*Article not assigned to an issue yet
Adjei-Hinneh George, Zoiku Felix Kwame, Asante-Kwatia Evelyn, Mensah Abraham Yeboah
Keywords: n Microdesmis puberula; plasmodium; oedema; cytotoxicity, Carrageenan
Microdesmis puberula (Pandaceae) is an edible shrub noted in traditional medicine for its antimalarial and anti-inflammatory effects. This study assessed the anti-plasmodial, antimalarial, anti-oedema, and radical scavenging potentials of the hydro-ethanolic leaf extract of M. puberula. In vitro anti-plasmodial activity was assessed by the SYBR green I assay against P. falciparum cultures. Antimalarial activity was evaluated in murine models by Peter’s 4-day suppressive and Rane’s curative assays. The carrageenan-induced paw oedema in chicks and DPPH radical scavenging assays were used to investigate the anti-inflammatory and antioxidant activities, respectively. The total phenolic content was determined by the Folin Ciocalteu assay. The leaf extract demonstrated significant anti-plasmodial activity with IC50 1.984 ± 0.092 μg/mL, 1.8180 ± 0.2596 μg/mL, and 2.11 ± 0.0357 μg/mL, respectively, for chloroquine-sensitive 3D7, chloroquine-resistant K1, and chloroquine-resistant Dd2 Plasmodium falciparum strains. The extract had no significant cytotoxicity towards uninfected red blood cells (CC50 = 80.45 µg/mL) and hepatic cell lines (CC5 = 82.01 µg/mL). A dose-dependent chemo-suppression of P. berghei infection was elicited by the extract (50–400 mg/kg) in the suppressive test with maximum parasitemia suppression of 81.69%. Further, the extract at 400 mg/kg caused 83.59% parasitemia reduction in established P. berghei infection in the curative assay. Significant reductions in body temperature, packed cell volume, and body weight were averted in infected animals. Increased paw oedema was reduced by 56.20 ± 15.08% by M. puberula leaf extract at 300 mg/kg. Low antioxidant activity was recorded in the DPPH radical scavenging assay (IC50 of 117.7 ± 17.97 µg/mL). Tannins, triterpenoids, alkaloids, coumarins, and flavonoids were identified in the phytochemical screening, and the total phenolic content was determined to be 85.06 ± 3.82 mg/g gallic acid equivalent. The study gives scientific credence to the traditional medicinal uses of M. puberula and reveals the plant as a potential source of antimalarial, anti-inflammatory, and antioxidant compounds.
Abowei N (2020) Assessment of the larvicidal efficacy of the hexane-leaf-extracts of selected tropical plant species. BirEx 2:136–140. https://doi.org/10.33258/birex.v2i2.870
Acheampong A, Amankwaa LT, Afriyie IO, Baah KA (2018) Antioxidant and antimicrobial activity of the methanol and petroleum ether extracts of the stem of Microdesmis puberula. Pharm Chem J 5:38–48
Adjei-Hinneh G, Komlaga G, Asante-Kwatia E, Mensah AY (2021) Quality control standardization and evaluation of the anti-inflammatory and antipyretic effects of the leaves and stem bark of Amphimas pterocarpoides harms (Leguminosae). J Pharmacogn Phytother 13:46–59
Akpanyung EO, Ita SO, Opara KA, Davies KG, Ndem JI, Uwah AF (2013) Phytochemical screening and effect of ethanol root extract of Microdesmis puberula on some haematological and biochemical parameters in normal male albino Wistar rats. J Med Plants Res 7:2338–2342. https://doi.org/10.5897/JMPR2013.5080
Amelo W, Makonnen E (2021) Efforts made to eliminate drug-resistant malaria and its challenges. BioMed Res Int. https://doi.org/10.1155/2021/5539544
Appiah-Opong R, Agyemang K, Dotse E, Atchoglo P, Owusu KB-A, Aning A et al (2022) Anti-plasmodial, cytotoxic and antioxidant activities of selected Ghanaian medicinal plants. JEBIM. https://doi.org/10.1177/2515690X21107370
Baah MK, Mensah AY, Asante-Kwatia E, Amponsah IK, Forkuo AD, Harley BK et al (2020) In Vivo Antiplasmodial activity of different solvent extracts of Myrianthus libericus stem bark and its constituents in plasmodium berghei-infected mice. Evid Based Complement Alternat Med. https://doi.org/10.1155/2020/8703197
Baidoo MF, Mensah AY, Ossei PPS, Asante-Kwatia E, Amponsah IK (2021) Wound healing, antimicrobial and antioxidant properties of the leaf and stem bark of Entada africana Guill. & Perr. S Afr J Bot 137:52–59. https://doi.org/10.1016/j.sajb.2020.09.037
Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M et al (2021) Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 385:1163–1171. https://doi.org/10.1056/NEJMoa2101746
Boakye-Gyasi E, Woode E, Ainooson G, Obiri D, Ansah C, Duwejua M et al (2008) Anti-Inflammatory and antipyretic effects of an ethanolic extract of Palisota hirsuta K. Schum Roots Afr J Pharm Pharmacol 2:191–199
Cagri-Mehmetoglu A, Sowemimo A, van de Venter M (2017) Evaluation of antibacterial activity and phenolic contents of four Nigerian medicinal plants. Int J Parasitol 4:13
Choomuenwai V, Schwartz BD, Beattie KD, Andrews KT, Khokhar S, Davis RA (2013) The discovery, synthesis and antimalarial evaluation of natural product-based polyamine alkaloids. Tetrahedron Lett 54:5188–5191. https://doi.org/10.1016/j.tetlet.2013.07.058
Das Gupta R, Krause-Ihle T, Br B, Müller IB, Khomutov AR, Müller S et al (2005) 3-Aminooxy-1-aminopropane and derivatives have an antiproliferative effect on cultured Plasmodium falciparum by decreasing intracellular polyamine concentrations. Antimicrob Agents Chemother 49:2857–2864. https://doi.org/10.1128/aac.49.7.2857-2864.2005
de Souza GE, Bueno RV, de Souza JO, Zanini CL, Cruz FC, Oliva G et al (2019) Antiplasmodial profile of selected compounds from Malaria Box: in vitro evaluation, speed of action and drug combination studies. Malar J 18:447. https://doi.org/10.1186/s12936-019-3069-3
Deharo E, Bourdy G, Quenevo C, Munoz V, Ruiz G, Sauvain M (2001) A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part V. Evaluation of the antimalarial activity of plants used by the Tacana Indians. J Ethnopharmacol 77:91–98. https://doi.org/10.1016/S0378-8741(01)00270-7
Dounias E (2008) Microdesmis puberula Hook. F. ex Planch. In: Schmelzer GH, Gurib-Fakim A (eds) Plant resources of tropical Africa, 11th edn. Backhuys Publishers, Netherlands
El Bissati K, Redel H, Ting L-M, Lykins JD, McPhillie MJ, Upadhya R et al (2019) Novel synthetic polyamines have potent antimalarial activities in vitro and in vivo by decreasing intracellular spermidine and spermine concentrations. Front Cell Infect Microbiol 9:9. https://doi.org/10.3389/fcimb.2019.00009
Esonu BO, Theukwumere FC, Iwuji TC, Akanu N, Nwugo OH (2003) Evaluation of Microdesmis puberula leaf meal as feed ingredient in broiler starter diets. Niger J Ani Prod 30:3–8. https://doi.org/10.51791/njap.v30i1.1429
Espíndola MR, Varotti FdP, Aguiar ACC, Andrade SN, Rocha EMMd (2022) In vitro assessment for cytotoxicity screening of new antimalarial candidates. Braz J Pharm Sci 58:e18308. https://doi.org/10.1590/s2175-97902022e18308
Evans WC (2009) Trease and Evans’ pharmacognosy e-book. Elsevier Health Sciences
Gomes ARQ, Cunha N, Varela ELP, Brígido HPC, Vale VV, Dolabela MF et al (2022) Oxidative stress in malaria: potential benefits of antioxidant therapy. Int J Mol Sci 23:5949. https://doi.org/10.3390/ijms23115949
Guo F-F, Meng F-G, Zhang X-N, Zeng T (2022) Spermidine inhibits LPS-induced pro-inflammatory activation of macrophages by acting on Nrf2 signaling but not autophagy. J Funct Foods 94:105115. https://doi.org/10.1016/j.jff.2022.105115
Habibi P, Shi Y, Fatima Grossi-de-Sa M, Khan I (2022) Plants as sources of natural and recombinant antimalaria agents. Mol Biotechnol 64:1177–1197. https://doi.org/10.1007/s12033-022-00499-9
Hailemeskel E, Tebeje SK, Behaksra SW, Shumie G, Shitaye G, Keffale M et al (2021) The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia. Malar J 20:1–10. https://doi.org/10.1186/s12936-021-03587-4
Jeong J-W, Cha H-J, Han MH, Hwang SJ, Lee D-S, Yoo JS et al (2018) Spermidine protects against oxidative stress in inflammation models using macrophages and zebrafish. Biomol Ther 26:146. https://doi.org/10.4062/biomolther.2016.272
Junaid QO, Khaw LT, Mahmud R, Ong KC, Lau YL, Borade PU et al (2017) Pathogenesis of Plasmodium berghei ANKA infection in the gerbil (Meriones unguiculatus) as an experimental model for severe malaria. Parasite. https://doi.org/10.1051/parasite/2017040
Kevin TDA, Cedric Y, Nadia NAC, Sidiki NNA, Azizi MA, Guy-Armand GN et al (2023) Antiplasmodial, antioxidant, and cytotoxic activity of Bridelia micrantha a cameroonian medicinal plant used for the treatment of malaria. BioMed Res Int. https://doi.org/10.1155/2023/1219432
Kingston DG, Cassera MB (2022) Antimalarial natural products. Prog Chem Org Nat Prod 111:1–106. https://doi.org/10.1007/978-3-030-89873-1_1
Kojom Foko LP, Kumar A, Hawadak J, Singh V (2023) Plasmodium cynomolgi in humans: current knowledge and future directions of an emerging zoonotic malaria parasite. Infection 51:623–640. https://doi.org/10.1007/s15010-022-01952-2
Kpemissi M, Metowogo K, Melila M, Veerapur VP, Negru M, Taulescu M et al (2020) Acute and subchronic oral toxicity assessments of Combretum micranthum (Combretaceae) in Wistar rats. Toxicol Rep 7:162–168. https://doi.org/10.1016/j.toxrep.2020.01.007
Liew LP, Kaiser M, Copp BR (2013) Discovery and preliminary structure–activity relationship analysis of 1, 14-sperminediphenylacetamides as potent and selective antimalarial lead compounds. Bioorg Med Chem Lett 23:452–454. https://doi.org/10.1016/j.bmcl.2012.11.072
Mesia G, Tona G, Nanga T, Cimanga R, Apers S, Cos P et al (2008) Antiprotozoal and cytotoxic screening of 45 plant extracts from Democratic Republic of Congo. J Ethnopharmacol 115:409–415. https://doi.org/10.1016/j.jep.2007.10.028
Organization for Economic Co-operation and Development (OECD), 2002. Test No. 420: Acute Oral Toxicity - Fixed Dose Procedure. OECD Guidelines for the Testing of Chemicals, Section "Discussion", OECD Publishing, Paris. https://doi.org/10.1787/9789264070943-en
Okany C, Ishola I, Ashorobi R (2012) Evaluation of analgesic and antistress potential of methanolic stem wood extract of Microdesmis puberula Hook. f. ex Planch (Pandaceae) in mice. Int J Appl Res Nat Prod 5:30–36
Okeke UB, Adeboye OM, Adeniyi FR, Agbebi EA (2023) A review on ethnobotany, phytochemistry, and pharmacology of Microdesmis keayana and Microdesmis puberula (Pandaceae). J App Pharm Sci 13:001–013. https://doi.org/10.7324/japs.2023.97651
Penha-Gonçalves C (2019) Genetics of malaria inflammatory responses: a pathogenesis perspective. Front Immunol 10:413409. https://doi.org/10.3389/fimmu.2019.01771
Philippe G, Angenot L, De Mol P, Goffin E, Hayette M-P, Tits M et al (2005) In vitro screening of some Strychnos species for antiplasmodial activity. J Ethnopharmacol 97:535–539. https://doi.org/10.1016/j.jep.2004.12.011
Roumy V, Hennebelle T, Zamblé A, Yao JD, Sahpaz S, Bailleul F (2008) Characterisation and identification of spermine and spermidine derivatives in Microdesmis keayana and Microdesmis puberula roots by electrospray ionisation tandem mass spectrometry and high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry. Eur J Mass Spectrom 14:111–115. https://doi.org/10.1255/ejms.9
Sharma OP, Bhat TK (2009) DPPH antioxidant assay revisited. Food Chem 113:1202–1205. https://doi.org/10.1016/j.foodchem.2008.08.008
Udo UE, Udo AU, Dan EU (2018) Determination of nutrient, antinutrient compositions and median lethal dose of leaves of Microdesmis puberula Grown in Nigeria. J Sci Res Rep 17:1–10. https://doi.org/10.9734/JSRR/2017/38683
Uwimana A, Legrand E, Stokes BH, Ndikumana J-LM, Warsame M, Umulisa N et al (2020) Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med 26:1602–1608. https://doi.org/10.1038/s41591-020-1005-2
van Brummelen AC, Olszewski KL, Wilinski D, Llinas M, Louw AI, Birkholtz L-M (2009) Co-inhibition of Plasmodium falciparum S-adenosylmethionine decarboxylase/ornithine decarboxylase reveals perturbation-specific compensatory mechanisms by transcriptome, proteome, and metabolome analyses. J Biol Chem 284:4635–4646. https://doi.org/10.1074/jbc.M807085200
Varo R, Chaccour C, Bassat Q (2020) Update on malaria. Med Clin (Barc) 155:395–402. https://doi.org/10.1016/j.medcle.2020.05.024
Vonthron-Sénécheau C, Weniger B, Ouattara M, Bi FT, Kamenan A, Lobstein A et al (2003) In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected Ivorian plants. J Ethnopharmacol 87:221–225. https://doi.org/10.1016/S0378-8741(03)00144-2
White NJ (2008) Qinghaosu (artemisinin): the price of success. Science 320:330–334. https://doi.org/10.1126/science.1155165
WHO (2022) World malaria report 2022, World Health Organization
Zamble A, Sahpaz S, Hennebelle T, Carato P, Bailleul F (2006) N1, N5, N10-Tris (4-hydroxycinnamoyl) spermidines from Microdesmis keayana Roots. Chem Biodivers 3:982–989
Zhang L, Gu C, Liu J (2022) Nature spermidine and spermine alkaloids: occurrence and pharmacological effects. Arab J Chem 15:104367. https://doi.org/10.1002/cbdv.200690107
Zhang X-G, Li G-X, Zhao S-S, Xu F-L, Wang Y-H, Wang W (2014) A review of dihydroartemisinin as another gift from traditional Chinese medicine not only for malaria control but also for schistosomiasis control. Parasitol Res 113:1769–1773. https://doi.org/10.1007/s00436-014-3822-z
Zieliński E, Kowalczyk M, Osowiecka K, Klepacki Ł, Dyśko Ł, Wojtysiak K (2023) The problem of antimalarial-drug abuse by the Inhabitants of Ghana. Med Clin (Barc) 59:257. https://doi.org/10.3390/medicina59020257
Department of Pharmaceutical Science, Sunyani Technical University, Sunyani, Ghana