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齐墩果酸的透皮给药可减轻伯氏疟原虫疟疾中促炎细胞因子的释放并改善贫血。

Transdermal delivery of oleanolic acid attenuates pro-inflammatory cytokine release and ameliorates anaemia in P. berghei malaria.

作者信息

Sibiya Happiness, Musabayane Cephas T, Mabandla Musa V

机构信息

School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.

School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.

出版信息

Acta Trop. 2017 Jul;171:24-29. doi: 10.1016/j.actatropica.2017.03.005. Epub 2017 Mar 7.

DOI:10.1016/j.actatropica.2017.03.005
PMID:28283442
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.

摘要

疟疾在许多热带地区仍然是一个主要的健康问题。严重的疟疾感染与包括贫血在内的继发性并发症相关,这导致需要寻找能够清除寄生虫血症并改善感染期间贫血状况的负担得起的抗疟药物。本研究调查了经皮递送的OA对感染伯氏疟原虫的雄性Sprague-Dawley大鼠体内疟原虫、血细胞比容(HCT)和选定血浆细胞因子浓度的影响。该研究为期21天,分为预处理期(第0 - 7天)、治疗期(第8 - 12天)和治疗后期(第13 - 21天)。在一次性应用OA - 果胶贴剂(34mg/kg)后,对未感染和感染的大鼠监测其寄生虫血症、HCT、红细胞计数、血红蛋白(Hgb)、血浆肿瘤坏死因子 - α(TNF - α)、白细胞介素 - 6(IL - 6)和白细胞介素 - 10(IL - 10)的浓度。分别用不含药物的果胶和氯喹(30mg/kg,口服)连续5天每天两次处理的动物作为阴性和阳性对照。感染的对照动物表现出寄生虫血症百分比增加、TNF - α、IL - 6、IL - 10升高以及HCT降低。有趣的是,应用OA - 果胶贴剂清除了疟原虫并使HCT值恢复正常。此外,在研究的第12天,TNF - α、IL - 6和IL - 10降低。这些发现表明,OA - 果胶贴剂递送的治疗剂量的OA能够在疟疾感染期间减弱细胞因子释放并改善贫血状况。因此,经皮递送的OA可能是一种有效的疟疾治疗药物和改善贫血的药物。

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