title: The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in P. berghei-Infected Male Sprague-Dawley Rats.
abstract: The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of P. berghei-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period. Animals treated with drug-free pectin and CHQ acted as untreated and treated positive controls, respectively. Infected control rats exhibited significantly increased parasitaemia which was accompanied by hypoglycaemia. Both OA monotherapy and CHQ-OA combination therapy reduced and cleared the malaria parasites within a period of 4 and 3 days, respectively. Compared to respective controls groups, OGT responses of animals treated with OA monotherapy or CHQ-OA combination therapy exhibited lower blood glucose levels at all time points. A once-off transdermal application of OA-patch or CHQ-OA combination patch significantly improved blood glucose concentrations inducing any changes in insulin concentration. Transdermal OA used as a monotherapy or in combination with CHQ is able to clear and reduce the malaria parasites within a shorter period of time without eliciting any adverse effects on glucose homeostasis of P. berghei-infected rats.
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Happiness P
authors.identifier: http://orcid.org/0000-0001-9985-4759
authors.initials: HP
authors.lastname: Sibiya
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Musa V
authors.initials: MV
authors.lastname: Mabandla
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Cephas T
authors.initials: CT
authors.lastname: Musabayane
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006003:Glycogen / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D008288:Malaria / Q000097:blood / Q000188:drug therapy*; D008297:Male; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D027842:Syzygium / Q000737:chemistry
chemical_list: D000962:Antimalarials; D001786:Blood Glucose; D007328:Insulin; D010936:Plant Extracts; D009828:Oleanolic Acid; D002738:Chloroquine; D006003:Glycogen