Antinociceptive and Behavioural Effects of the Leaves of Milicia excelsa (Welw.) C. C. Berg (Moraceae) doi.org/10.26538/tjnpr/v5i10.22
Main Article Content
Abstract
The leaves of Milicia excelsa (Welw.) C. C. Berg (Moraceae) is used in the treatment of inflammatory and painful disorders and as sedative in the treatment of insanity in Nigerian traditional medicine. The antinociceptive activity of the ethanol extract (50, 100 and 200 mg/kg, p.o.) was investigated using acetic acid-induced writhing, hot plate and formalin-induced paw licking tests while the behavioural assessment was evaluated in holeboard, elevated plus maze and phenobarbitone-induced sleeping time tests. Acetylsalicylic acid, morphine or diazepam and 1% Tween 20 (10 mL/kg) were employed as positive and negative control respectively. Acute toxicity of the extract (200-3200 mg/kg, p.o.) was also determined. The extract inhibited nociceptive response caused by acetic acid injection and increased latency time in the hot-plate test. In formalin test, the extract decreased paw licking time in both phases. The entry and the duration of time spent in the open arms of the elevated plus maze by animals treated with the extract (100 and 200 mg/kg) increased significantly compared to control. The number of head-dips and line crossed were decreased by the extract in hole board test, resembling the response of diazepam. In pentobarbital-induced sleeping time test, the extract reduced sleep latency and increased the duration of sleep compared to the negative control. No mortality was observed up to the dose of 3200 mg/kg. These results showed the antinociceptive, anxiolytic and sedative effects of the leaf extract of M. excelsa and provide evidence for the traditional use of the plant for pain management and insanity.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Ouinsavi C and Sokpon N. Morphological variation and ecological structure of Iroko (Milicia excelsa Welw. C. C. Berg) populations across different biogeographical zones in Benin. Int J Forestr Res. 2010; 1-10
Borokini TI, Onefeli AO, Babalola FD. Inventory analysis of Milicia excelsa (Welw C. C. Berg.) in Ibadan (Ibadan Metropolis and University of Ibadan), Nigeria. J Plant Stud. 2013; 2:97-109.
Ibrahim JAI, Muazzam IA, Jegede OF, Kunle J, Okogun I. Ethno-medicinal plants and methods used by Gwandara tribe of Sabo Wuse in Niger State, Nigeria, to treat mental Illness. African J Trad Compl Altern Med. 2007; 4 (2):211-218.
Burkill HM. The useful plants of West Tropical Africa, Families M-R, (2nd ed.). United Kingdom: Kew Royal botanical garden; 1997; 969p.
Olajide OA, Kolawole OT, Fagbohun TR, Ajayi FF. Evaluation of the anti-inflammatory properties of Chlorophora excelsa stem bark extract. Pharm Biol. 2005; 43(9):746-748.
Dzeufiet PDD, Tchamadeu MC, Bilanda DC, Ngadena YSM, Poumeni MK, Nana D, Dimo T, Kamtchouing P. Preventive effect of Milicia excelsa(Moraceae) aqueous extract on dexamethasone induced insulin resistance in rat. J Pharm Pharm Sci. 2014; 5:1232-1241.
Adebayo MA, Adedokun OA, Akinpelu LA, Okafor PO. Evaluation of anti-diarrheal activity of methanol root bark extract of Milicia excelsa (Welw) C. C Berg (Moraceae) in rats. Drug Res. 2019;69(08):439-444.
Mvondo MA, Sakock AJT, Ateba SB, Awounfack CF, Gueyo TN, Njamen D. Emmenagogue properties of Milicia excelsa (Welw.) C.C. Berg (Moraceae) based, at least in part, on its ability to correlate the activity of the hypothalamic-pituitary
axis to that of the ovaries. J Ethnopharmacol. 2017; 206:283-289.
Udegbunam SO, Nnaji TO, Udegbunam RI, Okafor JC, Agbo I. Evaluation of herbal ointment formulation of Milicia excelsa (Welw) C.C berg for wound healing. Afr J Biotechnol. 2013; 12(21):3351-3359.
Akinpelu LA, Akanmu MA, Obuotor EM.Antipsychotic effects of ethanol leaf extract and fractions of Milicia excelsa (Moraceae) in mice. J Pharm Res Int. 2018a; 22(6):1-10.
Akinpelu LA, Akanmu MA, Obuotor EM. Mechanism of anticonvulsant effects of ethanol leaf extract and fractions of Milicia excelsa (Moraceae) in Mice. J Pharm Res Int. 2018b; 23(4):1-11.
Christensen LP and Lam J. Excelsa octaphenol, a stilbene dimer from Chlorophora excelsa. Phytochem. 1989; 28:917-919.
Malan E, Swinny E, Ferreira D, Hall AJ. 5,5'-Dihydroxy-3,7,2',4'-tetramethoxyflavone from Chlorophora excelsa. Phytochem. 1990; 29:2741.
Grundon MF and King FE. Chlorophorin, a constituent of iroko, the timber of Chlorophora excelsa. Nature. 1949; 163:564-555.
Shimizu K, Yasutake S, Kondo R. A new stilbene with tyrosinase inhibitory activity from Chlorophora excelsa. Chem Pharm Bull. 2003; 51:318-319.
Kapche GC, Waffo-Teguo P, Massip S, Guillon J, Vitrac C, Krisa S, Ngadjui B, Merillon J. Crystal structure of Moracin M. Anal Sci. 2007; 23:59-60.
Ouete NJL, Sandjo LP, Kapche DWFG, Liermann JC, Opatz T, Simo IK, Ngadjui BT. A new flavone from the roots of Milicia excelsa (Moraceae). Z Naturforsch. 2013; 68:259-263.
Ouete NJL, Sandjo LP, Kapche DWFG, Yeboah S, Mapitse R, Abegaz BM, Opatz T, Ngadjui BT. Excelsoside: A new benzylic diglycoside from the leaves of Milicia excelsa. Z. Naturforsch. 2014; 69:271-275.
McDonald S, Prenzler PD, Autolovich M, Robards K. Phenolic content and antioxidant activity of olive extracts. Food Chem. 2001; 73:73-84.
Brighente IMC, Dias M, Verdi LG, Pizzolatti MG. Antioxidant activity and total phenolic content of some Brazilian species. Pharm Biol. 2007; 45:156-161.
Sun JS, Tsuang YW, Chen IJ, Huang WC, Hang YS, Lu FJ. An ultra-weak chemiluminescence study on oxidative stress in rabbits following acute thermal injury. Burns 1998; 24:225-231.
NIH Guide for the care and use of laboratory animals. (8th ed.) Washington, D.C: The National Academies Press; 2011; 1-246p.
Ganguly A, Al Mahmud Z, Saha SK, Abdur Rahman SM. Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice. Pharm Biol. 2016; 54(8):1413-1419.
Ishola IO, Agbaje EO, Adeyemi OO, Shukla R. Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants. Pharm Biol. 2014; 52:1208-1216.
Hunskaar S and Hole K. The formalin test in mice: dissociation between inflammatory and noninflammatory pain. Pain 1987; 30:103-114.
Mbagwu H, Anene R, Adeyemi O. Analgesic, antipyretic and anti-inflammatory properties of Mezoneuron benthamianum Baill (Caesalpiniaceae). Nig Q J Hosp Med. 2007; 17:35-41.
Basting RT, Spindola HM, Sousa IMO, Queiroz NCA, Trigo JR, de Carvalho JE, Foglio MA. Pterodon pubescens and Cordia verbenaceaassociation promotes a synergistic response in antinociceptive model and improves the anti-inflammatory results in animal models. Biomed Pharmacother. 2019; 112:108693.
Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacol. 1987; 92:180-185.
Akindele AJ and Adeyemi OO. Anxiolytic and sedative effects of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) extract. Int J Appl Res Nat Prod. 2010; 3(1):28-36.
File SE and Wardill AG. Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacol. 1975; 44:53-59.
Williamson EM, Okpako DT, Evans FJ. Pharmacological methods in phytotherapy research: Selection, preparation, and pharmacological evaluation of plant material. England: John Wiley & Sons Ltd; 1996; 247-263p.
Kaygisiz B, Kilic FS, Senguleroglu N, Baydemir C, Erol K. The antinociceptive effect and mechanisms of action of pregabalin in mice. Pharmacol Rep. 2015; 67:129-133.
McDougall JJ. Peripheral analgesia: Hitting pain where it hurts. Biochim Biophys Acta. 2011; 1812(4):459-567.
Scapinello J, Müller LG, Schindler MSZ, Anzolin GS, Siebel AM, Boligon AA, Niero R, Saraiva TES, Maus NP, Betti AH, Oliveira JV, Magro JD, de Oliveira D. Antinociceptive and anti-inflammatory activities of Philodendron bipinnatifidum Schott ex Endl (Araceae). J Ethnopharmacol. 2019; 236:21-30.
Coelho LP, Reis PA, de Castro FL, Gayer CRM, Lopes C. da S, Silva MC.da C.e, Sabino KC de C, Todeschini AR, Coelho MGP. Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds. J Ethnopharmacol. 2005; 98(1-2):109-116.
Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics. J Neurosci Meth. 1985; 14(1):69-76.
Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001; 53:597-652.
Chen Z, Quan L, Zhou H, Zhao Y, Chen P, Hu L, Yang Z, Hu C, Cao D. Screening of active fractions from Curcuma Longa Radix isolated by HPLC and GC-MS for promotion of blood circulation and relief of pain. J Ethnopharmacol. 2019; 234:68-75.
Silva DPB, Florentino IF, Oliveira LP, Lino RC, Galdino PM, Menegatti R, Costa EA. Antinociceptive and anti-inflammatory activities of 4-[(1-phenyl-1H-pyrazol-4-yl) methyl] 1-piperazine carboxylic acid ethyl ester: A new piperazine derivative. Pharmacol Biochem Behav. 2015; 137:86-92.
Sahoo S and Brijesh S. Anxiolytic activity of Coriandrum sativum seeds aqueous extract on chronic restraint stressed mice and effect on brain neurotransmitters. J Funct Foods. 2020; 68:103884.
Akinpelu LA, Aiyelero OM, Gbola O. Ethanol leaf extract of Milicia excelsa mitigates anxiety and depressive-like behaviours induced by acute restraint stress in mice. GSC Biol Pharm Sci. 2019; 06(02):030-039.
Takeda H, Tsuji M, Matsumiya T. Changes in headdipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998; 350:21-29.
Oztu¨rk Y, Aydin S, Beis R, Baser KHC, Berberoĝlu H. Effects of Hypericum perforatum L. and Hypericum calycinum L. extracts on the central nervous system in mice. Phytomed. 1996; 3:139-146.
Kumar D, Gupta SK, Ganeshpurkar A, Singh R, Kumar D, Das N, Krishnamurthy S, Singh SK Biological profiling of piperazinediones for the management of anxiety. Pharmacol Biochem Behav. 2019; 176:63-71.
Bakre AG, Aderibigbe AO, Ademowo OG. Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice. J Ethnopharmacol. 2013; 149:783-789.
Organization for Economic Cooperation and Development (OECD) Guideline for testing ofChemicals. Guideline 423: Acute Oral ToxicityAcute Toxic Class Method. France: OECD; 2001;1-14p.
Machado DG, Neis VB, Balen GO, Colla A, Cunha MP, Dalmarco JB, Pizzolatti MG, Prediger RD, Rodrigues ALS. Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav. 2012; 103(2):204-211.
Lucetti DL, Lucetti ECP, Bandeira MAM, Veras HNH, Silva AH, Leal LKAM, Lopes AA, Alves VCC, Silva GS, Brito GA, Viana GB. Antiinflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel. J Inflamm. 2010; 7:2-11.