohammed Ahmed</creatorcontrib><creatorcontrib>Elkhalifa, Modawy Elnour Modawy</creatorcontrib><creatorcontrib>Hamdoon, Alashary Adam Eisa</creatorcontrib><creatorcontrib>Salim, Liga Hasan Mohammed</creatorcontrib><creatorcontrib>Ahmad, Zeeshan</creatorcontrib><creatorcontrib>Ayaz, Muhammad</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Steroids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elawad, Mohammed Ahmed</au><au>Elkhalifa, Modawy Elnour Modawy</au><au>Hamdoon, Alashary Adam Eisa</au><au>Salim, Liga Hasan Mohammed</au><au>Ahmad, Zeeshan</au><au>Ayaz, Muhammad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives</atitle><jtitle>Steroids</jtitle><addtitle>Steroids</addtitle><date>2023-05</date><risdate>2023</risdate><volume>193</volume><spage>109196</spage><epage>109196</epage><pages>109196-109196</pages><artnum>109196</artnum><issn>0039-128X</issn><eissn>1878-5867</eissn><abstract>•Leishmaniasis is among the leading infectious tropical diseases, affecting about 350 million population worldwide.•Every year about 1–1.5 million cases of Cutaneous leishmaniasis and 0.5 million cases of Visceral leishmaniasis are reported.•Unfortunately, only a limited number of drugs are available against leishmaniasis.•Medicinal plants-derived steroidal moieties including steroidal saponins, steroidal alkaloids and phytosterols like β-sitosterol, stigmasterol and pentalinosterol have revealed considerable efficacy.•These steroids mediate their anti-leishmanial effects via liberation of ROS and initiation of apoptotic processes. Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 → 4)-α-rhamnopyranosyl-(1 → 4)-[a-rhamnopyranosyl-(1 → 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL−1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95–8.03 µg mL−1 and even better activity against amastigotes exhibiting an IC50 of 4.50–9.29 µg mL−1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K, dehydrosarsalignone, vagenine-A, sarcovagine-C, holaphylline, saracodine, holamine, 15-α hydroxyholamine, holacurtin, N-desmethyl holacurtine and elasticine has exhibited time and dose-dependent efficacy against various strains of leishmania. β-sitosterol was found active against multiple strains of leishmania. These compounds mainly exhibit their therapeutic efficacy via liberation of ROS, mitochondrial depolarization, morphological and ultra-structural changes, accumulation of lipid droplets, depletion of non-protein thiols and triggering apoptotic pathways. In conclusion, leishmaniasis is a major health problem in many countries. Plants-derived steroids moieties have reveled efficacy against leishmaniasis and is a source of lead compounds. Further detailed molecular studies are warranted for the discovery of more effective and safe anti-leishmanial drugs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36764565</pmid><doi>10.1016/j.steroids.2023.109196</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4299-2445</orcidid></addata></record>
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subjects Alkaloids
Amastigotes
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - pharmacology
Biological Products - pharmacology
Cutanious leishmaniasis
Humans
Leishmaniasis
Leishmaniasis - drug therapy
Phytosterols
Prevalence
Promastigotes
Saponins - therapeutic use
Steroids - pharmacology
Steroids - therapeutic use
Visceral leishmaniasis
title Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives
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