Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum

Introduction: Malaria control is hindered by drug-resistant parasites, leading to a shortage of effective drugs. There is a need to find new, better antimalarial drug. Traditional Chinese Medicine (TCM) are more accessible and cheaper alternative for combating resistance in the treatment of malaria,...

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Main Authors: Saurabh Kumar, Deepak Singh kapkoti, Pooja Rani Mina, Divya Bhatt, Parmanand Kumar, Manju Singh, Karuna Shanker, Dnyaneshwar Umrao Bawankule, Rajendra Singh Bhakuni, Anirban Pal, Mahendra P. Darokar
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Pharmacological Research - Modern Chinese Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S266714252400040X
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author Saurabh Kumar
Deepak Singh kapkoti
Pooja Rani Mina
Divya Bhatt
Parmanand Kumar
Manju Singh
Karuna Shanker
Dnyaneshwar Umrao Bawankule
Rajendra Singh Bhakuni
Anirban Pal
Mahendra P. Darokar
author_facet Saurabh Kumar
Deepak Singh kapkoti
Pooja Rani Mina
Divya Bhatt
Parmanand Kumar
Manju Singh
Karuna Shanker
Dnyaneshwar Umrao Bawankule
Rajendra Singh Bhakuni
Anirban Pal
Mahendra P. Darokar
author_sort Saurabh Kumar
collection DOAJ
description Introduction: Malaria control is hindered by drug-resistant parasites, leading to a shortage of effective drugs. There is a need to find new, better antimalarial drug. Traditional Chinese Medicine (TCM) are more accessible and cheaper alternative for combating resistance in the treatment of malaria, therefore the anti-malarial efficacy of root extracts and isolated phytomolecules from Glycyrrhiza glabra L was assessed. Methods: The anti-plasmodial potential of root extracts and isolated phytomolecules from Glycyrrhiza glabra L. was assessed using the Giemsa staining method. In- vivo, antimalarial efficacy was evaluated by conducting a four-day suppression test in a mouse model. The mechanistic studies of ISL were carried out using caspase-like activity, mitochondrial membrane potential, and reactive oxygen species (ROS) assay. Further, proteomics analysis was carried out by LC-MS/MS. The interaction of the combinations was evaluated using the fixed ratio method by calculating the fractional inhibitory concentration (FIC). Results: Extracts of G. glabra contain Phytomolecule(s) with moderate anti-plasmodial activity against multidrug-resistant strain (K1) of P. falciparum. Isoliquiritigenin (ISL) exhibited a significant reduction in parasitemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis infected mice. ISL showed potent activity with no cytotoxic effect and increased caspase-3 activity, leading increasing reactive oxygen species (ROS) and loss of mitochondrial potential. ISL also displayed synergy with chloroquine, glabridin and liquiritigenin against multi-drug-resistant P. falciparum. Discussion: The present study found ISL to be a potential phytomolecule of G. glabra. The study explored the mechanism of action of ISL and suggested its suitability for further study in managing drug-resistant malaria.
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spelling doaj.art-bc30bc5e9029446389a8378f0bdf4fc42024-03-21T05:38:08ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252024-03-0110100396Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparumSaurabh Kumar0Deepak Singh kapkoti1Pooja Rani Mina2Divya Bhatt3Parmanand Kumar4Manju Singh5Karuna Shanker6Dnyaneshwar Umrao Bawankule7Rajendra Singh Bhakuni8Anirban Pal9Mahendra P. Darokar10Molecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Blood Research Institute, Versiti Wisconsin, Watertown Plank Road, Milwaukee, WI, 53226 United StatesDepartment Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, IndiaMolecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Department of Immunology, Mayo Clinic, Scottsdale, AZ, USAMolecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, IndiaMolecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, IndiaDepartment Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, IndiaDepartment Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, IndiaMolecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, IndiaDepartment Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, IndiaMolecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Corresponding authors at: Molecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India.Molecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India; Technology Management Directorate, Council of Scientific and Industrial Research (CSIR), 14, Satsang Vihar Marg, New Delhi, India; Corresponding authors at: Molecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow-226015, India.Introduction: Malaria control is hindered by drug-resistant parasites, leading to a shortage of effective drugs. There is a need to find new, better antimalarial drug. Traditional Chinese Medicine (TCM) are more accessible and cheaper alternative for combating resistance in the treatment of malaria, therefore the anti-malarial efficacy of root extracts and isolated phytomolecules from Glycyrrhiza glabra L was assessed. Methods: The anti-plasmodial potential of root extracts and isolated phytomolecules from Glycyrrhiza glabra L. was assessed using the Giemsa staining method. In- vivo, antimalarial efficacy was evaluated by conducting a four-day suppression test in a mouse model. The mechanistic studies of ISL were carried out using caspase-like activity, mitochondrial membrane potential, and reactive oxygen species (ROS) assay. Further, proteomics analysis was carried out by LC-MS/MS. The interaction of the combinations was evaluated using the fixed ratio method by calculating the fractional inhibitory concentration (FIC). Results: Extracts of G. glabra contain Phytomolecule(s) with moderate anti-plasmodial activity against multidrug-resistant strain (K1) of P. falciparum. Isoliquiritigenin (ISL) exhibited a significant reduction in parasitemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis infected mice. ISL showed potent activity with no cytotoxic effect and increased caspase-3 activity, leading increasing reactive oxygen species (ROS) and loss of mitochondrial potential. ISL also displayed synergy with chloroquine, glabridin and liquiritigenin against multi-drug-resistant P. falciparum. Discussion: The present study found ISL to be a potential phytomolecule of G. glabra. The study explored the mechanism of action of ISL and suggested its suitability for further study in managing drug-resistant malaria.http://www.sciencedirect.com/science/article/pii/S266714252400040XGlycyrrhiza glabra LIsoliquiritigeninMalariaMultidrug-resistant P. falciparumApoptosisProteomic analysis
spellingShingle Saurabh Kumar
Deepak Singh kapkoti
Pooja Rani Mina
Divya Bhatt
Parmanand Kumar
Manju Singh
Karuna Shanker
Dnyaneshwar Umrao Bawankule
Rajendra Singh Bhakuni
Anirban Pal
Mahendra P. Darokar
Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
Pharmacological Research - Modern Chinese Medicine
Glycyrrhiza glabra L
Isoliquiritigenin
Malaria
Multidrug-resistant P. falciparum
Apoptosis
Proteomic analysis
title Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
title_full Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
title_fullStr Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
title_full_unstemmed Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
title_short Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum
title_sort isoliquiritigenin from licorice root a multi stage anti malarial with synergistic impact on multidrug resistant p falciparum
topic Glycyrrhiza glabra L
Isoliquiritigenin
Malaria
Multidrug-resistant P. falciparum
Apoptosis
Proteomic analysis
url http://www.sciencedirect.com/science/article/pii/S266714252400040X
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