Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of...

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Autores principales:	Madhuri Gupta, Saurabh Kumar, Ravi Kumar, Ashish Kumar, Riya Verma, Mahendra Pandurang Darokar, Prashant Rout, Anirban Pal
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Boswellia serrata Roxb Hydroxy-11-keto-β-boswellic acid Anti-plasmodial Heme detoxification Oxidative stress Acute oral toxicity Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0502c5202b5141d0aea6fc969ec88ab1
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spelling	oai:doaj.org-article:0502c5202b5141d0aea6fc969ec88ab12021-11-14T04:29:24ZInhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata0753-332210.1016/j.biopha.2021.112302https://doaj.org/article/0502c5202b5141d0aea6fc969ec88ab12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010866https://doaj.org/toc/0753-3322Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 μg/mL and 26.5 ± 4.5 μg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-β-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 μg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.Madhuri GuptaSaurabh KumarRavi KumarAshish KumarRiya VermaMahendra Pandurang DarokarPrashant RoutAnirban PalElsevierarticleBoswellia serrata RoxbHydroxy-11-keto-β-boswellic acidAnti-plasmodialHeme detoxificationOxidative stressAcute oral toxicityTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112302- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Boswellia serrata Roxb Hydroxy-11-keto-β-boswellic acid Anti-plasmodial Heme detoxification Oxidative stress Acute oral toxicity Therapeutics. Pharmacology RM1-950
spellingShingle	Boswellia serrata Roxb Hydroxy-11-keto-β-boswellic acid Anti-plasmodial Heme detoxification Oxidative stress Acute oral toxicity Therapeutics. Pharmacology RM1-950 Madhuri Gupta Saurabh Kumar Ravi Kumar Ashish Kumar Riya Verma Mahendra Pandurang Darokar Prashant Rout Anirban Pal Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
description	Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 μg/mL and 26.5 ± 4.5 μg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-β-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 μg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.
format	article
author	Madhuri Gupta Saurabh Kumar Ravi Kumar Ashish Kumar Riya Verma Mahendra Pandurang Darokar Prashant Rout Anirban Pal
author_facet	Madhuri Gupta Saurabh Kumar Ravi Kumar Ashish Kumar Riya Verma Mahendra Pandurang Darokar Prashant Rout Anirban Pal
author_sort	Madhuri Gupta
title	Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
title_short	Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
title_full	Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
title_fullStr	Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
title_full_unstemmed	Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata
title_sort	inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from boswellia serrata
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/0502c5202b5141d0aea6fc969ec88ab1
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Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-β-boswellic acid isolated from Boswellia serrata

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