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Al-Nemi R, Akkawi M, Sawalha K, Kusumastuti SA, Nuralih, Kusumaningrum S, Okselni T, Situmorang VC, Septama AW, Jaremko M, Emwas AH. Comprehensive Metabolomics Profiling and Bioactivity Study of Lycium shawii (Awsaj) Extracts with Particular Emphasis on Potential Anti-Malarial Properties. Metabolites 2025; 15:84. [PMID: 39997709 PMCID: PMC11857410 DOI: 10.3390/metabo15020084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/14/2024] [Accepted: 12/18/2024] [Indexed: 02/26/2025] Open
Abstract
Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.
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Affiliation(s)
- Ruba Al-Nemi
- Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;
| | - Mutaz Akkawi
- Life Sciences Department, Faculty of Science & Technology, Al-Quds University, Jerusalem P.O. Box 20002, Palestine; (M.A.); (K.S.)
| | - Khalid Sawalha
- Life Sciences Department, Faculty of Science & Technology, Al-Quds University, Jerusalem P.O. Box 20002, Palestine; (M.A.); (K.S.)
| | - Siska Andrina Kusumastuti
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Nuralih
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Susi Kusumaningrum
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Tia Okselni
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Vania Chlarisa Situmorang
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Abdi Wira Septama
- Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Kabupaten Bogor 16911, Indonesia; (S.A.K.); (N.); (S.K.); (T.O.); (V.C.S.); (A.W.S.)
| | - Mariusz Jaremko
- Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;
| | - Abdul-Hamid Emwas
- KAUST Core Laboratories, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
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Narzary C, Sarkar D, Das P, Papi D. Ethnobotany, Phytochemistry, and Pharmacological Activity of Dioscorea bulbifera: A Comprehensive Review. Chem Biodivers 2025; 22:e202401408. [PMID: 39283965 DOI: 10.1002/cbdv.202401408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/13/2024] [Indexed: 11/02/2024]
Abstract
Dioscorea bulbifera (Family: Dioscoreaceae) also referred to as 'Air potato,' carries significant importance in the traditional medicine of China, West Africa and India. It is a common ingredient in numerous herbals and Ayurvedic formulations used to treat a variety of ailments. The literature review extensively examined the historical usage, phytoconstituents, characterisation of phytoconstituents, and medicinal uses of tubers, leaves, rhizomes and bulbils, with a particular focus on comparing research findings. Among the bioactive constituents, aglycone forms of steroidal saponins such as dioscorine, dioscin, diosbulbins, and diosgenin exhibit significant biological activities. Extracts from different parts of the plant exhibited pharmacological activities like anti-viral, anti-malarial, analgesic, antidiabetic, and anticancer. It is necessary to conduct an in-depth investigation to bridge between traditional knowledge and scientific evidence. This comprehensive review aims to provide a detailed understanding of the ethnobotany, phytoconstituent, chemical characterization and pharmacological potential of D. bulbifera, highlighting its prospects and challenges for future research and medicinal application.
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Affiliation(s)
- Christina Narzary
- Department of Pharmacy, Regional College of Pharmaceutical Sciences, Patarkuchi Lane, Beside Dichang Resort, Tepesia, Sonapur, Guwahati, Assam, PIN 782402, India
- Assam down town University, Sankar Madhab Path, Gandhinagar, Panikhaiti, Guwahati, Assam, PIN 781026, India
| | - Dhrubajyoti Sarkar
- Assam down town University, Sankar Madhab Path, Gandhinagar, Panikhaiti, Guwahati, Assam, PIN 781026, India
| | - Priyanka Das
- Department of Pharmacy, Regional College of Pharmaceutical Sciences, Patarkuchi Lane, Beside Dichang Resort, Tepesia, Sonapur, Guwahati, Assam, PIN 782402, India
| | - Dakme Papi
- School of Pharmacy, Arunachal University of Studies, Namsai, Arunachal Pradesh, PIN-792103, India
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Godara P, Reddy KS, Sahu W, Naik B, Srivastava V, Das R, Mahor A, Kumar P, Giri R, Anirudh J, Tak H, Banavath HN, Bhatt TK, Goyal AK, Prusty D. Structure-based virtual screening against multiple Plasmodium falciparum kinases reveals antimalarial compounds. Mol Divers 2024; 28:3661-3681. [PMID: 38127294 DOI: 10.1007/s11030-023-10770-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 11/11/2023] [Indexed: 12/23/2023]
Abstract
The continuous emergence of resistance against most frontline antimalarial drugs has led to countless deaths in malaria-endemic countries, counting 619,000 deaths in 2021, with mutation in drug targets being the sole cause. As mutation is correlated frequently with fitness cost, the likelihood of mutation emergence in multiple targets at a time is extremely low. Hence, multitargeting compounds may seem promising to address drug resistance issues with additional benefits like increased efficacy, improved safety profile, and the requirement of fewer pills compared to traditional single and combinational drugs. In this study, we attempted to use the High Throughput Virtual Screening approach to predict multitarget inhibitors against six chemically validated Plasmodium falciparum (Pf) kinases (PfPKG, PfMAP2, PfCDPK4, PfTMK, PfPK5, PfPI4K), resulting in 21 multitargeting hits. The molecular dynamic simulation of the top six complexes (Myricetin-MAP2, Quercetin-CDPK4, Myricetin-TMK, Quercetin-PKG, Salidroside-PK5, and Salidroside-PI4K) showed stable interactions. Moreover, hierarchical clustering reveals the structural divergence of the compounds from the existing antimalarials, indicating less chance of cross-resistance. Additionally, the top three hits were validated through parasite growth inhibition assays, with quercetin and myricetin exhibiting an IC50 value of 1.84 and 3.93 µM, respectively.
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Affiliation(s)
- Priya Godara
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - K Sony Reddy
- School of Biotechnology, Kalinga Institute of Industrial Technology (Deemed University), Bhubaneswar, 751024, India
| | - Welka Sahu
- School of Biotechnology, Kalinga Institute of Industrial Technology (Deemed University), Bhubaneswar, 751024, India
| | - Biswajit Naik
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Varshita Srivastava
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Rusham Das
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Ajay Mahor
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Prateek Kumar
- School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, India
| | - Rajanish Giri
- School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, India
| | - Jivanage Anirudh
- Department of Sports Biosciences, School of Sport Sciences, Central University of Rajasthan, Ajmer, India
| | - Harshita Tak
- Department of Sports Biosciences, School of Sport Sciences, Central University of Rajasthan, Ajmer, India
| | - Hemanth Naick Banavath
- Department of Sports Biosciences, School of Sport Sciences, Central University of Rajasthan, Ajmer, India
| | - Tarun Kumar Bhatt
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Amit Kumar Goyal
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Dhaneswar Prusty
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India.
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Owumi S, Olanlokun JO, Wu B, Duro-Ladipo AM, Oyelere SE, Khan SI, Oyelere AK. Elucidation of the Active Agents in a West African Ground Herbal Medicine Formulation That Elicit Antimalarial Activities in In Vitro and In Vivo Models. Molecules 2024; 29:5658. [PMID: 39683816 DOI: 10.3390/molecules29235658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/25/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Agunmu (ground herbal medicine) is a form of West African traditional medicine consisting of a cocktail of herbs. The goal of this study is to evaluate a formulation of Agunmu made from M. indica, A. repens, E. chlorantha, A. boonei, and B. ferruginea, sold in the open market and commonly used for the treatment of malaria by the locals, for its antimalarial effects and to determine the active principles that may contribute to the antimalarial effect. The ethanolic extract obtained from this formulation (Ag-Iba) was analyzed, using TLC, LC-MS, and Tandem-MS techniques, to determine its phytochemical properties. The extract was tested in vitro against representative bacteria strains, cancer and normal human cell lines, and susceptible (D6) and resistant (W2) Plasmodium falciparum. In subsequent in vivo experiments, graded doses of the extract were used to treat mice infected with chloroquine-susceptible (NK-65) and chloroquine-resistant (ANKA) strains of Plasmodium berghei. Bacteria growth was monitored with a disc diffusion assay, cancer cell viability was determined with MTS assay, and percentage parasitemia and parasite clearance were determined by microscopy. Bound heme content, host mitochondria permeability transition (mPT) pore opening, F0F1-ATPase, and lipid peroxidation were determined via spectrophotometry. Indices of oxidative stress, anti-oxidant activities, toxicity, cell death, and inflammatory responses were obtained using biochemical and ELISA techniques. The histology of the liver and spleen was performed using the standard method. We elucidated the structures of the critical active principles in the extract to be flavonoids: kaempferol, quercetin, myricetin, and their glycosides with little or no detectable levels of the toxic Aristolochic acids that are found in Aristolochia repens, one of the components of the formulation. The extract also showed anti-plasmodial activity in in vitro and in vivo models. Furthermore, the extract dose-dependently decreased mitochondrial dysfunction, cell death, and inflammatory and oxidative damage but increased antioxidant potentials. Presumably, the active principles in the extract work as a combinatorial therapy to elicit potent antimalarial activity. Overall, our study unraveled the active components from a commercial herbal formulation that could be reformulated for antimalarial therapy.
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Affiliation(s)
- Solomon Owumi
- Cancer Research and Molecular Biology Laboratories, University of Ibadan, Ibadan 200005, Nigeria
| | - John O Olanlokun
- Laboratories for Biomembrane and Biotechnology Research, Department of Biochemistry, University of Ibadan, Ibadan 200005, Nigeria
| | - Bocheng Wu
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | | | | | - Shabana I Khan
- NCNPR, School of Pharmacy, University of Mississippi, University, MS 38677, USA
| | - Adegboyega K Oyelere
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Memariani H, Memariani M, Ghasemian A. Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues. BIOMED RESEARCH INTERNATIONAL 2024; 2024:7632408. [PMID: 38456097 PMCID: PMC10919984 DOI: 10.1155/2024/7632408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 01/20/2024] [Accepted: 02/12/2024] [Indexed: 03/09/2024]
Abstract
Despite tremendous advances in the prevention and treatment of infectious diseases, only few antiparasitic drugs have been developed to date. Protozoan infections such as malaria, leishmaniasis, and trypanosomiasis continue to exact an enormous toll on public health worldwide, underscoring the need to discover novel antiprotozoan drugs. Recently, there has been an explosion of research into the antiprotozoan properties of quercetin, one of the most abundant flavonoids in the human diet. In this review, we tried to consolidate the current knowledge on the antiprotozoal effects of quercetin and to provide the most fruitful avenues for future research. Quercetin exerts potent antiprotozoan activity against a broad spectrum of pathogens such as Leishmania spp., Trypanosoma spp., Plasmodium spp., Cryptosporidium spp., Trichomonas spp., and Toxoplasma gondii. In addition to its immunomodulatory roles, quercetin disrupts mitochondrial function, induces apoptotic/necrotic cell death, impairs iron uptake, inhibits multiple enzymes involved in fatty acid synthesis and the glycolytic pathways, suppresses the activity of DNA topoisomerases, and downregulates the expression of various heat shock proteins in these pathogens. In vivo studies also show that quercetin is effective in reducing parasitic loads, histopathological damage, and mortality in animals. Future research should focus on designing effective drug delivery systems to increase the oral bioavailability of quercetin. Incorporating quercetin into various nanocarrier systems would be a promising approach to manage localized cutaneous infections. Nevertheless, clinical trials are needed to validate the efficacy of quercetin in treating various protozoan infections.
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Affiliation(s)
- Hamed Memariani
- Department of Medical Microbiology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Memariani
- Department of Medical Microbiology, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
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Evbuomwan IO, Alejolowo OO, Elebiyo TC, Nwonuma CO, Ojo OA, Edosomwan EU, Chikwendu JI, Elosiuba NV, Akulue JC, Dogunro FA, Rotimi DE, Osemwegie OO, Ojo AB, Ademowo OG, Adeyemi OS, Oluba OM. In silico modeling revealed phytomolecules derived from Cymbopogon citratus (DC.) leaf extract as promising candidates for malaria therapy. J Biomol Struct Dyn 2024; 42:101-118. [PMID: 36974933 DOI: 10.1080/07391102.2023.2192799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 03/10/2023] [Indexed: 03/29/2023]
Abstract
The emergence of varying levels of resistance to currently available antimalarial drugs significantly threatens global health. This factor heightens the urgency to explore bioactive compounds from natural products with a view to discovering and developing newer antimalarial drugs with novel mode of actions. Therefore, we evaluated the inhibitory effects of sixteen phytocompounds from Cymbopogon citratus leaf extract against Plasmodium falciparum drug targets such as P. falciparum circumsporozoite protein (PfCSP), P. falciparum merozoite surface protein 1 (PfMSP1) and P. falciparum erythrocyte membrane protein 1 (PfEMP1). In silico approaches including molecular docking, pharmacophore modeling and 3D-QSAR were adopted to analyze the inhibitory activity of the compounds under consideration. The molecular docking results indicated that a compound swertiajaponin from C. citratus exhibited a higher binding affinity (-7.8 kcal/mol) to PfMSP1 as against the standard artesunate-amodiaquine (-6.6 kcal/mol). Swertiajaponin also formed strong hydrogen bond interactions with LYS29, CYS30, TYR34, ASN52, GLY55 and CYS28 amino acid residues. In addition, quercetin another compound from C. citratus exhibited significant binding energies -6.8 and -8.3 kcal/mol with PfCSP and PfEMP1, respectively but slightly lower than the standard artemether-lumefantrine with binding energies of -7.4 kcal/mol against PfCSP and -8.7 kcal/mol against PfEMP1. Overall, the present study provides evidence that swertiajaponin and other phytomolecules from C. citratus have modulatory properties toward P. falciparum drug targets and thus may warrant further exploration in early drug discovery efforts against malaria. Furthermore, these findings lend credence to the folkloric use of C. citratus for malaria treatment.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Ikponmwosa Owen Evbuomwan
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
- Department of Food Science and Microbiology, Landmark University, Omu-Aran, Nigeria
| | - Omokolade Oluwaseyi Alejolowo
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
| | | | - Charles Obiora Nwonuma
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
| | - Oluwafemi Adeleke Ojo
- Phytomedicine, Molecular Toxicology and Computational Biochemistry Research Group, Department of Biochemistry, Bowen University, Iwo, Nigeria
| | - Evelyn Uwa Edosomwan
- Department of Animal and Environmental Biology, University of Benin, Benin City, Nigeria
| | | | | | | | | | - Damilare Emmanuel Rotimi
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
| | | | | | - Olusegun George Ademowo
- Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria
- Drug Research Laboratory, Institute of Advanced Medical Research and Training (IMRAT), College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Oluyomi Stephen Adeyemi
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, Osaki, Miyagi, Japan
| | - Olarewaju Michael Oluba
- SDG #03 Group - Good Health and Well-Being Research Cluster, Landmark University, Omu-Aran, Nigeria
- Department of Biochemistry, Landmark University, Omu-Aran, Nigeria
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Fulgheri F, Manca ML, Fernàndez-Busquets X, Manconi M. Analysis of complementarities between nanomedicine and phytodrugs for the treatment of malarial infection. Nanomedicine (Lond) 2023; 18:1681-1696. [PMID: 37955573 DOI: 10.2217/nnm-2023-0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023] Open
Abstract
The use of nanocarriers in medicine, so-called nanomedicine, is one of the most innovative strategies for targeting drugs at the action site and increasing their activity index and effectiveness. Phytomedicine is the oldest traditional method used to treat human diseases and solve health problems. The recent literature on the treatment of malaria infections using nanodelivery systems and phytodrugs or supplements has been analyzed. For the first time, in the present review, a careful look at the considerable potential of nanomedicine in promoting phytotherapeutic efficacy was done, and its key role in addressing a translation through a significant reduction of the current burden of malaria in many parts of the world has been underlined.
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Affiliation(s)
- Federica Fulgheri
- Department of Life & Environmental Sciences, University of Cagliari, University Campus, S.P. Monserrato-Sestu Km 0.700, Monserrato, 09042 CA, Italy
| | - Maria Letizia Manca
- Department of Life & Environmental Sciences, University of Cagliari, University Campus, S.P. Monserrato-Sestu Km 0.700, Monserrato, 09042 CA, Italy
| | - Xavier Fernàndez-Busquets
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic-Universitat de Barcelona, Rosselló 1 49-153, 08036 Barcelona, Spain
- Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain
- Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
| | - Maria Manconi
- Department of Life & Environmental Sciences, University of Cagliari, University Campus, S.P. Monserrato-Sestu Km 0.700, Monserrato, 09042 CA, Italy
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Fulgheri F, Aroffu M, Ramírez M, Román-Álamo L, Peris JE, Usach I, Nacher A, Manconi M, Fernàndez-Busquets X, Manca ML. Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections. Int J Pharm 2023; 643:123195. [PMID: 37394159 DOI: 10.1016/j.ijpharm.2023.123195] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/04/2023]
Abstract
Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around -8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.
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Affiliation(s)
- Federica Fulgheri
- Dept. of Life and Environmental Sciences of the University of Cagliari, University Campus, Pad. A, S.P. Monserrato-Sestu Km 0.700, Monserrato 09042, CA, Italy
| | - Matteo Aroffu
- Dept. of Life and Environmental Sciences of the University of Cagliari, University Campus, Pad. A, S.P. Monserrato-Sestu Km 0.700, Monserrato 09042, CA, Italy
| | - Miriam Ramírez
- Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain; Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
| | - Lucía Román-Álamo
- Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain; Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
| | - José Esteban Peris
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
| | - Iris Usach
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
| | - Amparo Nacher
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain; Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain
| | - Maria Manconi
- Dept. of Life and Environmental Sciences of the University of Cagliari, University Campus, Pad. A, S.P. Monserrato-Sestu Km 0.700, Monserrato 09042, CA, Italy.
| | - Xavier Fernàndez-Busquets
- Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain; Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
| | - Maria Letizia Manca
- Dept. of Life and Environmental Sciences of the University of Cagliari, University Campus, Pad. A, S.P. Monserrato-Sestu Km 0.700, Monserrato 09042, CA, Italy
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Sulyman AO, Aje OO, Ajani EO, Abdulsalam RA, Balogun FO, Sabiu S. Bioprospection of Selected Plant Secondary Metabolites as Modulators of the Proteolytic Activity of Plasmodium falciparum Plasmepsin V. BIOMED RESEARCH INTERNATIONAL 2023; 2023:6229503. [PMID: 37388365 PMCID: PMC10307063 DOI: 10.1155/2023/6229503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/25/2023] [Accepted: 06/01/2023] [Indexed: 07/01/2023]
Abstract
Malaria is a devastating disease, and its management is only achieved through chemotherapy. However, resistance to available medication is still a challenge; therefore, there is an urgent need for the discovery and development of therapeutics with a novel mechanism of action to counter the resistance scourge consistent with the currently available antimalarials. Recently, plasmepsin V was validated as a therapeutic target for the treatment of malaria. The pepsin-like aspartic protease anchored in the endoplasmic reticulum is responsible for the trafficking of parasite-derived proteins to the erythrocytic surface of the host cells. In this study, a small library of compounds was preliminarily screened in vitro to identify novel modulators of Plasmodium falciparum plasmepsin V (PfPMV). The results obtained revealed kaempferol, quercetin, and shikonin as possible PfPMV inhibitors, and these compounds were subsequently probed for their inhibitory potentials using in vitro and in silico methods. Kaempferol and shikonin noncompetitively and competitively inhibited the specific activity of PfPMV in vitro with IC50 values of 22.4 and 43.34 μM, respectively, relative to 62.6 μM obtained for pepstatin, a known aspartic protease inhibitor. Further insight into the structure-activity relationship of the compounds through a 100 ns molecular dynamic (MD) simulation showed that all the test compounds had a significant affinity for PfPMV, with quercetin (-36.56 kcal/mol) being the most prominent metabolite displaying comparable activity to pepstatin (-35.72 kcal/mol). This observation was further supported by the compactness and flexibility of the resulting complexes where the compounds do not compromise the structural integrity of PfPMV but rather stabilized and interacted with the active site amino acid residues critical to PfPMV modulation. Considering the findings in this study, quercetin, kaempferol, and shikonin could be proposed as novel aspartic protease inhibitors worthy of further investigation in the treatment of malaria.
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Affiliation(s)
- Abdulhakeem Olarewaju Sulyman
- Department of Biochemistry, Faculty of Pure and Applied Sciences, Kwara State University, P.M.B. 1530, Malete, Ilorin, Nigeria
| | - Oluwapelumi Oluwaseun Aje
- Department of Biochemistry, Faculty of Pure and Applied Sciences, Kwara State University, P.M.B. 1530, Malete, Ilorin, Nigeria
| | - Emmanuel Oladipo Ajani
- Department of Biochemistry, Faculty of Pure and Applied Sciences, Kwara State University, P.M.B. 1530, Malete, Ilorin, Nigeria
| | - Rukayat Abiola Abdulsalam
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa
| | - Fatai Oladunni Balogun
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa
| | - Saheed Sabiu
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa
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Maciuk A, Mazier D, Duval R. Future antimalarials from Artemisia? A rationale for natural product mining against drug-refractory Plasmodium stages. Nat Prod Rep 2023; 40:1130-1144. [PMID: 37021639 DOI: 10.1039/d3np00001j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
Covering: up to 2023Infusions of the plants Artemisia annua and A. afra are gaining broad popularity to prevent or treat malaria. There is an urgent need to address this controversial public health question by providing solid scientific evidence in relation to these uses. Infusions of either species were shown to inhibit the asexual blood stages, the liver stages including the hypnozoites, but also the sexual stages, the gametocytes, of Plasmodium parasites. Elimination of hypnozoites and sterilization of mature gametocytes remain pivotal elements of the radical cure of P. vivax, and the blockage of P. vivax and P. falciparum transmission, respectively. Drugs active against these stages are restricted to the 8-aminoquinolines primaquine and tafenoquine, a paucity worsened by their double dependence on the host genetic to elicit clinical activity without severe toxicity. Besides artemisinin, these Artemisia spp. contain many natural products effective against Plasmodium asexual blood stages, but their activity against hypnozoites and gametocytes was never investigated. In the context of important therapeutic issues, we provide a review addressing (i) the role of artemisinin in the bioactivity of these Artemisia infusions against specific parasite stages, i.e., alone or in association with other phytochemicals; (ii) the mechanisms of action and biological targets in Plasmodium of ca. 60 infusion-specific Artemisia phytochemicals, with an emphasis on drug-refractory parasite stages (i.e., hypnozoites and gametocytes). Our objective is to guide the strategic prospecting of antiplasmodial natural products from these Artemisia spp., paving the way toward novel antimalarial "hit" compounds either naturally occurring or Artemisia-inspired.
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Affiliation(s)
| | - Dominique Mazier
- CIMI, CNRS, Inserm, Faculté de Médecine Sorbonne Université, 75013 Paris, France
| | - Romain Duval
- MERIT, IRD, Université Paris Cité, 75006 Paris, France.
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11
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Mahmud AR, Ema TI, Siddiquee MFR, Shahriar A, Ahmed H, Mosfeq-Ul-Hasan M, Rahman N, Islam R, Uddin MR, Mizan MFR. Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2023; 12:47. [PMID: 37216013 PMCID: PMC10183303 DOI: 10.1186/s43088-023-00387-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 05/07/2023] [Indexed: 05/24/2023] Open
Abstract
Background Flavonols are phytoconstituents of biological and medicinal importance. In addition to functioning as antioxidants, flavonols may play a role in antagonizing diabetes, cancer, cardiovascular disease, and viral and bacterial diseases. Quercetin, myricetin, kaempferol, and fisetin are the major dietary flavonols. Quercetin is a potent scavenger of free radicals, providing protection from free radical damage and oxidation-associated diseases. Main body of the abstract An extensive literature review of specific databases (e.g., Pubmed, google scholar, science direct) were conducted using the keywords "flavonol," "quercetin," "antidiabetic," "antiviral," "anticancer," and "myricetin." Some studies concluded that quercetin is a promising antioxidant agent while kaempferol could be effective against human gastric cancer. In addition, kaempferol prevents apoptosis of pancreatic beta-cells via boosting the function and survival rate of the beta-cells, leading to increased insulin secretion. Flavonols also show potential as alternatives to conventional antibiotics, restricting viral infection by antagonizing the envelope proteins to block viral entry. Short conclusion There is substantial scientific evidence that high consumption of flavonols is associated with reduced risk of cancer and coronary diseases, free radical damage alleviation, tumor growth prevention, and insulin secretion improvement, among other diverse health benefits. Nevertheless, more studies are required to determine the appropriate dietary concentration, dose, and type of flavonol for a particular condition to prevent any adverse side effects.
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Affiliation(s)
- Aar Rafi Mahmud
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902 Bangladesh
| | - Tanzila Ismail Ema
- Department of Biochemistry and Microbiology, North South University, Dhaka, 1229 Bangladesh
| | | | - Asif Shahriar
- Department of Microbiology, Stamford University Bangladesh, 51 Siddeswari Road, Dhaka, 1217 Bangladesh
| | - Hossain Ahmed
- Department of Biotechnology and Genetic Engineering, University of Development Alternative (UODA), Dhaka, 1208 Bangladesh
| | - Md. Mosfeq-Ul-Hasan
- Hajee Mohammad Danesh Science and Technology University, Dinajpur, 5200 Bangladesh
| | - Nova Rahman
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, 1342 Bangladesh
| | - Rahatul Islam
- Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh
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12
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Shinyuy LM, Loe GE, Jansen O, Mamede L, Ledoux A, Noukimi SF, Abenwie SN, Ghogomu SM, Souopgui J, Robert A, Demeyer K, Frederich M. Secondary Metabolites Isolated from Artemisia afra and Artemisia annua and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties-Pharmacokinetics and Pharmacodynamics: A Review. Metabolites 2023; 13:metabo13050613. [PMID: 37233654 DOI: 10.3390/metabo13050613] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/24/2023] [Accepted: 04/26/2023] [Indexed: 05/27/2023] Open
Abstract
There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.
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Affiliation(s)
- Lahngong Methodius Shinyuy
- Laboratory of Pharmacognosy, Department of Pharmacy, Center of Interdisciplinary Research on Medicine (CIRM), University of Liege, 4000 Liège, Belgium
- Laboratory of In Vitro Toxicology and Dermato-Cosmetology (IVTD), Department of Analytical, Applied Chemometrics and Molecular Modeling (FABI), Faculty of Medicine and Pharmacy, Vrije Universiteit of Brussel, 1050 Ixelles, Belgium
- Laboratory of Pharmacochemical and Natural Pharmaceutical Substances, Doctoral Training Unit in Health Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala P.O. Box 2701, Cameroon
| | - Gisèle E Loe
- Laboratory of Pharmacochemical and Natural Pharmaceutical Substances, Doctoral Training Unit in Health Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala P.O. Box 2701, Cameroon
| | - Olivia Jansen
- Laboratory of Pharmacognosy, Department of Pharmacy, Center of Interdisciplinary Research on Medicine (CIRM), University of Liege, 4000 Liège, Belgium
| | - Lúcia Mamede
- Laboratory of Pharmacognosy, Department of Pharmacy, Center of Interdisciplinary Research on Medicine (CIRM), University of Liege, 4000 Liège, Belgium
| | - Allison Ledoux
- Laboratory of Pharmacognosy, Department of Pharmacy, Center of Interdisciplinary Research on Medicine (CIRM), University of Liege, 4000 Liège, Belgium
| | - Sandra Fankem Noukimi
- Molecular and Cell Biology Laboratory (MCBL), Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
- Embryology and Biotechnology Laboratory, Université Libre de Bruxelles, 1050 Brussels, Belgium
| | - Suh Nchang Abenwie
- Epidemiology and Biostatistics Unit (EPiD), Institute of Clinical and Experimental Research (IREC), UCLouvain, 1200 Brussel, Belgium
| | - Stephen Mbigha Ghogomu
- Molecular and Cell Biology Laboratory (MCBL), Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
| | - Jacob Souopgui
- Embryology and Biotechnology Laboratory, Université Libre de Bruxelles, 1050 Brussels, Belgium
| | - Annie Robert
- Epidemiology and Biostatistics Unit (EPiD), Institute of Clinical and Experimental Research (IREC), UCLouvain, 1200 Brussel, Belgium
| | - Kristiaan Demeyer
- Laboratory of In Vitro Toxicology and Dermato-Cosmetology (IVTD), Department of Analytical, Applied Chemometrics and Molecular Modeling (FABI), Faculty of Medicine and Pharmacy, Vrije Universiteit of Brussel, 1050 Ixelles, Belgium
| | - Michel Frederich
- Laboratory of Pharmacognosy, Department of Pharmacy, Center of Interdisciplinary Research on Medicine (CIRM), University of Liege, 4000 Liège, Belgium
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13
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Mabuza JM, Kaiser M, Bapela MJ. In vitro antiplasmodial activity and cytotoxicity of extracts and chromatographic fractions of twigs from Pappea capensis EckI & Zeyh. (Sapindaceae). JOURNAL OF ETHNOPHARMACOLOGY 2022; 298:115659. [PMID: 36041692 DOI: 10.1016/j.jep.2022.115659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/14/2022] [Accepted: 08/16/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Vha-Venda people of South Africa use Pappea capensis EckI & Zeyh. (Sapindaceae) twigs to treat malaria and its related symptoms. AIM OF STUDY The main aim of this study was to evaluate the antiplasmodial and cytotoxic activity of P. capensis extracts and chromatographic fractions. Spectroscopy analysis was conducted using 1H NMR and GC-MS to tentatively identify the major classes of compounds and phytoconstituents that can be attributed to the observed antiplasmodial bioactivity. MATERIALS AND METHODS Pappea capensis twigs were dried and then ground to fine powder. A solvent mixture of dichloromethane: methanol: water (1:0.5:0.5, v/v) was used to extract. The polar extract was separated from the non-polar. The organic extract was dried to yield a DCM (I = 60 g) extract. The methanol in the aqueous extract was evaporated using a rotary vapour and the remaining water freeze dried to yield a water extract (II = 287 g). Extract I was further partitioned using a solvent mixture of DCM: MeOH (1:1, v/v), separated and concentrated under vacuum to yield dichloromethane (III = 40 g) and methanol (IV = 15 g) extracts. A water-based decoction (V = 10 g) was also prepared to establish the clinical relevance of the preparation administered by Vha-Venda people in South Africa. Extracts II, III and IV were further subjected to silica column chromatography, eluting with a series of different solvents with increasing polarity to yield a total of 25 fractions (A - Y). In vitro antiplasmodial tests on Plasmodium falciparum (NF54) and cytotoxicity screens on mammalian L-6 rat skeletal myoblast cells were performed on all extracts and fractions. Selectivity indices (SI) were also computed for all tested extracts and fractions which were further subjected to 1H NMR spectroscopy and GC-MS analysis for the identification of the major classes of compounds present in the extracts. RESULTS From the assayed extracts, only extract I (IC50 = 2.93 μg/ml; SI = 14), III (IC50 = 2.59 μg/ml; SI = 21) and IV (IC50 = 3.56 μg/ml; SI = 13) demonstrated the best antiplasmodial activity and selectivity. Of all assayed fractions, only N (0.6 μg/ml; SI = 91), D (0.85 μg/ml; SI = 37) and E (0.91 μg/ml; SI = 30) depicted the best antiplasmodial activity and selectivity. The 1H NMR analysis of the extracts and fractions identified the prominent class of constituents to be aliphatic based which was tentatively identified as terpenoids. When further GC-MS analysis was conducted, the presence of lupin-3-one, lupeol acetate, α-amyrin, and β-amyrin phytoconstituents were tentatively confirmed. These constituents are triterpenoids with established antiplasmodial activity which can be tentatively attributed to the bioactivity observed in P. capensis twigs. CONCLUSION The study validates the ethnomedicinal use of P. capensis for malaria treatment. It demonstrated the potential of discovering novel antiplasmodial constituents that could serve as drug hits through dereplication approaches where known compounds with established antimalarial activity can be bypassed to focus on the unknown.
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Affiliation(s)
- J Mcebisi Mabuza
- University of Pretoria, Department of Plant and Soil Sciences, Hatfield, 0028, South Africa; University of Pretoria Institute for Sustainable Malaria Control and Medical Research Council Collaborating Center for Malaria Research, South Africa.
| | - Marcel Kaiser
- Swiss Tropical and Public Health Institute, Allschwil, Switzerland; University of Basel, Basel, Switzerland
| | - M Johanna Bapela
- University of Pretoria, Department of Plant and Soil Sciences, Hatfield, 0028, South Africa; University of Pretoria Institute for Sustainable Malaria Control and Medical Research Council Collaborating Center for Malaria Research, South Africa
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Tajuddeen N, Swart T, Hoppe HC, van Heerden FR. Phytochemical, Antiplasmodial, and Cytotoxic Investigation of Euclea natalensis A.DC. subsp. natalensis Leaves. Chem Biodivers 2022; 19:e202200150. [PMID: 36253138 DOI: 10.1002/cbdv.202200150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/21/2022] [Indexed: 11/12/2022]
Abstract
Previous research shows that the root and bark extracts of Euclea natalensis have antiplasmodial activity, but the leaves have not been examined yet. This study investigated the phytochemical, antiplasmodial, and cytotoxic properties of the plant leaves. The activity against 3D7 Plasmodium falciparum was determined using the parasite lactate dehydrogenase assay, and the cytotoxicity against Vero and HeLa cells was evaluated using the MTT and resazurin assays, respectively. The bioactive compounds were isolated by chromatography, and their structures were established with spectroscopic and spectrometric techniques. The extract showed antiplasmodial activity (IC50 =25.6 μg/mL) and was not cytotoxic against Vero cells (IC50 =403.7 μg/mL). Purification of the extract afforded six flavonoid glycosides, four triterpenoids, and a coumarin. The glycosides showed antiplasmodial and cytotoxic activities, against HeLa cells, at 50 μg/mL, but the activity was reduced at 10 μg/mL. Naphthoquinones, which are among the predominant phytochemicals in the root and root bark of E. natalensis, were not detected in the leaves.
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Affiliation(s)
- Nasir Tajuddeen
- School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Scottsville, 3209, Pietermaritzburg, South Africa
| | - Tarryn Swart
- Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa
| | - Heinrich C Hoppe
- Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa
| | - Fanie R van Heerden
- School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Scottsville, 3209, Pietermaritzburg, South Africa
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15
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Kemal T, Feyisa K, Bisrat D, Asres K. In Vivo Antimalarial Activity of the Leaf Extract of Osyris quadripartita Salzm. ex Decne and Its Major Compound (-) Catechin. J Trop Med 2022; 2022:3391216. [PMID: 36249737 PMCID: PMC9568338 DOI: 10.1155/2022/3391216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 11/30/2022] Open
Abstract
Background The leaves of Osyris quadripartita Salzm. ex Decne, endemic to Ethiopia, are traditionally used for the treatment of malaria. Previous phytochemical investigations of Osyris species showed the presence of flavonoids, anthracene derivatives, and sesquiterpene lactones as the main constituents. The aim of the present study was to investigate the antimalarial activity of the leaf extract of O. quadripartita and its isolated constituent against mice infected with Plasmodium berghei. Methods Isolation of a compound was carried out on silica gel column chromatography of the extract eluting with gradient mixtures of CHCl3/MeOH. Structural elucidation of the isolated compound was achieved by ESI-MS and 1D-and 2D-NMR spectral data. Peter's 4-day suppressive test method was used to determine the antimalarial activity of the test substances. Level of parasitemia, survival time, and body weight change were used to determine the antimalarial activity of the test substances. Results (-) Catechin was isolated and characterized from the hydroalcoholic extract of O. quadripartita. At a concentration of 400 mg/kg, both the extract and (-) catechin exhibited antimalarial activity with the highest chemosuppression values of 70.61% and 64.26%, respectively. Conclusion These findings indicate that O. quadripartita is endowed with genuine antimalarial activity attributed in part, to its (-) catechin content. Hence, the present study may validate the traditional use of the plant for the treatment of malaria.
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Affiliation(s)
- Teyiba Kemal
- Department of Pharmacy, College of Health and Medical Science, Haramaya University, Harar, Ethiopia
- Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Kebede Feyisa
- Department of Pharmacy, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Daniel Bisrat
- Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Kaleab Asres
- Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Tali MBT, Dize D, Njonte Wouamba SC, Tsouh Fokou PV, Keumoe R, Ngansop CN, Nguembou Njionhou MS, Jiatsa Mbouna CD, Yamthe Tchokouaha LR, Maharaj V, Khorommbi NK, Naidoo-Maharaj D, Tchouankeu JC, Boyom FF. In vitro antiplasmodial activity-directed investigation and UPLC-MS fingerprint of promising extracts and fractions from Terminalia ivorensis A. Chev. and Terminalia brownii Fresen. JOURNAL OF ETHNOPHARMACOLOGY 2022; 296:115512. [PMID: 35788037 DOI: 10.1016/j.jep.2022.115512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL SIGNIFICANCE Medicinal plants from the Terminalia genus are widely used as remedies against many infectious diseases, including malaria. As such, Terminalia ivorensis A. Chev. and Terminalia brownii Fresen. are famous due to their usefulness in traditional medicines to treat malaria and yellow fever. However, further information is needed on the extent of anti-Plasmodium potency of extracts and fractions from these plants and their phytochemical profile. AIM OF THE STUDY This study was designed to investigate the in vitro antiplasmodial activity and to determine the chemical profile of promising extracts and fractions from T. ivorensis and T. brownii stem bark. MATERIALS AND METHODS Crude aqueous, ethanolic, methanolic, hydroethanolic and ethyl acetate extracts were prepared by maceration from the stem barks of T. brownii and T. ivorensis. They were subsequently tested against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum using the parasite lactate dehydrogenase (PfLDH) assay. Extracts showing very good activity on both plasmodial strains were further fractionated using column chromatography guided by evidence of antiplasmodial activity. All bioactive extracts and fractions were screened for their cytotoxicity on Vero and Raw cell lines using the resazurin-based assay and on erythrocytes using the hemolysis assay. The phytochemical profiles of selected potent extracts and fractions were determined by UPLC-QTOF-MS analysis. RESULTS Of the ten extracts obtained from both plant species, nine showed inhibitory activity against both P. falciparum strains (Pf3D7 and PfDd2), with median inhibitory concentration (IC50) values ranging from 0.13 μg/ml to 10.59 μg/ml. Interestingly, the aqueous extract of T. ivorensis (TiW) and methanolic extract of T. brownii (TbM) displayed higher antiplasmodial activities against both strains (IC50 0.13-1.43 μg/ml) and high selectivity indices (SI > 100). Their fractionation led to two fractions from T. ivorensis and two from T. brownii that showed very promising antiplasmodial activity (IC50 0.15-1.73 μg/mL) and SI greater than 100. The hemolytic assay confirmed the safety of crude extracts and fractions on erythrocytes. UPLC-MS-based phytochemical analysis of the crude aqueous extract of T. ivorensis showed the presence of ellagic acid (1) and leucodelphidin (2), while analysis of the crude methanol extract of T. brownii showed the presence of ellagic acid (1), leucodelphinidin (2), papyriogenin D (3), dihydroactinidiolide (4) and miltiodiol (5). CONCLUSIONS The extracts and fractions from T. ivorensis and T. brownii showed very good antiplasmodial activity, thus supporting the traditional use of the two plants in the treatment of malaria. Chemical profiling of the extracts and fractions led to the identification of chemical markers and the known antimalarial compound ellagic acid. Further isolation and testing of other pure compounds from the active fractions could lead to the identification of potent antiplasmodial compounds.
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Affiliation(s)
- Mariscal Brice Tchatat Tali
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Darline Dize
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Steven Collins Njonte Wouamba
- Laboratory of Natural Products and Organic Synthesis, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Chemistry, Higher Teacher's Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon.
| | - Patrick Valere Tsouh Fokou
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Biochemistry, Faculty of Science, University of Bamenda, PO Box 39, Bambili, Bamenda, Cameroon.
| | - Rodrigue Keumoe
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Cyrille Njanpa Ngansop
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Michelle Sidoine Nguembou Njionhou
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Cedric Derick Jiatsa Mbouna
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Lauve Rachel Yamthe Tchokouaha
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Institute for Medical Research and Medicinal Plants Studies (IMPM), Yaoundé, P.O. Box 6163, Yaoundé, Cameroon.
| | - Vinesh Maharaj
- Department of Chemistry, University of Pretoria, Hatfield Campus, Hatfield, 0028, South Africa.
| | | | - Dashnie Naidoo-Maharaj
- Department of Chemistry, University of Pretoria, Hatfield Campus, Hatfield, 0028, South Africa; Agricultural Research Council-Vegetables, Industrial and Medicinal Plants, Private Bag X293, Pretoria, 0001, South Africa.
| | - Jean Claude Tchouankeu
- Laboratory of Natural Products and Organic Synthesis, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
| | - Fabrice Fekam Boyom
- Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
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Daniyan MO, Fisusi FA, Adeoye OB. Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link? Front Mol Biosci 2022; 9:965569. [PMID: 36090033 PMCID: PMC9451049 DOI: 10.3389/fmolb.2022.965569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 07/28/2022] [Indexed: 12/02/2022] Open
Abstract
Plasmodium falciparum is responsible for the most severe and deadliest human malaria infection. The most serious complication of this infection is cerebral malaria. Among the proposed hypotheses that seek to explain the manifestation of the neurological syndrome in cerebral malaria is the vascular occlusion/sequestration/mechanic hypothesis, the cytokine storm or inflammatory theory, or a combination of both. Unfortunately, despite the increasing volume of scientific information on cerebral malaria, our understanding of its pathophysiologic mechanism(s) is still very limited. In a bid to maintain its survival and development, P. falciparum exports a large number of proteins into the cytosol of the infected host red blood cell. Prominent among these are the P. falciparum erythrocytes membrane protein 1 (PfEMP1), P. falciparum histidine-rich protein II (PfHRP2), and P. falciparum heat shock proteins 70-x (PfHsp70-x). Functional activities and interaction of these proteins with one another and with recruited host resident proteins are critical factors in the pathology of malaria in general and cerebral malaria in particular. Furthermore, several neurological impairments, including cognitive, behavioral, and motor dysfunctions, are known to be associated with cerebral malaria. Also, the available evidence has implicated glutamate and glutamatergic pathways, coupled with a resultant alteration in serotonin, dopamine, norepinephrine, and histamine production. While seeking to improve our understanding of the pathophysiology of cerebral malaria, this article seeks to explore the possible links between host/parasite chaperones, and neurotransmitters, in relation to other molecular players in the pathology of cerebral malaria, to explore such links in antimalarial drug discovery.
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Affiliation(s)
- Michael Oluwatoyin Daniyan
- Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Funmilola Adesodun Fisusi
- Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Olufunso Bayo Adeoye
- Department of Biochemistry, Benjamin S. Carson (Snr.) College of Medicine, Babcock University, Ilishan-Remo, Ogun State, Nigeria
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Okokon JE, Mobley R, Edem UA, Bassey AI, Fadayomi I, Drijfhout F, Horrocks P, Li WW. In vitro and in vivo antimalarial activity and chemical profiling of sugarcane leaves. Sci Rep 2022; 12:10250. [PMID: 35715548 PMCID: PMC9205285 DOI: 10.1038/s41598-022-14391-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 06/06/2022] [Indexed: 11/21/2022] Open
Abstract
Saccharum officinarum Linn. (sugarcane, Family-Poaceae) is employed in Ibibio traditional medicine for the treatment of various infections and diseases such as malaria. We This study aims to assess the antiplasmodial effect of the leaf extract and fractions on human malaria parasite (Plasmodium falciparum) in vitro, and rodent malaria parasite (P. berghei) in vivo, and analyse the bioactive components of the active fraction(s). The leaf extract and fractions of S. officinarum were prepared and their growth inhibitory effects tested against the chloroquine resistant P. falciparum strain (Dd2) and P. berghei infection in mice. An acute toxicity of the extract was determined. A combination of gas chromatography and liquid chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy was applied for metabolites profiling of crude extract and active fractions. The leaf extract and fractions demonstrated moderate activity against P. falciparum with the dichloromethane fraction producing the most potent activity (EC50 = 15.4 µg/mL). The leaf extract (170-510 mg/kg, p.o., LD50 = 1732 mg/kg) and fractions demonstrated significant (p < 0.05-0.001) effect on P. berghei infection in prophylactic tests as well as in established infection with n-butanol fractions producing the highest effect. An unusual sulphur-containing compound, dilaurylthiodipropionate, fatty acids, phenolic acids, flavonoid and flavonoid glycoside were identified in the active fractions. These results give credence to the use of sugarcane leaves as malarial remedy locally by confirming the in vitro and in vivo antiplasmodial potential of leaf extract/fractions of S. officinarum.
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Affiliation(s)
- Jude E Okokon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria.
| | - Rebecca Mobley
- School of Medicine, Keele University, Staffordshire, ST5 5BG, UK
| | - Utibe A Edem
- Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Uyo, Uyo, Nigeria
| | - Augustine I Bassey
- Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Uyo, Uyo, Nigeria
| | - Idowu Fadayomi
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, ST4 7QB, UK
| | - Falko Drijfhout
- School of Chemical and Physical Sciences, Keele University, Staffordshire, ST5 5BG, UK
| | - Paul Horrocks
- School of Medicine, Keele University, Staffordshire, ST5 5BG, UK
| | - Wen-Wu Li
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, ST4 7QB, UK.
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Vigbedor BY, Osei-Owusu J, Kwakye R, Neglo D. Bioassay-Guided Fractionation, ESI-MS Scan, Phytochemical Screening, and Antiplasmodial Activity of Afzelia africana. Biochem Res Int 2022; 2022:6895560. [PMID: 35465443 PMCID: PMC9020990 DOI: 10.1155/2022/6895560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/23/2022] [Indexed: 11/18/2022] Open
Abstract
Background Afzelia africana is a plant species with reported numerous medicinal potentials and secondary metabolites. Various parts of the plant have been applied for the treatment of hernia, rheumatism, pain, lumbago, malaria, etc. The study seeks to evaluate the phytochemical constituents, antiplasmodial, and ESI-MS scan of bioassay-guided fractions from the methanol extract of the bark of the plant. Aims The main aim of the study was to carry out bioassay-guided fractionation of the crude methanol extract of Afzelia africana in order to isolate fractions and to evaluate their antiplasmodial activities and ESI-MS fingerprints. Methods The methods employed include column chromatographic fractionation, phytochemical screening, antiplasmodial activity (malaria SYBER green assay (MSF)), and ESI-MS profile (full ESI-MS scan). Results The column chromatographic fractionation and phytochemical screening of the plant led to the separation of the following four fractions: 1 (flavonoids, phenolics, glycosides, terpenoids, and steroids), 2 (alkaloids, anthraquinones, flavonoids, phenolics, glycosides, terpenoids, and steroids), 3 (anthraquinones, flavonoids, phenolics, glycosides, terpenoids, and steroids), and 4 (alkaloids, flavonoids, phenolics, glycosides, terpenoids, and steroids). The antiplasmodial activities of the fractions were tested against the 3D7 strain of Plasmodium falciparum with reported stronger activities for 1 (IC50: 0.097 ± 0.034 μg/mL) and 3 (IC50: 1.43 ± 0.072 μg/mL), and weaker activities for 2 (IC50: >100 μg/mL) and 4 (IC50: 37.09 ± 6.14 μg/mL). The full ESI-MS fingerprint of fractions 1, 2, 3, and 4 revealed the presence of 14, 24, 34, and 37 major molecular ions or compounds in each fraction, respectively.
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Affiliation(s)
- Bright Yaw Vigbedor
- Department of Basic Sciences, School of Basic and Biomedical Sciences, University of Health and Allied Sciences, PMB31, Ho, Ghana
| | - Jonathan Osei-Owusu
- Department of Biological, Physical and Mathematical Sciences, University of Environment and Sustainable Development, PMB, Somanya, Ghana
| | - Ralph Kwakye
- Department of Basic Sciences, School of Basic and Biomedical Sciences, University of Health and Allied Sciences, PMB31, Ho, Ghana
| | - David Neglo
- Department of Basic Sciences, School of Basic and Biomedical Sciences, University of Health and Allied Sciences, PMB31, Ho, Ghana
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20
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Antiplasmodial activity of Benth. Leaf and bark extracts against infected mice. Saudi J Biol Sci 2022; 29:2475-2482. [PMID: 35531230 PMCID: PMC9073002 DOI: 10.1016/j.sjbs.2021.12.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 12/06/2021] [Accepted: 12/09/2021] [Indexed: 12/17/2022] Open
Abstract
Ethnopharmacology relevance Morinda lucida is an ethnopharmacologically important plant that has traditionally been used to treat malaria in the Southwest of Nigeria. The aim of this study is to look into the antiplasmodial properties of different solvent extracts of Morinda lucida bark and leaves. Materials and methods The antiplasmodial model, (or curative assay), was tested against Plasmodium berghei NK65, a chloroquine-sensitive Plasmodium berghei strain. In experimental mice, parasitaemia, percentage inhibition, weight changes, and packed cell volume were measured and compared to chloroquine (10 mg kg−1). Standard phytochemical procedures were used to evaluate the extracts' chemo-profile. Results and Discussion Phytochemical analysis of the extracts revealed the presence of tannins, alkaloids, steroids, saponins, phenols, and alkaloids, among other metabolites. The highest quantities of total phenolic, total tannins, and total flavonoid content were found in 50% ethanolic extracts. There was significant decrease in the body weight of the mice after inoculation, however, after administration of crude extracts, an increase in weight was observed. A negative variation (-3.00 g) was observed in group without treatment. The ethanolic crude extracts (200 and 400 mg/kg) significantly increased the packed cell volume compared to other extracts. CQ treated experimental mice showed 100% inhibition with activity greater than extracts treated groups. The lowest inhibitory effect was observed in 200 mg/kg ethanolic bark extract treated group with activity of 72.16%. The antiplasmodial activities exhibited by these extracts could be linked to the chemical constituents investigated. Conclusion The findings of this study suggest the use of M. lucida leaves and bark as a medicinal agent for malaria treatment and as a potential source of effective antimalarial templates. Further research is needed to determine the safety and toxicological profile of these extracts in vivo.
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Hasan MM, Khan Z, Chowdhury MS, Khan MA, Moni MA, Rahman MH. In silico molecular docking and ADME/T analysis of Quercetin compound with its evaluation of broad-spectrum therapeutic potential against particular diseases. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.100894] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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Antiplasmodial and Cytotoxic Flavonoids from Pappea capensis (Eckl. & Zeyh.) Leaves. Molecules 2021; 26:molecules26133875. [PMID: 34201912 PMCID: PMC8270286 DOI: 10.3390/molecules26133875] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/04/2021] [Accepted: 06/08/2021] [Indexed: 12/03/2022] Open
Abstract
Ethnobotanical surveys indicate that the Masai and Kikuyu in Kenya, the Venda in South Africa, and the Gumuz people of Ethiopia use Pappea capensis for the treatment of malaria. The present study aimed to investigate the phytochemical and antiplasmodial properties of the plant leaves. The bioactive compounds were isolated using chromatographic techniques. The structures were established using NMR, HRMS, and UV spectroscopy. Antiplasmodial activity of P. capensis leaf extract and isolated compounds against chloroquine-sensitive 3D7 P. falciparum was evaluated using the parasite lactate dehydrogenase assay. Cytotoxicity against HeLa (human cervix adenocarcinoma) cells was determined using the resazurin assay. The extract inhibited the viability of Plasmodium falciparum by more than 80% at 50 µg/mL, but it was also cytotoxic against HeLa cells at the same concentration. Chromatographic purification of the extract led to the isolation of four flavonoid glycosides and epicatechin. The compounds displayed a similar activity pattern with the extract against P. falciparum and HeLa cells. The results from this study suggest that the widespread use of P. capensis in traditional medicine for the treatment of malaria might have some merits. However, more selectivity studies are needed to determine whether the leaf extract is cytotoxic against noncancerous cells.
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Chaniad P, Mungthin M, Payaka A, Viriyavejakul P, Punsawad C. Antimalarial properties and molecular docking analysis of compounds from Dioscorea bulbifera L. as new antimalarial agent candidates. BMC Complement Med Ther 2021; 21:144. [PMID: 34006257 PMCID: PMC8132342 DOI: 10.1186/s12906-021-03317-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 05/06/2021] [Indexed: 01/27/2023] Open
Abstract
Background At present, the emergence and spread of antimalarial drug resistance has become a significant problem worldwide. There has been a challenge in searching for natural products for the development of novel antimalarial drugs. Therefore, this study aims to evaluate compounds from Dioscorea bulbifera responsible for antimalarial properties and investigate potential interactions of the compounds with Plasmodium falciparum lactate dehydrogenase (PfLDH), an essential glycolytic enzyme in the parasite’s life cycle. Methods An in vitro study of antimalarial activity against chloroquine (CQ)-resistant Plasmodium falciparum (K1 strain) and CQ-sensitive P. falciparum (3D7 strain) was performed using the 3H-hypoxanthine uptake inhibition method. The cytotoxic effects of the pure compounds were tested against Vero cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The interactions of the compounds with the PfLDH active site were additionally investigated using a molecular docking method. Results Quercetin (6) exhibited the highest antimalarial activity against the P. falciparum K1 and 3D7 strains, with IC50 values of 28.47 and 50.99 μM, respectively. 2,4,3′,5′-Tetrahydroxybibenzyl (9), 3,5-dimethoxyquercetin (4) and quercetin-3-O-β-D-galactopyranoside (14) also possessed antimalarial effects against these two strains of P. falciparum. Most pure compounds were nontoxic against Vero cells at a concentration of 80 μg/ml, except for compound 9, which had a cytotoxic effect with a CC50 value of 16.71 μM. The molecular docking results indicated that 9 exhibited the best binding affinity to the PfLDH enzyme in terms of low binding energy (− 8.91 kcal/mol) and formed strong hydrogen bond interactions with GLY29, GLY32, THR97, GLY99, PHE100, THR101 and ASN140, amino acids as active sites. In addition, 6 also possessed remarkable binding affinity (− 8.53 kcal/mol) to PfLDH by interacting with GLY29, ILE31, ASP53, ILE54, THR97 and THR101. Conclusion Quercetin is a major active compound responsible for the antimalarial activity of D. bulbifera and is an inhibitor of PfLDH. These findings provide more evidence to support the traditional use of D. bulbifera for malaria treatment. Structural models of its interactions at the PfLDH active site are plausibly useful for the future design of antimalarial agents.
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Affiliation(s)
- Prapaporn Chaniad
- School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | - Mathirut Mungthin
- Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, 10400, Thailand
| | - Apirak Payaka
- School of Science, Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | - Parnpen Viriyavejakul
- Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
| | - Chuchard Punsawad
- School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
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Rama JLR, Mallo N, Biddau M, Fernandes F, de Miguel T, Sheiner L, Choupina A, Lores M. Exploring the powerful phytoarsenal of white grape marc against bacteria and parasites causing significant diseases. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:24270-24278. [PMID: 31939019 DOI: 10.1007/s11356-019-07472-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/19/2019] [Indexed: 06/10/2023]
Abstract
Natural extracts containing high polyphenolic concentration possess antibacterial, anti-parasitic and fungicidal activities. The present research characterises two extracts based on white grape marc, a winemaking by-product, describing their physicochemical features and antimicrobial capacities. The main components of these extracts are phenolic acids, flavan-3-ols and their gallates and flavonols and their glycosides. As a result of this complex composition, the extracts showed pronounced bioactivities with potential uses in agricultural, pharmaceutical and cosmetic industries. Polyphenol compounds were extracted by using hydro-organic solvent mixtures from the by-product of Albariño white wines (Galicia, NW Spain) production. The in vitro antimicrobial activity of these extracts was evaluated on Gram-positive and Gram-negative bacteria and Apicomplexan and Oomycota parasites. Microbial species investigated are causing agents of several human and animal diseases, such as foodborne illnesses (Bacillus cereus, Escherichia coli, Salmonella enterica, and Toxoplasma gondii), skin infections and/or mastitis (Staphylococcus aureus and Streptococcus uberis), malaria (Plasmodium falciparum) and plant infections as "chestnut ink" or "root rot" (Phytophthora cinnamomi). Both extracts showed activity against all the tested species, being nontoxic for the host. So, they could be used for the development of biocides to control a wide range of pathogenic agents and contribute to the enhancement of winemaking industry by-products.
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Affiliation(s)
- José-Luis Rodríguez Rama
- Department of Microbiology and Parasitology, University of Santiago de Compostela, Santiago de Compostela, E-15782, A Coruña, Spain
| | - Natalia Mallo
- Wellcome Centre for Integrative Parasitology. Department of Infection, Immunity and Inflamation., University of Glasgow, 120 University Place, Glasgow, UK
| | - Marco Biddau
- Wellcome Centre for Integrative Parasitology. Department of Infection, Immunity and Inflamation., University of Glasgow, 120 University Place, Glasgow, UK
| | - Francisco Fernandes
- Department of Socioeconomical systems, I. Politécnico Bragança, 5300-253, Terras Trás-os-Montes, Portugal
| | - Trinidad de Miguel
- Department of Microbiology and Parasitology, University of Santiago de Compostela, Santiago de Compostela, E-15782, A Coruña, Spain.
| | - Lilach Sheiner
- Wellcome Centre for Integrative Parasitology. Department of Infection, Immunity and Inflamation., University of Glasgow, 120 University Place, Glasgow, UK
| | - Altino Choupina
- Department of Socioeconomical systems, I. Politécnico Bragança, 5300-253, Terras Trás-os-Montes, Portugal
| | - Marta Lores
- Department of Analytical Chemistry, Nutrition and Food Science, Laboratory of Research and Development of Analytical Solutions (LIDSA), University of Santiago de Compostela, Santiago de Compostela, E-15782, A Coruña, Spain
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Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria. Pharmaceuticals (Basel) 2021; 14:ph14030248. [PMID: 33803419 PMCID: PMC7999989 DOI: 10.3390/ph14030248] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/04/2021] [Accepted: 02/09/2021] [Indexed: 12/19/2022] Open
Abstract
Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects.
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In vitro analyses of Artemisia extracts on Plasmodium falciparum suggest a complex antimalarial effect. PLoS One 2021; 16:e0240874. [PMID: 33651845 PMCID: PMC7924776 DOI: 10.1371/journal.pone.0240874] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 01/20/2021] [Indexed: 11/19/2022] Open
Abstract
Dried-leaf Artemisia annua L. (DLA) antimalarial therapy was shown effective in prior animal and human studies, but little is known about its mechanism of action. Here IC50s and ring-stage assays (RSAs) were used to compare extracts of A. annua (DLAe) to artemisinin (ART) and its derivatives in their ability to inhibit and kill Plasmodium falciparum strains 3D7, MRA1252, MRA1240, Cam3.11 and Cam3.11rev in vitro. Strains were sorbitol and Percoll synchronized to enrich for ring-stage parasites that were treated with hot water, methanol and dichloromethane extracts of DLA, artemisinin, CoArtem™, and dihydroartemisinin. Extracts of A. afra SEN were also tested. There was a correlation between ART concentration and inhibition of parasite growth. Although at 6 hr drug incubation, the RSAs for Cam3.11rev showed DLA and ART were less effective than high dose CoArtem™, 8 and 24 hr incubations yielded equivalent antiparasitic results. For Cam3.11, drug incubation time had no effect. DLAe was more effective on resistant MRA-1240 than on the sensitive MRA-1252 strain. Because results were not as robust as observed in animal and human studies, a host interaction was suspected, so sera collected from adult and pediatric Kenyan malaria patients was used in RSA inhibition experiments and compared to sera from adults naïve to the disease. The sera from both age groups of malaria patients inhibited parasite growth ≥ 70% after treatment with DLAe and compared to malaria naïve subjects suggesting some host interaction with DLA. The discrepancy between these data and in-vivo reports suggested that DLA’s effects require an interaction with the host to unlock their potential as an antimalarial therapy. Although we showed there are serum-based host effects that can kill up to 95% of parasites in vitro, it remains unclear how or if they play a role in vivo. These results further our understanding of how DLAe works against the malaria parasite in vitro.
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Yang D, Wang T, Long M, Li P. Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8825387. [PMID: 33488935 PMCID: PMC7790550 DOI: 10.1155/2020/8825387] [Citation(s) in RCA: 296] [Impact Index Per Article: 59.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 11/24/2020] [Accepted: 12/14/2020] [Indexed: 12/23/2022]
Abstract
Quercetin is a flavonoid compound widely present in plants and exhibits a variety of biological activities. Research on quercetin has shown its potential for medical application. In this research, we elucidate its antioxidant mechanism and the broad-spectrum antibacterial and antiparasite properties; summarise its potential application in antioncology and cardiovascular protection and anti-immunosuppression treatment; and demonstrate its ability to alleviate the toxicity of mycotoxins. This research is expected to offer some insights and inspirations for the further study of quercetin, its properties, and the scientific basis for its better application in clinical practice.
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Affiliation(s)
- Dengyu Yang
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Tiancheng Wang
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Miao Long
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Peng Li
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
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Prebble DW, Holland DC, Robertson LP, Avery VM, Carroll AR. Citronamine A, an Antiplasmodial Isoquinoline Alkaloid from the Australian Marine Sponge Citronia astra. Org Lett 2020; 22:9574-9578. [PMID: 33232166 DOI: 10.1021/acs.orglett.0c03633] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Citronamine A (1), an isoquinoline alkaloid containing an unprecedented pentacyclic ring system, was isolated from the Australian marine sponge Citronia astra. Based on the combination of MS and NMR analyses and comparison of experimental and TDDFT calculated ECD spectra, the absolute structure of 1 was determined. Compound 1 displayed moderate activity against drug sensitive (3D7) and drug resistant (Dd2) strains of the parasite, Plasmodium falciparum, responsible for malaria.
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Affiliation(s)
- Dale W Prebble
- School of Environment and Science, Griffith University, Southport, Queensland 4222, Australia.,Environmental Futures Research Institute, Griffith University, Southport, Queensland 4222, Australia.,Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia
| | - Darren C Holland
- School of Environment and Science, Griffith University, Southport, Queensland 4222, Australia.,Environmental Futures Research Institute, Griffith University, Southport, Queensland 4222, Australia
| | - Luke P Robertson
- School of Environment and Science, Griffith University, Southport, Queensland 4222, Australia.,Environmental Futures Research Institute, Griffith University, Southport, Queensland 4222, Australia
| | - Vicky M Avery
- Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.,Discovery Biology, Griffith University, Brisbane, Queensland 4111, Australia
| | - Anthony R Carroll
- School of Environment and Science, Griffith University, Southport, Queensland 4222, Australia.,Environmental Futures Research Institute, Griffith University, Southport, Queensland 4222, Australia.,Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia
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Mahmoud AB, Mäser P, Kaiser M, Hamburger M, Khalid S. Mining Sudanese Medicinal Plants for Antiprotozoal Agents. Front Pharmacol 2020; 11:865. [PMID: 32581814 PMCID: PMC7295952 DOI: 10.3389/fphar.2020.00865] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 05/26/2020] [Indexed: 11/13/2022] Open
Abstract
Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested in vitro against Plasmodium falciparum (erythrocytic stages), Trypanosoma brucei rhodesiense (bloodstream forms), Trypanosoma cruzi (intracellular amastigotes), and Leishmania donovani (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 μg/ml, and >50% at 2 μg/ml against at least one of the protozoan parasites. Plasmodium falciparum was the most sensitive of the parasites, followed by T. b. rhodesiense and L. donovani. Only few hits were identified for T. cruzi, and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against T. brucei and P. falciparum. HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from Guiera senegalensis J.F.Gmel.; pseudosemiglabrin from Tephrosia apollinea (Delile) DC; ellagic acid and quercetin from Terminalia leiocarpa (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from Vachellia nilotica (L.) P.J.H.Hurter & Mabb. Also the extracts of Croton gratissimus var. gratissimus and Cuscuta hyalina Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites.
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Affiliation(s)
- Abdelhalim Babiker Mahmoud
- Parasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,Faculty of Science, University of Basel, Basel, Switzerland.,Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan
| | - Pascal Mäser
- Parasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,Faculty of Science, University of Basel, Basel, Switzerland
| | - Marcel Kaiser
- Parasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,Faculty of Science, University of Basel, Basel, Switzerland
| | | | - Sami Khalid
- Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan.,Faculty of Pharmacy, University of Science and Technology, Omdurman, Sudan
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30
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Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, Sharifi-Rad M, Sharopov F, Martins N, Martorell M, Cho WC. Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health. ACS OMEGA 2020; 5:11849-11872. [PMID: 32478277 PMCID: PMC7254783 DOI: 10.1021/acsomega.0c01818] [Citation(s) in RCA: 319] [Impact Index Per Article: 63.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 05/01/2020] [Indexed: 05/03/2023]
Abstract
Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.
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Affiliation(s)
- Bahare Salehi
- Student
Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran
| | - Laura Machin
- Institute
of Pharmacy and Food, University of Havana, Havana, Cuba
| | - Lianet Monzote
- Parasitology
Department, Institute of Medicine Tropical
Pedro Kourí, Havana, Cuba
| | - Javad Sharifi-Rad
- Phytochemistry
Research Center, Shahid Beheshti University
of Medical Sciences, Tehran 1991953381, Iran
| | - Shahira M. Ezzat
- Department
of Pharmacognosy, Faculty of Pharmacy, Cairo
University, Kasr El-Aini
Street, Cairo 11562, Egypt
- Department
of Pharmacognosy, Faculty of Pharmacy, October
University for Modern Sciences and Arts (MSA), 6th October 12566, Egypt
| | - Mohamed A. Salem
- Department
of Pharmacognosy, Faculty of Pharmacy, Menoufia
University, Gamal Abd
El Nasr st., Shibin Elkom, Menoufia 32511, Egypt
| | - Rana M. Merghany
- Department
of Pharmacognosy, National Research Centre, Giza 12622, Egypt
| | - Nihal M. El Mahdy
- Department
of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th of October 12566, Egypt
| | - Ceyda Sibel Kılıç
- Department
of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey
| | - Oksana Sytar
- Department of Plant Biology Department, Institute of Biology, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, Kyiv 01033, Ukraine
- Department of Plant Physiology, Slovak
University of Agriculture, Nitra, A. Hlinku 2, Nitra 94976, Slovak Republic
| | - Mehdi Sharifi-Rad
- Department
of Medical Parasitology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran
| | - Farukh Sharopov
- Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139, Dushanbe 734003, Tajikistan
| | - Natália Martins
- Faculty of Medicine, University
of Porto, Porto 4200-319, Portugal
- Institute
for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy,
and Centre
for Healthy Living, University of Concepción, Concepción 4070386, Chile
- Universidad de Concepción, Unidad
de Desarrollo Tecnológico,
UDT, Concepción 4070386, Chile
| | - William C. Cho
- Department
of Clinical Oncology, Queen
Elizabeth Hospital, 30
Gascoigne Road, Kowloon, Hong
Kong
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31
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Ezenyi IC, Verma V, Singh S, Okhale SE, Adzu B. Ethnopharmacology-aided antiplasmodial evaluation of six selected plants used for malaria treatment in Nigeria. JOURNAL OF ETHNOPHARMACOLOGY 2020; 254:112694. [PMID: 32092499 DOI: 10.1016/j.jep.2020.112694] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 02/20/2020] [Accepted: 02/21/2020] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sub - Saharan Africa has a high malaria burden and Nigeria accounts for majority of malaria cases worldwide. The aim of this study was to evaluate selected plants extracts used against malaria in Nigeria for antiplasmodial activity. MATERIALS AND METHODS An ethnomedicinal based - approach by literature survey was used to identify plants used in the study. The parts of the plant used were collected and extracted with 70% v/v ethanol; a portion of each extract was used to prepare successive solvent and residual fractions. Chloroquine-sensitive (3D7) P. falciparum strain and human embryonic kidney cells (HEK293) were used for antiplasmodial and cytotoxicity screening respectively. Hemolysis assay was also carried out on red blood cells (RBCs). Test for in vivo efficacy of an active extract was conducted in a mouse model of established P. berghei ANKA-infection. RESULTS A total of six plants; Andropogon schirensis, Celtis durandii, Chasmanthera dependens, Daniellia ogea, Icacina trichantha and Triumfetta cordifolia were selected and screened. Triumfetta cordifolia leaf extract was observed to display moderate in vitro antiplasmodial activity (IC50 = 48.09 μg/ml) and was non-toxic to HEK293 cells and erythrocytes. At a dose of 400 mg/kg, T. cordifolia significantly (p<0.001) suppressed parasitemia, significantly (p<0.001) inhibited RBC depletion and prolonged survival in infected mice. CONCLUSIONS T. cordifolia ethanol extract possesses antiplasmodial efficacy and this is the first report of its kind on the plant. It is a potential candidate for further studies to identify its mechanism of action.
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Affiliation(s)
- I C Ezenyi
- Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development (NIPRD), Idu, Abuja, Nigeria.
| | - V Verma
- Special Center for Molecular Medicine, Jawaharlal Nehru University, Delhi, 110067, India
| | - S Singh
- Special Center for Molecular Medicine, Jawaharlal Nehru University, Delhi, 110067, India.
| | - S E Okhale
- Department of Medicinal Plant Research and Traditional Medicine, National Institute for Pharmaceutical Research and Development (NIPRD), Idu, Abuja, Nigeria
| | - B Adzu
- Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development (NIPRD), Idu, Abuja, Nigeria
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Abstract
As the world gets closer to eliminating malaria, the scientific community worldwide has begun to realize the importance of malaria transmission-blocking interventions. The onus of breaking the life cycle of the human malaria parasite Plasmodium falciparum predominantly rests upon transmission-blocking drugs because of emerging resistance to commonly used schizonticides and insecticides. This third part of our review series on malaria transmission-blocking entails transmission-blocking potential of preclinical transmission-blocking antimalarials and other non-malaria drugs/experimental compounds that are not in clinical or preclinical development for malaria but possess transmission-blocking potential. Collective analysis of the structure and the activity of these experimental compounds might pave the way toward generation of novel prototypes of next-generation transmission-blocking drugs.
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Gruessner BM, Cornet-Vernet L, Desrosiers MR, Lutgen P, Towler MJ, Weathers PJ. It is not just artemisinin: Artemisia sp. for treating diseases including malaria and schistosomiasis. PHYTOCHEMISTRY REVIEWS : PROCEEDINGS OF THE PHYTOCHEMICAL SOCIETY OF EUROPE 2019; 18:1509-1527. [PMID: 33911989 PMCID: PMC8078015 DOI: 10.1007/s11101-019-09645-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 09/11/2019] [Indexed: 05/13/2023]
Abstract
Artemisia sp., especially A. annua and A. afra, have been used for centuries to treat many ailments. While artemisinin is the main therapeutically active component, emerging evidence demonstrates that the other phytochemicals in this genus are also therapeutically active. Those compounds include flavonoids, other terpenes, coumarins, and phenolic acids. Artemisia sp. phytochemicals also improve bioavailability of artemisinin and synergistically improve artemisinin therapeutic efficacy, especially when delivered as dried leaf Artemisia as a tea infusion or as powdered dry leaves in a capsule or compressed into a tablet. Here results from in vitro, and in vivo animal and human studies are summarized and critically discussed for mainly malaria, but also other diseases susceptible to artemisinin and Artemisia sp. including schistosomiasis, leishmaniasis, and trypanosomiasis.
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Affiliation(s)
- B M Gruessner
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
| | | | - M R Desrosiers
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
| | - P Lutgen
- IFVB-BELHERB, Niederanven, Luxembourg
| | - M J Towler
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
| | - P J Weathers
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
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Phytochemical Constituents, Antioxidant, Cytotoxicity, Antimicrobial, Antitrypanosomal, and Antimalarial Potentials of the Crude Extracts of Callistemon citrinus. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5410923. [PMID: 31558912 PMCID: PMC6735214 DOI: 10.1155/2019/5410923] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 07/28/2019] [Indexed: 12/17/2022]
Abstract
Plants are reservoir for potentially useful bioactive compounds, and owing to the rising occurrences of drug resistance to malaria parasites, there is a need to discover and develop new phytochemicals in plant that can be used as antimalarial agents. In this study, we gave a detailed description of the phytochemicals present in both ethyl acetate and methanolic extracts of Callistemon citrinus (C. citrinus) using Gas Chromatography-Mass Spectrometry (GC-MS) analysis; both extracts were also evaluated for their in vitro antimalarial, antitrypanosomal, and cytotoxicity activities against Trypanosoma brucei brucei (T. b brucei) parasites, Plasmodium falciparum (P. falciparum) malaria parasites 3D7 strain, and human cervix adenocarcinoma cells (HeLa cells); in addition, the antimicrobial and antioxidant efficacies were determined using standard methods. Both extracts were characterized by a high amount of fatty acids (52.88 and 62.48%). The ethyl acetate extract exhibited a greater activity with minimum inhibitory concentration (MIC) values ranging from 0.025 to 0.10 mg/mL while the methanol extract ranged from 0.025 to 0.15 mg/mL. Both extracts were bactericidal to Escherichia coli ATCC 35150 (E. coli) and Pseudomonas aeruginosa ACC (P. aeruginosa). Qualitative and quantitative phytochemical screenings conducted for both extracts revealed the presence of alkaloids, glycosides, saponins, steroids, and triterpenoids, fat and oils, flavonoids, phenols, and tannins in varying amounts. Both crude extracts exhibited antitrypanosomal potentials with an IC50 of 6.6/9.7 μg/mL and antiplasmodial activities with an IC50 of 8.4/13.0 μg/mL. Conclusion from this study indicates that apart from the folkloric uses of this plant in traditional settings, the extracts possess a broad spectrum of antimicrobial, antitrypanosomal, and antimalarial activities and some pharmaceutically essential bioactive components with remarkable antioxidant capacities that may be used in the synthesis of novel drugs for the management of different varieties of ailments.
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35
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Boniface PK, Ferreira EI. Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue. Phytother Res 2019; 33:2473-2517. [PMID: 31441148 DOI: 10.1002/ptr.6383] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 04/04/2019] [Accepted: 04/13/2019] [Indexed: 12/21/2022]
Abstract
Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually with over 500,000 deaths. Among the NTDs, some of the most severe consist of leishmaniasis, Chagas disease, and dengue. The impact of the combined NTDs closely rivals that of malaria. According to the World Health Organization, 216 million cases of malaria were reported in 2016 with 445,000 deaths. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Flavonoids are a class of compounds that has been the subject of considerable scientific interest. New developments of flavonoids have made promising advances for the potential treatment of malaria, leishmaniasis, Chagas disease, and dengue, with less toxicity, high efficacy, and improved bioavailability. This review summarizes the current standings of the use of flavonoids to treat malaria and neglected diseases such as leishmaniasis, Chagas disease, and dengue. Natural and synthetic flavonoids are leading compounds that can be used for developing antiprotozoal and antiviral agents. However, detailed studies on toxicity, pharmacokinetics, and mechanisms of action of these compounds are required to confirm the in vitro pharmacological claims of flavonoids for pharmaceutical applications. HIGHLIGHTS: In the current review, we have tried to compile recent discoveries on natural and synthetic flavonoids as well as their implication in the treatment of malaria, leishmaniasis, Chagas disease, and dengue. A total of 373 (220 natural and 153 synthetic) flavonoids have been evaluated for antimalarial, antileishmanial, antichagasic, and antidengue activities. Most of these flavonoids showed promising results against the above diseases. Reports on molecular modeling of flavonoid compounds to the disease target indicated encouraging results. Flavonoids can be prospected as potential leads for drug development; however, more rigorously designed studies on toxicity and pharmacokinetics, as well as the quantitative structure-activity relationship studies of these compounds, need to be addressed.
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Affiliation(s)
- Pone Kamdem Boniface
- Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Elizabeth Igne Ferreira
- Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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Gutiérrez YI, Scull R, Monzote L, Rodríguez KM, Bello A, Setzer WN. Comparative Pharmacognosy, Chemical Profile and Antioxidant Activity of Extracts from Phania matricarioides (Spreng.) Griseb. Collected from Different Localities in Cuba. PLANTS 2018; 7:plants7040110. [PMID: 30558108 PMCID: PMC6313911 DOI: 10.3390/plants7040110] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 11/20/2018] [Accepted: 12/05/2018] [Indexed: 12/23/2022]
Abstract
Phania matricarioides (Spreng.) Griseb. is a traditionally used plant with various pharmacological properties. However, there are only scarce reports about the phytochemistry and biological activity of this plant. In this work, P. matricarioides was collected from three different localities of Cuba: PmB (collected in Bauta, Artemisa), PmC (collected in Cangrejeras, Artemisa), and PmI (collected in La Lisa, Havana), extracted with aqueous ethanol, and analyzed macroscopically and microscopically. The extracts were screened for phytochemical contents, analyzed by TLC and HPLC, and screened for antioxidant activity using the FRAP and DPPH assays. Macroscopic analysis showed similar results for all samples; however, microscopic, physicochemical and phytochemical studies showed appreciable differences. In particular, the total solid of PmC extract was higher (1.94 ± 0.03%) than the other samples. In HPLC profiles, quercetin was identified in the three samples and a greater similarity between samples PmB and PmI was observed. All samples demonstrated radical-scavenging antioxidant activity by the DPPH assay, which PmC also demonstrated the smaller (p < 0.05) value (IC50 = 27.4 ± 0.1 µg/mL), but was statistically superior (p < 0.05) to vitamin C (IC50 = 23.7 ± 0 µg/mL). Also, in the FRAP assay, a higher vitamin C equivalent of PmC was significantly superior (p < 0.05) to the other extracts at the evaluated concentrations, which is likely due to a higher concentration of quercetin. In conclusion, P. matricarioides could constitute a potential resource in the field of phytotherapeutic products, and the results obtained can contribute to the development of the quality control norms for this species.
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Affiliation(s)
- Yamilet I Gutiérrez
- Department of Chemistry, Institute of Pharmacy and Food, Havana University, Coronela, Lisa, Havana 13600, Cuba.
| | - Ramón Scull
- Department of Chemistry, Institute of Pharmacy and Food, Havana University, Coronela, Lisa, Havana 13600, Cuba.
| | - Lianet Monzote
- Parasitology Department, Institute of Tropical Medicine "Pedro Kouri", Havana 10400, Cuba.
| | | | - Adonis Bello
- Facultad de Ciencias Químicas, Universidad de Guayaquil, P.O. Box 0901-5738, Guayaquil 090514, Ecuador.
| | - William N Setzer
- Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA.
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Niu B, Lu Y, Wang J, Hu Y, Chen J, Chen Q, He G, Zheng L. 2D-SAR, Topomer CoMFA and molecular docking studies on avian influenza neuraminidase inhibitors. Comput Struct Biotechnol J 2018; 17:39-48. [PMID: 30595814 PMCID: PMC6305694 DOI: 10.1016/j.csbj.2018.11.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/15/2018] [Accepted: 11/23/2018] [Indexed: 12/18/2022] Open
Abstract
Avian influenza is a serious zoonotic infectious disease with huge negative impacts on local poultry farming, human health and social stability. Therefore, the design of new compounds against avian influenza has been the focus in this field. In this study, computational methods were applied to investigate the compounds with neuraminidase inhibitory activity. First, 2D-SAR model was built to recognize neuraminidase inhibitors (NAIs). As a result, the accuracy of 10 cross-validation and independent tests is 96.84% and 98.97%, respectively. Then, the Topomer CoMFA model was constructed to predict the inhibitory activity and analyses molecular fields. Two models were obtained by changing the cutting methods. The second model is employed to predict the activity (q2 = 0.784 and r2 = 0.982). Molecular docking was also used to further analyze the binding sites between NAIs and neuraminidase from human and avian virus. As a result, it is found that same binding Total Score has some differences, but the binding sites are basically the same. At last, some potential NAIs were screened and some optimal opinions were taken. It is expected that our study can assist to study and develop new types of NAIs.
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Affiliation(s)
- Bing Niu
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yi Lu
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Jianying Wang
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yan Hu
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Jiahui Chen
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Qin Chen
- School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Guangwu He
- Department of Radiology, Shanghai First People's Hospital, Baoshan Branch, Shanghai 200940, China
| | - Linfeng Zheng
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
- Department of Radiology, Shanghai First People's Hospital, Baoshan Branch, Shanghai 200940, China
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Riaz H, Raza S, Aslam M, Ahmad M, Ahmad M, Maria P. An Updated Review of Pharmacological, Standardization Methods and Formulation Development of Rutin. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2018; 12:127-132. [DOI: https:/doi.org/10.22207/jpam.12.1.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024] Open
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39
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Riaz H, Raza S, Aslam M, Ahmad M, Ahmad M, Maria P. An Updated Review of Pharmacological, Standardization Methods and Formulation Development of Rutin. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2018; 12:127-132. [DOI: 10.22207/jpam.12.1.16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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40
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Liu Y, Tong J, Tong Y, Li P, Cui X, Cao H. In vitro anti-influenza virus effect of total flavonoid from Trollius ledebouri Reichb. J Int Med Res 2018; 46:1380-1390. [PMID: 29444614 PMCID: PMC6091840 DOI: 10.1177/0300060517750284] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective To investigate the in vitro antivirus effect of total flavonoid from Trollius ledebouri Reichb (TFTLR). Methods Madin-Darby canine kidney (MDCK) and Human epithelial type 2 (HEp-2) cell lines were used to test the antivirus effect of TFTLR on nine virus subtypes: four H1N1, one H3N2, and four other subtypes prevalent in North China. Tamiflu, Ribavirin and Lianhua Qingwen were used as active comparators. Comprehensive molecular pathway analyses of TFTLR-H1N1 and TFTLR-H3N2 relationships were also conducted. Results TFTLR inhibited MDCK cell lesions induced by H1N1 subtypes (A/FM1/1/47, A/Puerto Rico/8/1934 H1N1, A1/Tianjin Jinnan/15/2009, and A/Brisbane/59/2007) and by the H3N2 Brisbane/10/2009 strain. TFTLR inhibitory concentration (IC)50 values against these viruses were 0.13, 0.07, 0.06, 0.14, and 0.07 mg/ml, respectively; and therapeutic index (TI) values were 8.62, 16.0, 18.67, 8.0, and 16.0, respectively. TFTLR showed no effect on parainfluenza virus type 1, herpes simplex virus type 1, respiratory syncytial virus, and coxsackie group B virus type 4. Pathway analysis revealed possible functional therapeutic mechanisms for TFTLR against H1N1 and H3N2 infections. Conclusion TFTLR may represent a potential therapeutic agent against influenza A subtypes H1N1 and H3N2 that are prevalent in North China, and should be investigated further.
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Affiliation(s)
- Yongping Liu
- 1 Laboratory of Pharmacology and Toxicology of Key Laboratory for Research and Development of Chinese Materia Medica in Hebei Province, China; Department of Pharmacology and Toxicology, Institute of Chinese Materia Medica, 92979 Chengde Medical University , China
| | - Jiming Tong
- 1 Laboratory of Pharmacology and Toxicology of Key Laboratory for Research and Development of Chinese Materia Medica in Hebei Province, China; Department of Pharmacology and Toxicology, Institute of Chinese Materia Medica, 92979 Chengde Medical University , China
| | - Ying Tong
- 2 Radiology Department, Affiliated Hospital of 92979 Chengde Medical University , Chengde, China
| | - Ping Li
- 1 Laboratory of Pharmacology and Toxicology of Key Laboratory for Research and Development of Chinese Materia Medica in Hebei Province, China; Department of Pharmacology and Toxicology, Institute of Chinese Materia Medica, 92979 Chengde Medical University , China
| | - Xiaolan Cui
- 3 Department of Pharmacology, 417459 Institute of Chinese Materia Medica, Chinese Academy of Chinese Medicine sciences , Beijing, China
| | - Hongbao Cao
- 4 Department of Genomics Research, R&D Solutions, Elsevier Inc., Rockville, MD, USA
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41
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Okokon JE, Augustine NB, Mohanakrishnan D. Antimalarial, antiplasmodial and analgesic activities of root extract of Alchornea laxiflora. PHARMACEUTICAL BIOLOGY 2017; 55:1022-1031. [PMID: 28183236 PMCID: PMC6130711 DOI: 10.1080/13880209.2017.1285947] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 11/21/2016] [Accepted: 01/19/2017] [Indexed: 05/31/2023]
Abstract
CONTEXT Alchornea laxiflora (Benth.) Pax. & Hoffman (Euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in Nigeria. OBJECTIVE To assess the antimalarial, antiplasmodial and analgesic potentials of root extract and fractions against malarial infections and chemically-induced pains. MATERIAL AND METHODS The root extract and fractions of Alchornea laxiflora were investigated for antimalarial activity against Plasmodium berghei infection in mice, antiplasmodial activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method and analgesic activity against experimentally-induced pain models. Acute toxicity study of the extract, cytotoxic activity against HeLa cells and GCMS analysis of the active fraction were carried out. RESULTS The root extract (75-225 mg/kg, p.o.) with LD50 of 748.33 mg/kg exerted significant (p < 0.05-0.001) antimalarial activity against P. berghei infection in suppressive, prophylactive and curative tests. The root extract and fractions also exerted moderate activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC50 value of 38.44 ± 0.89 μg/mL (Pf 3D7) and 40.17 ± 0.78 μg/mL (Pf INDO). The crude extract was not cytotoxic to HeLa cells with LC50 value >100 μg/mL. The crude extract and ethyl acetate fraction exerted significant (p < 0.05-0.001) analgesic activity in all pain models used. DISCUSSION AND CONCLUSIONS These results suggest that the root extract/fractions of A. laxiflora possess antimalarial, antiplasmodial and analgesic potentials and these justify its use in ethnomedicine to treat malaria and pain.
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Affiliation(s)
- Jude E. Okokon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria
- Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
| | | | - Dinesh Mohanakrishnan
- Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
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Okokon JE, Antia BS, Mohanakrishnan D, Sahal D. Antimalarial and antiplasmodial activity of husk extract and fractions of Zea mays. PHARMACEUTICAL BIOLOGY 2017; 55:1394-1400. [PMID: 28320254 PMCID: PMC6130627 DOI: 10.1080/13880209.2017.1302966] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 02/01/2017] [Accepted: 03/02/2017] [Indexed: 05/31/2023]
Abstract
CONTEXT Zea mays L. (Poacae) husk decoctions are traditionally used in the treatment of malaria by various tribes in Nigeria. OBJECTIVE To assess the antimalarial and antiplasmodial potentials of the husk extract and fractions on malaria parasites using in vivo and in vitro models. MATERIALS AND METHODS The ethanol husk extract and fractions (187-748 mg/kg, p.o.) of Zea mays were investigated for antimalarial activity against Plasmodium berghei using rodent (mice) malaria models and in vitro activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using the SRBR green assay method. Median lethal dose and cytotoxic activities against HeLa and HEKS cells were also carried out. The GCMS analysis of the most active fraction was carried out. RESULTS The husk extract (187-748 mg/kg, p.o.) with LD50 of 1874.83 mg/kg was found to exert significant (p < 0.05-0.001) antimalarial activity against P. berghei infection in suppressive, prophylactive and curative tests. The crude extract and fractions also exerted prominent activity against both chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC50 values of 9.31 ± 0.46 μg/mL (Pf 3D7) and 3.69 ± 0.66 μg/mL (Pf INDO). The crude extract and fractions were not cytotoxic to the two cell lines tested with IC50 values of >100 μg/mL against both HeLa and HEKS cell lines. DISCUSSION AND CONCLUSION These results suggest that the husk extract/fractions of Zea mays possesses antimalarial and antiplasmodial activities and these justify its use in ethnomedicine to treat malaria infections.
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Affiliation(s)
- Jude E. Okokon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria
- Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | | | - Dinesh Mohanakrishnan
- Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Dinkar Sahal
- Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
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Masike K, Khoza BS, Steenkamp PA, Smit E, Dubery IA, Madala NE. A Metabolomics-Guided Exploration of the Phytochemical Constituents of Vernonia fastigiata with the Aid of Pressurized Hot Water Extraction and Liquid Chromatography-Mass Spectrometry. Molecules 2017; 22:molecules22081200. [PMID: 28749445 PMCID: PMC6152066 DOI: 10.3390/molecules22081200] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 07/10/2017] [Accepted: 07/11/2017] [Indexed: 11/16/2022] Open
Abstract
Vernonia fastigiata is a multi-purpose nutraceutical plant with interesting biological properties. However, very little is known about its phytochemical composition and, thus the need for its phytochemical characterization. In the current study, an environmentally friendly method, pressurized hot water extraction (PHWE), was used to extract metabolites from the leaves of V. fastigiata at various temperatures (50 °C, 100 °C, 150 °C and 200 °C). Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-qTOF-MS) analysis in combination with chemometric methods, particularly principal component analysis (PCA) and liquid/gas chromatography mass spectrometry (XCMS) cloud plots, were used to descriptively visualize the data and identify significant metabolites extracted at various temperatures. A total of 25 different metabolites, including hydroxycinnamic acid derivatives, clovamide, deoxy-clovamide and flavonoids, were noted for the first time in this plant. Overall, an increase in extraction temperature resulted in an increase in metabolite extraction during PHWE. This study is the first scientific report on the phytochemical composition of V. fastigiata, providing insight into the components of the chemo-diversity of this important plant.
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Affiliation(s)
- Keabetswe Masike
- Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
| | - Bradley S Khoza
- Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
| | - Paul A Steenkamp
- Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
| | - Elize Smit
- Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
| | - Ian A Dubery
- Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
| | - Ntakadzeni E Madala
- Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
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Jansen O, Tchinda AT, Loua J, Esters V, Cieckiewicz E, Ledoux A, Toukam PD, Angenot L, Tits M, Balde AM, Frédérich M. Antiplasmodial activity of Mezoneuron benthamianum leaves and identification of its active constituents. JOURNAL OF ETHNOPHARMACOLOGY 2017; 203:20-26. [PMID: 28323050 DOI: 10.1016/j.jep.2017.03.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 03/10/2017] [Accepted: 03/16/2017] [Indexed: 05/20/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Decoctions of the leaves of M. benthamianum Baill. are used by traditional healers in Guinea to treat malaria and this use was validated by a preliminary clinical assay. AIM OF THE STUDY To evaluate the in vitro antiplasmodial activity and to identify active compounds from extracts of M. benthamianum leaves. MATERIAL AND METHODS Antiplasmodial activity of extracts, fractions and pure compounds was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity. Selectivity of extracts and purified compounds for Plasmodium parasites was evaluated by using WST-1 test on HeLa human cells. Compounds were isolated using normal phase silica gel column chromatography and prepHPLC and their structures elucidated using extensive spectroscopic analysis. RESULTS Hydroethanolic extracts (70% v/v) of M. benthamianum leaves showed a moderate in vitro activity against P. falciparum 3D7, with IC50 in the range 22.5 - 32.6µg/mL, depending on the batch; while a dark precipitate formed during ethanol evaporation showed higher activity (IC50 =6.5µg/mL). The fractionation was performed on this most active fraction and was followed by in vitro antiplasmodial assay. Active compounds (5, 7, 8) belong to several phytochemical classes, contributing together to the global antiplasmodial activity of the hydroethanolic extract against P. falciparum parasite. This study finally allowed the isolation of three diterpenes including two new compounds named Mezobenthamic acids A (1) and B (2) and neocaesalpin H (3), as well as quercetin (4), kaempferol (7), resveratrol (6), gallic acid (9) and its ethylester (5), β-sitosterol glucoside (10) and 13b-hydroxy-pheophorbide a (8). CONCLUSION This study gives some concrete evidence to support the ethnopharmacological use of Mezoneuron benthamianum leaves extract in the management of malaria. The active compounds can be further studied for their antiplasmodial potential, as well as their suitability to be used as quality markers for the standardization of this herbal drug from the Guinean traditional pharmacopeia.
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Affiliation(s)
- Olivia Jansen
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium.
| | - Alembert T Tchinda
- Center for Studies on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 6163 Yaoundé, Cameroon
| | - Jean Loua
- Research and Valorization Center on Medicinal Plants of Dubreka, Dubreka, Guinea; Department of Pharmacy, University Gamal Abdel Nasser of Conakry, Conakry, Guinea
| | - Virginie Esters
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
| | - Ewa Cieckiewicz
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
| | - Allison Ledoux
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
| | - Paul D Toukam
- Center for Studies on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 6163 Yaoundé, Cameroon
| | - Luc Angenot
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
| | - Monique Tits
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
| | - Aliou M Balde
- Research and Valorization Center on Medicinal Plants of Dubreka, Dubreka, Guinea; Department of Pharmacy, University Gamal Abdel Nasser of Conakry, Conakry, Guinea
| | - Michel Frédérich
- Laboratory of Pharmacognosy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, CHU B36, 4000 Liège, Belgium
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Wang S, Towler MJ, Weathers PJ. Root regulation of artemisinin production in Artemisia annua: trichome and metabolite evidence. PLANTA 2016; 244:999-1010. [PMID: 27339275 DOI: 10.1007/s00425-016-2560-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 06/15/2016] [Indexed: 05/21/2023]
Abstract
Roots of plants with high artemisinin-producing leaves increased leaf production of artemisinin in low-producing plants and vice versa indicating roots are involved in controlling artemisinin biosynthesis in shoots. The anti-malarial sesquiterpene, artemisinin, is produced and stored in glandular trichomes (GLTs) of Artemisia annua. Evidence suggested roots, which produce no significant artemisinin nor precursor compounds, regulate production of artemisinin biosynthesis in the leaves. Using grafting, we studied the relationship between rootstock and scion by measuring GLTs and five artemisinic metabolites (artemisinin, deoxyartemisinin, dihydroartemisinic acid, artemisinic acid, arteannuin B) in scions of ungrafted, self-grafted, and cross-grafted plants among three cultivars: S and 15 both having GLTs with artemisinin at 1.49 and 0.57 %, respectively, and G producing neither GLTs nor detectable artemisinin. All artemisinin-producing self-grafts, e.g., S/S (scion/rootstock) and 15/15, produced more artemisinin than ungrafted plants, likely from grafting stress. S/S grafts also produced more GLTs. The 15/S grafts produced more artemisinin than S/15, suggesting rootstocks from high producing S plants stimulated artemisinin production in 15 scions. S/15 grafts yielded less artemisinin than S/S, but more than either 15/15 or ungrafted n15 and nS; S/15 grafts also had a lower density of GLTs than S/S, suggesting rootstock inhibition of the scion. The S rootstock induced trace artemisinin production in G scions, but did not induce GLT formation in G/S grafts. Different grafts exhibited different trichome morphologies and effects on artemisinic pathway flux. This study provides new information regarding the role of roots in GLT development and artemisinin production in this important medicinal plant.
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Affiliation(s)
- Sibo Wang
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Melissa J Towler
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Pamela J Weathers
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, USA.
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Houël E, Nardella F, Jullian V, Valentin A, Vonthron-Sénécheau C, Villa P, Obrecht A, Kaiser M, Bourreau E, Odonne G, Fleury M, Bourdy G, Eparvier V, Deharo E, Stien D. Wayanin and guaijaverin, two active metabolites found in a Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh) (Myrtaceae) antimalarial decoction from the Wayana Amerindians. JOURNAL OF ETHNOPHARMACOLOGY 2016; 187:241-8. [PMID: 27132714 DOI: 10.1016/j.jep.2016.04.053] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 04/14/2016] [Accepted: 04/28/2016] [Indexed: 05/20/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Psidium acutangulum Mart. ex DC is a small tree used by the Wayana Amerindians from the Upper-Maroni in French Guiana for the treatment of malaria. AIM OF THE STUDY In a previous study, we highlighted the in vitro antiplasmodial, antioxidant and anti-inflammatory potential of the traditional decoction of P. acutangulum aerial parts. Our goal was then to investigate on the origin of the biological activity of the traditional remedy, and eventually characterize active constituents. MATERIALS AND METHODS Liquid-liquid extractions were performed on the decoction, and the antiplasmodial activity evaluated against chloroquine-resistant FcB1 ([(3)H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains, and on a chloroquine sensitive NF54 ([(3)H]-hypoxanthine bioassay) P. falciparum strain. The ethyl acetate fraction (D) was active and underwent bioguided fractionation. All the isolated compounds were tested on P. falciparum FcB1 strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) of the ethyl acetate fraction and of an anti-Plasmodium active compound, was concurrently assessed on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the fractions and pure compounds was measured on VERO cells, L6 mammalian cells, PBMCs, and RAW cells. RESULTS Fractionation of the ethyl acetate soluble fraction (IC50 ranging from 3.4 to <1µg/mL depending on the parasite strain) led to the isolation of six pure compounds: catechin and five glycosylated quercetin derivatives. These compounds have never been isolated from this plant species. Two of these compounds (wayanin and guaijaverin) were found to be moderately active against P. falciparum FcB1 in vitro (IC50 5.5 and 6.9µM respectively). We proposed the name wayanin during public meetings organized in June 2015 in the Upper-Maroni villages, in homage to the medicinal knowledge of the Wayana population. At 50µg/mL, the ethyl acetate fraction (D) significantly inhibited IL-1β secretion (-46%) and NO production (-21%), as previously observed for the decoction. The effects of D and guiajaverin (4) on the secretion of other cytokines or NO production were not significant. CONCLUSIONS The confirmed antiplasmodial activity of the ethyl acetate soluble fraction of the decoction and of the isolated compounds support the previous results obtained on the P. acutangulum decoction. The antiplasmodial activity might be due to a mixture of moderately active non-toxic flavonoids. The anti-inflammatory activities were less marked for ethyl acetate fraction (D) than for the decoction.
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Affiliation(s)
- Emeline Houël
- CNRS, UMR EcoFoG (AgroParisTech, CIRAD, INRA, UA, UG), Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana.
| | - Flore Nardella
- Laboratoire d'Innovation Thérapeutique UMR CNRS 7200, LabEx Medalis, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch cedex, France; Institut de Parasitologie et de Pathologie Tropicale de Strasbourg (IPPTS) - Faculté de Médecine, Université de Strasbourg, Strasbourg, France
| | - Valérie Jullian
- UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France
| | - Alexis Valentin
- UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France
| | - Catherine Vonthron-Sénécheau
- Laboratoire d'Innovation Thérapeutique UMR CNRS 7200, LabEx Medalis, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch cedex, France
| | - Pascal Villa
- Plate-forme de Chimie Biologique Intégrative de Strasbourg UMS 3286 CNRS-Université de Strasbourg, LabEx Medalis et FMTS, ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch Cedex, France
| | - Adeline Obrecht
- Plate-forme de Chimie Biologique Intégrative de Strasbourg UMS 3286 CNRS-Université de Strasbourg, LabEx Medalis et FMTS, ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch Cedex, France
| | - Marcel Kaiser
- Swiss Tropical and Public Health Institution, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland
| | - Eliane Bourreau
- Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana
| | - Guillaume Odonne
- Laboratoire Ecologie,évolution, interactions des systèmes amazoniens (LEEISA), CNRS, Université de Guyane, IFREMER, 97300 Cayenne, French Guiana
| | - Marie Fleury
- Museum National d'Histoire Naturelle, UMR 208 PALoc, MNHN-IRD, BP 165, 97323 Cayenne cedex, French Guiana
| | | | - Véronique Eparvier
- CNRS - Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
| | - Eric Deharo
- UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France
| | - Didier Stien
- CNRS - Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France; Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire Océanologique, 66650 Banyuls/Mer, France.
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Shitlani D, Choudhary R, Pandey DP, Bodakhe SH. Ameliorative antimalarial effects of the combination of rutin and swertiamarin on malarial parasites. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2016. [DOI: 10.1016/s2222-1808(16)61067-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Abstract
The contemporary scientific community has presently recognized flavonoids to be a unique class of therapeutic molecules due to their diverse therapeutic properties. Of these, rutin, also known as vitamin P or rutoside, has been explored for a number of pharmacological effects. Tea leaves, apples, and many more possess rutin as one of the active constituents. Today, rutin has been observed for its nutraceutical effect. The present review highlights current information and health-promoting effects of rutin. Along with this, safety pharmacology issues and SAR of the same have also been discussed.
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López D, Cherigo L, Spadafora C, Loza-Mejía MA, Martínez-Luis S. Phytochemical composition, antiparasitic and α-glucosidase inhibition activities from Pelliciera rhizophorae. Chem Cent J 2015; 9:53. [PMID: 26435737 PMCID: PMC4586009 DOI: 10.1186/s13065-015-0130-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 09/11/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Panama has an extensive mangrove area and it is one of the countries with the highest biodiversity in America. Mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in America. Given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. This study was designed to evaluate the potential of Pelliciera rhizophorae as a source of bioactive compounds. RESULTS The present investigation was undertaken to explore the possible antiparasitic potential and α-glucosidase inhibition by compounds derived from the Panamanian mangrove Pelliciera rhizophorae. Bioassay-guided fractionation of the crude extract led to the isolation of ten chemical compounds: α-amyrine (1), β-amyrine (2), ursolic acid (3), oleanolic acid (4), betulinic acid (5), brugierol (6) iso-brugierol (7), kaempferol (8), quercetin (9), and quercetrin (10). The structures of these compounds were established by spectroscopic analyses including APCI-HR-MS and NMR. Compounds 4 (IC50 = 5.3 µM), 8 (IC50 = 22.9 µM) and 10 (IC50 = 3.4 µM) showed selective antiparasitic activity against Leishmania donovani, while compounds 1 (IC50 = 19.0 µM) and 5 (IC50 = 18.0 µM) exhibited selectivity against Tripanosoma cruzi and Plasmodium falciparum, respectively. Moreover, compounds 1-5 inhibited α-glucosidase enzyme in a concentration-dependent manner with IC50 values of 1.45, 0.02, 1.08, 0.98 and 2.37 µM, respectively. Their inhibitory activity was higher than that of antidiabetic drug acarbose (IC50 217.7 µM), used as a positive control. Kinetic analysis established that the five compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bind at the same site that acarbose in the human intestinal α-glucosidase (PDB: 3TOP). CONCLUSIONS Three groups of compounds were isolated in this study (triterpenes, flavonols and dithiolanes). Triterpenes and flavones showed activity in at least one bioassay (antiparasitic or α-glucosidase). In addition, only the pentacyclic triterpenes exhibited a competitive type of inhibition against α-glucosidase.
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Affiliation(s)
- Dioxelis López
- />Center for Drug Discovery and Biodiversity, Institute for Scientific Research and Technology Services (INDICASAT), Clayton, P.O. Box 0843-01103, Panama City, Republic of Panama
- />Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, 522510 India
| | - Lilia Cherigo
- />Department of Organic Chemistry, Chemistry School, Faculty of Natural Sciences, Exact and Technology, University of Panama, P.O. Box 3366, Panama City, Republic of Panama
| | - Carmenza Spadafora
- />Center for Cellular and Molecular Biology of Diseases, Institute for Scientific Research and Technology Services (INDICASAT), Clayton, P.O. Box 0843-01103, Panama City, Republic of Panama
| | - Marco A. Loza-Mejía
- />Facultad de Ciencias Químicas, Universidad La Salle, Benjamín Franklin 47, Cuauhtémoc, 06140 Mexico City, Mexico
| | - Sergio Martínez-Luis
- />Center for Drug Discovery and Biodiversity, Institute for Scientific Research and Technology Services (INDICASAT), Clayton, P.O. Box 0843-01103, Panama City, Republic of Panama
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Lamien-Meda A, Kiendrebeogo M, Compaoré M, Meda RNT, Bacher M, Koenig K, Pacher T, Fuehrer HP, Noedl H, Willcox M, Novak J. Quality assessment and antiplasmodial activity of West African Cochlospermum species. PHYTOCHEMISTRY 2015; 119:51-61. [PMID: 26429632 DOI: 10.1016/j.phytochem.2015.09.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 09/15/2015] [Accepted: 09/16/2015] [Indexed: 05/03/2023]
Abstract
The present study focuses on development of phytochemical methods for quality assessment of two West-African Cochlospermum species (Cochlospermum planchonii and Cochlospermum tinctorium) traditionally used for malaria treatment in Burkina Faso. Antimalarial activity of preparations from dried rhizomes (decoction) was tested against the chloroquine-sensitive Plasmodium strain 3D7 using the histidine-rich protein II (HRP2) drug susceptibility assay and compared with extract preparations using organic solvents of different polarity. Two main apocarotenoids were isolated from rhizomes of C. planchonii and unambiguously identified as dihydrocochloxanthine and cochloxanthine by spectroscopic methods. Comparative HPLC analyses of thirty-nine (39) samples from markets and from collections in natural habitats of both species showed a high variability in the accumulation of cochloxanthines and related carotenoids which were proven to be characteristic for rhizomes of both species and generally absent in leaves. Furthermore, content of total phenolics and antioxidant activities (DPPH and FRAP) as well as haemolytic activity of various extracts was tested. The HPLC method presented here was validated and provides a good separation of both compounds including 10 minor carotenoids. Extracts from both species and pure cochloxanthine offered pronounced antioxidant activities and weak haemolytic activity while, in contrast, dihydrocochloxanthine had a strong haemolytic effect at the highest concentration analysed. However, cochloxanthine as well as dihydrocochloxanthine showed erythroprotective effects against the haemolytic activity of the reference saponin. Moderate antiplasmodial activity between 16 and 63 μg/ml were observed with all tested extracts, and lower IC50 values were obtained with pure dihydrocochloxanthine (IC50=6.9 μg/ml), cochloxanthine (IC50=6.8 μg/ml), the DCM fraction (IC50=2.4 μg/ml) and the ethyl acetate fraction (IC50=11.5μg/ml) derived from a methanolic extract of C. planchonii. This study shows a major variability of carotenoid content and antiplasmodial activity of both C. planchonii and C. tinctorium. The high haemolytic activity of dihydrocochloxanthine (at 100 μg/ml) should be considered as a selection criterion for choosing species phenotypes for treatment.
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Affiliation(s)
- Aline Lamien-Meda
- Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria.
| | - Martin Kiendrebeogo
- Laboratoire de Biochimie et Chimie Appliquées, LABIOCA, University of Ouagadougou, 03 BP 7021 Ouagadougou 03, Burkina Faso
| | - Moussa Compaoré
- Laboratoire de Biochimie et Chimie Appliquées, LABIOCA, University of Ouagadougou, 03 BP 7021 Ouagadougou 03, Burkina Faso
| | - Roland N T Meda
- UFR Sciences et Techniques, Polytechnic University of Bobo Dioulasso, 01 BP 1091 Bobo 01, Burkina Faso
| | - Markus Bacher
- Division of Chemistry of Renewables, Department of Chemistry, University of Natural Resources and Life Sciences, Konrad Lorenz Straße 24, A-3430 Tulln an der Donau, Austria
| | - Karin Koenig
- Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria
| | - Thomas Pacher
- Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria
| | - Hans-Peter Fuehrer
- Institute of Parasitology, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria
| | - Harald Noedl
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, A-1090 Vienna, Austria
| | - Merlin Willcox
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK
| | - Johannes Novak
- Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria
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