Startling rate of malaria parasite resistance to artemisinin and its derivatives has led to possible herb–drug antimalarial combination therapy. This study assessed the effect of co-administration of artemisinin and Ricinodendron heudelotii extract on certain liver and antioxidant indices in rats. Four groups containing ten rats each were administered distilled water (group A), artemisinin only (group B), artemisinin with R. heudelotii extract (group C), and R. heudelotii extract only (group D). Serum biochemical values and antioxidant parameters were determined using standard methods respectively. The results revealed that the total protein level increased significantly (p < 0.05) in group C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities increased significantly (p < 0.05) in the group administered artemisinin only but was regulated to control level both in groups C and D. The liver reduced gutathione (GSH) concentration decreased in the group administered artemisinin only. Similarly, malondialdehyde (MDA) level significantly increased (p < 0.05) in group A while groups C and D showed decrease in MDA and catalase concentrations. Histological examination showed that few of the hepatocytes were necrotic in the group administered artemisinin only while the group administered artemisinin and extract showed mild to moderate central venous congestion and periportal cellular infiltration. The study indicates that the bioactive constituents of the R. heudelotii extract might either have a regulatory effect on artemisinin toxicity or synergistically enhance its activity. Such bioconstituents can further be isolated and characterized for drug development to tackle Plasmodium falciparum resistance.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Adebayo AH, Aliyu R, Gatsing D, Garba IH (2006) The effects of ethanolic leaf extract of Commiphora africana (Buseraceae) on lipid profile in rats. Int J Pharmacol 2:618–622
Adedosu OT, Adedosu AN, Badmus JA, Adeleke GE, Akintola AO, Oyeyomi SA (2015) Co-administration of artesunate and Azadirachta indica extract: effects on antioxidants and certain liver parameters in male Wistar rats. Asian J Sci Technol 6(04):1338–1343
Aliyu R, Adebayo AH, Gatsing D, Garba H (2007) The effects of ethanolic leaf extract of Commiphora africana (Burseraceae) on rat liver and kidney functions. J Pharmacol Toxicol 2:373–379
Bergmeyer HU, Herder M, Rej R (1986a) International Federation of Clinical Chemistry (IFCC) Scientific Committee, analytical section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 2. IFCC method for aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6 1:1.) J Clin Chem Clin Biochem 24(7):497–510
Bergmeyer HU, Horder M, Rej R (1986b) International Federation of Clinical Chemistry (IFCC) Scientific Committee, analytical section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6 1:2.) J Clin Chem Clin Biochem 24(7):481–495
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Chance B, Greenstein DS (1992) The mechanism of catalase actions-steady state analysis. Arch Biochem Biophys 37:301–339. https://doi.org/10.1016/0003-9861(52)90194-X
Claiborne A (1986) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 283–284
Clark LE, Sunderland TCH (2004) The key non-timber forest products of central Africa: state of the knowledge. Paper no. 122, Office of Sustainable Development, Bureau for Africa, U. S. Agency for International Development, USA
Clark RL, Lerman SA, Cox EM, Gristwood WE, White TE (2008) Development toxicity of artesunate in the rat: comparison to other artemisinins, comparison of embryotoxicity and kinetics by oral and intravenous routes, and relationship to maternal reticulocyte count. Birth Defects Res B Dev Reprod Toxicol 83:397–406
Dimitrios B (2006) Sources of natural phenolic antioxidants. Trends Food Sci Technol 17(9):505–201
Effiong GS, Akpan HD (2015) The effect of Nauclea latifolia leaf extract on some biochemical parameters in streptozotocin diabetic rat models. J Med Med Sci 6(3):47–52
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Farombi EO, Olowu BI, Emerole GO (2000) Effect of three structurally related antimalarial drugs on lipid microsomal components and lipid peroxidation in rats. Comp Biochem Physiol 126:217–224
Fasinu PS, Bouic PJ, Rosenkranz B (2012) An overview of the evidence and mechanisms of herb-drug interactions. Front Pharmacol 3:1–19
Fondoun JM, Manga TT, Kengue J (1999) Ricinodendron heudelotii (Djansang): ethnobotany and importance for forest dwellers in southern Cameroon. Plant Genet Resour Newsl 118:1–6
Gorman GS (2012) Mechanisms and implication of drug-herbal interactions. J Bioequivalence Bioavailability 4:13–14
Guha M, Kumar S, Choubey V, Maity P, Bandyopadhyay U (2006) Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J 7:1224–1226
Gülçin İ, Zübeyr H, Mahfuz E, Hassan Y (2010) Radical scavenging and antioxidant activity of tannic acid. Arab J Chem 3(1):43–53
Harborne JB (1973) Methods of plant analysis. In: Phytochemical methods. Chapman and Hall, Ltd., London, pp 49–188
Izundu I, Nnacho N (2011) Nutritional and A-nutritional composition of Ricinodendron heudelotii. Nat Appl Sci J 12:108–116
Kremsner PG, Krishna S (2004) Antimalarial combinations. Lancet 364(9430):285–294
Li Q, Xie LH, Haeberle A, Zhang J, Weina P (2006) The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans. Am J Trop Med Hyg 75(5):817–826
Lipkin R (1995) Secondary plant metabolites. Sci News 14:8–9
Momeni J, Djoulde RD, Akam MT, Kimbu SF (2005) Chemical constituents and antibacterial activities of the stem bark extracts of Ricinodendron heudelotii (Euphorbiaceae). Indian J Pharm Sci 67:386–389
National Institute of Health (NIH) (2011) Guide for the care and use of laboratory animals. US. Department of Health Education and Welfare. NIH Publication, USA
Obi E, Orisakwe OE, Asongha LA, Udemezue OO, Orish VN (2004) The hepatotoxic effect of halofantrine in guinea pigs. Indian J Pharmacol 26:303–305
Prakash M, Upadhya S, Prabhu R (2004) Protein thiol oxidation and lipid peroxidation in patients with uremia. Scand J Clin Lab Invest 64:599–604
Ridley RG (2002) Medical need, scientific opportunity and the drive for anti-malaria drugs. Nature 415:686–693
Schmidt TJ, Khalid SA, Romanha AJ et al (2012) The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases—part I. Curr Med Chem 19(14):2128–2175
Shashank K, Abhay KP (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J2013, Article ID 162750, 16 pages, 2013. https://doi.org/10.1155/2013/162750
Siddhuraju P, Becker K (2003) Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves. J Agric Food Chem 51:2144–2155
Souza MF, Rao VSN, Silveira ER (1997) Inhibition of lipid peroxidation by ternatin, a tetramethoxyflavone from Egletes viscosa L. Phytomedicine 4:25–29
Subramanion LJ, Azlan A, Yeng C, Sreenivasan S (2012) Antioxidant activity and hepatoprotective potential of Polyalthia longifolia and Cassia spectabilis leaves against paracetamol-induced liver injury. Evid Based Complement Alternat Med 2012, Article ID 561284, 10 pages. https://doi.org/10.1155/2012/561284
Sullivan DJ, Kaludov N, Martinov MN (2011) Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation. Malar J 10:274
Tarirai C, Viljoen AM, Hamman JH (2010) Herb–drug pharmacokinetic interactions reviewed. Expert Opin Drug Metab Toxicol 6:1515–1538
Tietz NW, Rinker AD, Shaw LM (1983) International Federation of Clinical Chemistry. IFCC methods for the measurement of catalytic concentration of enzymes, part 5. IFCC method for alkaline phosphatase (orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 188.8.131.52). J Clin Chem Clin Biochem 21(11):731–748
Udayashekhara RP (1987) Chemical composition and biological evaluation of debitterised and defatted neem (Azadirachta indica) seed kernel cake. J AOCS 64:1348–1352
Udobre A, Edoho EJ, Eseyin O, Etim EJ (2009) Effect of artemisinin with folic acid on the activities of aspartate amino transferase, alanine aminotransferase and alkaline phosphatase in rats. Asian. J Biochem 4:55–59
Vudaa M, Roshan D, Suhas U, Vijay K, Namita R, Vasanth K, Colette B, Prakash M (2012) Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats. Exp Toxicol Pathol 64:855–859
Wanwimolruk S, Prachayasittikul V (2014) Cytochrome P450 enzyme mediated herbal drug interactions. Exp Clin Serv J 13:347–391
Weichselbaum TE (1946) Biuret method of serum total protein estimation. Am J Clin Pathol 16:40
White NJ (1997) Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob Agents Chemother 41(7):1413–1422
Zhishen J, Mengcheng T, Jianming W (1999) The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 64:555–559
We greatly appreciate the support from the technical staff of the Department of Biochemistry, Covenant University.
Conflict of interest
The authors declare that they have no competing interests.
Informed consent was obtained from all authors included in the study.
The research was approved by the Ethics Committee of the Department of Biological Sciences Covenant University, Nigeria. All animals were also treated in line with the National institute of Health (NIH) guidelines for the use and care for animals in the laboratory (NIH 2011).
About this article
Cite this article
Yakubu, O.F., Adebayo, A.H., Okechukwu, E.S. et al. Co-administration of artemisinin and Ricinodendron heudelotii leaf extract—effects on selected antioxidants and liver parameters in male Wistar rats. Comp Clin Pathol 27, 765–772 (2018). https://doi.org/10.1007/s00580-018-2663-z
- Ricinodendron heudelotii