Evaluation of the Spasmolytic and Antiulcer Effect of The Fruit Extract and Fractions of Cucumis metuliferus: doi.org/10.26538/tjnpr/v3i6.3

Ebere E. Okpalaeke; Stella A. Ihim; Emmanuel I. Peter; Nneoma  M. Ofokansi; Chukwuemeka S. Nworu

Authors

Ebere E. Okpalaeke Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.
Stella A. Ihim Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.
Emmanuel I. Peter Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.
Nneoma M. Ofokansi Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.
Chukwuemeka S. Nworu Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria.

Keywords:

Cucumismetuliferus, peptic ulcer,, antispasmolytic,, antiulcer.

Abstract

The plant Cucumis metuliferus (Cucurbitaceae) locally called ‘bùurarzaàki’ is used by traditional medical practitioners in parts of Plateau state of Nigeria to treat disease such as peptic ulcer, diabetes mellitus, hypertension and HIV/AIDS. This study was undertaken to give credence to the traditional use of Cucumis metuliferus in the treatment of peptic ulcers. The methanol extract of the fruit plant material was fractionated sequentially using n-hexane, ethyl acetate, butanol and water to yield HFCM, EAFCM, BFCM and WFCM fractions, respectively and evaluated for antiulcer properties using experimentally-induced ulcers in mice and rats. In vitro antiulcer activity was also evaluated. Ethanol-induced ulcer was significantly (p<0.05) protected by MECM (100, 200 and 400 mg/kg). The extracts MECM (100, 200 and 400 mg/kg), EAFCM (200, 400 mg/kg), and WFCM (200, 400 mg/kg) exhibited dose-dependent and significant (p<0.05) protection of rats against indomethacin-induced ulcers. Gastrointestinal propulsion in mice was significantly (p<0.05) reduced in a dose-dependent manner with MECM (400 mg/kg) and WFCM (400 mg/kg) showing the highest level of antiperistaltic activity. The contractions evoked by acetylcholine and histamine on the rabbit jejunum were antagonized by the extracts and fractions in a concentration-dependent antispasmolytic manner. Acute toxicity tests showed an oral LD50 greater than 5000 mg/kg in mice. Rich varieties of bioactive constituents in MECM include alkaloids, terpenoids, flavonoids, carbohydrates and steroids. These findings demonstrated that the plant possesses pharmacological properties which lend credence to its ethnomedicinal use as an antiulcer and antidiarrhoeal agent.

References

Klein-Junior LC, Gandolfi RB, Santin JR, Lemos M, Cechinel FV, Andrade SF. Antiulcerogenic activity of extract, fractions, and some compounds obtained from Polygolacyparissias St Hillaire&Moquin (Poligalaceae). NaunynSchmiedebergs Arch Pharmacol. 2010; 381:121-126.

Zelickson MS, Bronder CM, Johnson BL,Camunas JA, Smith DE, Eawlinson D, Von S, Stone HH, Taylor SM. Helicobacter pylori is not the predominant etiology for peptic ulcers requiring operation. Am Surgeon J. 2011; 77:1054-1060.

Freitas CS, Baggio CH, Finau J, Anginoni M, Pizzolatti MG, Santos AR, Marques MA. Inhibition of H+/K+ ATPase in the gastroprotective effect of Baccharisillinita DC. J Pharm Pharmacol. 2008; 60:1105-1110.

Gosh S and Kinnear M. Peptic ulcer disease. In: clinical pharmacy and therapeutics. Roger W(Ed) (3rd Ed).Churchill living stone; 2003. 143-161 p.

Howden CW, Jones DB, Peace PK, Burget DW, Hunt RH. The treatment of gastric ulcer with antisecretory drugs: relationship of pharmacological effect to healing rates. Dig Dis Sci. 1988; 33:619-624.

Akah PA, NnaetoOluchi, Nworu CS, Ezike AC. Medicinal plants used in the traditional treatment of peptic ulcer diseases: a case study of Napoleonavogelii Hook and Planch (Lecythidaceae). Res JPharmacol. 2007; 1(3):67-74.

Akah PA, John-Afica L, Nworu CS. Gastroprotective properties of OcimumgratissimumL. against experimental ulcers in rat. IntJ Pharmacol. 2007; 3(5):461- 467

Burkill HM. Useful Plants of West Tropical Africa. Vol.1 ( 2nded). Royal botanic gardens, London; 1985. 570-605 p.

Anon A. Mienkie Welman National Herbarium, Pretoria 2009. http://www.plantzafrica.com/planted /cucumismet.htm. Accessed on 15th March 2016.

Jimam NS, Wannang NN, Anuka JA, Omale S, Falang JD, Adolong AA. Histopathologic effects of Cucumismetuliferus E. Meyer (Cucurbitaceae) fruits in albino rats. IntJ Pharm Sci Res. 2011; 2(8):2190-2194.

Wannang NN, Jiman NS, Gyang SS, Saleh G. Effects of Cucumismetuliferus E. Meyer ex. naud. (Cucurbitaceae) fruit extract on some male reproductive parameters in adult rats. Afr J Pharm Pharmacol. 2008; 2(3):48-51.

Cheiji R. Encyclopedia of medicinal plants. MacDonald 15 BUO, 1984; 356:10541-10545.

Wannang NN, Jimam NS, Omale S, Aguiyi JC. Effects of Cucumismetuliferus (Cucurbitaceae) fruits on enzymes and haematological parameters in albino rats.AfrJ Biotech. 2007; 6(22):2515-2518.

Usman JG. Phytochemical screening and antibacterial effects of Cucumismetuliferus (Jelly Melon) E. Meyer. Ex naudin (Cucurbitaceae) fruits against fowl typhoid. A dissertation submitted to the school of postgraduate studies, University of Maiduguri, in partial fulfilment of the requirement for the degree of master of science in Pharmacology 2014. 155 p.

Roodt V. Common wild flowers of the Okavango Delta; medicinal uses and nutritional value. 1998. The shell Field Guide Series: Part II.

Moore PS and Pizza C. Observations on the inhibition of HIV-1 reverse transcriptase by catechins. Biochem J. 1992; 288:717-719.

Usman JG, Sodipo OA, Kwaghe AV, Sandabe UK. Uses of Cucumismetuliferus.A review. Cancer Biol. 2015; 5(1):24-34.

Jimam NS, Wannang NN, Omale S, Gotom B. Evaluation of the hypoglycemic activity of Cucumismetuliferus (Cucurbitaceae) fruit pulp extract in normoglycemic and alloxan-induced hyperglycemic rats. J Young Pharm. 2010; 2(4):384-387.

Gotep J. Glycosides fraction extracted from fruit pulp of Cucumismetuliferus E. Meyer has antihyperglycemic effect in rats with alloxan induced diabetes. J Nat Pharmacol. 2011; 2:48-51.

Abubakar A, Iliyasu B, Ojiegbu FN, Igweh AC, Shamaki BU, Dung EC, Domtur LL, Okogun JI, Gbodi TA, Ogbadoyi EO. Evaluation of the antitrypanosomal activity of Cucumismetuliferus pulp extract in rabbits.J Med Plant Reseserv. 2011; 5(11):2136-2142.

Harborne JB. Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis (3rd ed.) London: Chapman & Hall 1998.

Evans WC. Trease and Evans Pharmacognosy (16th ed) Edinburgh: WB Saunders 2009.

Lorke D. A new approach to practical acute toxicity testing.Arch Toxicol. 1983; 54:275–287.

Robert A, Nezamis JE, Lancaster C, Hanchar AJ, Klepper MS. Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury.Gastroenterol. 1979; 77:433-443.

Morimoto Y, Shimohara K, Oshima S, Sukamoto T. Effects of the new anti- ulcer agent KB- 5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of terpenone and cimetidine. Jap J Pharmacol. 1991; 57:495-505.

Urishidani T, Kasuya Y, Okabe S. The mechanism of aggravation Indomethacin-induced ulcer by adrenalectomy in rats.Jap J Pharmacol. 1979; 29:775-780.

Al-Mashhadani WM, Karim KH, Al- Taie RI, Al-Zahawi HM. Nifedipine versus cimetidine in prevention of stress– induced gastric ulcers in rats. Eur J Pharmacol. 1991; 192:117-121.

Akah PA and Nwafor SV. Studies on the anti-ulcer properties of Cissampelosmucronata leaf extract. Indian J Exp Bio. 1999; 37:936-938.

Nwafor PA, Okwuasaba FK, Binda LG. Anti-diarrhoeal and anti-ulcerogenic effects of methanol extract of Asparagus pubescens root in rats. J Ethnopharmacol. 2000; 72:21-427.

Venkataranganna MV, Gopumadhavan R, Sundaram R,Mitra SK. Evaluation of possible mechanism of anti-ulcerogenic activity of UL-409 an herbal preparation. J Ethnopharmacol. 1998; 63:187-192.

Afifi FU, Khalit E, Tamini SO, Disi A. Evaluation of gastroprotective effects of Laurusnobilisseeds on ethanol- induced gastric ulcer in rats. J Ethnopharmacol.1997; 58:9-14.

Nwafor SV and Akah PA. Effect of methanol leaf extract of Cissampelosmucronata A Rich against Indomethacin-induced ulcer.Indian J Exp Bio. 2003; 41:181-183.

Awaad AS, El-Meligy RM, Soliman GA. Natural products in the treatment of ulcerative colitis and peptic ulcer. J Saudi Chem Soc. 2013; 17(1):101-124.

Sener G, Paskaloglu K, Ayanoglu-Dülger G. Protective effect of increasing doses of famotidine, omeprazole, lansoprazole, and melatonin against ethanol-induced gastric damage in rats. Ind J Pharmacol. 2004; 36:171.

Marhuenda E, Martin MJ, Alarcon L. Antiulcerogenic activity of aescine in different experimental models. Phytother Res. 1993; 7:13-16.

Galvin GB and Szabo S. Experimental gastric mucosal injury: Laboratory models reveal mechanism of pathogenesis and new therapeutic strategy. Fed Am SocExp Bio J. 1992; 6:825- 831.

Banoob DW, McCloskey WW, Webster W. Risk of gastric injurywith enteric-coated versus nonenteric coasted aspirin. Ann Pharmacother. 2002; 36:163-166.

Wightkin WT: Stress ulcer: Pathophysiology and prevention. Am J Hosp Pharm. 1980; 37:1651–1655.

Coblijn UK, Goucham AB, Lagarde SM, kuiken SD, Van- Wagensveld BA. Development of ulcer disease after Roux-en

-Y gastric bypass, incidence, risk factors, and patient presentation: A systematic review. Obes Surg. 2014; 24:299- 309.

Yedgar S, Krimsky M, Cohen Y, Flower RJ. Treatment of inflammatory diseases by selective eicosanoid inhibition: A double-edged sword?.Trends Pharmacol Sci. 2007; 28:459- 64.

Jia YT, Wei W, Ma B, Xu Y, Liu WJ, Wang Y, Lv KY, Tang HT, Wei D, Xia Z . Activation of p38 MAPK by reactive oxygen species is essential in a rat model of stress-induced gastric mucosal injury. J Immunol. 2007; 179:7808-7819.

Murakami M, Lam SA, Inada M. Pathophysiological and pathogenesis of acute gastric mucosal lesions after hypothermic restraint stress in rats. Gastroenterol. 1985; 88:660-665.

Hua XY, Dahlen Se, Lundberg JM, Hedqvist P. Leukotrienes C4, D4 and E4 causes widespread and extensive plasma extravasation in guinea pig. Naunyn-Schmiedebergs.Arch Pharmacol. 1985; 330:136-142.

Mersereau WA and Hinchey EJ. Relationship between myoelectric and mechanical activity in the genesis of ulcers in Indomethacin-insulin treated rats. Dig Dis Sci. 1988; 33:200- 208.

Hoogerwerf WA and Pasricha PJ. Agents Used for Control of Gastric acidity and treatment of peptic ulcers and gastroesophageal reflux disease. In: J.G.Hardman, L.E.Limbird, A.G.Gilman( Eds.) .Goodman &Gilman.s The Pharmacological Basis of Therapeutics., (10th Ed). McGraw- Hill, New York, 2001. 1005-1020 p.

Brunton LL. Agents for control of gastric acididty and treatment of peptic ulcer. In: The pharmacological basis of therapeutics. (9th Ed). In: Hardman LE, Limbird JG, Molinoff PB, Ruddon RW, Gilman AG (Eds). McGraw-Hill New York, 1996. 901-915 p.