|Year : 2021 | Volume
| Issue : 1 | Page : 66-70
Synergistic effect of cumin (Cuminum cyminum L.) decoction alongside with three-drug and four-drug treatment protocols on Helicobacter pylori eradication
Touraj Ahmadi-Jouybari1, Abbas Aghaei2, Mary Ataee1, Jafar Navabi1, Bita Anvari1, Hadi Ahmadi Jouybari3, Mohammad Bagher Majnooni4
1 Clinical Research Development Center, Imam Khomeini Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
3 Infectious Disease and Tropical Medicine Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4 Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
|Date of Submission||31-Mar-2020|
|Date of Acceptance||08-Sep-2020|
|Date of Web Publication||31-May-2021|
Dr. Mohammad Bagher Majnooni
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah.
Source of Support: None, Conflict of Interest: None
Background: Helicobacter pylori is a major cause of peptic ulcer. On the other hand, cumin (Cuminum cyminum L.) is an effective medicinal plant for the treatment of gastrointestinal disease in traditional Persian medicine. This study aimed at investigating the synergistic effect of the decoction of cumin with the three- and four-drug protocols against H. pylori in patients with peptic ulcer. Patients with peptic ulcer infected with H. pylori were treated with cumin decoction, three- and four-drug protocols, and their co-administration to eradicate H. pylori. Materials and Methods: Patients were randomly divided into five groups, including group (1) omeprazole with cumin decoction, (2) cumin decoction with the three-protocol treatment, (3) cumin decoction with the four-drug protocol treatment, and (4 and 5) three- and four-drug protocols alone. The cumin fruit powder was given to patients in 3-g packages and decoction was prepared according to the traditional Iranian medicine guidelines. H. pylori eradication was measured by the 14C–urea breath test (14C-UBT) after 4 weeks of intervention. The Kolmogorov–Smirnov test, χ2 test, logistic regression, and ANOVA (SPSS, 11.5) were used for data analyses. Results: In total, 75 patients (48 male and 27 female patients) participated in this study. The results showed that eradication of H. pylori was observed in all five study groups. Eradication of H. pylori in cumin decoction with the three-drug protocol group was more than the other groups (85.72%), although this difference was not statistically significant. In addition, this eradication was 61.5% in the cumin + omeprazole group, while the H. pylori eradication rates for the three-drug and four-drug protocols were 77.8% and 58.33%, respectively. Conclusions: The results showed that decoction of cumin could be used as a complementary treatment alongside conventional medicine therapy to increase the H. pylori eradication.
Keywords: Cuminum cyminum L, four-drug treatment protocol, Helicobacter pylori eradication, peptic ulcer, three-drug treatment protocol
|How to cite this article:|
Ahmadi-Jouybari T, Aghaei A, Ataee M, Navabi J, Anvari B, Jouybari HA, Majnooni MB. Synergistic effect of cumin (Cuminum cyminum L.) decoction alongside with three-drug and four-drug treatment protocols on Helicobacter pylori eradication. J Rep Pharma Sci 2021;10:66-70
|How to cite this URL:|
Ahmadi-Jouybari T, Aghaei A, Ataee M, Navabi J, Anvari B, Jouybari HA, Majnooni MB. Synergistic effect of cumin (Cuminum cyminum L.) decoction alongside with three-drug and four-drug treatment protocols on Helicobacter pylori eradication. J Rep Pharma Sci [serial online] 2021 [cited 2021 Jun 15];10:66-70. Available from: https://www.jrpsjournal.com/text.asp?2021/10/1/66/317247
| Introduction|| |
Helicobacter pylori, as a human pathogen, are a Gram-negative bacillus that exists in the gastrointestinal tract of humans. The prevalence of H. pylori is between 30 and 50% in industrialized countries and more than 80% in developing countries., According to statistical studies, H. pylori infection is greater than 74% in some provinces of Iran. This bacterium not only causes 70 to 90% of gastrointestinal ulcers, especially peptic ulcers, but also causes adenocarcinoma, chronic gastritis, and iron deficiency anemia.,,H. pylori cause gastric ulcers through various mechanisms, including the stimulation of the inflammatory response of gastric epithelial cells to the secretion of some H. pylori biomolecules and cytotoxins., According to approved guidelines, the three-drug treatment protocol including one pump inhibitor (e.g., omeprazole) and two antibiotics (clarithromycin and amoxicillin), and the four-drug treatment protocol including a pump inhibitor (e.g., omeprazole) with bismuth subcitrate and two antibiotics (metronidazole and tetracycline) are the conventional treatments for H. pylori eradication.,, In the past, these treatments led to more than 90% eradication of H. pylori, but today the bacteria show resistance to the antibiotics in these protocols and sometimes lead to treatment failure.,, On the other hand, medicinal plants and their constitutions can treat several targets simultaneously, so they have always been one of the options for discovering new drugs for complex diseases, especially infectious diseases. Several medicinal herbs including Acacia nilotica, Calotropis procera, Trachyspermum copticum, Glycyrrhiza glabra, Curcuma longa, Zingiber officinale, Petroselinum crispum, and Pimpinella anisum were showed anti-H. pylori activities in different studies.,,,, Besides, in Iranian traditional medicine, the fruit of cumin (Cuminum cyminum L.), as an annual herbaceous medicinal plant from the Apiaceae family, is used to treat the gastrointestinal diseases such as dyspepsia, bloating, and intestinal spasms. Also, the fruit of cumin showed prominent anti-H. pylori effects in several studies.,In vitro study showed anti-H. pylori effects of cumin at minimum inhibitory concentration of 691 μg/mL. Nostro et al. showed that ethanolic extract of the cumin fruit eradicated 90% of the H. pylori at 0.075 mg/mL. O’Mahony et al. showed that 50 mg/mL of the cumin decoction eradicated 100% H. pylori in culture medium. Cumin has also been proven to have wound regenerative effects. On the other hand, several clinical trial investigations reported the anti-H. pylori activity of some medicinal plants such as Cinnamomum zelanicum and Nigella sativa., In a similar study, the use of Pistacia atlantica alongside the three-drug treatment protocol was the subject of clinical studies in the treatment of peptic ulcers. Their results showed a significant reduction of H. pylori infection (P < 0.01) compared to the control group (three-drug treatment protocol alone) in a 14-day treatment. Based on the above-mentioned need for eradicating H. pylori, the present study was designed to investigate the synergistic effect of cumin decoction with three- and four-drug treatment protocols against H. pylori in patients with peptic ulcer.
| Subjects and Methods|| |
Patients and design
In this study, patients with peptic ulcer in whom the presence of H. pylori was confirmed by biopsy tests were participated. They were randomly divided into one of the five study groups. Inclusion criteria were not being pregnant and not having the following cases: kidney, liver and lung failure, any cancer, gastrointestinal surgery, glucose-6-phosphate dehydrogenase enzyme deficiency and not to use NSAIDs and any antibiotics until the implementation of measures related to the project and not have any allergies to studied medications.
Each group is investigated based on age, sex, smoking, duration of illness, number of visits, and weight., The project is recorded before starting in the Ethics Committee of Kermanshah University of Medical Sciences by the number of c/7/420/4148 and the system for recording clinical trials by (I RCT) IRCT2012071510291N1 number. The five studied groups included were (1) 20 mg omeprazole before breakfast and one cup of cumin decoction (100 mL) after breakfast and dinner; (2) 20 mg omeprazole before breakfast, one cup of cumin decoction (100 mL) after breakfast and dinner, 500 mg clarithromycin every 12 h, and amoxicillin 500 mg every 6 h; (3) omeprazole 20 mg before breakfast, one cup of cumin decoction (100 mL) after breakfast and dinner, bismuth subcitrate 120 mg every 6 h, amoxicillin 500 mg every 6 h, and metronidazole 500 mg every 12 h. The fourth and fifth groups included the three-drug protocol (omeprazole 20 mg, clarithromycin 1000 mg, and amoxicillin 2000 mg) and four-drug treatment protocol (omeprazole 20 mg, bismuth subcitrate 480 mg, amoxicillin 2000 mg, and metronidazole 1000 mg). All patients were treated for 14 days.
Preparation of studied medicines
Cumin has been provided from a trusted store of medicinal plants and the plant identity was confirmed by the herbarium of Pharmacognosy Department, School of Pharmacy, Kermanshah University of Medical Sciences, Iran. The cumin fruit powder was given to patients in 3-g packages. The subjects, based on the traditional Iranian medicine guidelines, boiled every cumin powder package in two glasses of water (500 mL) for 5 min. It should be noted that patients prepared the other prescribed medicines from drug stores and approved by the physician.
Measurement of H. pylori eradication rate
The amount of H. pylori eradication was measured by 14C–urea breath test (14C-UBT) for each patient after 4 weeks of interventions. Subjects take orally a capsule containing 37 kBq (1 µCi) 14C–urea with 20 mL of drinking water. After 10 min, patients were asked to exhale in the indicator card for 5–10s, the card was connected to UBT device and the results were recorded. This test was performed before treatment and 4 weeks after completion of the treatment, and eradication rates were calculated in percentage.,
The SPSS 11.5 software (IBM Corp., Armonk, NY, USA) was used for data analysis. Kolmogorov–Smirnov test, χ2 test, logistic regression, and ANOVA were utilized for comparative data.
| Results|| |
In this study, 75 patients, including 48 male and 27 female patients, with peptic ulcer and with H. pylori infection diagnosed by urease test after endoscopy at the baseline participated. All subjects were divided into five groups. The mean age and body weight of subjects were 43.97 ± 15.72 years and 69.73 ± 12.18kg, respectively. Furthermore, the average number of visits was 1.7 times and the average length of disease was 262 days. The number of smokers was 21 subjects who all were male patients. Quantitative variables has been separately listed for study groups in [Table 1]. Kolmogorov–Smirnov test was used to confirm the normal distribution of the variables.
|Table 1: General characteristics of the groups in the study of the synergistic effect of cumin decoction (C. cyminum L.) alongside three-drug and four-drug treatment protocols on H. pylori eradication|
Click here to view
According to χ2 test for qualitative variables and variance analysis for quantitative variables related to background variables (age, sex, smoking, duration of illness, number of visits, and weight), there was no significant difference between the study groups (P > 0.05). Chi-square test was used to compare the consequence between groups, i.e., elimination of H. pylori. The results of this test showed that there was no significant difference between the groups in terms of elimination of H. pylori (P > 0.05). The results showed that the co-administration of omeprazole and cumin decoction eradicated 61.5% of H. pylori. However, the eradication rates for the three-drug and four-drug protocols were 77.8% and 58.33%, respectively [Table 2]. On the other hand, the cumin plus three-drug protocol (85.3%) and three-drug protocol without cumin (77.8%) had the highest rate of eradication of H. pylori.
|Table 2: Comparison of the results of different H. pylori eradication groups based on χ2 test|
Click here to view
| Discussion|| |
Today, drug resistance to antibiotics by microorganisms has become a global problem. Drug resistance of some bacteria such as H. pylori is also growing rapidly. Accordingly, finding new treatment strategies to eradicate H. pylori has been always an important issue for researchers. One of these new approaches is the use of herbs as a complementary treatment for their synergistic effects with other antibiotics. This makes not only the eradication of H. pylori consumption alongside other antibiotics but also reduces drug resistance and side effects of these drugs., In this study, the efficacy of cumin on H. pylori eradication has been investigated (as it was seen in vitro studies) for patients with peptic ulcers infected by these bacteria. On the basis of our results, high efficacy of adding cumin to four- and three-drug treatment protocols can be explained by the synergistic effect of cumin on the eradication of H. pylori. Besides, the anti-H. pylori activities of aqueous cumin fruit extract may be attributed to the presence of alkaloids, flavonoids, sesquiterpene glycosides, saponins, and essential oil that these phytochemicals showed antimicrobial activity in several studies.,,, However, the healing role of cumin wounds should not be overlooked. Al Kofahi and Atta reported that the ethanolic extract of cumin fruit has gastroprotective effects against the ethanol-induced peptic ulcer in rats at 400 mg/kg. On the other hand, the similar results were reported for H. pylori eradication with medicinal plants. Imani et al. showed that adding cinnamon extract (40 mg) to three-drug protocol (clarithromycin 500 mg, amoxicillin 1000 mg, and pantoprazole 20 mg) after 14 days increased H. pylori elimination to 73.47% in patients. However, eradication was 53.06% in patients taking the three-drug protocol without cinnamon extract. Also Alizadeh-naini et al. reported that administration of 1g of N. sativa for twice a day plus four-drug protocol therapy including metronidazole, amoxicillin, bismuth subcitrate, and omeprazole for 14 days significantly (P = 0.1) eradicates H. pylori (87.5%) compared to the control group (four-drug protocol without N. sativa, 54.54%). One of the noticeable results of this study was the low efficacy of four-drug protocol treatment which it had response only in 58.3% of patients. This low response can be due to the small size of samples or the drug resistance of H. pylori to antibiotics (amoxicillin and metronidazole) as reported in other studies., Finally, the effectiveness of cumin decoction studied in the first group can be considered for further investigation.
| Conclusion|| |
The results of this study showed that the decoction of cumin could be used as a complementary treatment along with common protocols to increase their effectiveness. In addition, the results showed that there is no significant difference between the intervention groups to eradicate H. pylori, so it may be possible to use cumin fruit instead of antibiotics with high side effects, although its confirmation requires large-scale clinical trial studies. The small size of samples and the lack of patients’ return after receiving one of the treatment protocols were limitations of this study. Therefore, cultural policies and necessary training are required for patients to assist in clinical research activities.
The authors appreciate the Clinical Research Development Center experts and stuff of Imam Khomeini hospital, Medical Biology Research Center, and Kermanshah University of Medical Sciences.
Financial support and sponsorship
Kermanshah University of Medical Sciences.
Conflict of interest
There is no conflict of interest.
| References|| |
Leja M, Grinberga-Derica I, Bilgilier C, Steininger C. Review: Epidemiology of Helicobacter pylori
infection. Helicobacter 2019;24(Suppl 1):e12635.
Malaty HM. Epidemiology of Helicobacter pylori
infection. Best Pract Res Clin Gastroenterol 2007;21:205-14.
Maleki I, Mohammadpour M, Zarrinpour N, Khabazi M, Mohammadpour RA. Prevalence of Helicobacter pylori
infection in Sari Northern Iran; A population based study. Gastroenterol Hepatol Bed Bench 2019;12:31.
Ahmed N. 23 years of the discovery of Helicobacter pylori
: Is the debate over? Ann Clin Microbiol Antimicrob 2005;4:17.
Fischbach LA, Goodman KJ, Feldman M, Aragaki C. Sources of variation of Helicobacter pylori
treatment success in adults worldwide: A meta-analysis. Int J Epidemiol 2002;31:128-39.
Lim SG, Park RW, Shin SJ, Yoon D, Kang JK, Hwang JC, et al
. The relationship between the failure to eradicate helicobacter pylori and previous antibiotics use. Dig Liver Dis 2016;48:385-90.
Yamaoka Y. Mechanisms of disease: Helicobacter pylori
virulence factors. Nat Rev Gastroenterol Hepatol 2010;7:629-41.
Zhang F, Chen C, Hu J, Su R, Zhang J, Han Z, et al
. Molecular mechanism of Helicobacter pylori
-induced autophagy in gastric cancer. Oncol Lett 2019;18:6221-7.
Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori
infection. Am J Gastroenterol 2007;102:1808-25.
Nguyen CT, Davis KA, Nisly SA, Li J. Treatment of Helicobacter pylori
in special patient populations. Pharmacotherapy 2019;39:1012-22.
Sezgin O, Aydın MK, Özdemir AA, Kanık AE. Standard triple therapy in Helicobacter pylori
eradication in turkey: Systematic evaluation and meta-analysis of 10-year studies. Turk J Gastroenterol 2019;30:420-35.
De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, et al
. Worldwide H. pylori
antibiotic resistance: A systematic review. J Gastrointestin Liver Dis 2010;19:409-14.
Fischbach L, Evans EL. Meta-analysis: The effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori
. Aliment Pharmacol Ther 2007;26:343-57.
O’Connor A, Liou JM, Gisbert JP, O’Morain C. Review: Treatment of Helicobacter pylori
infection 2019. Helicobacter 2019;24(Suppl 1):e12640.
Amin M, Anwar F, Naz F, Mehmood T, Saari N. Anti-Helicobacter pylori
and urease inhibition activities of some traditional medicinal plants. Molecules 2013;18:2135-49.
Asha MK, Debraj D, Prashanth D, Edwin JR, Srikanth HS, Muruganantham N, et al
. In vitro anti-Helicobacter pylori
activity of a flavonoid rich extract of glycyrrhiza glabra and its probable mechanisms of action. J Ethnopharmacol 2013;145:581-6.
O’Mahony R, Al-Khtheeri H, Weerasekera D, Fernando N, Vaira D, Holton J, et al
. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori
. World J Gastroenterol 2005;11:7499-507.
Robles-Zepeda RE, Velázquez-Contreras CA, Garibay-Escobar A, Gálvez-Ruiz JC, Ruiz-Bustos E. Antimicrobial activity of northwestern Mexican plants against Helicobacter pylori
. J Med Food 2011;14:1280-3.
Perel’son M, Sheinker YN, Syrova G, Turchin K. NMR spectra of natural coumarin derivatives. Chem Nat Compd 1970;6: 5-11.
Zargari A. Medicinal Plants. 6 ed. Tehran: Tehran University Press;1997. p. 519-21.
Nakhaei M, Ramezani M, Karamoddin M, Malekzadeh F. In vitro anti-Helicobacter pylori
activity of cumin (Cuminum cyminum
L.) and tarragon (Artemisia dracunculus
L.) extracts. Iranian J Basic Med Sci 2006;9:193-200.
Nostro A, Cellini L, Di Bartolomeo S, Di Campli E, Grande R, Cannatelli MA, et al
. Antibacterial effect of plant extracts against helicobacter pylori. Phytother Res 2005;19:198-202.
Alkofahi A, Atta AH. Pharmacological screening of the anti-ulcerogenic effects of some Jordanian medicinal plants in rats. J Ethnopharmacol 1999;67:341-5.
Alizadeh-naini M, Yousefnejad H, Hejazi N. The beneficial health effects of Nigella sativa
on Helicobacter pylori
eradication, dyspepsia symptoms, and quality of life in infected patients: A pilot study. Phytother Res2020;34:1367-76 .
Imani G, khalilian A, Dastan D, Imani B, Mehrpoya M. Effects of cinnamon extract on complications of treatment and eradication of Helicobacter pylori
in infected people. J Herbmed Pharmacol 2020;9:55-60.
Dabos KJ, Sfika E, Vlatta LJ, Giannikopoulos G. The effect of mastic gum on helicobacter pylori: A randomized pilot study. Phytomedicine 2010;17:296-9.
Kato I, Nomura AM, Stemmermann GN, Chyou PH. A prospective study of gastric and duodenal ulcer and its relation to smoking, alcohol, and diet. Am J Epidemiol 1992;135:521-30.
Furuta T, Kato M, Sugimoto M, Sasaki M, Kamoshida T, Furukawa K, et al
; Japan Gast Study Group. Triple therapy with ecabet sodium, amoxicillin and lansoprazole for 2 weeks as the rescue regimen for H. pylori
infection. Intern Med 2011;50:369-74.
Mohammed SA, Al-lela OQ, Hussein NR, Hajany RS, Alduhoky LS. Clarithromycin versus levofloxacin-based regimens for Helicobacter pylori
eradication in the Kurdistan Region of Iraq: A randomized clinical trial. Gastroenterol Insights2019;10:5-9.
Lee SY, Shin YW, Hahm KB. Phytoceuticals: Mighty but ignored weapons against Helicobacter pylori
infection. J Dig Dis 2008;9:129-39.
Graham DY, Fischbach L. Helicobacter pylori
treatment in the era of increasing antibiotic resistance. Gut 2010;59:1143-53.
Gohari AR, Saeidnia S. A review on phytochemistry of Cuminum cyminum
seeds and its standards from field to market. Pharmacogn J 2011;3:1-5.
Kalaivani P, Saranya RB, Ramakrishnan G, Ranju V, Sathiya S, Gayathri V, et al
. Cuminum cyminum
, a dietary spice, attenuates hypertension via endothelial nitric oxide synthase and NO pathway in renovascular hypertensive rats. Clin Exp Hypertens 2013;35:534-42.
Salehi B, Sharopov F, Martorell M, Rajkovic J, Ademiluyi AO, Sharifi-Rad M, et al
. Phytochemicals in Helicobacter pylori
infections: What are we doing now? Int J Mol Sci 2018; 19:2361.
Prajapati M, Jayswal S, Maitreya B. Phytochemical screening and comparative study of antioxidant activity of Cuminum cyminum
L. and Nigella sativa
L. Int J Basic Appl Res 2019;9:1305-15.
Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori
: A systematic review and meta-analysis in world health organization regions. Gastroenterology 2018;155:1372-82.e17.
[Table 1], [Table 2]