Gastroprotective effect of Berberis vulgaris on ethanol-induced gastric mucosal injury: Histopathological evaluations

Document Type : Original Research Article


1 Faculty of Medicine and Health Sciences, UNIMAS, Kota Samarahan, Sarawak, Malaysia

2 Faculty of Medicine MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia

3 Medicinal Products Safety, Scientific Centre for Expert Evaluation of Medicinal Products, Moscow, Russia. Department of Pharmacology, Sechenov University, Moscow, Russia

4 Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia

5 Institute of Medical Molecular Biotechnology, and Faculty of Medicine, UiTM, Sungai Buloh, Selangor, Malaysia

6 Department of Pharmacognosy, Sechenov University, Moscow, Russia


Objective: Modern treatment of peptic ulcers includes antibacterial and gastroprotective medications. However, current anti-ulcer drugs possess severe side effects. Therefore, all attempts to find new effective medications free from side effects are justified. Though Berberis vulgaris is a medicinal plant commonly used for the treatment of numerous disorders, gastroprotective effect of its leaf extract was not investigated before.
Materials and Methods: Gastric ulcer was modelled in Sprague-Dawley rats after treatment with B. vulgaris leaf extract containing 0.07% of alkaloids, 0.48% of flavonoids and 8.05% of tanning substances, 10 or 50 mg of dry extract/kg, changes in the stomach mucosa were assessed semi-quantitatively, and the gastric wall was evaluated for prostaglandin E2 level using ELISA and assessed histologically by calculation of the lesion index.
Results: B. vulgaris leaf extract at the dose of 50 mg/kg reduced the macroscopic ulcer score and the microscopic lesion index, increased prostaglandin E2 concentration in the gastric wall significantly higher than atropine and B. vulgaris leaf extract 10 mg/kg.
Conclusion: The gastroprotective effect of the high dose of B. vulgaris leaf extract may be due to stimulation of prostaglandin E2 secretion in the stomach, and anti-oxidative and anti-inflammatory properties of polyphenolic complex of flavonoids and tannins present in the leaves of this plant.


Abushouk AI, Salem AMA, Abdel-Daim MM.
2017. Berberis vulgaris for cardiovascular
disorders: a scoping literature review. Iran
J Basic Med Sci, 20: 503-510.
Ahmad M, Aslam B, Muhammad F, Mohsin
M, Raza A. 2019. Gastroprotective and
antioxidant potential of Euphorbia
prostrata against aspirin induced gastric
ulcers in rabbits. Pak J Pharm Sci, 32: 7-
Ajmera AV, Shastri GS, Gajera MJ, Judge TA.
2012. Suboptimal response to ferrous
sulfate in iron-deficient patients taking
omeprazole. Am J Ther, 19: 185-189.
Al-Quraishy S, Othman MS, Dkhil MA, Abdel
Moneim AE. 2017. Olive (Olea europaea)
leaf methanolic extract prevents
HCl/ethanol-induced gastritis in rats by
attenuating inflammation and augmenting
Gastroprotective effect of Berberis vulgaris
AJP, Vol. 12, No. 1, Jan-Feb 2022 39
antioxidant enzyme activities. Biomed
Pharmacother, 91: 338-349.
Alamzeb M, Omer M, Ur-Rashid M, Raza M,
Ali S, Khan B, Ullah A. 2018. NMR,
novel pharmacological and in silico
docking studies of oxyacanthine and
tetrandrine: Bisbenzylisoquinoline
alkaloids isolated from Berberis
glaucocarpa roots. J Anal Methods Chem,
2018: 7692913.
Al-Sayed E, Michel HE, Khattab MA, ElShazly M, Singab AN. 2020. Protective
role of casuarinin from melaleuca
leucadendra against ethanol-induced
gastric ulcer in rats. Planta Med, 86: 32-
Alvarez-Suarez JM, Dekanski D, Ristić S,
Radonjić NV, Petronijević ND, Giampieri
F, Astolfi P, González-Paramás AM,
Santos-Buelga C, Tulipani S, Quiles JL,
Mezzetti B, Battino M. 2011. Strawberry
polyphenols attenuate ethanol-induced
gastric lesions in rats by activation of
antioxidant enzymes and attenuation of
MDA increase. PLoS One, 6: e25878.
Arab HH, Salama SA, Omar HA, Arafa ESA,
Maghrabi IA. 2015. Diosmin protects
against ethanol-induced gastric injury in
rats: Novel anti-ulcer actions. PLoS One,
10: e0122417.
Asadi NS, Heidari MM, Khatami M. 2019.
Protective effect of Berberis vulgaris on
Fenton reaction-induced DNA cleavage.
Avicenna J Phytomed, 9: 213-220.
Berenguer B, Sánchez LM, Quílez A, LópezBarreiro M, de Haro O, Gálvez J, Martín
MJ. 2006. Protective and antioxidant
effects of Rhizophora mangle L. against
NSAID-induced gastric ulcers. J
Ethnopharmacol, 103: 194-200.
Berłowski A, Zawada K, Wawer I,
Paradowska K. 2013. Antioxidant
properties of medicinal plants from Peru.
Food Sci Nutr, 4: 71-77.
Bhatia S, Sharma K, Sharma A, Nagpal K,
Bera T. 2015. Anti-inflammatory,
analgesic and antiulcer properties of
Porphyra vietnamensis. Avicenna J
Phytomed, 5: 69-77.
Boushra AF, Elsayed AM, Ibrahim NA,
Abdelwahed MK, Ahmed EI. 2019. A
comparative study on the possible
protective effect of esomeprazole,
spirulina, wheatgrass on indomethacininduced gastric ulcer in male albino rats.
Mol Biol Rep, 46: 4843-4860.
Cooksey R, Kennedy J, Dennis MS, EscottPrice V, Lyons RA, Seaborne M, Brophy
S. 2020. Proton pump inhibitors and
dementia risk: Evidence from a cohort
study using linked routinely collected
national health data in Wales, UK. PLoS
One, 15: e0237676.
Cryer B. 2001. Mucosal defence and repair.
Role of prostaglandins in the stomach and
duodenum. Gastroenterol Clin North Am,
30: 877-894.
Dashputre N, Naikwade N. 2011. Evaluation
of anti-ulcer activity of methanolic extract
of Abutilon indicum Linn leaves in
experimental rats. Int J Pharm Sci Drug
Res, 3: 97-100.
El-Wahab AEA, Ghareeb DA, Sarhan EEM,
Abu-Serie MM, El-Demellawy MA. 2013.
In vitro biological assessment of Berberis
Vulgaris and its active constituent,
berberine: antioxidants, antiacetylcholinesterase, anti-diabetic and
anticancer effects. BMC Complement
Altern Med, 13: 218.
Eusebi LH, Rabitti S, Artesiani ML, Gelli D,
Montagnani M, Zagari RM, Bazzoli F.
2017. Proton pump inhibitors: Risks of
long-term use. J Gastroenterol Hepatol,
32: 1295-1302.
Farzaei MH, Abdollahi M, Rahimi R. 2015.
Role of dietary polyphenols in the
management of peptic ulcer. World J
Gastroenterol, 21: 6400-517.
Farzaei MH, Shams-Ardekani MR,
Abbasabadi Z, Rahimi R. 2013. Scientific
evaluation of edible fruits and spices used
for the treatment of peptic ulcer in
traditional Iranian medicine. ISRN
Gastroenterol, 2013: 136932.
FDA News Release. FDA requests removal of
all ranitidine products (Zantac) from the
market. 2020. available at:
Freedberg DE, Kim LS, Yang YX. 2017. The
risks and benefits of long-term use of
proton pump inhibitors: Expert review and
best practice advice from the American
gastroenterological association.
Gastroenterology, 152: 706-715
Gupta M, Dey S, Marbaniang D, Pal P, Ray S,
Mazumder B. 2020. Grape seed extract:
having a potential health benefits. J Food
Kapitonova et al.
AJP, Vol. 12, No. 1, Jan-Feb 2022 40
Sci Technol, 57: 1205-1215.
Imenshahidi M, Hosseinzade H. 2016.
Berberis vulgaris and berberine: An update
review. Phytother Res, 30: 1745-1764.
Imenshahidi M, Hosseinzadeh H. 2019.
Berberine and barberry (Berberis
vulgaris): A clinical review. Phytother
Res, 33: 504-523.
Hálfdánarson ÓÖ, Pottegård A, Björnsson ES,
Lund SH, Ogmundsdottir MH,
Steingrímsson E, Ogmundsdottir HM,
Zoega H. 2018. Proton-pump inhibitors
among adults: a nationwide drugutilization study. Therap Adv
Gastroenterol, 11: 1756284818777943.
Jabri MA, Rtibi K, Tounsi H, Hosni K,
Marzouki L, Sakly M, Sebai H. 2017.
Fatty acid composition and mechanisms of
the protective effects of myrtle berry seed
aqueous extract in alcohol-induced peptic
ulcer in rat. Can J Physiol Pharmacol, 95:
Kalmarzi RN, Naleini SN, Ashtary-Larky D,
Peluso I, Jouybari L, Rafi A, Ghorat F,
Heidari N, Sharifian F, Mardaneh J, Aiello
P, Helbi S, Kooti W. 2019. Antiinflammatory and immunomodulatory
effects of barberry (Berberis vulgaris) and
its main compounds. Oxid Med Cell
Longev, 19: 6183965.
Karampour NS, Arzi A, Rezaie A,
Pashmforoosh M, Kordi F. 2019.
Gastroprotective effect of Zingerone on
ethanol-induced gastric ulcers in rats.
Medicina (Kaunas, Lithuania), 55: 64.
Kavitt RT, Lipowska AM, Anyane-Yeboa A,
Gralnek IM. 2019. Diagnosis and
treatment of peptic ulcer disease. Am J
Med, 132: 447-456.
Komar OM, Kizlova NM, Trylevych OD,
Kravchenko VV. 2018. Risk factors for
adverse course of gastric and duodenal
peptic ulcer. Wiad Lek, 71: 160-164.
Kupeli E, Kosar M, Yesilada E, Husnu K,
Baser C. 2002. A comparative study on the
anti-inflammatory, antinociceptive and
antipyretic effects of isoquinoline
alkaloids from the roots of turkish berberis
species. Life Sci, 72: 645-657.
Lazarus B, Chen Y, Wilson FP, Sang Y,
Chang AR, Coresh J, Grams ME. 2016.
Proton pump inhibitor use and the risk of
chronic kidney disease. JAMA Intern
Med, 176: 238-46.
Lv H, Lin Y, Liu P, Liang W, Wei K, Pu J,
Zhang H. 2019. Protective effects and
potential underlying mechanisms of
sodium copper chlorophyllin against
ethanol-induced gastric ulcer in mice. Acta
Biochim Biophys Sin (Shanghai), 51: 925-
Majeed W, Aslam B, Javed I, Khaliq T,
Muhammad T, Ali A, Raza A. 2015.
Histopathological evaluation of
gastroprotective effect of Berberis vulgaris
(Zereshk) seeds against aspirin induced
ulcer in albino mice. Pak J Pharm Sci, 28:
Miller JW. 2018. Proton pump inhibitors, H2-
receptor antagonists, metformin, and
vitamin B-12 deficiency: Clinical
implications. Adv Nutr, 9: 511S-518S.
Minaiyan M, Sajjadi SE, Amini K. 2018.
Antiulcer effects of Zataria multiflora
Boiss. on indomethacin-induced gastric
ulcer in rats. Avicenna J Phytomed, 8:
Mirhadi E, Rezaee M, Malaekeh-Nikouei B.
2018. Nano strategies for berberine
delivery, a natural alkaloid of berberis.
Biomed Pharmacother, 104: 465-473.
Mokhber-Dezfuli N, Soodabeh Saeidnia S,
Gohari AR, Mahdieh KurepazMahmoodabadi M. 2014. Phytochemistry
and pharmacology of berberis species.
Pharmacogn Rev, 8: 8-15.
More D, Boutagy J, Shenfield G. 1983. pH
testing paper for measurement of
intragastric acidity: an assessment.
Anaesth Intens Care, 11: 147-150.
Narayanan M, Reddy KM, Marsicano E. 2018.
Peptic ulcer disease and Helicobacter
pylori infection. Mo Med, 115: 219-224.
Nassar Y, Richter S. 2018. Proton-pump
inhibitor use and fracture risk: An updated
systematic review and meta-analysis. J
Bone Metab, 25: 141-151.
Nur Azlina MF, Kamisah Y, Chua KH,
Qodriyah HM. 2013. Tocotrienol
attenuates stress-induced gastric lesions
via activation of prostaglandin and
upregulation of COX-1 mRNA. Evid
Based Complement Alternat Med, 804796:
Ortiz-Guerrero G, Amador-Muñoz D,
Calderón-Ospina CA, López-Fuentes D,
Nava Mesa MO. 2018. Proton pump
inhibitors and dementia:
physiopathological mechanisms and
clinical consequences. Neural Plast, 2018:
Gastroprotective effect of Berberis vulgaris
AJP, Vol. 12, No. 1, Jan-Feb 2022 41
Pan L, Tan Q, Fu Q, Hu B, Xiang J, Qian J.
2005. Roles of nitric oxide in protective
effect of berberine in ethanol-induced
gastric ulcer mice. Acta Pharmacol Sin,
26: 1334-1338.
Quach DT, Vilaichone RK, Vu KV, Yamaoka
Y, Sugano K, Mahachai K. 2018.
Helicobacter pylori infection and related
gastrointestinal diseases in Southeast
Asian countries: An expert opinion survey.
Asian Pac J Cancer Prev, 19: 3565-3569.
Rad SZK, Rameshrad M, Hosseinzadeh H.
2017. Toxicology effects of Berberis
vulgaris (barberry) and its active
constituent, berberine: a review. Iran J
Basic Med Sci, 20: 516-529.
Raeesi M, Eskandari-Roozbahani N, Shomali
T. 2019. Gastro-protective effect of
Biebersteinia multifida root hydromethanolic extract in rats with ethanolinduced peptic ulcer. Avicenna J
Phytomed, 9: 410-418.
Rahimi-Madiseh M, Lorigoini Z, ZamaniGharaghoshi H, Rafieian-Kopaei M. 2017.
Berberis vulgaris: specifications and
traditional uses. Iran J Basic Med Sci, 20:
Roberts-Thomson I. 2018. Rise and fall of
peptic ulceration: A disease of
civilization? J Gastroenterol Hepatol, 33:
Sumbul S, Ahmad MA, Mohd A, Mohd A.
2011. Role of phenolic compounds in
peptic ulcer: An overview. J Pharm
Bioallied Sci, 3: 361-377.
Suzuki S, Esaki M, Kusano C, Ikehara H,
Gotoda T. 2019. Development of
Helicobacter pylori treatment: How do we
manage antimicrobial resistance? World J
Gastroenterol, 25: 1907-1912.
Tabeshpour J, Imenshahidi M, Hosseinzadeh
H. 2017. A review of the effects of
Berberis vulgaris and its major
component, berberine, in metabolic
syndrome. Iran J Basic Med Sci, 20: 557-
Tang HL, Li Y, Hu YF, Xie HG, Zhai SD.
2013. Effects of CYP2C19 loss-offunction variants on the eradication of H.
pylori infection in patients treated with
proton pump inhibitor-based triple therapy
regimens: a meta-analysis of randomized
clinical trials. PloS One, 8: e62162.
Tarasconi A, Coccolini F, Biffl WL, Tomasoni
M, Ansaloni L, Picetti E, Catena F. 2020.
Perforated and bleeding peptic ulcer:
WSES guidelines. World J Emerg Surg,
15: 1-24.
Tytgat GNJ. 2011. Etiopathogenetic principles
and peptic ulcer disease classification. Dig
Dis, 29: 454-458.
Toma W, Hiruma-Lima CA, Guerrero RO,
Souza Brito ARM. 2005. Preliminary
studies of Mammea americana L.
(Guttiferae) bark/latex extract point to an
effective anti-ulcer effect on gastric ulcer
models in mice. Phytomedicine, 12: 345-
Ueberschaer H, Allescher HD. 2017. Proton
pump inhibitor - side effects and
complications of long-term proton pump
inhibitor administration. Z Gastroenterol,
55: 63-74.
Yegen BC. 2018. Lifestyle and peptic ulcer
disease. Curr Pharm Des, 24: 2034-2040.
Yesilada E, Kupeli E. 2002. Berberis
crataegina DC. root exhibits potent antiinflammatory, analgesic and febrifuge
effects in mice and rats. J Ethnopharmacol,
79: 237-248.
Zaidi SF, Muhammad JS, Shahryar S,
Usmanghani K, Gilani A-H, Jafri W,
Sugiyama T. 2012. Anti-inflammatory and
cytoprotective effects of selected Pakistani
medicinal plants in Helicobacter pyloriinfected gastric epithelial cells. J
Ethnopharmacol, 141: 403-410.
Zarei A, Changizi-Ashtiyani S, Taheri S,
Ramezani M. 2015. A quick overview on
some aspects of endocrinological and
therapeutic effects of Berberis vulg