Generic placeholder image

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry


ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

Anti-Nociceptive and Anti-Inflammatory Effects of Stem Bark Extract of Ficus Capensis Thunb (Moraceae) by Bioactivity Fractionation

Author(s): Oluwaseyi K. Wakeel*, Abraham I. Abe, Oluropo B. Awosan, Mokaila K. Olapade, Temitope J. Olatoyan-Layonu, Olugbenga A. Olowe and Oluwaseyi A. Adeyeba

Volume 20 , Issue 2 , 2021

Published on: 25 August, 2020

Page: [206 - 218] Pages: 13

DOI: 10.2174/1871523019666200825194616

Price: $65


Objective: This study investigated the antinociceptive and anti-inflammatory activities of the aqueous extract of Ficus capensis (AEFC) by bio-guided fractionation.

Methods: The anti-nociceptive and anti-inflammatory effects of AEFC (250, 500, 1000 mg/kg, i.p) were assessed using acetic acid-induced writhing, hot plate, tail-flick, formalin tests, and carrageenan- induced paw edema, respectively. The AEFC was fractionated base on polarity difference into butanol, ethyl acetate, and n-hexane fractions. The fractions (500 mg/kg) obtained were subjected to the same experimental procedures mentioned above. The EAF, which exerted the most productive activities, was further subjected to fractionation procedures that yielded six fractions (labeled CF1-CF6). These fractions (200 mg/kg) were tested for potential antinociceptive and anti-inflammatory activities. Notable antagonists (Naloxone and atropine) of the nociceptive pathway were used to evaluate the mechanism of the antinociceptive action of F. capensis.

Results and Discussion: The AEFC, BF, EAF, and CF4 caused a significant (p<0.05) reduction in the number of abdominal writhes, an increase in reaction time against the hot plate, tail-flick tests, and a significant (p<0.05) inhibition in both phases of formalin test. The AEFC, BF, EAF, CF4, and CF6 caused a significant (p<0.05) inhibition of paw edema development due to carrageenan. Atropine significantly reversed the antinociceptive effect of CF4 in both phases of the formalin test. The results obtained revealed that CF4 produced central and peripheral antinociceptive effects, while CF6 is peripherally mediated.

Conclusion: The results support the traditional uses of F. capensis in the treatment of various diseases associated with pain and inflammation. The column fraction CF4 exhibited muscarinic receptor- mediated antinociceptive activity.

Keywords: Ficus capensis, antinociceptive, anti-inflammatory, fractionation, atropine, activity-guided.

Graphical Abstract
Kruger, L. Method in pain research; CRC Company: Florida, 2010, pp. 18-30.
Fatemeh, Z.; Farzaneh, E.; Malihe, A.; Amir, H.E.; Majid, V.R.; Sadegh, S.; Kaivan, R. Evaluation of topical antinociceptive effect of Artemisia absinthium extract in mice and possible mechanisms. Afr. J. Pharm. Pharmacol., 2014, 8, 492-496.
Chen, Y.; Geis, C.; Sommer, C. Activation of TRPV1 contributes to morphine tolerance: involvement of the mitogen-activated protein kinase signaling pathway. J. Neurosci., 2008, 28(22), 5836-5845.
[] [PMID: 18509045]
Le Bars, D.; Gozariu, M.; Cadden, S.W. Animal models of nociception. Pharmacol. Rev., 2001, 53(4), 597-652.
[PMID: 11734620]
IASP. Pain terms: a list with definations and notes on usage. Recommended by the IASP subcommittee on Toxonomy. Pain, 1979, 6, 249-252.
[PMID: 460932]
Simoes, C.M.O.; Schenkel, E.P.; Gosmann, G.; Mello, J.C.P.; Mentz, L.A.; Petrovick, P.R. Da Planta ao Medicamento, UFGRS, Porto Alegre, Brazil. Farmacognosia, 2003, 6, 117-119.
González-Trujano, M.E.; Peña, E.I.; Martínez, A.L.; Moreno, J.; Guevara-Fefer, P.; Déciga-Campos, M.; López-Muñoz, F.J. Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three different experimental models in rodents. J. Ethnopharmacol., 2007, 111(3), 476-482.
[] [PMID: 17223299]
Falcao, H.S.; Lima, I.O.; Santos, V.L.; Dantas, H.F.; Diniz, M.F.F.M.; Barbosha-Filho, J.M.; Batista, L.M. Review of plants with anti-inflammatory activity studies in Brazil. Rev. Bras. Farmacogn., 2015, 15, 381-391.
Olowokudejo, J.D.; Kadiri, A.B.; Travih, V.A. An ethnobotanical survey of herbal markets and medicinal Plants in Lagos State of Nigeria. Ethnobotanical Leaflets, 2008, 12, 851-865.
Owolabi, O.J.; Nworgu, Z.A.; Falodun, A.; Ayinde, B.A.; Nwako, C.N. Evaluation of tocolytic activity of ethanol extract of the stem bark of Ficus capensis Thunb. (Moraceae). Acta Pol. Pharm., 2009, 66(3), 293-296.
[PMID: 19645329]
Igoli, J.O.; Ogaji, O.G.; Tor-Aryiin, A.; Igoli, N.P. Traditional Medicinal Practices amongst the Igede people of Nigeria. Part 11. African Journal of Tradition. Complement, 2005, 2(2), 134-152.
Mpiana, P.T.; Mudogo, V.; Tshibangu, D.S.T.; Kitwa, E.K.; Kanangila, A.B.; Lumbu, J.B.S.; Ngbolua, K.N.; Atibu, E.K.; Kakule, M.K. Antisickling activity of anthocyanins from Bombax pentadrum, Ficus capensis and Ziziphus mucronata: photodegradation effect. J. Ethnopharmacol., 2008, 120(3), 413-418.
[] [PMID: 18930798]
Umeokoli, B.O.; Onyegbule, F.A.; Gugu, T.H.; Igboeme, S.O. Evaluation of the erythropoietic and anti-sickling properties of Ficus capensis leaf extract in the treatment of anaemia. Planta Med., 2013, 79-PE29.
Njoku-Oji, N.N.; Nwike, C.V.; Dimkpa, U.; Ifegwu, N.O.; Anike, L.C.; Maduka, S.O.; Sobanke, O.A.; Uchefuna, R.C. Hematological changes following oral administration of aqueous leaf extract of Ficus capensis in albino rats. Int. Blood Res. Rev., 2016, 5(1), 1-7.
Oyeleke, S.B.; Dauda, B.E.N.; Boye, O.A. Antibacterial activity of Ficus capensis. Afr. J. Biotechnol., 2008, 7(10), 1414-1417.
Daikwo, O.A.; Tende, J.A.; Okey, S.M.; Eze, E.D.; Isa, A.S. The effect of aqueous extract of leaf of Ficus capensis Thunb (Moraceae) on invivo leukocyte mobilization in Wistar rats. Br. J. Pharmacol. Toxicol., 2012, 3(3), 110-114.
Owolabi, O.J. Active ileum relaxant fractions from the leaves of Ficus capensis Thunb (Moraceae). Niger. J. Pharm. Sci., 2013, 12(1), 1-7.
Ramde-Tiendrebeogo, A.; Tibiri, A.; Hilou, A.; Lomp, O.M.; Millogo-Kone, H.; Nacoulma, O.G.; Guissou, I.P. Antioxidative and antibacterial activities of phenolic compounds from Ficus sur Forssk. and Ficus sycomorus L. (Moraceae): Potential for sickle cell disease treatment in Burkina Faso. Int. J. Biol. Chem. Sci., 2012, 6(1), 328-336.
Gelfand, M.; Mavi, S.; Drummond, R.B.; Ndemera, B. The traditional medicinal practitioner in Zimbabwe; Mambo Press: Gweru, Zimbabwe, 1985, p. 411.
Akomolafe, S.F.; Oboh, G.; Oyeleye, S.I.; Boligon, A.A. Aqueous extract from Ficus capensis leaves inhibits key enzymes linked to erectile dysfunction and prevent oxidative stress in rats’ penile tissue. NFS J., 2016, 4, 15-21.
Bahadir, O.; Citoğlu, G.S.; Smejkal, K.; Dall’Acqua, S.; Ozbek, H.; Cvacka, J.; Zemlicka, M.; Zemlicka, M. Analgesic compounds from ˇ S. latifolia (Fisch. and Mey.) DC. J. Ethnopharmacol., 2010, 131(1), 83-87.
[] [PMID: 20541001]
Trease, G.E.; Evans, M.C. Textbook of Pharmacognosy, 13th ed; Bailliere, Tindall: London, 1989, pp. 683-684.
Koster, R.; Anderson, M.; Debeer, E.J. Acetic acid induced analgesic screening. Fed. Proc., 1959, 18, 418-420.
Arihan, O.; Boz, M.; İskit, A.B.; Ilhan, M. Antinociceptive activity of coniine in mice. J. Ethnopharmacol., 2009, 125(2), 274-278.
[] [PMID: 19580858]
Eddy, N.B.; Leimbach, D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. Exp. Ther., 1953, 107(3), 385-393.
[PMID: 13035677]
Espejo, E.F.; Mir, D. Structure of the rat’s behaviour in the hot plate test. Behav. Brain Res., 1993, 56(2), 171-176.
[] [PMID: 8240711]
Hunskaar, S.; Berge, O.G.; Hole, K. Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test. Pain, 1986, 25(1), 125-132.
[] [PMID: 3714284]
D'amour, FE; Smith, DL A Method for determining loss of pain sensation. Journal of Pharmacology and Experimental Therapeutics May, , 1941, 72(1), 74-79.
Miller, A.L.; Leach, M.C. Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice. Lab. Anim., 2015, 49(2), 117-120.
[] [PMID: 25378137]
Abbott, F.V.; Grimes, R.W.; Melzack, R. Single nerve capsaicin: effects on pain and morphine analgesia in the formalin and foot-flick tests. Brain Res., 1984, 295(1), 77-84.
[] [PMID: 6713178]
Hunskaar, S.; Hole, K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain, 1987, 30(1), 103-114.
[] [PMID: 3614974]
Dirosa, M.; Giroud, P.J.; Willoughby, D.A. Study of mediators of acute inflammatory response induced in rats in different sites by carragenan and turpine. J. Pathol., 1971, 101, 15-29.
Winter, C.; Risley, E.; Nuss, O. Carrageenan-induced inflammation in the hind limb of rats. Fed. Proc., 1962, 46, 118-126.
Ferreira, L.C.; Grabe-Guimarães, A.; de Paula, C.A.; Michel, M.C.; Guimarães, R.G.; Rezende, S.A.; de Souza Filho, J.D.; Saúde-Guimarães, D.A.; Saúde-Guimarães, A. Anti-inflammatory and antinociceptive activities of Campomanesia adamantium. J. Ethnopharmacol., 2013, 145(1), 100-108.
[] [PMID: 23123269]
Sudo, R.T.; Neto, M.L.; Monteiro, C.E.; Amaral, R.V.; Resende, Â.C.; Souza, P.J.; Zapata-Sudo, G.; Moura, R.S. Antinociceptive effects of hydroalcoholic extract from Euterpe oleracea Mart. (Açaí) in a rodent model of acute and neuropathic pain. BMC Complement. Altern. Med., 2015, 15, 208-210.
[] [PMID: 26134625]
Nunez-Guillen, M.E.; Silva-Emini, J.A.; Lmdala, A.J.; Souccar, C. Int. J. Pharmacol., 1997, 35, 99-104.
Khan, H.; Saeed, M.; Gilani, A.U.; Khan, M.A.; Dar, A.; Khan, I. The antinociceptive activity of Polygonatum verticillatum rhizomes in pain models. J. Ethnopharmacol., 2010, 127(2), 521-527.
[] [PMID: 19853648]
Ibrar, M.; Muhammed, N.; Barkatullah, P.; Khan, H.; Jahan, F.; Asrha, N. Antinociceptive and Anticonvulsant activities of essential oils of Zanthoxylum armatum. Phytopharmacology., 2012, 3, 191-198.
Collier, HDJ; Dinnin, LC; Johnson, CA; Schneider, C The abdominal response and its suppression by analgesic drugs in the mouse. Britsh, J. Pharmacol, Chemo., 1968, 32, 295-310.
Temponi, Vdos.S.; da Silva, J.B.; Alves, M.S.; Ribeiro, A.; de Jesus Ribeiro Gomes de Pinho, J.; Yamamoto, C.H.; Pinto, M.A.; Del-Vechio-Vieira, G.; Vieira de Sousa, O.V. Antinociceptive and anti-inflammatory effects of ethanol extract from Vernonia polyanthes leaves in Rodents. Int. J. Mol. Sci., 2012, 13(3), 3887-3899.
[] [PMID: 22489187]
Gené, R.M.; Segura, L.; Adzet, T.; Marin, E.; Iglesias, J. Heterotheca inuloides: anti-inflammatory and analgesic effect. J. Ethnopharmacol., 1998, 60(2), 157-162.
[] [PMID: 9582006]
Mazid, M.A.; Datta, B.K.; Nahar, L.; Rashid, M.A.; Bachar, S.C.; Bashar, S.A.; Sarker, S.D. Analgesic and diuretic properties of alpha-santalone from Polygonum flaccidum. Phytother. Res., 2010, 24(7), 1084-1087.
[PMID: 20077435]
Murakami, K.; Ohara, Y.; Haneda, M.; Tsubouchi, R.; Yoshino, M. Prooxidant action of hinokitiol: hinokitiol-iron dependent generation of reactive oxygen species. Basic Clin. Pharmacol. Toxicol., 2005, 97(6), 392-394.
[] [PMID: 16364055]
Tjølsen, A.; Berge, O.G.; Hunskaar, S.; Rosland, J.H.; Hole, K. The formalin test: an evaluation of the method. Pain, 1992, 51(1), 5-17.
[] [PMID: 1454405]
Santos, B.V.D.O.; Chaves, E.M.C.D.O.; Gray, A.I. Phenylalkanoids from Piper marginatum. Phytochemistry, 1998, 49, 1381-1384.
Noureddine, B; Francesca, A; Alba, R.; Jose, G; Terrassa, V; Fadila, M; Maria, PU; Julio, G. Antinociceptive and anti-inflammatory effects of Total Alkaloid extract from Fumaria capreolata. Evid. Based Complement. Alternat. Med., 2015, 87, 102-106.
Okuda-Ashitaka, E.; Minami, T.; Tachibana, S.; Yoshihara, Y.; Nishiuchi, Y.; Kimura, T.; Ito, S. Nocistatin, a peptide that blocks nociceptin action in pain transmission. Nature, 1998, 392(6673), 286-289.
[] [PMID: 9521323]
Marahel, S.; Umesha, S. Anti-inflammatory and antinociceptive effect of Pachygone ovata leaves. Pharm. Biol., 2016, 54(12), 3046-3054.
[] [PMID: 27417523]
Hahn, Y.S.; Kim, J.G. Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis. Korean J. Pediatr., 2010, 53(11), 921-930.
[] [PMID: 21218013]
Wigdor, S.; Wilcox, G.L. Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways. J. Pharmacol. Exp. Ther., 1987, 242(1), 90-95.
[PMID: 3612540]
Chapman, C.R.; Casey, K.L.; Dubner, R.; Foley, K.M.; Gracely, R.H.; Reading, A.E. Pain measurement: An overview. Pain, 1985, 22(1), 1-31.
[] [PMID: 4011282]
Vogel, H.G. Drug discovery and evaluation, pharmacological assay, 2nded; Springer: New York, 2002, p. 670.
Yaksh, T.L.; Rudy, T.A. Analgesia Mediated bya direct spinal actions of narcotics. Surv. Anesthesiol., 1977, 21(2), 122-123.
Ridtitid, W.; Sae-Wong, C.; Reanmongkol, W.; Wongnawa, M. Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals. J. Ethnopharmacol., 2008, 118(2), 225-230.
[] [PMID: 18486374]
Ripoll, N.; Hascoët, M.; Bourin, M. The four-plates test: anxiolytic or analgesic paradigm? Prog. Neuropsychopharmacol. Biol. Psychiatry, 2006, 30(5), 873-880.
[] [PMID: 16644084]
Tzschentke, T.M.; Christoph, T.; Kogel, B. A novel opioid receptor agonist/norepineprine reuptake inhibitor with broad spectrum analgesic properties. J. Pharmacol. Exp. Ther., 2007, 323, 265-276.
[] [PMID: 17656655]
Ramabadran, K.; Bansinath, M. A critical analysis of the experimental evaluation of nociceptive reactions in animals. Pharm. Res., 1986, 3(5), 263-270.
[] [PMID: 24271708]
South, S.M.; Smith, M.T. Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats. J. Pharmacol. Exp. Ther., 1998, 286(3), 1326-1332.
[PMID: 9732396]
Nakamura, H.; Shimoda, A.; Ishii, K.; Kadokawa, T. Central and peripheral analgesic action of non-acidic non-steroidal anti-inflammatory drugs in mice and rats. Arch. Int. Pharmacodyn. Ther., 1986, 282(1), 16-25.
[PMID: 3767523]
Zakaria, Z.A.; Hussain, M.K.; Mohamad, A.S.; Abdullah, F.C.; Sulaiman, M.R. Anti-inflammatory activity of the aqueous extract of ficus deltoidea. Biol. Res. Nurs., 2012, 14(1), 90-97.
[] [PMID: 21278166]
Damas, J.; Remacle-Volon, G.; Deflandre, E. Further studies of the mechanism of counter irritation by turpentine. Naunyn Schmiedebergs Arch. Pharmacol., 1986, 332(2), 196-200.
[] [PMID: 3517657]
Vinegar, R.; Schreiber, W.; Hugo, R. Biphasic development of carrageenin edema in rats. J. Pharmacol. Exp. Ther., 1969, 166(1), 96-103.
[PMID: 5776026]
Crunkhorn, P.; Meacock, S.C. Mediators of the inflammation induced in the rat paw by carrageenin. Br. J. Pharmacol., 1971, 42(3), 392-402.
[] [PMID: 4104654]
Borsini, F.; Cesana, R.; Kelly, J.; Leonard, B.E.; McNamara, M.; Richards, J.; Seiden, L. BIMT 17: a putative antidepressant with a fast onset of action? Psychopharmacology (Berl.), 1997, 134(4), 378-386.
[] [PMID: 9452180]
Havsteen, B. Flavonoids, a class of natural products of high pharmacological potency. Biochem. Pharmacol., 1983, 32(7), 1141-1148.
[] [PMID: 6342623]
Gaille, C.; Kast, P.; Haas, D. Salicylate biosynthesis in Pseudomonas aeruginosa. Purification and characterization of PchB, a novel bifunctional enzyme displaying isochorismate pyruvate-lyase and chorismate mutase activities. J. Biol. Chem., 2002, 277(24), 21768-21775.
[] [PMID: 11937513]
Honda, K.; Harada, A.; Takano, Y.; Kamiya, H. Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice. Brain Res., 2000, 859(1), 38-44.
[] [PMID: 10720613]
Sanders, R.D.; Maze, M. Adrenergic and cholinergic compounds. Handb. Exp. Pharmacol., 2007, 177(177), 251-264.
[PMID: 17087126]
Jones, P.G.; Dunlop, J.; Chen, J. Targeting the cholinergic system as a therapeutic strategy for the treatment of pain. Neuropharmacology, 2007, 53(2), 197-206.
[] [PMID: 17543355]
Jinsmaa, Y.; Okada, Y.; Tsuda, Y.; Shiotani, K.; Sasaki, Y.; Ambo, A.; Bryant, S.D.; Lazarus, L.H. Novel 2′,6′-dimethyl-L-tyrosine-containing pyrazinone opioid mimetic mu-agonists with potent antinociceptive activity in mice. J. Pharmacol. Exp. Ther., 2004, 309(1), 432-438.
[] [PMID: 14718580]
Liang, Y.C.; Huang, Y.T.; Tsai, S.H.; Lin-Shiau, S.Y.; Chen, C.F.; Lin, J.K. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis, 1999, 20(10), 1945-1952.
[] [PMID: 10506109]
Mills, S.; Bone, K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone, 2000, 23–24-31–34, 229–231.
Morteza-Semnani, K.; Mahmoudi, M.; Heidar, M.R. Analgesic activity of the methanolic extract and total alkaloids of Glaucium paucilobum. Methods Find. Exp. Clin. Pharmacol., 2006, 28(3), 151-155.
[] [PMID: 16810340]
Anjaneyulu, M.; Chopra, K. Quercetin, a bioflavonoid, attenuates thermal hyperalgesia in a mouse model of diabetic neuropathic pain. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2003, 27(6), 1001-1005.
[] [PMID: 14499317]
Katavic, P.L.; Lamb, K.; Navarro, H.; Prisinzano, T.E. Flavonoids as opioid receptor ligands: identification and preliminary structure-activity relationships. J. Nat. Prod., 2007, 70(8), 1278-1282.
[] [PMID: 17685652]
Starec, M.; Waitzová, D.; Elis, J. [Evaluation of the analgesic effect of RG-tannin using the “hot plate” and “tail flick” method in mice Cesk. Farm., 1988, 37(7), 319-321.
[PMID: 3197132]
Viana, G.S.B.; Bandeira, M.A.M.; Moura, L.C.; Souza‐Filho, M.V.P.; Matos, F.J.A.; Ribeiro, R.A. Analgesic and Antiinflammatory Effects of the Tannin Fraction from Myracrodruon urundeuva Fr. All. Phytother. Res., 1998, 11(2), 118-122.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy