In Vitro Anti-Helicobacter Pylori Effects of Hydroxycinnamic Acid Derivatives and Their Urease Inhibition Studies On H. Pylori Urease Enzyme
Abstract
Helicobacter pylori H. pylori is a human pathogen that can persist in the stomach of infected people for their life spans. It causes chronic gastric inflammation leading to serious gastric diseases such as gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. To colonize in the acidic environment of the stomach, H. pylori produces urease enzyme that catalyzes the hydrolysis of urea to yield into ammonia and carbon dioxide. This enzyme neutralizes the acidic environment of the gastric lumen, and gives the bacteria a short-term survival in this highly acidic environment. There are numerous antibiotic-based therapies for the treatment of H. pylori infection. However, antibiotic resistance has a significant impact on the failure of these treatments.Hydroxycinnamic acid derivatives are simple phenolic acids, found mainly in cereals, fruits, seeds of fruits and vegetables. Ferulic acid, Caffeic acid, p-Coumaric acid, and Sinapic acid belong to this phenolic acid group. These derivatives act as antioxidant, anti-inflammatory, antimicrobial agents and have been used for the treatment of some bacterial infections as alternatives to drugs.The objective of this study was to investigate the anti-H. pylori and urease enzyme inhibitory effects of Ferulic acid, Caffeic acid, p-Coumaric acid and Sinapic acid.The effect of hydroxycinnamic acid derivatives was tested on H. pylori standard train G27. MIC was determined by serial tube dilution method in which the final concentration ranged between 512 to 0.5 µg/ml and MBC was determined by calculating the relative proportion of live and dead bacteria with the same concentration range used in MIC. For MIC, the CLSI M07-A9and for MBC CLSI M26-A protocols were used. Urease inhibitory activity was detected by Helicheck, H. pylori-specific growth media shows urease activity by changing the color of the media. Nucleotide release was measured by spectrophotometry. The MIC was 64 µg/ml and MBC was 128 µg/ml for all compounds and they had no effect on urease enzyme. There was no detectable nucleotide release from the bacterial membrane because of the hydroxycinnamic acid derivatives damage
Keywords
H. pylori anti-helicobacter pylori effect hydroxycinnamic acid derivatives urease inhibition nucleotide release assay
References
- Sipponen P, Hyvärinen H. Role of Helicobacter pylori in the Pathogenesis of Gastritis, Peptic Ulcer and Gastric Cancer. Scand J Gastroenterol 1993;28:196:3–6. [CrossRef]
- Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 1995;19:37–43.
- Ceylan A, Kırımi E, Tuncer O, Türkdoğan K, Arıyuca S, Ceylan N. Prevalence of Helicobacter pylori in Children and Their Family Members in a District in Turkey. J Health Popul Nutr 2007;25:4:422–7. Erişim: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754017/
- Maurizio ZR, Rabitti S, Eusebi LH, Bazzoli F. Treatment of Helicobacter pylori infection: A clinical practice update. Eur J Clin Invest 2018;48:e12857. [CrossRef]
- Alba C, Blanco A, Alarcon T. Antibiotic resistance in Helicobacter pylori. Curr Opin Infect Dis 2017;30:5:489–97. [CrossRef]
- Testerman TL, McGee DJ, Mobley HLT. Adherence and Colonization, Chap. 4. In: Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001.
- Hassan S, Šudomová M. The Development of Urease Inhibitors: What Opportunities Exist for Better Treatment of Helicobacter pylori Infection in Children? Children 2017;4:1. [CrossRef]
- Prior RL, Cao G, Martin A, Sofic E, McEwen J, O’Brien C, et al. Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agric Food Chem 1998;46:2686–93. [CrossRef]
- Heinonen IM, Meyer AS, Frankel EN. Antioxidant activity of berry phenolics on human low-density lipoprotein and liposome oxidation. J Agric Food Chem 1998;46:4107–12. [CrossRef]
- Sellappan S, Akoh CC, Krewer G. Phenolic compounds and antioxidant capacity of Georgia-grown blueberries and blackberries. J Agric Food Chem 2002;50:2432–8. [CrossRef]
- Borowska J, Szajdek A. Antioxidant activity of berry fruits and beverages. Pol J Natl Sci 2003;14.
- Moyer RA, Hummer KE, Finn CE, Frei B, Wrolstad RE. Anthocyanins, phenolics, and antioxidant capacity in diverse small fruits: Vaccinium, Rubus, and Ribes. J Agric Food Chem 2002;50:519–25. [CrossRef]
- Benvenuti S, Pellati F, Melegari M, Bertelli D. Polyphenols, anthocyanins, ascorbic acid, and radical scavenging activity of Rubus, Ribes, and Aronia. J Food Sci 2004;69:FCT164–9. [CrossRef]
- Wang SY, Stretch AW. Antioxidant capacity in cranberry is influenced by cultivar and storage temperature. J Agric Food Chem 2001;49:969–74. [CrossRef]
- Zheng W, Wang SY. Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. J Agric Food Chem 2003;51:502–9. [CrossRef]
- De Ancos B, González EM, Cano MP. Ellagic acid, vitamin C, and total phenolic contents and radical scavenging capacity affected by freezing and frozen storage in raspberry fruit. J Agric Food Chem 2000;48:4565–70. [CrossRef]
- Anttonen MJ, Karjalainen RO. Environmental and genetic variation of phenolic compounds in red raspberry. J Food Comp Anal 2005;18:759–69. [CrossRef]
- Wada L, Ou B. Antioxidant activity and phenolic content of Oregon caneberries. J Agric Food Chem 2002;50:3495–500. [CrossRef]
- Proteggente AR, Pannala AS, Paganga, G, Buren, LV, Wagner, E, Wiseman S, et al. The antioxidant activity of regularly consumed fruit and vegetables reflects their phenolic and vitamin C composition. Free Radic Res 2002;36:217–33. [CrossRef]
- Skupień K, Oszmiański J. Influence of titanium treatment on antioxidants content and antioxidant activity of strawberries. Acta Sci Pol Tech Aliment 2007;6:83–94. Erişim: https://www.food. actapol.net/pub/8_4_2007.pdf
- Zheng, Y, Wang, SY, Wang, CY, Zheng W. Changes in strawberry phenolics, anthocyanins, and antioxidant capacity in response to high oxygen treatments. LWT - Food Sci Tech 2007;40:49–57. [CrossRef]
- Barış Tuncel N, Yılmaz N. Kaz Dağları’ndan Toplanan Bazı Bitkilerin Fenolik Asit Kompozisyonlarının Yüksek Performanslı Sıvı Kromatografisinde Belirlenmesi. Akademik Gıda 2010;8:18–23. Erişim: http://www.academicfoodjournal.com/archive/2010/3/18-23.pdf
- Kafarski P, Talma M. Recent advances in design of new urease inhibitors: A review. J Adv Res 2018;13:101–12. [CrossRef]
- Cheng JC, Dai F, Zhou B, Yang L, Liu ZL. Antioxidant activity of hydroxycinnamic acid derivatives in human low density lipoprotein: Mechanism and structure-activity relationship. Food Chem 2007;104:1:132–9. [CrossRef]
- Alam MA, Subhan N, Hossain H, Hossain M, Reza HM, Rahman MM, Ullah MO. Hydroxycinnamic acid derivatives: a potential class of natural compounds for the management of lipid metabolism and obesity. Nutr Metab 2016;13:27. [CrossRef]
- Kuczkowiak U, Petereit F, Nahrstedt A. Hydroxycinnamic Acid Derivatives Obtained from a Commercial Crataegus Extract and from Authentic Crataegus spp. Sci Pharma 2014;82:4:835–46. [CrossRef]
- Calik Z, Karamese M, Acar O, Aksak SK, Dicle Y, Albayrak F, et al. Investigation of Helicobacter pylori antigen in stool samples of patients with upper gastrointestinal complaints. Braz J Microbiol 2016;47:167–71. [CrossRef]
- Perumal S, Mahmud R, Ismail S. Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa. Pharmacogn Mag 2017;13:S311–5. [CrossRef]
- Taofiq O, González-Paramás AM, Barreiro MF, Ferreira IC. Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review. Molecules 2017;22:281. [CrossRef]
Hidroksisinamik Asit Türevlerinin Canlı-Dışı Helicobacter Pylori Karşıtı Etkileri ile Üreaz Enzimini Engelleme Etkinliklerinin Araştırılması
Abstract
Helicobacter pylori H. pylori , insanlarda, gastrit, peptik ülser, gastrik kanser ve mukoza ilintili lenfoid doku lenfoması gibi ciddi mide hastalıklarına yol açan önemli bir hastalık etkenidir. H. pylori, ürettiği üreaz enzimleri sayesinde üreyi, karbondioksit ve amonyağa parçalayarak mide çeperinin asidik koşullarını normal pH’ya getirip hayatta kalabildiği için bu bakterilerle vücudun savaşımı kolay değildir. H. pylori enfeksiyonları için antibiyotikler mevcut olsa da antibiyotik direnci gelişimi nedeniyle bu tedaviler sonuçsuz kalabilmekte ve yeni antibiyotiklere gereksinim her geçen gün artmaktadır.Hidroksisinamik asit türevleri basit fenolik asitler olup meyvelerde, meyve çekirdeklerinde ve sebzelerde bulunmaktadır. Ferulik asit, kafeik asit, p-kumarik asit, sinapik asit, sözü edilen bu fenolik asit grubuna ait olup antioksidan, anti-inflamatuvar, antimikrobiyal özelliklere sahiptir ve bu nedenle bazı bakteri enfeksiyonlarının tedavisinde, ilaçlara seçenek olarak kullanılmaktadır. Bu çalışmamızda, bu üç fenolik asidin H. pylori üzerindeki antimikrobiyal etkinliği ve ürez enzimini engelleme etkisi araştırıldı.Hidroksisinamik asit türevlerinin anti-H. pylori etkisi H. pylori G27 standart suşu üzerinde test edildi. Minimum inhibisyon konsantrasyonu MİK , değerleri 512 ila 0,5 ug/mL arasında değiştiği seri tüp seyreltme yöntemiyle, minimum bakterisidal konsantrasyon MBK değerleri ise MİK içinde kullanılan aynı konsantrasyonlarda canlı ve ölü bakterilerin nispi oranının hesaplanması ile belirlendi. MİK için CLSI M07-A9, MBC için CLSI M26-A protokolleri kullanıldı. Ureaz inhibisyon aktivitesi Helicheck, üreaz aktivitesine özgü indikatörlü besiyerinde ölçülmüştür.H. pylori’ye karşı test edilen tüm bileşikler için MİK 64 ug/mL ve MBK 128 ug/mL idi. Test edilen bileşiklerin H. pylori tarafından salgılanan üreaz enzimi üzerinde hiçbir inhibisyonu saptanmadı. Nükleotid salma deneyi sonuçlarına göre, hidroksisinamik asit türevlerinin bakteri zarında hasara sebep olması ile zarda oluşan deliklerden dışarı salınma eğiliminde olması beklenen herhangi bir nüklotit miktarı ölçülememiştir.Gerçekleştirilen bu çalışma, literatür taramalarımız doğrulutusunda, hidroksisinamik asit türevlerinin anti-H. pylori aktivitesini gösteren ilk çalışmadır. Bu bileşiklerin anti-H. pylori üzerindeki etki mekanizmasını anlamak için daha ileri analizlere ihtiyaç vardır
Keywords
H. pylori Anti-H. pylori Etki hidroksisinamik asit türevleri üreaz i̇nhibisyon nüklotid salınım testleri
References
- Sipponen P, Hyvärinen H. Role of Helicobacter pylori in the Pathogenesis of Gastritis, Peptic Ulcer and Gastric Cancer. Scand J Gastroenterol 1993;28:196:3–6. [CrossRef]
- Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 1995;19:37–43.
- Ceylan A, Kırımi E, Tuncer O, Türkdoğan K, Arıyuca S, Ceylan N. Prevalence of Helicobacter pylori in Children and Their Family Members in a District in Turkey. J Health Popul Nutr 2007;25:4:422–7. Erişim: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754017/
- Maurizio ZR, Rabitti S, Eusebi LH, Bazzoli F. Treatment of Helicobacter pylori infection: A clinical practice update. Eur J Clin Invest 2018;48:e12857. [CrossRef]
- Alba C, Blanco A, Alarcon T. Antibiotic resistance in Helicobacter pylori. Curr Opin Infect Dis 2017;30:5:489–97. [CrossRef]
- Testerman TL, McGee DJ, Mobley HLT. Adherence and Colonization, Chap. 4. In: Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001.
- Hassan S, Šudomová M. The Development of Urease Inhibitors: What Opportunities Exist for Better Treatment of Helicobacter pylori Infection in Children? Children 2017;4:1. [CrossRef]
- Prior RL, Cao G, Martin A, Sofic E, McEwen J, O’Brien C, et al. Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agric Food Chem 1998;46:2686–93. [CrossRef]
- Heinonen IM, Meyer AS, Frankel EN. Antioxidant activity of berry phenolics on human low-density lipoprotein and liposome oxidation. J Agric Food Chem 1998;46:4107–12. [CrossRef]
- Sellappan S, Akoh CC, Krewer G. Phenolic compounds and antioxidant capacity of Georgia-grown blueberries and blackberries. J Agric Food Chem 2002;50:2432–8. [CrossRef]
- Borowska J, Szajdek A. Antioxidant activity of berry fruits and beverages. Pol J Natl Sci 2003;14.
- Moyer RA, Hummer KE, Finn CE, Frei B, Wrolstad RE. Anthocyanins, phenolics, and antioxidant capacity in diverse small fruits: Vaccinium, Rubus, and Ribes. J Agric Food Chem 2002;50:519–25. [CrossRef]
- Benvenuti S, Pellati F, Melegari M, Bertelli D. Polyphenols, anthocyanins, ascorbic acid, and radical scavenging activity of Rubus, Ribes, and Aronia. J Food Sci 2004;69:FCT164–9. [CrossRef]
- Wang SY, Stretch AW. Antioxidant capacity in cranberry is influenced by cultivar and storage temperature. J Agric Food Chem 2001;49:969–74. [CrossRef]
- Zheng W, Wang SY. Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. J Agric Food Chem 2003;51:502–9. [CrossRef]
- De Ancos B, González EM, Cano MP. Ellagic acid, vitamin C, and total phenolic contents and radical scavenging capacity affected by freezing and frozen storage in raspberry fruit. J Agric Food Chem 2000;48:4565–70. [CrossRef]
- Anttonen MJ, Karjalainen RO. Environmental and genetic variation of phenolic compounds in red raspberry. J Food Comp Anal 2005;18:759–69. [CrossRef]
- Wada L, Ou B. Antioxidant activity and phenolic content of Oregon caneberries. J Agric Food Chem 2002;50:3495–500. [CrossRef]
- Proteggente AR, Pannala AS, Paganga, G, Buren, LV, Wagner, E, Wiseman S, et al. The antioxidant activity of regularly consumed fruit and vegetables reflects their phenolic and vitamin C composition. Free Radic Res 2002;36:217–33. [CrossRef]
- Skupień K, Oszmiański J. Influence of titanium treatment on antioxidants content and antioxidant activity of strawberries. Acta Sci Pol Tech Aliment 2007;6:83–94. Erişim: https://www.food. actapol.net/pub/8_4_2007.pdf
- Zheng, Y, Wang, SY, Wang, CY, Zheng W. Changes in strawberry phenolics, anthocyanins, and antioxidant capacity in response to high oxygen treatments. LWT - Food Sci Tech 2007;40:49–57. [CrossRef]
- Barış Tuncel N, Yılmaz N. Kaz Dağları’ndan Toplanan Bazı Bitkilerin Fenolik Asit Kompozisyonlarının Yüksek Performanslı Sıvı Kromatografisinde Belirlenmesi. Akademik Gıda 2010;8:18–23. Erişim: http://www.academicfoodjournal.com/archive/2010/3/18-23.pdf
- Kafarski P, Talma M. Recent advances in design of new urease inhibitors: A review. J Adv Res 2018;13:101–12. [CrossRef]
- Cheng JC, Dai F, Zhou B, Yang L, Liu ZL. Antioxidant activity of hydroxycinnamic acid derivatives in human low density lipoprotein: Mechanism and structure-activity relationship. Food Chem 2007;104:1:132–9. [CrossRef]
- Alam MA, Subhan N, Hossain H, Hossain M, Reza HM, Rahman MM, Ullah MO. Hydroxycinnamic acid derivatives: a potential class of natural compounds for the management of lipid metabolism and obesity. Nutr Metab 2016;13:27. [CrossRef]
- Kuczkowiak U, Petereit F, Nahrstedt A. Hydroxycinnamic Acid Derivatives Obtained from a Commercial Crataegus Extract and from Authentic Crataegus spp. Sci Pharma 2014;82:4:835–46. [CrossRef]
- Calik Z, Karamese M, Acar O, Aksak SK, Dicle Y, Albayrak F, et al. Investigation of Helicobacter pylori antigen in stool samples of patients with upper gastrointestinal complaints. Braz J Microbiol 2016;47:167–71. [CrossRef]
- Perumal S, Mahmud R, Ismail S. Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa. Pharmacogn Mag 2017;13:S311–5. [CrossRef]
- Taofiq O, González-Paramás AM, Barreiro MF, Ferreira IC. Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review. Molecules 2017;22:281. [CrossRef]
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | December 1, 2020 |
| Published in Issue | Year 2020Issue: 4 |