PROFILING OF PHYLLANTHUS AMARUS PHYTOCHEMICAL CONSTITUENTS AND EVALUATION OF ASSOCIATED ANTIMALARIAL ACTIVITY AND ANTIOXIDANT POTENTIAL IN EXPERIMENTAL MICE

Main Article Content

Theresa Ezedom
Innocent Onyesom
Prosper Ejiro Awhin
Chinwendu Obogheneophruhe Elu
Joy Onyewonuwa Acha

Abstract

The failing curative ability of antimalarials has prompted an open discussion for the use of antioxidants in combination with antimalarials for effective chemotherapy. This study profiled the phytochemical constituents of Phyllanthus amarus and evaluated their antimalarial and antioxidant activities. Phytochemical screening, antimalarial and acute oral toxicity were determined according to standard procedures. Blood antioxidant activity was assessed by measuring antioxidant enzymes and nitric oxide (NO), concentrations of malarial infected mice treated with P. amarus phytochemicals. Alkaloids, the most abundant phytochemical, demonstrated the highest malarial parasite chemosuppression and greatly improved NO concentration in infected mice. However, flavonoid extract demonstrated the highest antioxidant potential with most significant impact on catalase and malondialdehyde activity. Alkaloid may function as antimalarial agent by inhibiting haem polymerization to hemozoin as judged by its increased effect on NO concentration which bears an reverse relationship with hemozoin.

Article Details

Section
Articles

References

World Health Organization (WHO). World Malaria Report 2021; World Health Organization Press: Geneva, Switzerland, 2021.

Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S, Ginsburg H. 2004. Oxidative stress in malaria parasite-infected erythrocytes: Host-parasite interactions. Int J Parasitol. 34:163–189.

Abolghasemi E, Moosa-Kazemi SM, Davoudi M, Reisi A, Satvat MT. 2012. Comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis. Asian Pac J Trop Biomed. 2(4):311–331.

Reis PA, Comim CM, Hermani F, Silva B, Barichello T, Portella AC, Gomes FC, Sab IM, Frutuoso VS, Oliveira MF, et al. 2010. Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria and is reduced by additive antioxidant therapy. PLoS Pathog. 6(6):e1000963.

Arreesrisom P, Dondorp AM, Looareesuwan S, Udomsangpetch R. 2007. Suppressive effects of the anti-oxidant N-Acetylcysteine on the anti-malarial activity of artesunate. Parasitol Int. 56(3):221–226.

Arama C, Troye-Blomberg M. 2014. The path of malaria vaccine development, challenges and perspectives. J Intern Med. 275:456–466.

Adeneye AA, Benebo AS, Agbaje EO. 2006. Protective effect of the aqueous leaf and seed extract of Phyllanthus amarus on alcohol- induced hepatotoxity rats. West Afri J Pharmocol Drug Res. 22&23:42-50.

Uzuegbu UE, Opajobi OA, Utalor JE, Elu CO, Onyesom I. 2020. Cytotoxicity and antiplasmodial of alkaloid extracts prepared from eight African medicinal plants used in Nigeria. Thai J Pharm Sci. 44(4):237-244.

Ukoha PO, Cemaluk EAC, Nnamdi OL, Madus EP. 2011. Tannins and other phytochemical of the Samanaea saman pods and their antimicrobial activities. Afr J Pure Appl Chem. 5(8):237-244.

Cai W, Gu X, Tang J. 2010. Extraction, purification, and characterisation of the flavonoids from Opuntia milpa alta skin. Czech J Food Sci. 28(2):108-116.

Klujanabhagavad T, Wmk M. 2009. Biological activities and chemistry of saponins from chenopodium zuinoa wild. Phytochemistry. 8(2):473-90.

Bruneton J. 1995. Pharmacologyphytochemistry, medicinal plants. Lavoisier Publishing, Paris.

Sharma M, Panthari P, Pushpangadan P, Varma A, Kharkwal H. 2014. Phytochemical analysis of glycosides from leaves of Trigonella Foenum Graecum. Int J Pharm Sci. 29(1):146-152.

Onyesom I, Onumaechi IF, Ehiwario J, Dagana R. 2015. Antiplasmodial activity of Phyllanthus amarus preserves renal function in Plasmodium berghei infected mice. European J Med Plants. 5(1):109-16.

Hadwan MH. 2016. New method for assessment of serum catalase activity. Indian J Sci Technol. 9(4):1-5.

Moron MS, Depierre JW, Mannervik B. 1979. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochem Biophys Acta (BBA)-Gen Subj. 582: 67-78.

Marzec-Wroblewska U, Kaminski P, Lakota P, Szymanski M, Wasilow K, Ludwikowski G, Kuligowska-Prusińska M, Odrowąż-Sypniewska G, Stuczyński T, Michałkiewicz J. 2011. Zinc and iron concentration and SOD activity in human serum and seminal plasma. Biol Trace Elem Res. 143:167-177.

Russell M, Prokoph N, Henderson N, Eketjäll S, Balendran CA, Michaëlsson E, et al. Determining myeloperoxidase activity and protein concentration in a single assay: Utility in biomarker and therapeutic studies. J Immunol Methods. 2017: 449:76–9.

Esterbauer H, Cheeseman KH. 1990. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 186:407-421.

Bryan NS, Grisham MB. 2007. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med. 43(5):645-657.

Taylor R. 1990. Interpretation of the correlation coefficient: A basic review. J Diagn Med Sonogr. 6(1):35-39.

Mutala AH, Badu K, Owusu C, Agordzo S, Tweneboah A, Abbas DA, Addo MG. 2020. Impact of malaria on haematological parameters of urban, peri-urban and rural residents in the Ashanti region of Ghana: a cross-sectional study. AAS Open Res. 2:27-94.

Sudan R, Bhagat M, Gupta S, Singh J, Koul A. 2014. Iron (FeII) chelation, ferric reducing antioxidant power and immune modulating potential of Arisaema jacquemontii (Himalayan Cobra Lily). BioMed Res Int. 2014: 179865.

McKenzie FE, Prudhomme WA, Magill AJ, Forney JR, Permpanich B, Lucas C,Gasser RA, Wongsrichanalai C. 2005. White blood cell counts and malaria. J Infect Dis. 192(2): 323–330.

Totino-Paulo RR, Daniel-Ribeiro Cláudio T, Ferreira-da-Cruz Maria de Fátima. 2016. Evidencing the role of erythrocytic apoptosis in malarial anemia. Front Cell Infect Microbiol. 6:176-186.

Komlaga G, Cojean S, Beniddir M, Dicksona R, Champy P, Merlin L, Mensah K, Soulaf S, Jonathan J, Philippe L. 2015. The antimalarial potential of three Ghanaian medicinal plants. Herb Med. 1:1-16.

Maina RN, Walsh D, Gaddy C, Hongo G, Waitumbi J, Otieno L, Jones D, Ogutu BR. 2010. Impact of Plasmodium falciparum infection on haematological parameters in children living in Western Kenya. Malar J. 9(3):S4.

Akinosoglou KS, Solomou EE, Gogos CA. 2012. Malaria: a haematological disease. Hematology. 17(2):106-14

Chandra P, D'Souza V, D'Souza B. 2006. Comparative study on lipid peroxidation and antioxidant Vitamins E and C in falciparum and vivax malaria. Ind J Clin Biochem. 21:103-106.

Evans KJ, Hansen DS, van Rooijen N, Buckingham LA, Schofield L. 2006. Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes. Blood. 107(3):1192–1199.

Nwankpa P, Agomuo EN, Uloneme GC, Egwurugwu JN, Omeh YN, Nwakwuo GC. 2014. Effect of Phyllanthus amarus leaf extract on alterations of haematological parameters in Salmonellae typhi infested wistar albino rats. Sci Res Essays. 9(1):2342-2347.

Kolawole AI, Blessing N, Oyebimpe AF, Francis OS. 2019. Effects of aqueous leaf extracts of Phyllanthus amarus on liver function and blood parameters in male wister rats. J Bio Innov. 8(4): 471-483.

Pabón A, Carmona J, Burgos LC, Blair S. 2003. Oxidative stress in patients with non-complicated malaria. Clin Biochem. 36(1):71-78.

Sakyi SA, Ephraim RKD, Antoh EO, Obirikorang C, Berchie GO. 2012. Lipid peroxidation and catalase levels among Children Presenting with Severe Falciparum Malaria in the Sefwi Wiawso Municipality, Ghana. J Med Sci 12(5):141-147.

Prabhu S, Patharkar SA, Patil NJ, Nerurkar AV, Shinde UR, Shinde KU. 2021. Study of malondialdehyde level and glutathione peroxidase activity in patients suffering from malaria. J Pharm Res Int. 33(26A): 35-41.

Bilgin R, Yalcini MS, Kilic E, Kaya E, Yazar S, Koltas IS. 2013. Catalase activity expression in patients with Plasmodium vivax malaria. Asian J Chem. 25(5):2500-2502

Cramer JP, Nussler AK, Ehrhardt S, Burkhardt J, Otchwemah RN, Zanger P, Dietz E, Gellert S, Bienzle U, Mockenhaupt FP. 2005. Age-dependent effect of plasma nitric oxide on parasit density in Ghanaian children with severe malaria. Trop Med Int Health. 10:672-680.

Halaris A, Plietz J. 2007. Agmatine: metabolic pathway and spectrum of activity in brain. CNS drugs. 21:885–900.

Corbett Y, D’Alessandro S, Parapini S, Scaccabarozzi D, Kalantari P, Zava S, Giavarini F, Caruso D, Colombo I, Egan TJ, et al. 2018. Interplay between Plasmodium falciparum haemozoin and L-arginine: implication for nitric oxide production. Malar J. 17:456-469.

Cabrales P, Zanini GM, Meays D, Frangos JA, Carvalho LJM. 2011. Nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology. J Inf Dis. 203(10):1454–1463.

Oluba OM. 2019. Erythrocyte lipid and antioxidant changes in Plasmodium falciparum-infected children attending mother and child hospital in Akure, Nigeria. Pak J Biol Sci. 22:257-264.

Chikezie PC, Chikezie CM, Uwakwe AA, Monago CC. 2009. Comparative study of glutathione S-transferase activity of three human erythrocyte genotypes infected with Plasmodium falciparum. J Appl Sci Environ Manage. 13(3):13–18.

Theeß W, Sellau J, Steeg C, Klinke A, Baldus S, Cramer JP, Jacobs T. 2016. Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection. Infect Immun. 29;85(1):e00475-16.

Mohammed AO, Elghazali G, Mohammed HB, Elbashir MI, Xu S, Berzins K, Venge P. 2003. Human neutrophil lipocalin: a specific marker for neutrophil activation in severe Plasmodium falciparum malaria. Acta Tropica. 87:279-285.