Evaluation of acute and sub-chronic toxicities of ulcer fast®: a bi-herbal formula in male Wistar albino rats

Kingsley C. Patrick-Iwuanyanwu, Jane A. Emerue


The acute and sub-chronic toxicities of ulcer fast® (UF) - A commercial bi-herbal formula prepared with Alstonia boonei and Xylopia aethiopica in male Wistar albino rats was evaluated. There was no mortality in rats administered 2000 mg/kg body weight (BW) of UF in an acute toxicity study. A significant (p≤0.05) increase in daily consumption of feed and fluid intake in experimental rats after 28 days was recorded followed by a progressive increase in BW of rats administered 50, 100 and 200 mg/kg BW of UF in a dose-dependent manner. Alanine amino transferase, aspartate amino transferase, alkaline phosphatase, lactate dehydrogenase, triacylglycerides and creatinine increased significantly (p≤0.05) in rats treated with UF, whereas urea and fasting blood sugar decreased significantly (p≤0.05) in a dose-dependent manner when compared with control. There was a marginal decrease in serum calcium ion and phosphate ion following the administration of UF when compared with control. Packed cell volume and hemoglobin decreased significantly (p≤0.05) in rats treated with UF, whereas white blood cell increased significantly (p≤0.05) in a dose-dependent manner when compared with control. Histological examination of the liver, kidney, heart and lungs showed normal architecture in control group, whereas hepatocytes of rats treated with 50, 100 and 200 mg/kg BW of UF were characterized by slight periportal fatty change, marked change and ballooning degeneration. Heart muscle of rats treated with 200mg/kg BW of UF showed slight inflammation while histological examination of the lungs showed areas of interstitium damage and diffuse alveolar damage in rats treated with UF. In conclusion, indiscriminate administration of UF could be of public health concern and long-term exposure may cause a significant potential health risk.


Ulcer fast, Bi-herbal formula, Sub-chronic toxicity, Acute toxicity, Histological examination, Risk assessment

Full Text:



Baldi A, Goyal S. Hypoglycemic effect of polyherbal formulation in alloxan induced diabetic rats. Pharmacologyonline. 2011;3:764-73.

Bateman J, Chapman RD, Simpson D. Possible toxicity of herbal remedies. Scott Med J. 1998;43(1):7-15.

Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280(18):1569-75.

Walker JB. Evaluation of the ability of seven herbal resources to answer questions about herbal products asked in drug information centers. Pharmacotherapy. 2002;22(12):1611-5.

ZhouY, Chuan KB, Chen S. An information system model in Chinese herbal medicine manufacturing enterprises. J Manuf Technol. 2005;16:145-55.

Rivera JO, Ortiz M, González-Stuart A, Hughes H. Bi-national evaluation of herbal product use on the United States/México border. J Herb Pharmacother. 2007;7(3 4):91 106.

Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008:1-23.

Tilburt JC, Kaptchuk TJ. Herbal medicine research and global health: an ethical analysis. Bull World Health Organ. 2008;86(8):594-9.

Robinson MM, Zhang X. Traditional medicines: global situation, issues and challenges. The World Medicines Situation. 3rd edition. Geneva: WHO; 2011: 1-14.

World Health Organization. Resolution WHA62.13. Traditional Medicine. Geneva: World Health Organization; 2009.

Cohen PA. American roulette – Contaminated dietary supplements. N Engl J Med. 2009;361(16):1523-5.

Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Arch Intern Med. 1997;157(8):913-9.

Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000;343(25):1833-8.

Teschke R. Kava hepatotoxicity – A clinical review. Ann Hepatol. 2010;9(3):251-65.

Osadebe PO. Anti-inflammatory properties of the root bark of A. boonei. Niger J Nat Prod Med. 2002;6:39-41.

Betti JL. An ethnobotanical study of medicinal plants among the baka pygmies in the djabiosphere reserve, Cameroon. Afr Stud Monogr. 2004;25:1-27.

Majekodunmi SO, Adegoke OA, Odeku OA. Formulation of the extract of the stem bark of Alstonia boonei as tablet dosage form. Trop J Pharm Res. 2008;7:987-94.

Alshawsh MA, Mothana RA, Al-Shamahy HA, Alsllami SF, Lindequist U. Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants. Evid Based Complement Alternat Med. 2009;6(4):453-6.

Tepongning RN, Lucantoni L, Nasuti CC, Dori GU, Yerbanga SR, Lupidi G. Potential of a Khaya ivorensis - Alstonia boonei extract combination as antimalarial prophylactic remedy. J Ethnopharmacol. 2011;137:743-51.

Ojewole AO. Studies on the pharmacology of echitamine, an alkaloid-from the stem bark of Alstonia boonei L. (Apocynaceae). Int J Crude Drug Res. 1984;22:121-43.

Dalzie JM. The Useful Plants of West Tropical Africa. London: ;1955: 9.

Irvine F. Woody Plants of Ghana. London: Oxford University Press; 1961.

Tatsadjieu N, Ngang JJE, Ngassoum MB, Etoa FX. Antibacterial and antifungal activity of Xylopia aethiopica, Monodora myristica, Zanthoxylum X. aethiopica nthoxyloïdes and Zanthoxylum leprieurii from Cameroon. Fitoterapia. 2003;74:469.

Konning GH, Agyare C, Ennison B. Antimicrobial activity of some medicinal plants from Ghana. Fitoterapia. 2004;75(1):65-7.

Fleischer TC, Mensah ML, Mensah AY, Komlaga G, Gbedema SY, Skaltsa H. Antimicrobial activity of essential oils of Xylopia aethiopica. Afr J Tradit Complement Altern Med. 2008;5(4):391-3.

Kuete V. Potential of Cameroonian plants and derived products against microbial infections: a review. Planta Med. 2010;76:1479.

Boyom FF, Ngouana V, Zollo PH, Menut C, Bessiere JM, Gut J, et al. Composition and anti-plasmodial activities of essential oils from some Cameroonian medicinal plants. Phytochemistry. 2003;64(7):1269-75.

Karioti A, Hadjipavlou-Litina D, Mensah ML, Fleischer TC, Skaltsa H. Composition and antioxidant activity of the essential oils of Xylopia aethiopica (Dun) A. Rich. (Annonaceae) leaves, stem bark, root bark, and fresh and dried fruits, growing in Ghana. J Agric Food Chem. 2004;52:8094-8.

Adaramoye OA, Adedara IA, Popoola B, Farombi EO. Extract of Xylopia aethiopica (Annonaceae) protects against gamma-radiation induced testicular damage in Wistar rats. J Basic Clin Physiol Pharmacol. 2010;21(4):295-313.

Adaramoye OA, Okiti OO, Farombi EO. Dried fruit extract from Xylopia aethiopica (Annonaceae) protects Wistar albino rats from adverse effects of whole body radiation. Exp Toxicol Pathol. 2011;63(7-8):635-43.

OECD, Organisation for Economic Cooperation and Development. Guidelines for the Testing of Chemicals/Section 4: Health Effects Test No. 423: Acute Oral Toxicity-Acute Toxic Class Method. Paris: Organization for Economic Cooperation and Development; 2002.

OECD, Organisation for Economic Cooperation and Development. Repeated dose 28-day oral toxicity test method guideline 407 adopted 23.03.1996. In: OECD, Guidelines for Testing of Chemicals. Paris: Organisation for Economic Co-Operation and Development; 1995.

Trinder P. A rapid method for the determination of sodium in serum. Analyst. 1951;76(907):596-9.

Maruna R, Oei ET. Physiological & pathological chemical research in Indonesia. I. [Standard values of blood]. Clin Chim Acta. 1958;3(6):519.

Dacie JV, Lewis SM. Practical Haematology. 7th edition. England: ELBS with Churchill Livingstone; 1991: 37-85.

Galigher AE, Kayloff EN. Essentials of Practical Microtechniques. Philadelphia: Lea and Febiger; 1971.

Corns CM. Herbal remedies and clinical biochemistry. Ann Clin Biochem. 2003;40(Pt 5):489-507.

Wallace H. Principles and Methods of Toxicology. Volume 4. Boca Raton: CRC Press; 2001: 871-3.

Shatoor AS. Acute and sub-acute toxicity of Crataegus aronia syn. azarolus (L.) whole plant aqueous extract in wistar rats. Am J Pharmacol Toxicol. 2011;6:37-45.

Aniagu SO, Nwinyi FC, Akumka D, Ajoku GA, Dzarma S. Toxicity studies in rats fed nature cure bitters. Afr J Biotechnol. 2005;4:72-8.

Mukinda JT, Syce JA. Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol. 2007;112(1):138-44.

Sharon A. Interpretation of liver enzymes. Vet Clin North Am Small Anim Pract. 2007;37:297-333.

Patrick-Iwuanyanwu KC, Okon EA, Orisakwe OE. Evaluation of acute and sub-chronic toxicities of vensestin cleansers: a polyherbal supplement in female Wistar Albino rats. J Appl Pharm Sci. 2014;4:(06) 74-78.

Rahman MF, Siddiqui MK, Jamil K. Effects of Vepacide (Azadirachta indica) on aspartate and alanine aminotransferase profiles in a sub chronic study with rats. J Hum Exp Toxicol. 2000;20:243-9.

Feldman BV, Zinkl JG. Veterinary Hematology. 5th edition. Philadelphia: Lea Febiger; 2000: 1210-8.

Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194-205.

Willianson EM, Okapako DT, Evans FJ. Selection, Preparation and Pharmacological Evaluation of Plant Material. England: John Wiley; 1996.

Predes FS, da Matta SLP, Monteiro JC, de Oliveira TT. Investigation of liver tissue and biochemical parameters of adult Wistar rats treated with Arctium lappa L. Braz Arch Biol Technol. 2009;52(2):335-40.

Parmar MY, Shah PA, Gao J, Gandhi TR. Hepatoprotection through regulation of voltage dependent anion channel expression by Amomum subulatum Roxb seeds extract. Indian J Pharmacol. 2011;43(6):671-5.

Schumann G, Klauke R, Canalias F, Reuther SB. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 378C. Part 9: Reference procedure for the measurement of catalytic concentration of alkaline phosphatase. Clin Chem Lab Med. 2011;49(9):143946.

Bennett WM, Parker RA, Elliott WC, Gilbert DN, Houghton DC. Sex-related differences in the susceptibility of rats to gentamicin nephrotoxicity. J Infect Dis. 1982;145(3):370-3.

Anwar S, Khan NA, Amin KM, Ahmad G. Effects of banadiq al buzoor in some renal disorder. J Int Med. 1999;4:21-9.

Patwardhan B, Warude D, Pushpangadan P, Bhatt N. Ayurveda and traditional Chinese medicine: a comparative overview. Evid Based Complement Alternat Med. 2005;2(4):465-73.

Mayne PD. The kidneys and renal calculi. In: Clinical Chemistry in Diagnosis and Treatment. Volume 6. London: Edward Arnold Publications; 1994: 2-24.

Sugimoto T, Yamashita S, Ishigami M, Sakai N, Hirano K, Tahara M, et al. Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats. J Hepatol. 2002;36(2):157-62.

You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem. 2002;277(32):29342-7.

Borhanuddin M, Shamsuzzoha M, Hussain AH. Hypoglycaemic effects of Andrographis paniculata Nees on non-diabetic rabbits. Bangladesh Med Res Counc Bull. 1994;20(1):24-6.

Fairbarks VF. Mechanism of haemolutic drug action. Lancet. 1967;1:512-20.

Igbokwe IO, Esievo KA, Saror DI, Obagaiye OK. Increased susceptibility of erythrocytes to in vitro peroxidation in acute Trypanosoma brucei infection of mice. Vet Parasitol. 1994;55(4):279-86.

Igbokwe IO, Umar IA, Omage JJ, Ibrahim ND, Kadima KB, Obagaiye OK, et al. Effect of acute Trypanosoma vivax infection on cattle erythrocyte glutathione and susceptibility to in vitro peroxidation. Vet Parasitol. 1996;63(3-4):215-24.

Akanji MA, Adeyemi OS, Oguntoye SO, Sulyman F. Psidium guajava `extract reduces trypanosomosis associated lipid per-oxidation and raises glutathione concentrations in infected animals. EXCLI J. 2009;8:148-54.

Adisa OA, Ajayi OA, Awujo NC, Thomas, BN. Haematolobiochemical changes in albino rats infected with Trypanosoma brucei brucei. Nig. Quart J Hosp Med. 1999;9:238-40.