Trypanostatic activity of geranylacetone: Mitigation of Trypanosoma congolense-associated pathological pertubations and insight into the mechanism of anaemia amelioration using in vitro and in silico models

Trypanostatic activity of geranylacetone: Mitigation of Trypanosoma congolense-associated pathological pertubations and insight into the mechanism of anaemia amelioration using in vitro and in silico models

Trypanosoma congolense is an important pathogen that wreaks havoc in the livestock industry of the African continent. This study evaluated the in vivo antitrypanosomal activity of geranylacetone and its ameliorative effect on the disease-induced anaemia and organ damages as well as its inhibitory ef...

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Veröffentlicht in:Experimental parasitology 2019-06, Vol.201, p.49-56
Hauptverfasser: Saad, Saad Bello, Ibrahim, Mohammed Auwal, Jatau, Isa Danladi, Shuaibu, Mohammed Nasir
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Anaemia
Geranylacetone
Hepatosplenomegaly
Molecular docking
Sialidase
Trypanosoma congolense
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container_title Experimental parasitology
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Ibrahim, Mohammed Auwal
Jatau, Isa Danladi
Shuaibu, Mohammed Nasir
description Trypanosoma congolense is an important pathogen that wreaks havoc in the livestock industry of the African continent. This study evaluated the in vivo antitrypanosomal activity of geranylacetone and its ameliorative effect on the disease-induced anaemia and organ damages as well as its inhibitory effects against trypanosomal sialidase using in vitro and in silico techniques. Geranylacetone was used to treat T. congolense infected rats, at a dose of 50 and 100 mg/kg BW, for 14 days where it was found to reduce the parasite burden in the infected animals. Moreover, 100 mg/kg BW of geranylacetone significantly (p 
doi_str_mv 10.1016/j.exppara.2019.04.011
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This study evaluated the in vivo antitrypanosomal activity of geranylacetone and its ameliorative effect on the disease-induced anaemia and organ damages as well as its inhibitory effects against trypanosomal sialidase using in vitro and in silico techniques. Geranylacetone was used to treat T. congolense infected rats, at a dose of 50 and 100 mg/kg BW, for 14 days where it was found to reduce the parasite burden in the infected animals. Moreover, 100 mg/kg BW of geranylacetone significantly (p &lt; 0.05) ameliorated the anaemia, hepatic and renal damages caused by the parasite. This is in addition to the alleviation of the parasite-induced hepatosplenomegaly and upsurge in free serum sialic acid levels in the infected animals which were associated with the observed anaemia amelioration by the compound. Consequently, bloodstream T. congolense sialidase was partially purified on DEAE cellulose column and inhibition kinetic studies revealed that the enzyme was inhibited by geranylacetone via an uncompetitive inhibition pattern. In silico analysis using molecular docking with Autodock Vina indicated that geranylacetone binds to trypanosomal sialidase with a minimum free binding energy of −5.8 kcal/mol which was mediated by 26 different kinds of non-covalent interactions excluding hydrogen bond whilst Asp163 and Phe421 had the highest number of the interactions. The data suggests that geranylacetone has trypanostatic activity and could protect animals against the T. congolense-induced anaemia through the inhibition of sialidase and/or the protection of the parasite-induced hepatosplenomegaly. 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Consequently, bloodstream T. congolense sialidase was partially purified on DEAE cellulose column and inhibition kinetic studies revealed that the enzyme was inhibited by geranylacetone via an uncompetitive inhibition pattern. In silico analysis using molecular docking with Autodock Vina indicated that geranylacetone binds to trypanosomal sialidase with a minimum free binding energy of −5.8 kcal/mol which was mediated by 26 different kinds of non-covalent interactions excluding hydrogen bond whilst Asp163 and Phe421 had the highest number of the interactions. The data suggests that geranylacetone has trypanostatic activity and could protect animals against the T. congolense-induced anaemia through the inhibition of sialidase and/or the protection of the parasite-induced hepatosplenomegaly. [Display omitted] •Geranylacetone demonstrated trypanostatic activity towards Trypanosoma congolense in animals.•Geranylacetone mitigates T. congolense-induced anaemia and organ damage.•Bloodstream Trypanosoma congolense sialidase was inhibited by geranylacetone in an uncompetitive pattern.•26 non-covalent interactions were formed between trypanosomal sialidase and geranylacetone.</description><subject>Anaemia</subject><subject>Geranylacetone</subject><subject>Hepatosplenomegaly</subject><subject>Molecular docking</subject><subject>Sialidase</subject><subject>Trypanosoma congolense</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkctu1DAUhi0EokPhEUBeskmwE-fGBqGKm1TEpqytE-ckc0aJHWyn6rwkz4SHmbJl9S_8X3z0MfZailwKWb875PiwruAhL4TscqFyIeUTtpOiE1mhVPeU7YSQKlNtp67YixAOQohWFuo5uyqlKLpGiB37feePK1gXIkQyHEyke4pH7kY-oQd7nMFgdBbf8-8UaUouZ0-vjzm3ADfOTm5GGzCDEJwhiDjwFeLezW4iAzNf0cet_5sOHOzAyQaa9jFpdDzukS9o9mApLKd2sIALAYcFZ3L-vLoFslMK8PRD7y4tPNBMxvHFDTiHl-zZCHPAVxe9Zj8_f7q7-Zrd_vjy7ebjbWbKuopZX_Zta7DtDZZYQVMn6QqspWqGAsZmRFBtPapB4dgVZd8MNQojh67sSqOqsbxmb8-9q3e_NgxRLxQMzjNYdFvQRSHrpqlaIZK1OluNdyF4HPXqaQF_1FLoE0p90BeU-oRSC6UTypR7c5nY-gWHf6lHdsnw4WxId-M9odfBEFqDA3k0UQ-O_jPxB5UDupA</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Saad, Saad Bello</creator><creator>Ibrahim, Mohammed Auwal</creator><creator>Jatau, Isa Danladi</creator><creator>Shuaibu, Mohammed Nasir</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190601</creationdate><title>Trypanostatic activity of geranylacetone: Mitigation of Trypanosoma congolense-associated pathological pertubations and insight into the mechanism of anaemia amelioration using in vitro and in silico models</title><author>Saad, Saad Bello ; Ibrahim, Mohammed Auwal ; Jatau, Isa Danladi ; Shuaibu, Mohammed Nasir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-b3b88ce8bce3e5a76e3e92e6147d2af7fea486f4d4ef923b7d6e0c1d9393c45f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anaemia</topic><topic>Geranylacetone</topic><topic>Hepatosplenomegaly</topic><topic>Molecular docking</topic><topic>Sialidase</topic><topic>Trypanosoma congolense</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saad, Saad Bello</creatorcontrib><creatorcontrib>Ibrahim, Mohammed Auwal</creatorcontrib><creatorcontrib>Jatau, Isa Danladi</creatorcontrib><creatorcontrib>Shuaibu, Mohammed Nasir</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saad, Saad Bello</au><au>Ibrahim, Mohammed Auwal</au><au>Jatau, Isa Danladi</au><au>Shuaibu, Mohammed Nasir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypanostatic activity of geranylacetone: Mitigation of Trypanosoma congolense-associated pathological pertubations and insight into the mechanism of anaemia amelioration using in vitro and in silico models</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>201</volume><spage>49</spage><epage>56</epage><pages>49-56</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><abstract>Trypanosoma congolense is an important pathogen that wreaks havoc in the livestock industry of the African continent. This study evaluated the in vivo antitrypanosomal activity of geranylacetone and its ameliorative effect on the disease-induced anaemia and organ damages as well as its inhibitory effects against trypanosomal sialidase using in vitro and in silico techniques. Geranylacetone was used to treat T. congolense infected rats, at a dose of 50 and 100 mg/kg BW, for 14 days where it was found to reduce the parasite burden in the infected animals. Moreover, 100 mg/kg BW of geranylacetone significantly (p &lt; 0.05) ameliorated the anaemia, hepatic and renal damages caused by the parasite. This is in addition to the alleviation of the parasite-induced hepatosplenomegaly and upsurge in free serum sialic acid levels in the infected animals which were associated with the observed anaemia amelioration by the compound. Consequently, bloodstream T. congolense sialidase was partially purified on DEAE cellulose column and inhibition kinetic studies revealed that the enzyme was inhibited by geranylacetone via an uncompetitive inhibition pattern. In silico analysis using molecular docking with Autodock Vina indicated that geranylacetone binds to trypanosomal sialidase with a minimum free binding energy of −5.8 kcal/mol which was mediated by 26 different kinds of non-covalent interactions excluding hydrogen bond whilst Asp163 and Phe421 had the highest number of the interactions. The data suggests that geranylacetone has trypanostatic activity and could protect animals against the T. congolense-induced anaemia through the inhibition of sialidase and/or the protection of the parasite-induced hepatosplenomegaly. 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subjects Anaemia
Geranylacetone
Hepatosplenomegaly
Molecular docking
Sialidase
Trypanosoma congolense
title Trypanostatic activity of geranylacetone: Mitigation of Trypanosoma congolense-associated pathological pertubations and insight into the mechanism of anaemia amelioration using in vitro and in silico models
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