title: Stigmasterol retards the proliferation and pathological features of Trypanosoma congolense infection in rats and inhibits trypanosomal sialidase in vitro and in silico.
abstract: Stigmasterol has been reported to possess antitrypanosomal activity using in vitro model but information on the in vivo antitrypanosomal effects which is necessary in drug development process has not been evaluated. Hence, the present study investigates the in vivo effects of stigmasterol against T. congolense in addition to its inhibitory effects of trypanosomal sialidase. Stigmasterol, at 100mg/kg BW, did not significantly (p>0.05) reduce the progression of T. congolense infection in animals but a 200mg/kg BW stigmasterol treatment significantly (p<0.05) reduced the parasitemia, although, it did not completely eliminate the parasite from the bloodstream of infected animals. However, the stigmasterol treatments significantly (p<0.05) ameliorated the T. congolense induced anemia as well as hepatic and renal damages. Furthermore, the T. congolense-associated increase in free serum sialic acid with a corresponding decrease in membrane bound sialic acid were prevented, though insignificantly (p>0.05), by the 200mg/kg BW treatment. Subsequently, in vitro enzyme kinetic studies revealed that stigmasterol is an uncompetitive inhibitor of a partially purified bloodstream T. congolense sialidase with an inhibition binding constant of 356.59μM. Using molecular docking studies, stigmasterol formed a single hydrogen bonding interaction with a major residue (D63) at the catalytic domain of T. rangeli sialidase with a predicted binding free energy of -24.012kcal/mol. We concluded that stigmasterol could retard the proliferation and the major pathological features of T. congolense infection whilst the anemia amelioration was mediated via inhibition of sialidase.
authors.affiliation: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
authors.forename: Raphael
authors.initials: R
authors.lastname: Aminu
authors.affiliation: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
authors.forename: Ismaila Alhaji
authors.initials: IA
authors.lastname: Umar
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong 4331, Bangladesh.
authors.forename: Md Atiar
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. Electronic address: mauwalibrahim@gmail.com.
authors.forename: Mohammed Auwal
authors.initials: MA
authors.lastname: Ibrahim
mesh_terms: D000818:Animals; D003198:Computer Simulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008954:Models, Biological; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013265:Stigmasterol / Q000627:therapeutic use*; D014348:Trypanosoma congolense / Q000201:enzymology*; D014352:Trypanosomiasis / Q000188:drug therapy*
chemical_list: D013265:Stigmasterol; D009439:Neuraminidase
keywords: Anemia; Liver damage; Sialic acid; Sialidase; Stigmasterol; Trypanosoma congolense