Abstract
Rutin (3, 3', 4' 5 and 7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Severe malaria is an inflammatory response triggered by oxidative stress that results in multi-organ pathologies and a high mortality rate in children and pregnant women worldwide. Rutin is recommended as a food supplement for the treatment of various diseases due to its anti-oxidative and anti-inflammatory properties, which prompted us to investigate its ameliorative effects in severe malaria pathogenesis against oxidative stress and inflammatory response using in vitro and in vivo bioassays. Rutin was examined in this work for its anti-plasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains, as well as its anti-oxidative and anti-inflammatory activity against LPS-stimulated macrophage cells. The in vitro data were subsequently verified in mice fed orally with rutin alone or in combination with chloroquine in Plasmodium berghei-induced malaria pathogenesis. The anti-plasmodial and anti-inflammatory properties of rutin were demonstrated in in vitro results. Apart from its anti-inflammatory and anti-oxidant effects in malaria pathogenesis, in vivo efficacy studies indicated that oral treatment with rutin reduced parasitaemia, increased mean survival time, and restored haemoglobin and glucose levels in mice at lower dose. Interestingly, both rutin and chloroquine demonstrated synergy in in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria in combination with standard anti-malarial drugs.
Highlights
Malaria is arguably the main public health concern worldwide due to its high rate of mortality and morbidity across the Tropical and Sub-tropical regions with an estimated 229 million cases in 2019 (WHO 2020)
Modulation of the host inflammatory response exerted by the malaria parasite could be a considerable therapeutic approach against malaria pathogenesis such as the signalling kinases activated in the host in response to the malaria infection manifested a promising target for the antimalarial interference (Adderley et al 2020)
The efficacy study performed in vivo in mice infected with P. berghei showed that peak parasiatemia in vehicle-treated group was found on day 8 and the oral treatment of rutin exhibited significant reduction in parasitaemia when compared to infected mice as well as found dose-dependent improvement in the mean survival time in rutin treated mice
Summary
Malaria is arguably the main public health concern worldwide due to its high rate of mortality and morbidity across the Tropical and Sub-tropical regions with an estimated 229 million cases in 2019 (WHO 2020). The host undergo severe oxidative stress (Franklin et al 2011), which variously challenge the immune system of the infected host to activate macrophages, leading to the production of free radicals and pro-inflammatory cytokines such as TNF-α, IFN-γ and IL1-β ( (De Souza et al 2016). Any imbalance in this inflammatory response may result in immunopathology (Drewry et al 2018). The plants or plant-derived bioactives by exerting immunomodulatory effects on the host immune system are considered as the desirable source (Wright et al 2005)
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