دورية أكاديمية
Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins.
| العنوان: | Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins. |
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| المؤلفون: | Asanga EE; Department of Biochemistry, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Ekpo ND; Department of Biochemistry, University of Uyo, Uyo, Akwa Ibom State, Nigeria., Edeke AA; Department of Biochemistry, TopFaith University, Mkpatak, Akwa Ibom State, Nigeria., Ekeleme CM; Department of Biochemistry, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Okoroiwu HU; Department of Medical Laboratory Science, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria. okoroiwuhenshaw@gmail.com., Edet UO; Department of Microbiology, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Umoh EA; Department of Human Physiology, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Umoaffia NE; Department of Microbiology, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Eseyin OA; Department of Medicinal and Pharmaceutical Chemistry, University of Uyo, Uyo, Akwa Ibom State, Nigeria., Nkang A; Department of Biological Sciences, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Akpanabiatu M; Department of Biochemistry, AkwaIbom State University, IkotAkpaden, Mkpatenin, Akwa Ibom State, Nigeria., Okokon JE; Department of Pharmacology and Toxicology, University of Uyo, Uyo, Akwa Ibom State, Nigeria., Akpotuzor S; Department of Mathematics and Computer Science, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Effiong BA; Department of Biochemistry, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria., Ettaba M; Department of Biochemistry, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria. |
| المصدر: | BMC complementary medicine and therapies [BMC Complement Med Ther] 2024 Feb 07; Vol. 24 (1), pp. 79. Date of Electronic Publication: 2024 Feb 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101761232 Publication Model: Electronic Cited Medium: Internet ISSN: 2662-7671 (Electronic) Linking ISSN: 26627671 NLM ISO Abbreviation: BMC Complement Med Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, [2020]- |
| مواضيع طبية MeSH: | Antimalarials*/chemistry , Malaria*/drug therapy , Malaria*/parasitology , Triterpenes*/pharmacology , Rubiaceae*/chemistry, Mice ; Animals ; Ursolic Acid ; Molecular Docking Simulation ; Plant Extracts/chemistry ; Plasmodium falciparum |
| مستخلص: | Background: Chemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease's high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice. Methods: Standard protocols were followed for the collection of the plant's roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction's components, and the Swis-ADME program made it possible to estimate the drug's likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis. Results: The residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood-brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski's criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds. Conclusion: In addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index. (© 2024. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Betulinic acid; Docking; GCMS; Malaria; Nauclea latifolia; Plasmodium berghei; Ursolic acid |
| المشرفين على المادة: | 0 (Antimalarials) P3M2575F3F (Ursolic Acid) 0 (Plant Extracts) 0 (Triterpenes) |
| تواريخ الأحداث: | Date Created: 20240207 Date Completed: 20240209 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10848498 |
| DOI: | 10.1186/s12906-023-04324-x |
| PMID: | 38326823 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2662-7671 |
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| DOI: | 10.1186/s12906-023-04324-x |