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Abdullajanov O, Ganiev A, Turak A, Begmatov N, Bobakulov K, Zhao J, Zhao B, Abdullaev N, He F, Aisa HA. Sesquiterpene lactones from Artemisia porrecta Krasch.ex Poljakov and their anti-inflammatory, cytotoxic and anti-vitiligo activities. PHYTOCHEMISTRY 2025; 234:114419. [PMID: 39889862 DOI: 10.1016/j.phytochem.2025.114419] [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: 10/18/2024] [Revised: 01/27/2025] [Accepted: 01/29/2025] [Indexed: 02/03/2025]
Abstract
This experiment focused on investigating the chemical constituents of the plant Artemisia porrecta Krasch.ex Poljakov, resulting in the isolation and characterization of twenty-seven sesquiterpene lactones belonging to the eudesmanolides, germacronolides, melampolides, and heliangolide types. These compounds include ten undescribed sesquiterpene lactones, Porrectolide A-I, 11-epi-Deacetylherbolide D and seventeen known ones. All known compounds were isolated from this plant for the first time. Their structures were established by 1D, 2D NMR spectroscopic and HR-ESI-MS data, electronic circular dichroism, and single crystal X-ray diffraction analysis. Evaluations of the anti-inflammatory activity revealed that 6 had moderate anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells with the IC50 value of 14.57 ± 0.24 μM.
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Affiliation(s)
- Oybek Abdullajanov
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Adkham Ganiev
- Acad. S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, 77, M. Ulugbek str., 100170, Tashkent, Uzbekistan
| | - Ablajan Turak
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
| | - Nurmirza Begmatov
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; Acad. S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, 77, M. Ulugbek str., 100170, Tashkent, Uzbekistan
| | - Khayrulla Bobakulov
- Acad. S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, 77, M. Ulugbek str., 100170, Tashkent, Uzbekistan; National Research University "Tashkent Institute of Irrigation and Agricultural Mechanization Engineers", 39, Kary Niyoziy str., 100000, Tashkent, Uzbekistan
| | - Jiangyu Zhao
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Bo Zhao
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
| | - Nasrulla Abdullaev
- Acad. S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, 77, M. Ulugbek str., 100170, Tashkent, Uzbekistan
| | - Fei He
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Haji Akber Aisa
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
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Xu F, Shan X, Li J, Li J, Yuan J, Zou D, Wang M. The plant matrix of Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies. PLoS One 2025; 20:e0322835. [PMID: 40334250 PMCID: PMC12058161 DOI: 10.1371/journal.pone.0322835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 03/28/2025] [Indexed: 05/09/2025] Open
Abstract
Artemisinin-based combination therapies (ACTs) constitute the principal strategy for combating malaria in contemporary times, and research into the multifaceted components of Artemisia annua L. (A. annua) has garnered widespread interest among scientists. The aim of this study was to prepare A. annua extracts (nACTs) and to explore whether nACTs have higher bioavailability and efficacy than artemisinin (ART) alone due to its multiple bioactive components. Initially, the in vivo antimalarial activity of nACTs was evaluated by two murine malaria models. The results revealed that the antimalarial effect of nACTs was about 10-fold higher than that of ART alone when administered at the same dosage of ART. Then, we analyzed the pharmacokinetic characteristics of nACTs in rat plasma. Remarkably, nACTs exhibited significantly enhanced oral bioavailability, longer half-life as well as extended mean retention time in rats. In addition, the impact of nACTs on P-glycoprotein (P-gp) was evaluated using the Caco-2 cell line. The results showed that both ART and nACTs reduced the efflux rate of the P-gp substrate rhodamine 123 (R123) and induced the expression of P-gp in Caco-2 cells over a range of concentrations. nACTs had certain components-deoxyartemisinin (DEART), artemisinic acid (AA), and dihydroartemisinic acid (DHAA)-that inhibited the efflux and translocation of P-gp and facilitated the reduction of ART efflux. In conclusion, A. annua extracts significantly improved the antimalarial efficacy and bioavailability compared with ART.
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Affiliation(s)
- Fujie Xu
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Xiaohang Shan
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jialin Li
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Jing Li
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Jiqiao Yuan
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Daozeng Zou
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Manyuan Wang
- Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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Rauf A, Olatunde A, Hafeez N, Hemeg HA, Aljohani ASM, Al Abdulmonem W, Ribaudo G. From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from Genus Artemisia. Mini Rev Med Chem 2025; 25:208-218. [PMID: 39192639 DOI: 10.2174/0113895575320559240820113540] [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: 04/16/2024] [Revised: 06/04/2024] [Accepted: 06/11/2024] [Indexed: 08/29/2024]
Abstract
While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and nature-inspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.
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Affiliation(s)
- Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan
| | - Ahmed Olatunde
- Department of Medical Biochemistry, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria
| | - Nabia Hafeez
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan
| | - Hassan A Hemeg
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Al-Medinah Al-Monawara, Saudi Arabia
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Giovanni Ribaudo
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
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Angupale JR, Ajayi CO, Tusiimire J, Ngwuluka NC. Optimization of in vivo antimalarial efficacy of combinations of aqueous leaf extracts of Artemisia annua L., Vernonia amygdalina Del, and Microglossa pyrifolia (Lam.) Kuntze using factorial design. BMC Complement Med Ther 2024; 24:393. [PMID: 39538287 PMCID: PMC11562369 DOI: 10.1186/s12906-024-04691-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: 01/22/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Malaria continues to be among the leading causes of mortality in Africa including Uganda, with the emergence of parasite resistance to the first-line therapeutics (Artemisinin- based Combination Therapy). To find new therapeutics, this study has reported an in vivo antimalarial efficacy of combinations of Artemisia annua (Aa), Vernonia amygdalina (Va), and Microglossa pyrifolia (Mp) in mice model using factorial design. METHODS The Aa and Va were extracted by hot infusion, and Mp by cold maceration using distilled water. The dry extracts were screened for different phytochemicals, and later subjected to in vivo antimalarial activity using Peter's 4-day suppressive test. The 23 factorial design used Aa, Va, and Mp aqueous extracts as independent variables at two levels (-1 and 1), and the percentage chemo suppression and survival time as response variables. The data was analyzed using Design Expert 13 and GraphPad Prism employing ANOVA linear regression modelling and t-test respectively. RESULTS All the extracts had alkaloids, phenols, saponins, terpenoids, cardiac glycosides, tannins, steroids, and carbohydrates. The various combinations showed chemo suppression from 41.5 to 91.0% and survival time of 19 to 23 days. The first three combinations having lower levels of Aa (200 mg/kg) exhibited higher chemo suppression (> 90%) compared to Artemisinin-Lumefantrine positive control at 4 mg/kg with 87.5%. Lower levels of Aa in the combinations contributed to high chemo suppression while higher levels of Va prolonged survival times. Interactions between Aa and Mp showed higher chemo suppression, and that between Aa and Va increased survival time. An optimized prediction of 94.4% chemo suppression was made by the ANOVA model at lower levels of Aa and Va, and a higher level of Mp, which is similar to an experimental run which gave a response of 90. 6%. CONCLUSION An optimum combination of the three plants as a natural herbal antimalarial therapy was obtained using factorial design, and it offers an alternative to first line Artemisinin based Combination Therapy (ACTs) as parasite resistance looms. This combination could be further developed into a standard phytopharmaceutical and subjected to Randomized Controlled Trials (RCTs).
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Affiliation(s)
- Jimmy R Angupale
- Department of Pharmaceutical Sciences, Faculty of Medicine, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda.
- Pharm-Biotechnology and Traditional Medicine Centre, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda.
| | - Clement O Ajayi
- Pharm-Biotechnology and Traditional Medicine Centre, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda
| | - Jonans Tusiimire
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda
| | - Ndidi C Ngwuluka
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Jos, Jos, Nigeria
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Walz A, Lehmann U, Duthaler U, Mäser P, Wittlin S. In vivo antimalarial efficacy of Artemisia afra powder suspensions. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155644. [PMID: 38761524 DOI: 10.1016/j.phymed.2024.155644] [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: 01/04/2024] [Revised: 04/02/2024] [Accepted: 04/13/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia annua, urge the development of novel antimalarials. A clinical trial has found high antimalarial potency for aqueous extracts of A. annua as well as its African counterpart Artemisia afra, which contains only trace amounts of artemisinin. The artemisinin-independent antimalarial activity of A. afra points to the existence of other antimalarials present in the plant. However, the publication was retracted due to ethical and methodological concerns in the trial, so the only evidence for antimalarial activity of A. afra is built on in vitro studies reporting efficacy only in the microgram per milliliter range. HYPOTHESIS Our study aims to shed more light on the controversy around the antimalarial activity of A. afra by assessing its efficacy in mice. In particular, we are testing the hypothesis that A. afra contains a pro-drug that is inactive in vitro but active in vivo after metabolization by the mammalian host. METHODS Plasmodium berghei-infected mice were treated once or thrice (on three consecutive days) with various doses of A. afra, A. annua, or pure artemisinin. RESULTS Aqueous powder suspensions of A. annua but not A. afra showed antimalarial activity in mice. CONCLUSION Our experiments conducted in mice do not support the pro-drug hypothesis.
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Affiliation(s)
- Annabelle Walz
- Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; University of Basel, 4001 Basel, Switzerland
| | - Ursula Lehmann
- Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; University of Basel, 4001 Basel, Switzerland
| | - Urs Duthaler
- Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland
| | - Pascal Mäser
- Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; University of Basel, 4001 Basel, Switzerland
| | - Sergio Wittlin
- Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; University of Basel, 4001 Basel, Switzerland.
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Ferreira AM, Sales I, Santos SAO, Santos T, Nogueira F, Mattedi S, Pinho SP, Coutinho JA, Freire MG. Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic Liquids. CHEM & BIO ENGINEERING 2024; 1:44-52. [PMID: 38434799 PMCID: PMC10906083 DOI: 10.1021/cbe.3c00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 11/12/2023] [Accepted: 12/06/2023] [Indexed: 03/05/2024]
Abstract
Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs.
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Affiliation(s)
- Ana M. Ferreira
- CICECO
− Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Isabela Sales
- CICECO
− Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
- Escola
Politécnica, Universidade Federal
da Bahia, Bahia 40210-630, Brazil
| | - Sónia A. O. Santos
- CICECO
− Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Tiago Santos
- Global
Health and Tropical Medicine, GHTM, Associate Laboratory in Translation
and Innovation towards Global Health, LA-REAL, Instituto de Higiene
e Medicina Tropical, IHMT, Universidade
Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
| | - Fátima Nogueira
- Global
Health and Tropical Medicine, GHTM, Associate Laboratory in Translation
and Innovation towards Global Health, LA-REAL, Instituto de Higiene
e Medicina Tropical, IHMT, Universidade
Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
- LAQV-REQUIMTE,
MolSyn, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal
| | - Silvana Mattedi
- Escola
Politécnica, Universidade Federal
da Bahia, Bahia 40210-630, Brazil
| | - Simão P. Pinho
- Mountain
Research Center − CIMO, Polytechnic
Institute of Bragança, Bragança 5300-253, Portugal
- SusTEC, Instituto Politécnico de Bragança, Bragança 5300-253, Portugal
| | - João A.
P. Coutinho
- CICECO
− Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Mara G. Freire
- CICECO
− Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
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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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Angupale JR, Tusiimire J, Ngwuluka NC. A review of efficacy and safety of Ugandan anti-malarial plants with application of RITAM score. Malar J 2023; 22:97. [PMID: 36932389 PMCID: PMC10021060 DOI: 10.1186/s12936-023-04486-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/11/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants. METHODS Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020-December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (µg/ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety (LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development. RESULTS Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 - 0.05 µg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation. CONCLUSION There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed.
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Affiliation(s)
- Jimmy R Angupale
- Department of Pharmaceutical Sciences, Faculty of Medicine, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda.
- Pharm-Biotechnology and Traditional Medicine Centre, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda.
| | - Jonans Tusiimire
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda
| | - Ndidi C Ngwuluka
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Jos, Jos, Nigeria
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Kim HK, Choi YH, Verpoorte R. Natural Products Drug Discovery: On Silica or In-Silico? Handb Exp Pharmacol 2023; 277:117-141. [PMID: 36318326 DOI: 10.1007/164_2022_611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Natural products have been the most important source for drug development throughout the human history. Over time, the formulation of drugs has evolved from crude drugs to refined chemicals. In modern drug discovery, conventional natural products lead-finding usually uses a top-down approach, namely bio-guided fractionation. In this approach, the crude extracts are separated by chromatography and resulting fractions are tested for activity. Subsequently, active fractions are further refined until a single active compound is obtained. However, this is a painstakingly slow and expensive process. Among the alternatives that have been developed to improve this situation, metabolomics has proved to yield interesting results having been applied successfully to drug discovery in the last two decades. The metabolomics-based approach in lead-finding comprises two steps: (1) in-depth chemical profiling of target samples, e.g. plant extracts, and bioactivity assessment, (2) correlation of the chemical and biological data by chemometrics. In the first step of this approach, the target samples are chemically profiled in an untargeted manner to detect as many compounds as possible. So far, NMR spectroscopy, LC-MS, GC-MS, and MS/MS spectrometry are the most common profiling tools. The profile data are correlated with the biological activity with the help of various chemometric methods such as multivariate data analysis. This in-silico analysis has a high potential to replace or complement conventional on-silica bioassay-guided fractionation as it will greatly reduce the number of bioassays, and thus time and costs. Moreover, it may reveal synergistic mechanisms, when present, something for which the classical top-down approach is clearly not suited. This chapter aims to give an overview of successful approaches based on the application of chemical profiling with chemometrics in natural products drug discovery.
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Affiliation(s)
- Hye Kyong Kim
- Natural Products Laboratory, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands
| | - Young Hae Choi
- Natural Products Laboratory, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.,College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
| | - Robert Verpoorte
- Natural Products Laboratory, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
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Ekiert H, Klimek-Szczykutowicz M, Rzepiela A, Klin P, Szopa A. Artemisia Species with High Biological Values as a Potential Source of Medicinal and Cosmetic Raw Materials. Molecules 2022; 27:6427. [PMID: 36234965 PMCID: PMC9571683 DOI: 10.3390/molecules27196427] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/11/2022] [Accepted: 09/20/2022] [Indexed: 01/19/2023] Open
Abstract
Artemisia species play a vital role in traditional and contemporary medicine. Among them, Artemisia abrotanum, Artemisia absinthium, Artemisia annua, Artemisia dracunculus, and Artemisia vulgaris are the most popular. The chemical composition and bioactivity of these species have been extensively studied. Studies on these species have confirmed their traditional applications and documented new pharmacological directions and their valuable and potential applications in cosmetology. Artemisia ssp. primarily contain sesquiterpenoid lactones, coumarins, flavonoids, and phenolic acids. Essential oils obtained from these species are of great biological importance. Extracts from Artemisia ssp. have been scientifically proven to exhibit, among others, hepatoprotective, neuroprotective, antidepressant, cytotoxic, and digestion-stimulating activities. In addition, their application in cosmetic products is currently the subject of several studies. Essential oils or extracts from different parts of Artemisia ssp. have been characterized by antibacterial, antifungal, and antioxidant activities. Products with Artemisia extracts, essential oils, or individual compounds can be used on skin, hair, and nails. Artemisia products are also used as ingredients in skincare cosmetics, such as creams, shampoos, essences, serums, masks, lotions, and tonics. This review focuses especially on elucidating the importance of the most popular/important species of the Artemisia genus in the cosmetic industry.
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Affiliation(s)
- Halina Ekiert
- Chair and Department of Pharmaceutical Botany, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
| | - Marta Klimek-Szczykutowicz
- Department of Dermatology, Cosmetology and Aesthetic Surgery, The Institute of Medical Sciences, Medical College, Jan Kochanowski University, IX Wieków Kielc 19a, 25-516 Kielce, Poland
| | - Agnieszka Rzepiela
- Museum of Pharmacy, Medical College, Jagiellonian University, Floriańska 25, 31-019 Kraków, Poland
| | - Paweł Klin
- US Army Health Clinic, Urlas Kaserne, Building 8156, 91522 Ansbach, Germany
| | - Agnieszka Szopa
- Chair and Department of Pharmaceutical Botany, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
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Ekiert H, Świątkowska J, Klin P, Rzepiela A, Szopa A. Artemisia annua - Importance in Traditional Medicine and Current State of Knowledge on the Chemistry, Biological Activity and Possible Applications. PLANTA MEDICA 2021; 87:584-599. [PMID: 33482666 DOI: 10.1055/a-1345-9528] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Artemisia annua (annual mugwort) is a species that has long been used in traditional Asian medicine, mainly Chinese and Hindu. The species is widespread and known as a medicinal plant not only in Asia but also in Europe, in both Americas, and Australia. The species has become a subject of particular interest due to the 2015 Nobel Prize awarded for detecting the sesquiterpene lactone artemisinin in it and proving its antimalarial activities. The raw materials obtained from this species are Artemisiae annuae folium and Artemisiae annuae herba. The leaves are a raw material in the Chinese Pharmacopoeia and Vietnamese Pharmacopoeia. Both raw materials are in the International Pharmacopoeia published by the WHO. The main components of these raw materials are mainly specific sesquiterpene lactones, essential oil, flavonoids, coumarins, and phenolic acids. In traditional Asian medicine, the species is used, for example, in the treatment of jaundice and bacterial dysentery, as an antipyretic agent in malaria and tuberculosis, in the treatment of wounds and haemorrhoids, and in viral, bacterial, and autoimmune diseases. Professional pharmacological studies conducted today have confirmed its known traditional applications and explain previously unknown mechanisms of its biological action and have also found evidence of new directions of biological activity, including, among others, anti-inflammatory, analgesic, antioxidant, antitumour, and nephroprotective activities. The species is of growing importance in the cosmetics industry.
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Affiliation(s)
- Halina Ekiert
- Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
| | - Joanna Świątkowska
- Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
| | - Paweł Klin
- Family Medicine Clinic, Medizinisches Versorgungszentrum (MVZ) Burgbernheim GmbH, Burgbernheim, Germany
| | - Agnieszka Rzepiela
- Museum of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland
| | - Agnieszka Szopa
- Chair and Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland
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Snider D, Weathers PJ. In vitro reduction of Plasmodium falciparum gametocytes: Artemisia spp. tea infusions vs. artemisinin. JOURNAL OF ETHNOPHARMACOLOGY 2021; 268:113638. [PMID: 33271239 PMCID: PMC7855472 DOI: 10.1016/j.jep.2020.113638] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 10/27/2020] [Accepted: 11/25/2020] [Indexed: 05/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Artemisia annua has a long history of use in Southeast Asia where it was used to treat "fever", and A. afra has a similar history in southern Africa. Since their discovery, A. annua use, in particular, has expanded globally with millions of people using the plant in therapeutic tea infusions, mainly to treat malaria. AIM OF THE STUDY In this study, we used in vitro studies to query if and how A. annua and A. afra tea infusions being used across the globe affect asexual Plasmodium falciparum parasites, and their sexual gametocytes. MATERIALS AND METHODS P. falciparumstrain NF54 was grown in vitro, synchronized, and induced to form gametocytes using N-acetylglucosamine. Cultures during asexual, early, and late stage gametocytogenesis were treated with artemisinin, methylene blue, and A. annua and A. afra tea infusions (5 g DW/L) using cultivars that contained 0-283 μM artemisinin. Asexual parasitemia and gametocytemia were analyzed microscopically. Gametocyte morphology also was scored. Markers of early (PfGEXP5) and late stage (Pfs25) gametocyte gene expression also were measured using RT-qPCR. RESULTS Both A. annua and A. afra tea infusions reduced gametocytemia in vitro, and the effect was mainly artemisinin dependent. Expression levels of both marker genes were reduced and also occurred with the effect mainly attributed to artemisinin content of four tested Artemisia cultivars. Tea infusions of both species also inhibited asexual parasitemia and although mainly artemisinin dependent, there was a weak antiparasitic effect from artemisinin-deficient A. afra. CONCLUSIONS These results showed that A. annua and to a lesser extent, A. afra, inhibited parasitemia and gametocytemia in vitro.
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Affiliation(s)
- Danielle Snider
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
| | - Pamela J Weathers
- Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
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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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Tibiri A, Boria S, Traoré TK, Ouédraogo N, Nikièma A, Ganaba S, Compaoré JM, Ouédraogo I, Guissou IP, Carraz M. Countrywide Survey of Plants Used for Liver Disease Management by Traditional Healers in Burkina Faso. Front Pharmacol 2021; 11:563751. [PMID: 33597863 PMCID: PMC7883685 DOI: 10.3389/fphar.2020.563751] [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: 05/19/2020] [Accepted: 10/06/2020] [Indexed: 11/17/2022] Open
Abstract
Liver disease is highly prevalent in Africa, especially in the western African country Burkina Faso, due to the presence of multiple biological and chemical aggressors of the liver. Furthermore, diagnosis and appropriate care for liver disease are uneven and usually insufficient. This drives local communities to turn to folk medicine based on medicinal plants from healers. Small scale, ethnopharmacological studies on reputed hepatoprotective plants have been carried out in defined regions worldwide, but so far, no study has been carried out on a countrywide scale. Therefore, we have explored traditional healers’ practices in all thirteen regions of Burkina Faso. We interviewed 575 healers and we compiled a database with 2,006 plant entries. Here, we report results on liver nosology, liver pathologies, medicinal plants used for liver disease, and traditional practices through the lens of Burkinabe healers. Our goal was to give a full inventory of medicinal plants used to treat liver disease and to determine if there was consensus on the use of specific plants for specific symptoms. Analysis of the medicinal plants in use across the whole country provides local communities with a wider evidence base to determine which plants may be more effective in treating liver disease and could provide the scientific community, with a shortlist of plants suitable for chemical and pharmacological investigation to validate the plants’ therapeutic role.
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Affiliation(s)
- André Tibiri
- Laboratoire De Biologie Appliquée, Département De Médecine Et Pharmacopée Traditionnelles-Pharmacie (MEPHATRA-PH), Institut De Recherche En Science De La Santé, CNRST, Ouagadougou, Burkina Faso
| | | | - Tata Kadiatou Traoré
- Laboratoire De Développement Du Médicament, Université De Ouagadougou, Ouagadougou, Burkina Faso
| | - Noufou Ouédraogo
- Laboratoire De Biologie Appliquée, Département De Médecine Et Pharmacopée Traditionnelles-Pharmacie (MEPHATRA-PH), Institut De Recherche En Science De La Santé, CNRST, Ouagadougou, Burkina Faso
| | - Aude Nikièma
- UMI CNRS 3189, Institut Des Sciences Des Sociétés, CNRST Ouagadougou, Ouagadougou, Burkina Faso
| | - Souleymane Ganaba
- Département Environnement Et Forêts, Institut De L'Environnement Et De Recherches Agricoles, Ouagadougou, Burkina Faso
| | - Jean-Marie Compaoré
- Fédération Nationale Des Tradipraticiens De Santé Du Burkina (FENATRAB), Ministère De La Santé Du Burkina Faso, Ouagadougou, Burkina Faso
| | - Issiaka Ouédraogo
- Service De Gastro-Entérologie, Centre Hospitalier Universitaire Yalgado Ouédraogo (CHU-YO), Ouagadougou, Burkina Faso
| | - Innocent Pierre Guissou
- Laboratoire De Biologie Appliquée, Département De Médecine Et Pharmacopée Traditionnelles-Pharmacie (MEPHATRA-PH), Institut De Recherche En Science De La Santé, CNRST, Ouagadougou, Burkina Faso.,Laboratoire De Développement Du Médicament, Université De Ouagadougou, Ouagadougou, Burkina Faso
| | - Maëlle Carraz
- UMR 152 Pharma-Dev, Université De Toulouse, IRD, UPS, Toulouse, France
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A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes. Sci Rep 2021; 11:2770. [PMID: 33531542 PMCID: PMC7854678 DOI: 10.1038/s41598-021-82201-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 12/24/2020] [Indexed: 11/28/2022] Open
Abstract
Fungal endophytes are a major source of anti-infective agents and other medically relevant compounds. However, their classical blinded-chemical investigation is a challenging process due to their highly complex chemical makeup. Thus, utilizing cheminformatics tools such as metabolomics and computer-aided modelling is of great help deal with such complexity and select the most probable bioactive candidates. In the present study, we have explored the fungal endophytes associated with the well-known antimalarial medicinal plant Artemisia annua for their production of further antimalarial agents. Based on the preliminary antimalarial screening of these endophytes and using LC-HRMS-based metabolomics and multivariate analyses, we suggested different potentially active metabolites (compounds 1–8). Further in silico investigation using the neural-network-based prediction software PASS led to the selection of a group of quinone derivatives (compounds 1–5) as the most possible active hits. Subsequent in vitro validation revealed emodin (1) and physcion (2) to be potent antimalarial candidates with IC50 values of 0.9 and 1.9 µM, respectively. Our approach in the present investigation therefore can be applied as a preliminary evaluation step in the natural products drug discovery, which in turn can facilitate the isolation of selected metabolites notably the biologically active ones.
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16
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Ezzat SM, Salem MA, Zayed A. Plants against malarial and typhoid fever. PHYTOCHEMISTRY, THE MILITARY AND HEALTH 2021:285-312. [DOI: 10.1016/b978-0-12-821556-2.00024-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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17
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Manya MH, Keymeulen F, Ngezahayo J, Bakari AS, Kalonda ME, Kahumba BJ, Duez P, Stévigny C, Lumbu SJB. Antimalarial herbal remedies of Bukavu and Uvira areas in DR Congo: An ethnobotanical survey. JOURNAL OF ETHNOPHARMACOLOGY 2020; 249:112422. [PMID: 31765762 DOI: 10.1016/j.jep.2019.112422] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 11/20/2019] [Accepted: 11/20/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The main objective of the present study was to collect and gather information on herbal remedies traditionally used for the treatment of malaria in Bukavu and Uvira, two towns of the South Kivu province in DRC. MATERIAL AND METHODS Direct interview with field enquiries allowed collecting ethnobotanical data; for each plant, a specimen was harvested in the presence of the interviewed traditional healers (THs). The recorded information included vernacular names, morphological parts of plants, methods of preparation and administration of remedies, dosage and treatment duration. Plants were identified with the help of botanists in the herbaria of INERA/KIPOPO (DRC) and the Botanic Garden of Meise (Belgium), where voucher specimens have been deposited. The results were analysed and discussed in the context of previous published data. RESULTS Interviewees cited 45 plant species belonging to 41 genera and 21 families used for the treatment of malaria. These plants are used in the preparation of 52 recipes, including 25 multi-herbal recipes and 27 mono-herbal recipes. Apart of Artemisia annua L. (Asteraceae; % Citation frequency = 34%) and Carica papaya L. (Caricaceae; % Citation frequency = 34%), the study has highlighted that the most represented families are Asteraceae with 12 species (26%), followed by Fabaceae with 7 species (16%) and Rubiaceae with 4 species (9%). For a majority of plants, herbal medicines are prepared from the leaves in the form of decoction and administered by oral route. CONCLUSION Literature data indicate that part of cited species are already known (38%) and/or studied (30%) for antimalarial properties, which gives credit to the experience of Bukavu and Uvira interviewees and some level of confidence on collected information. The highly cited plants should be investigated in details for the isolation and identification of active ingredients, a contribution to the discovery of new possibly effective antimalarials.
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Affiliation(s)
- Mboni Henry Manya
- Laboratoire de Pharmacognosie, Faculté des Sciences Pharmaceutiques, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo; Service de Chimie Organique, Département de Chimie, Faculté des Sciences, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo; Unité de Pharmacognosie, Bioanalyse et Médicaments, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine - CP205/9, Boulevard du Triomphe, B-1050, Bruxelles, Belgium.
| | - Flore Keymeulen
- Unité de Pharmacognosie, Bioanalyse et Médicaments, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine - CP205/9, Boulevard du Triomphe, B-1050, Bruxelles, Belgium
| | - Jérémie Ngezahayo
- Unité de Pharmacognosie, Bioanalyse et Médicaments, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine - CP205/9, Boulevard du Triomphe, B-1050, Bruxelles, Belgium
| | - Amuri Salvius Bakari
- Laboratoire de Pharmacognosie, Faculté des Sciences Pharmaceutiques, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo
| | - Mutombo Emery Kalonda
- Service de Chimie Organique, Département de Chimie, Faculté des Sciences, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo
| | - Byanga Joh Kahumba
- Laboratoire de Pharmacognosie, Faculté des Sciences Pharmaceutiques, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo
| | - Pierre Duez
- Service de Chimie Thérapeutique et de Pharmacognosie, Université de Mons (UMONS), 20 Place du Parc, 7000, Mons, Belgium
| | - Caroline Stévigny
- Unité de Pharmacognosie, Bioanalyse et Médicaments, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine - CP205/9, Boulevard du Triomphe, B-1050, Bruxelles, Belgium
| | - Simbi Jean-Baptiste Lumbu
- Service de Chimie Organique, Département de Chimie, Faculté des Sciences, Université de Lubumbashi, BP. 1825, Lubumbashi, Congo
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18
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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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The modulatory effect of Artemisia annua L. on toll-like receptor expression in Acanthamoeba infected mouse lungs. Exp Parasitol 2019; 199:24-29. [PMID: 30796912 DOI: 10.1016/j.exppara.2019.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 12/30/2018] [Accepted: 02/19/2019] [Indexed: 11/21/2022]
Abstract
The genus Acanthamoeba, which may cause different infections in humans, occurs widely in the environment. Lung inflammation caused by these parasites induces pulmonary pathological changes such as pulmonary necrosis, peribronchial plasma cell infiltration, moderate desquamation of alveolar cells and partial destruction of bronchial epithelial cells, and presence of numerous trophozoites and cysts among inflammatory cells. The aim of this study was to assess the influence of plant extracts from Artemisia annua L. on expression of the toll-like receptors TLR2 and TLR4 in lungs of mice with acanthamoebiasis. A. annua, which belongs to the family Asteraceae, is an annual plant that grows wild in Asia. In this study, statistically significant changes of expression of TLR2 and TLR4 were demonstrated. In the lungs of infected mice after application of extract from A. annua the expression of TLRs was observed mainly in bronchial epithelial cells, pneumocytes (to a lesser extent during the outbreak of infection), and in the course of high general TLR expression. TLR4 in particular was also visible in stromal cells of lung parenchyma. In conclusion, we confirmed that a plant extract of A. annua has a modulatory effect on components of the immune system such as TLR2 and TLR4.
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20
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Wojtkowiak-Giera A, Derda M, Kosik-Bogacka D, Kolasa-Wołosiuk A, Solarczyk P, Cholewiński M, Wandurska-Nowak E, Jagodziński PP, Hadaś E. Influence of Artemisia annua L. on toll-like receptor expression in brain of mice infected with Acanthamoeba sp. Exp Parasitol 2018; 185:17-22. [PMID: 29317241 DOI: 10.1016/j.exppara.2018.01.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 12/16/2017] [Accepted: 01/05/2018] [Indexed: 01/10/2023]
Abstract
The treatment of acanthamoebiasis is a still a problem. Our previous studies showed that the application of extracts from Artemisia annua L. significantly prolonged the survival of mice infected by Acanthamoeba. This plant has medicinal properties in the treatment of human parasitic diseases. The aim of this study was to evaluate the effects of A. annua on expression of Toll-like receptors (TLRs) 2 and 4 in brain of mice with Acanthamoeba infection. Mice were infected with Acanthamoeba sp. strain Ac309 (KY203908) by intranasal inoculation without and after application of A. annua extract. The administration of extract from A. annua significantly reduced the level of expression of TLR2 and modified the level of expression of TLR4. A. annua extract is a natural substance that is well tolerated in animals and may be considered as a combination therapy in treatment of acanthamoebiasis. Our study suggested that A. annua extract may be used as an alternative therapeutic tool.
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Affiliation(s)
- Agnieszka Wojtkowiak-Giera
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
| | - Monika Derda
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland.
| | - Danuta Kosik-Bogacka
- Department of Biology and Medical Parasitology, Pomeranian Medical University, 72 Powstancow Wielkopolskich Street, 70-111 Szczecin, Poland
| | - Agnieszka Kolasa-Wołosiuk
- Department of Histology and Embryology, Pomeranian Medical University, 71 Powstancow Wielkopolskich Street, 70-111 Szczecin, Poland
| | - Piotr Solarczyk
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
| | - Marcin Cholewiński
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
| | - Elżbieta Wandurska-Nowak
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
| | - Paweł P Jagodziński
- Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznań, Poland
| | - Edward Hadaś
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
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Medicinal plants for in vitro antiplasmodial activities: A systematic review of literature. Parasitol Int 2017; 66:713-720. [PMID: 28890153 DOI: 10.1016/j.parint.2017.09.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/25/2017] [Accepted: 09/06/2017] [Indexed: 01/24/2023]
Abstract
The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and their active compounds are the most promising source the new antimalarial agents. This study aimed to identify the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentration (IC50)≤1μg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and data extraction were performed by two independent reviewers. The herbs were categorized as very good, good, moderate and inactive if the IC50 values were <0.1μg/ml, 0.1-1μg/ml, >1-5μg/ml and >5μg/ml respectively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive. Among plants identified as having very good to good antiplasmodial crude extracts are Harungana madagascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma desmanthum, and Artemisia annua were reported to have individual compound isolates with very good antiplasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant genera needs to be designed.
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Ali M, Abbasi BH, Ahmad N, Khan H, Ali GS. Strategies to enhance biologically active-secondary metabolites in cell cultures of Artemisia - current trends. Crit Rev Biotechnol 2017; 37:833-851. [PMID: 28049347 DOI: 10.1080/07388551.2016.1261082] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The genus Artemisia has been utilized worldwide due to its immense potential for protection against various diseases, especially malaria. Artemisia absinthium, previously renowned for its utilization in the popular beverage absinthe, is gaining resurgence due to its extensive pharmacological activities. Like A. annua, this species exhibits strong biological activities like antimalarial, anticancer and antioxidant. Although artemisinin was found to be the major metabolite for its antimalarial effects, several flavonoids and terpenoids are considered to possess biological activities when used alone and also to synergistically boost the bioavailability of artemisinin. However, due to the limited quantities of these metabolites in wild plants, in vitro cultures were established and strategies have been adopted to enhance medicinally important secondary metabolites in these cultures. This review elaborates on the traditional medicinal uses of Artemisia species and explains current trends to establish cell cultures of A. annua and A. absinthium for enhanced production of medicinally important secondary metabolites.
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Affiliation(s)
- Mohammad Ali
- a Center for Biotechnology and Microbiology , Department of Biotechnology, University of Swat , Pakistan.,b Department of Biotechnology, Faculty of Biological Sciences , Quaid-i-Azam University Islamabad , Pakistan
| | - Bilal Haider Abbasi
- b Department of Biotechnology, Faculty of Biological Sciences , Quaid-i-Azam University Islamabad , Pakistan
| | - Nisar Ahmad
- a Center for Biotechnology and Microbiology , Department of Biotechnology, University of Swat , Pakistan
| | - Haji Khan
- a Center for Biotechnology and Microbiology , Department of Biotechnology, University of Swat , Pakistan
| | - Gul Shad Ali
- c Mid-Florida Research and Education Center and Department of Plant Pathology , University of Florida/Institute of Food and Agricultural Sciences , Apopka , FL , USA
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Effects of oral administration of whole plants of Artemisia annua on Ichthyophthirius multifiliis and Aeromonas hydrophila after parasitism by I. multifiliis. Parasitol Res 2016; 116:91-97. [DOI: 10.1007/s00436-016-5265-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 09/15/2016] [Indexed: 10/20/2022]
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Zhang C, Gong MX, Qiu F, Li J, Wang MY. Effects of arteannuin B, arteannuic acid and scopoletin on pharmacokinetics of artemisinin in mice. ASIAN PAC J TROP MED 2016; 9:677-81. [DOI: 10.1016/j.apjtm.2016.05.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 05/16/2016] [Accepted: 05/23/2016] [Indexed: 11/25/2022] Open
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Derda M, Hadaś E, Cholewiński M, Skrzypczak Ł, Grzondziel A, Wojtkowiak-Giera A. Artemisia annua L. as a plant with potential use in the treatment of acanthamoebiasis. Parasitol Res 2016; 115:1635-9. [PMID: 26782959 PMCID: PMC4799240 DOI: 10.1007/s00436-016-4902-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 01/06/2016] [Indexed: 12/01/2022]
Abstract
The treatment of acanthamoebiasis is a great problem. Most cerebral invasions end with death, and the treatment of ocular invasions is usually long-lasting and not very effective. Numerous plant extracts and substances isolated from plants, which are effective against trophozoites or cysts, have been studied in the treatment of acanthamoebiasis. However, no agents that are simultaneously effective against both developing forms of amoebae have been discovered yet. It seems that such a plant which fulfils both tasks is Artemisia annua L. Our studies showed that water, alcohol and chloroform extracts from the herb A. annua L. can be applied in general and local treatment or in combined therapy with antibiotics in the treatment of acanthamoebiasis. Extracts from this plant show not only in vitro but also in vivo effects. Studies carried out on experimental animals infected with amoebae show that the application of these extracts significantly prolongs the survival of the animals.
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Affiliation(s)
- Monika Derda
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland.
| | - Edward Hadaś
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland
| | - Marcin Cholewiński
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland
| | - Łukasz Skrzypczak
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland
| | - Anna Grzondziel
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland
| | - Agnieszka Wojtkowiak-Giera
- Department of Biology and Medical Parasitology, Poznan University of Medical Sciences, 10 Fredry Street, 61-701, Poznan, Poland
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Chagas-Paula DA, Zhang T, Da Costa FB, Edrada-Ebel R. A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition. Metabolites 2015; 5:404-30. [PMID: 26184333 PMCID: PMC4588803 DOI: 10.3390/metabo5030404] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 06/23/2015] [Accepted: 06/30/2015] [Indexed: 11/16/2022] Open
Abstract
The application of metabolomics in phytochemical analysis is an innovative strategy for targeting active compounds from a complex plant extract. Species of the Asteraceae family are well-known to exhibit potent anti-inflammatory (AI) activity. Dual inhibition of the enzymes COX-1 and 5-LOX is essential for the treatment of several inflammatory diseases, but there is not much investigation reported in the literature for natural products. In this study, 57 leaf extracts (EtOH-H2O 7:3, v/v) from different genera and species of the Asteraceae family were tested against COX-1 and 5-LOX while HPLC-ESI-HRMS analysis of the extracts indicated high diversity in their chemical compositions. Using O2PLS-DA (R2 > 0.92; VIP > 1 and positive Y-correlation values), dual inhibition potential of low-abundance metabolites was determined. The O2PLS-DA results exhibited good validation values (cross-validation = Q2 > 0.7 and external validation = P2 > 0.6) with 0% of false positive predictions. The metabolomic approach determined biomarkers for the required biological activity and detected active compounds in the extracts displaying unique mechanisms of action. In addition, the PCA data also gave insights on the chemotaxonomy of the family Asteraceae across its diverse range of genera and tribes.
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Affiliation(s)
- Daniela A Chagas-Paula
- University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK.
- School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Department of Pharmaceutical Sciences, Av. Café s/n, Ribeirão Preto-SP 14040-903, Brazil.
| | - Tong Zhang
- University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK.
| | - Fernando B Da Costa
- School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Department of Pharmaceutical Sciences, Av. Café s/n, Ribeirão Preto-SP 14040-903, Brazil.
| | - RuAngelie Edrada-Ebel
- University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK.
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Edayadulla N, Basavegowda N, Lee YR. Green synthesis and characterization of palladium nanoparticles and their catalytic performance for the efficient synthesis of biologically interesting di(indolyl)indolin-2-ones. J IND ENG CHEM 2015. [DOI: 10.1016/j.jiec.2014.06.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Weathers PJ, Towler M, Hassanali A, Lutgen P, Engeu PO. Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries? World J Pharmacol 2014; 3:39-55. [PMID: 25678989 PMCID: PMC4323188 DOI: 10.5497/wjp.v3.i4.39] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 09/09/2014] [Accepted: 10/10/2014] [Indexed: 02/06/2023] Open
Abstract
Artemisinin from the plant Artemisia annua (A. annua) L., and used as artemisinin combination therapy (ACT), is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat “fever”. More recently, investigators have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic efficacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and efficacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes (mainly mono and sesqui), flavonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. annua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T½ and Tmax and greater Cmax and AUC in Plasmodium chabaudi-infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for > 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the arsenal of drugs to combat malaria and other artemisinin-susceptible diseases.
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Suberu JO, Romero-Canelón I, Sullivan N, Lapkin AA, Barker GC. Comparative cytotoxicity of artemisinin and cisplatin and their interactions with chlorogenic acids in MCF7 breast cancer cells. ChemMedChem 2014; 9:2791-7. [PMID: 25209896 PMCID: PMC4506560 DOI: 10.1002/cmdc.201402285] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Indexed: 12/18/2022]
Abstract
In parts of Africa and Asia, self-medication with a hot water infusion of Artemisia annua (Artemisia tea) is a common practice for a number of ailments including malaria and cancer. In our earlier work, such an extract showed better potency than artemisinin alone against both chloroquine-sensitive and -resistant parasites. In this study, in vitro tests of the infusion in MCF7 cells showed high IC50 values (>200 μm). The combination of artemisinin and 3-caffeoylquinic acid (3CA), two major components in the extract, was strongly antagonistic and gave a near total loss of cytotoxicity for artemisinin. We observed that the interaction of 3CAs with another cytotoxic compound, cisplatin, showed potentiation of activity by 2.5-fold. The chelation of cellular iron by 3CA is hypothesized as a possible explanation for the loss of artemisinin activity.
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Affiliation(s)
- John O Suberu
- Chemical Engineering and Biotechnology, University of CambridgeCB2 3RA (UK)
| | | | - Neil Sullivan
- SensaPharm Ltd., 123i Bioscience CentreSunderland, SR5 2TA (UK)
| | - Alexei A Lapkin
- Chemical Engineering and Biotechnology, University of CambridgeCB2 3RA (UK)
| | - Guy C Barker
- School of Life Sciences, University of WarwickCV4 7AL (UK) E-mail:
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Suberu JO, Gorka AP, Jacobs L, Roepe PD, Sullivan N, Barker GC, Lapkin AA. Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract--possible synergistic and resistance mechanisms. PLoS One 2013; 8:e80790. [PMID: 24244716 PMCID: PMC3828274 DOI: 10.1371/journal.pone.0080790] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 10/07/2013] [Indexed: 12/11/2022] Open
Abstract
Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L(-1)), dihydroartemisinic acid (70.0±0.3 mg L(-1)), arteannuin B (1.3±0.0 mg L(-1)), isovitexin (105.0±7.2 mg L(-1)) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B's potentiation of artemisinin.
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Affiliation(s)
- John O. Suberu
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Alexander P. Gorka
- Centre for Infectious Disease, Department of Chemistry, Georgetown University, Washington, District of Columbia, United States of America
| | - Lauren Jacobs
- Centre for Infectious Disease, Department of Chemistry, Georgetown University, Washington, District of Columbia, United States of America
| | - Paul D. Roepe
- Centre for Infectious Disease, Department of Chemistry, Georgetown University, Washington, District of Columbia, United States of America
| | - Neil Sullivan
- Sensapharm Ltd, Business and Innovation Centre, Sunderland, United Kingdom
| | - Guy C. Barker
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Alexei A. Lapkin
- Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
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van der Kooy F, Sullivan SE. The complexity of medicinal plants: the traditional Artemisia annua formulation, current status and future perspectives. JOURNAL OF ETHNOPHARMACOLOGY 2013; 150:1-13. [PMID: 23973523 DOI: 10.1016/j.jep.2013.08.021] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 08/01/2013] [Accepted: 08/06/2013] [Indexed: 05/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Artemisia annua has a long tradition of use for the treatment of intermittent fevers which we now relate to malarial infections. The active principle artemisinin has been isolated from Artemisia annua and today forms the backbone of the global fight against malaria. The traditionally prepared Artemisia annua formulation is however still being used on a global scale for the treatment of malaria, and it is claimed that its action is superior to the single purified drug. Artemisia annua is therefore on the forefront of the heated debate between the single drug-single target approach of western based medicine and the holistic approach of traditional medicinal systems. This review aims to highlight the complexities we face in the general study of medicinal plants at the hand of three levels of complexity. These levels consist of (a) the chemistry of the medicinal plant, (b) the influence of the preparation method on the chemistry of the final formulation and (c) the influence of metabolism on the chemistry of the formulation. We also aim to provide an up-to-date report on all scientific work that has been conducted and published in English on the traditional formulation of Artemisia annua. MATERIALS AND METHODS All English scientific literatures published until the first quarter of 2013 were retrieved from well-known scientific databases (Scifinder scholar, Web of Science, PubMed, Google scholar) and Non-governmental organisations active in this field were consulted. A draft version of this manuscript was sent to the African office of the World Health Organisation (WHO), and to the Non-governmental organisations "Action Médicine Naturelle" (ANAMED) and "Iwerliewen fir bedreete Volleker - Réseau belgo-luxembourgeois pour la valorisation des herbes médicinales" (IFBV-BELHERB) for comments. RESULTS Very little scientific work has been conducted on the Artemisia annua formulation. The available literature contains many discrepancies which are unfortunately selectively being used by the two different sides in this debate to further their arguments. On one side of the argument we have the low content of artemisinin in Artemisia annua, the low bioavailability of artemisinin when the traditional formulation is administered and the high levels of recrudescence, which are being emphasised, while on the other side the possible role of synergism and prodrugs are being highlighted. This review reports that there are still too many gaps in our existing knowledge to provide conclusive evidence for either of the two sides of the argument. CONCLUSIONS Much more research is needed into Artemisia annua formulations. We stand to gain invaluable knowledge into how traditional medicinal plant works, discover the identities of new active compounds (which can be used against other diseases such as HIV, diarrhoea, and cancer) and possibly bring both sides of this debate closer together.
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Affiliation(s)
- Frank van der Kooy
- Centre for Complementary Medicine Research, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia.
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