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.
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Abbreviations
- P. falciparum :
-
Plasmodium falciparum
- MAPK:
-
Mitogen-activated protein kinase
- NOS:
-
Nitric oxide synthase
- NF-κB:
-
Nuclear factor-kappa B
- iNOS:
-
Inducible nitric oxide synthase
- RPMI-1640:
-
Roswell park memorial institute 1640
- CQ:
-
Chloroquine
- DMSO:
-
Dimethylsulfoxide
- DMEM:
-
Dulbecco’s modified eagle medium
- FBS:
-
Fetal bovine serum
- PBS:
-
Phosphate-buffered saline
- LPS:
-
Lipopolysaccharide
- BSA:
-
Bovine serum albumin
- MTT:
-
(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium)
- ELISA:
-
Enzyme-linked immunosorbent assay
- ROS:
-
Reactive oxygen species
- CMH2DCFDA:
-
Chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate
- TNF-α:
-
Tumour necrosis factor-alpha
- IL-6:
-
Interleukin-6
- IL-1β:
-
Interleukin-1-beta
- P. berghei :
-
Plasmodium berghei
- RBC:
-
Red blood cell
- ACD:
-
Acid citrate dextrose saline
- CMC:
-
Carboxymethylcellulose
- IFN-γ:
-
Interferon-gamma
- TMB:
-
Tetramethylbenzidine
- MDA:
-
Malondialdehyde
- TBA:
-
Thiobarbituric acid
- TCA:
-
Trichloroacetic acid
- SDS:
-
Sodium dodecyl sulphate
- FIC:
-
Fractional inhibitory concentrations
- ƩFIC:
-
Summation fractional inhibitory concentrations
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Acknowledgements
We are thankful to Director, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India for rendering essential research facilities and support. The study was financially supported by CSIR under projects HCP-0007 and HCP-00352. The first author also acknowledges the fellowship provided by the Department of Science and Technology (DST), New Delhi, India.
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Bhatt, D., Kumar, S., Kumar, P. et al. Rutin ameliorates malaria pathogenesis by modulating inflammatory mechanism: an in vitro and in vivo study. Inflammopharmacol 30, 159–171 (2022). https://doi.org/10.1007/s10787-021-00920-w
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DOI: https://doi.org/10.1007/s10787-021-00920-w