Antioxidant activity and gastro-protective effets of carob podsa queous extracts on indomethacin-induced gastric ulcer in wistar rats

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Antioxidant activity and gastro-protective effets of carob podsa queous extracts on indomethacin-induced gastric ulcer in wistar rats

Mansouria Belhocine, Chahrazed Sakmeche, Fatima Azzouz
Int. J. Biosci.12( 5), 48-69, June 2018.
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Gastroduodenal ulcer is a reccurent chronic disease aggravated by the use of non-steroidal anti-inflammatory drugs (NSAIDs), and long-term low-dose aspirin therapy.This study aimed at searching a natural anti-ulcer remedy without side effects. The carob pod antioxidant activity was tested on DPPH and its gastro-protective effect was investigated in Wistar rats submitted to a gastric ulcer, induced by a NSAID drug, indomethacin. The study was performed on twenty rats allocated into four groups. The negative control group received distilled water, the positive control group received indomethacin, the standard group received ranitidine, and group four received carob pods aqueous extract (CPAE). Animals were per-orally pretreated during 15 days, and the indomethacin was administrated the 16th day to all rats, except those of the negative control group. Carob exhibited important antioxidant activity (85%). Indomethacin-ulcerated rats showed congested, odemateus and fissured gastric mucosa by numerous ulcer lesions, an increased ulcer index and significantly decreased adherent gastric mucus content. Pepsin activity and gastric juice volume increased, while pH diminished significantly. CPAE reduced the volume and increased the pH of the gastric juice, and lowered the pepsin activity. Ulcer lesions and ulcer index were strongly lowered. The gastric mucus was reconstituted and the mucosa appeared almost competely healed, with normal color and thickness. The carob protection percentage was similar to that of ranitidine. Carob therefore, undoubtedly has antiulcer potential, through an anti-secretory effect, possibly related to its strong antioxidant capacity. It can be proposed as a therapeutic opportunity in the management of peptic ulcers.


Abdel-Rahman M, Salem FEHS, Bauomy AA, Khalifa MA. 2017. Ameliorative effect of carob aqueous extract on water pipe smoke induced toxicity in adult male albino rats. International Journal of Pharmacy and Pharmaceutical Sciences 9(1), 246-253.

Adefegha SA. 2017. Functional foods and nutraceuticals as dietary intervention in chronic diseases ; Novel perspectives for health promotion and disease prevention. Journal of Dietary Supplements 1-33.

AidiWannes W, Saidani Tounsi M. 2017. Research advances in ulcer treatment using Tunisian medicinal plants. Biointer face Research in Applied Chemistry 7(3), 2035-2039.

Akkaya H, Yilmaz O. 2012.Antioxidant capacity and radical scavenging activity of Silybum marianum and Ceratoniasiliqua. Ekoloji 21(82), 9-16.

Akpamu U, Owoyele VB, Ozor M, Osifo UC. 2013. Indomethacin-induced gastric ulcer : Model in female Wistar rats. International Journal of Basic, Applied and Innovative Research 2(4), 78-84.

Ali Khan MS, Nazan S, Mat Jais AM. 2017. Flavonoids and anti-oxidant activity mediated gastroprotective action of Leathery Murdah, Terminalia coriacea (roxb.) Wight & Arn. Leaf methanolic extract in rats. Arquivos De Gastroenterologia 54(3), 183-191.

Alkushi AGR, Elsawy NAM. 2017. Quercetin attenuates indomethacin-induced acute gastric ulcer in rats. Folia Morphologica 76(2), 252-261.

See comment in PubMed Commons below Al-Olayan EM, El-Khadragy MF, Alajmi RA, Othman MS, Bauomy AA, Ibrahim SR, Moneim AE. 2017. Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress. BMC Complementary and Alternative Medicine 17(1), 51.

Al-wabel NA, Hassan A, Abba H, Muosa H. 2012.Antiulcerogenic effect of camel milk against ethanol induced gastric ulcers in rats. Webmed Central Veterinary Medicine 3(3), WMC002804.

Al-Wajeeh NS, Hajerezaie M, Noor SM, Halabi MF, Al-Henhena N, Azizan AH, Kamran S, Hassandarvish P, Shwter AN, Karimian H, Ali HM, Abdulla MA. 2017. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.BMC Veterinary Research 13, 27.

Anson ML. 1938. The estimation of pepsin, trypsin, papain, and cathepsin with hemoglobin. Journal of General Physiology 22(1), 79-89.

Aragão TP, Prazeres LDKTD, Brito SA, Neto PJR, Rolim LA, Almeida JRGDS, Caldas GFR, Wanderley AG. 2018. Contribution of secondary metabolites to the gastroprotective effect of aqueous extract of Ximenia americana L. (Olacaceae) stem bark in rats. Molecules 23(1), 112.

Backert S, Schmidt TP, Harrer A, Wessler S. 2017. Exploiting the gastric epithelial barrier : Helicobacter pylori’s attack on tight and adherens junctions. Current Topics in Microbiology and Immunology 400, 195-226.

Bakhtaoui FZ, Lakmichi H, Chait A, Gadhi CA. 2014.In vivo Gastro-protective effects of five Moroccan medicinal plants against gastric ulcer. American Journal of Phytomedicine and Clinical Therapeutics 2(11), 1262-1276.

Barak S, Mudgil D. 2014. Locust bean gum : Processing, properties and food applications-a review. International Journal of Biological Macromolecules 66, 74-80.

Batlle I, Tous J. 1997.Carob tree. Ceratonia siliqua L. promoting the conservation and use of underutilized and neglected crops. 17. Institute of Plant Genetics and Crop Plant Research, Gatersleben/International Plant Genetic Resources Institute, Rome, Italy.

Benchikh Y, Louaileche H. 2014.Effects of extraction conditions on the recovery of phenolic compounds and in vitro antioxidant activity of carob (Ceratonia siliqua L.) pulp. Acta Botanica Gallica 161(2), 175-181.

Benchikh Y, Louaileche H, George B, Merlin A. 2014. Changes in bioactive phytochemical content and in vitro antioxidant activity of carob (Ceratonia siliqua L.) as influenced by fruit ripening. Industrial Crops and Products 60, 298-303.

Benchikh Y, Paris C, Louaileche H, Charbonnel C, Ghoul M, Chebil L. 2016. Comparative characterization of green and ripe carob (Ceratonia siliqua L.) : Physicochemical attributes and phenolic profile. SDRP-Journal of Food Science and Technology 1(3), 1-7.

Benmahioul B, Kaïd-Harche M, Daguin F. 2011. Le caroubier, une espèce méditerranéenne à usages multiples. Forêt Méditerranéenne 17(1), 51-58.

Bi W, Hu L, Man MQ. 2017. Anti-ulcerogenic efficacy and mechanisms of edible and natural ingredients in NSAID-induced animal models. African Journal of Traditional, Complementary and Alternative Medicines 14(4), 221-238. http://dx.doi.org10.21010/ajtcam.v14i4.25

Boeing T, da Silva LM, Somensi LB, Cury BJ, Michels Costa AP, Petreanu M, Niero R, de Andrade SF. 2016. Antiulcer mechanisms of Vernonia condensata Baker : A medicinal plant used in the treatment of gastritis and gastric ulcer. Journal of Ethno pharmacology 184, 196-207.

Boufadi YM, Elaoufi M, Tabet F, Benali M, Riazi A. 2015. Chemical composition and antioxidant activity of carob pulp (Ceratonia Siliqua L.) extracts. South Asian Journal of Experimental Biology 5(2), 76-83.

Brand-Williams W, Cuvelier ME, Berset C. 1995.Use of a free radical method to evaluate antioxidant activity. Lebensm Wiss Techno l28, 25-30.

Choi YJ, Kim N, Lee JY, Nam RH, Seo JH, Lee S, Kim HJ, Choi YJ, Lee HS, Lee DH. 2016.Gastroprotective effects of PMK-S005 against ethanol-induced acute gastric damage in rats. Gut and Liver 10(3), 348-355.

Corne SJ, Morrissey SM, Woods RJ. 1974. Proceedings : A method for the quantitative estimation of gastric barrier mucus.Journal of Physiology 242(2), 116P-117P.

Custódio L, Escapa AL, Fernandes E, Fajardo A, Aligué R, Alberício F, Neng N, Nogueira JM, Romano A. 2011. Phytochemical profile, antioxidant and cytotoxic activities of the carob tree (Ceratonia siliqua L.) germ flour extracts. Plant Foods for Human Nutrition 66(1), 78-84.

Custódio L, Patarra J, Alberício F, Neng NR, Nogueira JM, Romano A. 2015. In vitro antioxidant and inhibitory activity of water decoctions of carob tree (Ceratonia siliqua L.) on cholinesterases, α-amylase and α-glucosidase. Natural Product Research 29(22), 2155-2159.

Da Silva Lm, Boeing T, Somensi LB, Cury BJ, Steimbach VM, Silveria AC, Niero R, Cechinel Filho V, Santin JR, de Andrade SF. 2015. Evidence of gastric ulcer healing activity of Maytenus robusta Reissek : In vitro and in vivo studies. Journal of Ethnopharmacology 175, 75-85.

See comment in PubMed Commons belowDas SK, Roy C. 2012. The protective role of Aegle marmelos on aspirin-induced gastro-duodenal ulceration in albino rat model : A possible involvement of antioxidants. Saudi Journal of Gastroenterology 18, 188-194.

Dionísio M, Grenha A. 2012. Locust bean gum : Exploring its potential for biopharmaceutical applications.Journal of Pharmacy and Bioallied Sciences 4(3), 175-185.

Drini M. 2017. Peptic ulcer disease and non-steroidal anti‑inflammatory drugs. Australian Prescriber 40, 91-93.

Durazzo A, Turfani V, Narducci V, Azzini E, Maiani G,Carcea M. 2014. Nutritional characterisation and bioactive components of commercial carobs flours. Food Chemistry 153, 109-113.

El Batal H, Hasib A, Dehbi F, Zaki N, Ouatmane A, Boulli A. 2016. Assessment of nutritional composition of carob pulp (Ceratonia Siliqua L.) collected from various locations in Morocco. Journal of Materials and Environmental Science 7(9), 3278-3285.

El Bouzdoudi B, Saïdi R, Embarch K, El Mzibri M, Nejjar El Ansari Z, El Kbiach M, Badoc A, Patrick M, Lamarti A. 2017a. Mineral composition of mature carob (Ceratonia siliqua L.) pod : A study. International Journal of Food Science and Nutrition Engineering 7(4), 91-103.

El Bouzdoudi B, Ammouri N, Joly N, Martin P, Saïdi R, Nejjar El Ansari Z, Bouras M, Badoc A, Lamarti A. 2017b. Total polyphenols and gallic acid contents in domesticated carob (Ceratonia siliqua L.) pods and leaves. International Journal of Pure and Applied Bioscience 5(4), 22-30.

El-Deen EEZ, El-Mahdy NA, El Rashidy MA, Ghorab MM, Gad S, Yassin HA. 2016. Diclofenac-induced gastric ulceration in rats : Protective roles of pantoprazole and misoprostol. British Journal of Pharmaceutical Research 11(3), 1-12.

El Hajaji H, Lachkar N, Alaoui K, Cherrah Y, Farah A, Ennabili A, El Bali B, Lachkar M. 2010. Antioxidant properties and total phenolic content of threevarieties of carob tree leaves from Morocco. Records of Natural Products 4(4), 193-204.

El Hajaji H, Lachkar N, Alaoui K, Cherrah Y, Farah A, Ennabili A, El Bali B, Lachkar M. 2011. Antioxidant activity, phytochemical screening and total phenolic content of extracts from three genders of carob tree barks growing in Morocco. Arabian Journal of Chemistry 4, 321-324.

El Hajaji H, Farah A, Ennabili A, Bousta D, Greche H, El Bali B, Lachkar M. 2013. Etude comparative de la composition minérale des constituants de troiscatégories de Ceratonia siliqua L. (Comparative study of the mineral composition of the constituents of three varieties of Ceratonia siliqua L.). Journal of Materials and Environmental Science 4, 165-170.

Elimam A, Baragob A. 2014.Therapeutic value of camel milk as antiulcerogenic effect against ethanol-induced gastric ulcers in rats. Biochemistry and Biotechnology Research 2(3), 32-36.

El Rabey HA, Al-Seeni MN, Al-Ghamdi HB. 2017. Comparison between the hypolipidemic activity of parsley and carob in hypercholesterolemic male rats. BioMed Research International 2017 (2017).

El-Sayyad HIH, Elkholy WME, Hamed WAE. 2017. Promising role of carob (Ceratonia siliqua L.) phytochemical components against neurotoxicity induced by monosodium glutamate. Global Journal of Zoology 2(1), 024-032.

See comment in PubMed Commons below Farzaei MH, Abdollahi M, Rahimi R. 2015. Role of dietary polyphenols in the management of peptic ulcer. World Journal of Gastroenterology 21(21), 6499-6517.

Goldstein JL, Cryer B. 2015. Gastrointestinal injury associated with NSAID use : A case study and review of risk factors and preventative strategies. Drug, Healthcare and Patient Safety 7, 31-41.

Goulas V, Stylos E, Chatziathanasiadou MV, Mavromoustakos T, Tzakos AG. 2016. Functional components of carob fruit : Linking the chemical and biological space. International Journal of Molecular Sciences 17(11), 1875.

Halim SZ, Zakaria ZA, Omar MH, Mohtarrudin N, Wahab IRA, Abdullah MNH. 2017. Synergistic gastroprotective activity of methanolic extract of a mixture of Melastoma malabathricum and Muntingia calabura leaves in rats.BMC Complementary and Alternative Medicine 17(1), 488.

Hamid I, Janbaz KH. 2017.Ethnopharmacological basis for antispasmodic, antidiarrheal and antiemetic activities of Ceratonia siliqua pods. Bangladesh Journal of Pharmacology 12, 384-92.

Hunt RH, Camilleri M, Crowe SE, El-Omar EM, Fox JG, Kuipers EJ, Malfertheiner P, McColl KE, Pritchard DM, Rugge M, Sonnenberg A, Sugano K, Tack J. 2015. The stomach in health and disease. Gut 64(10), 1650-1668.

Ibrahim FM, Attia HN, Aly Maklad YA, Ahmed KA, Ramadan MF. 2017. Biochemical characterization, anti-inflammatory properties and ulcerogenic traits of some cold-pressed oils in experimental animals. Pharmaceutical Biology 55(1), 740-748.

Jaccob AA. 2016. Effect of pharmacological doses of garlic and omega 3 on gastric lesions induced by ethanol in mice. Asian Journal of Pharmaceutical and Clinical Research 9, 153-157.

Katary MA, Salahuddin A. 2017.Gastroprotective effect of vanillin on indomethacin-induced gastric ulcer in rats : Protective pathways and anti-secretory mechanism. Journal of Clinical and Experimental Pharmacology 7, 232.

Khlifa M, Bahloul A, Kitane S. 2013.Determination of chemical composition of carob pod (ceratoniasiliqua L.) and its morphological study. Journal of Materials and Environmental Science 4(3), 348-353.

Kim JH, Jin S, Kwon HJ, Kim BW. 2016. Curcumin blocks naproxen-induced gastric antral ulcerations through inhibition of lipid peroxidation and activation of enzymatic scavengers in rats. Journal of Microbiology and Biotechnology 26(8), 1392-1397.

Lachkar N, Al-Sobarry M, El Hajaji H, Lamkinsi T, Lachkar M, Cherrah Y, Alaoui K. 2016. Anti-inflammatory and antioxidant effect of Ceratonia siliquaL. methanol barks extract. Journal of Chemical and Pharmaceutical Research 8(3), 202-210.

Lanas A, Chan FKL. 2017. Peptic ulcer disease. The Lancet 390(10094), 613-624.

Lijima K, Shimosegawa T. 2015. Risk factors for upper GI damage in low-dose aspirin users and the interaction between H. pylori infection and low-dose aspirin use. Current Pharmaceutical Design 21(35), 5056-5065.

Loullis A, Pinakoulaki E. 2017. Carob as cocoa substitute : A review on composition, health benefits and food applications. European Food Research and Technology 1-19

Luiz-Ferreira A, Almeida AC, Cola M, Barbastefano V, Almeida AB, Batista LM, Farias-Silva E, Pellizzon CH, Hiruma-Lima CA, Santos LC, Vilegas W, Brito AR. 2010. Mechanisms of the gastric antiulcerogenic activity of Anacardium humile St. Hil on ethanol-induced acute gastric mucosal injury in rats. Molecules 15(10), 7153-7166.

Luiz-Ferreira A, Cola M, Barbastefano V, de-Faria FM, Almeida AB, Farias-Silva E, Calvo TR, Hiruma-Lima CA, Vilegas W, Souza-Brito AR. 2012. Healing, antioxidant and cytoprotective properties of Indigofera truxillensis in different models of gastric ulcer in rats. International Journal of Molecular Sciences 13(11), 14973-14991.

Macho-González A, Garcimartín A, López-Oliva ME, Bertocco G, Naes F, Bastida S, Sánchez-Muniz FJ, Benedí J. 2017. Fiber purified extracts of carob fruit decrease carbohydrate absorption. Food and Function 8(6), 2258-2265.

Mahtout R, Ortiz-Martínez VM, Salar-García MJ, Gracia I, Hernández-Fernández FJ, de los Ríos AP, Zaidia F, Sanchez-Segado S, Lozano-Blanco LJ. 2018. Algerian carob tree products : A comprehensive valorization analysis and future prospects. Sustainability 10, 90.

Martins JL, Rodrigues OR, da Silva DM, Galdin PM, de Paula JR, Romão W, da Costa HB, Vaz BG, Ghedini PC, Costa EA. 2014. Mechanisms involved in the gastroprotective activity of Celtisiguanaea (Jacq.) Sargent on gastric lesions in mice. Journal of Ethnopharmacology155(3), 1616-1624.

Meziani S, Oomah BD, Zaidi F, Simon-Levert A, Bertrand C, Zaidi-Yahiaoui R. 2015. Antibacterial activity of carob (Ceratonia siliqua L.) extracts against phytopathogenic bacteria Pectobacterium atrosepticum. Microbial Pathogenesis 78, 95-102.

Nasar-Abbas SM, e-Huma Z, Vu TH, Khan MK, Esbenshade H, Jayasena V. 2016. Carob Kibble : A bioactive-rich food ingredient. Comprehensive Reviews of Food Science and Food Safety 15, 63-72.

Parvan M, Sajjadi SE, Minaiyan M. 2017. Protective effect of two extracts of Cydoniaoblonga miller (quince) fruits on gastric ulcer induced by indomethacin in rats. International Journal of Preventive Medicine 8, 58.

Paulrayer A, Adithan A, Lee JH, Moon KH, Kim DG, Im SY, Kang CW, Kim NS, Kim JH. 2017. Aronia melanocarpa (Black Chokeberry) reduces ethanol-induced gastric damage via regulation of HSP-70, NF-κB, and MCP-1 signaling. International Journal of Molecular Sciences 18(6), pii : E1195.

Petkova N, Petrova I, Ivanov I, Mihov R, Hadjikinova R, Ognyanov M, Nikolova V. 2017. Nutritional and antioxidant potential of carob (Ceratonia siliqua) flour and evaluation of functional properties of its polysaccharide fraction. Journal of Pharmaceutical Sciences and Research 9(10), 2189-2195.

Pradeepkumar B, Bhavyamadhuri CP, Padmanabhareddy Y, Veerabhadrappa KV, Narayana G, Haranath C, Somasekharreddy K, Sudheer A. 2017. Evaluation of antiulcer activity of Peltophorum pterocarpum. Journal of Clinical and Diagnosis Research 11(6), FF01-FF03.

Różyło R, Dziki D, Gawlik-Dziki U, Biernacka B, Wójcik M, Ziemichód A. 2017. Physical and antioxidant properties of gluten-free bread enriched with carob fibre. International Agrophysics31, 411-418.

Rtibi K, Jabri MA, Selmi S, Souli A, Sebai H, El-Benna J, Amri M, Marzouki L. 2015. Gastroprotective effect of carob (Ceratoniasiliqua L.) against ethanol-induced oxidative stress in rat. BMC Complementary and Alternative Medicine 15, 292.

Rtibi K, Jabri MA, Selmi S, Sebai H, Amri M, El-Benna J, Marzouki L. 2016a. Ceratonia siliqua leaves exert a strong ROS-scavenging effect in human neutrophils, inhibit myeloperoxydase in vitro and protect against intestinal fluid and electrolytes secretion in rats.  RSC Advances 6, 65483-65493.

Rtibi K, Selmi S, Jabri MA, El-Benna J, Amri M, Marzouki L, Sebai H. 2016b. Protective effect of Ceratonia siliqua L. against a dextran sulfate sodium-induced alterations in liver and kidney in rat. Journal of Medicinal Food 19(9), 882-889.

RtibiK, Selmi S,Jabri MA, Mamadou G,Limas-Nzouzi NSebai H, El-Benna J,Marzouki L,Eto B,  Amri M. 2016c.  Effects of aqueous extracts from Ceratonia siliqua L. pods on small intestinal motility in rats and jejunal permeability in mice. RSC Advances 6, 44345-44353.

Rtibi K,  Jabri MA,  Selmi S,  Sebai H, Marie JC,  Amri M, MarzoukiL, El-Benna J. 2016d. Preventive effect of carob (Ceratonia siliqua L.) in dextran sulfate sodium-induced ulcerative colitis in rat. RSC Advances 6, 19992-20000.

Rtibi K, Selmi S, Grami D, Amri M, Eto B, El-Benna J, Sebai H, Marzouki L. 2017a. Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract : A review. Biomedicine and Pharmacotherapy 93, 522-528.

Rtibi K, Selmi S, Grami D, Saidani K, Sebai H, Amri M, Eto B, Marzouki L. 2017b. Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat. Journal of the Science of Food and Agriculture 97(8), 2664-2670.

Sebai H, Souli A, Chehimi L, Rtibi K, AmriM, El-Benna J, SaklyM. 2013. In vitro and in vivo antioxidant properties of Tunisian carob (Ceratonia siliqua L.).Journal of Medicinal Plants Research 7(2), 85-90.

Sebai H, Jabri MA, Souli A, Hosni K, Selmi S, Tounsi H, Tebourbi O, Boubaker S, El-Benna J, Sakly M. 2014. Protective effect of Artemisia campestris extract against aspirin-induced gastric lesions and oxidative stress in rat. RSC Advances 4, 49831-49841.

Shahrokhi N, Keshavarzi Z, Khaksari M. 2015. Ulcer healing activity of Mumijo aqueous extract against acetic acid induced gastric ulcer in rats. Journal of Pharmacy and Bioallied Sciences 7(1), 56-59.

Shim YK, Kim N. 2017.Nonsteroidal anti-inflammatory drug and aspirin-induced peptic ulcer disease.Korean Journal of Gastroenterology 67(6), 300-312.

Silva DM, Martins JL, Florentino IF, Oliveira DR, Fajemiroye JO, Tresnvenzol LM, Paula JR, Costa EA. 2016. The gastroprotective effect of Memoranodosa roots against experimental gastric ulcer in mice. Anais da Academia Brasileira de Ciências 88(3), 1819-1828.

Sinha M, Gautam L, Shukla PK, Kaur P, Sharma S, Singh TP. 2013. Current perspectives in NSAID-induced gastropathy. Mediators of Inflammation 2013, 258209.

Singh P, Dutta SR, Guha D. 2015. Gastric mucosal protection by Aeglemarmelos against gastric mucosal damage : Role of enterochromaffin cell and serotonin. Saudi Journal of Gastroenterology 21(1), 35-42.

Souli A, Sebai H, Chehimi L, Rtibi K, Tounsi H, Boubaker S, Sakly M, El-Benna J, Amri M. 2015. Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat. Toxicology and Industrial Health 31(9), 802-810.

Sostres C, Gargallo CJ, Lanas A. 2014. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use : Old question new insights. World Journal of Gastroenterology 20(28), 9439-9450

Suzek H, Celik I, Dogan A. 2017. Nephroprotective hepatoprotective potential and antioxidant role of carob pods (Cerotonia siliqua L.) against carbon tetrachloride-induced toxicity in rats. Indian Journal of Pharmaceutical Education and Research 51(2), 312-320.

Suzuki H, Nishizawa T, Tsugawa H, SMogami S, Hibi T. 2012.Roles of oxidative stress in stomach disorders.Journal of Clinical Biochemistry and Nutrition 50(1), 35-39.

Tarique M, Siddiqui HH, Khushtar M, Rahman MA. 2016. Protective effect of hydro-alcoholic extract of Rutagraveolens Linn. Leaves on indomethacin and pylorus ligation-induced gastric ulcer in rats.Journal of Ayurveda and Integrative Medicine 7(1), 38-43.

Tsatsaragkou K, Gounaropoulos G, Mandala I. 2014. Development of gluten free bread containing carob flour and resistant starch. LWT-Food Science and Technology 58, 124-129.

Theophilou IC, Neophytou CM, Kakas A, Constantinou AI. 2017. Carob and its components in the management of gastrointestinal disorders. Journal of Hepatology and Gastroenterology 1, 005.

Untersmayr E. 2015. Acid suppression therapy and allergic reactions.Allergo Journal International 24(8), 303-311.

Wang XY, Yin JY, Zhao MM, Liu SY, Nie SP, Xie MY. 2018. Gastroprotective activity of polysaccharide from Hericiumerinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities. Carbohydrate Polymers 186, 100-109.

Ydjedd S, Chaalal M, Richard G, Kati DE, López-Nicolás R, Fauconnier ML, Louaileche H. 2017a. Assessment of antioxidant potential of phenolic compounds fractions of Algerian Ceratonia siliqua L. pods during ripening stages. International Food Research Journal 24(5), 2041-2049.

Ydjedd S, Bouriche S, López-Nicolás R, Sánchez-Moya T, Frontela-Saseta C, Ros-Berruezo G, Rezgui F, Louaileche H, Kati DE.2017b. Effect of in vitro gastrointestinal digestion on encapsulated and nonencapsulated phenolic compounds of carob (Ceratonia siliqua L.) pulp extracts and their antioxidant capacity. Journal of Agricultural and Food Chemistry 65(4), 827-835.

Yuniarto A, Susilawati E, Khairunnisa I, Juanda D, Setiawan F. 2017.Antioxidant and gastric ulcer healing effect of Orthosiphon stamineus (benth.) leaves extract in aspirin-induced rats. Asian Journal of Pharmaceutical and Clinical Research 10, 397-399.

Zakaria ZA, Balan T, Suppaiah V, Ahmad S, Jamaludin F. 2014. Mechanism(s) of action involved in the gastroprotective activity of Muntingia calabura. Journal of Ethnopharmacology 151(3), 1184-1193.

Zakaria ZA, Balan T, Azemi AK, Omar MH, Mohtarrudin N, Ahmad Z, Abdullah MN, Desa MN, Teh LK, Salleh MZ. 2016. Mechanism(s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura. BMC Complementary and Alternative Medicine 16, 78.

Zanatta F, Gandolfi RB, Lemos M, Ticona JC, Gimenez A, Clasen BK, CechinelFilho V, de Andrade SF. 2009. Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae). Chemico-Biological Interactions 180(2), 312-317.