title: Transdermal delivery of oleanolic acid attenuates pro-inflammatory cytokine release and ameliorates anaemia in P. berghei malaria.
abstract: Malaria remains a major health problem in many tropical areas. Severe malaria infection is associated with secondary complications including anaemia leading to a need for the search of affordable antimalarial agents that can clear the parasitaemia and ameliorate anaemia during infection. The current study investigated the effects of transdermally delivered OA on malaria parasites, HCT and selected plasma cytokine concentrations in P. berghei-infected male Sprague-Dawley rats. The study was carried out over a period of 21days, divided into pre-treatment (day 0-7), treatment (day 8-12) and post-treatment (day 13-21) periods. Parasitaemia, HCT, RBC count, Hgb, plasma TNF-α, IL-6 and IL-10 concentrations were monitored in non-infected and infected rats following a once-off application of an OA-pectin patch (34mg/kg). Animals treated with drug-free pectin and CHQ (30mg/kg, p.o) twice daily for 5 consecutive days acted as negative and positive controls respectively. Infected control animals exhibited increased percentage parasitaemia, TNF-α, IL-6, IL-10 and a reduction in HCT. Interestingly, OA-pectin patch application cleared the malaria parasites and increased HCT values back to normalcy. Furthermore, TNF-α, IL-6 and IL-10 were reduced by day 12 of the study. These findings suggest that the OA-pectin patch delivers therapeutic doses of OA which are able to attenuate cytokine release and ameliorate anaemia during malaria infection. Therefore, transdermally delivered OA may be a potent therapeutic agent for malaria and amelioration of anaemia.
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa. Electronic address: 208512882@stu.ukzn.ac.za.
authors.forename: Happiness
authors.initials: H
authors.lastname: Sibiya
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Cephas T
authors.initials: CT
authors.lastname: Musabayane
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Musa V
authors.initials: MV
authors.lastname: Mabandla
mesh_terms: D000740:Anemia / Q000517:prevention & control*; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D016753:Interleukin-10; D015850:Interleukin-6; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D008297:Male; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018512:Parasitemia / Q000469:parasitology; D010962:Plasmodium berghei / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009828:Oleanolic Acid
keywords: Anaemia; Cytokines; Inflammation; Malaria; Oleanolic acid; Plasmodium berghei; Transdermal patch