Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence
Abstract
:1. Introduction
2. Interplay between Polyphenols and Gut Microbiome
3. Polyphenols and the Production of Various Metabolites and Their Influence on Host Health Status
4. Overview of the Pathophysiology of Major Gastrointestinal Disease/Disorders and Its Association with Gut Microbiome
5. Gastroprotective Activity of Dietary Polyphenols and Their Bioactive Metabolites through Modulating GM
5.1. Green Tea Polyphenols (GTPs)
5.1.1. Proposed Gastroprotective Activity of GTP
5.1.2. Clinical Evidence
5.2. Resveratrol (Resv)
5.2.1. Proposed Gastroprotective Activity of Resveratrol
5.2.2. Clinical Evidence
5.3. Curcumin (Curm)
5.3.1. Proposed Gastroprotective Activity of Curcumin
5.3.2. Clinical Evidence
5.4. Quercetin (Quer)
5.4.1. Proposed Gastroprotective Activity of Quercetin
5.4.2. Clinical Evidence
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Abbas, M.; Saeed, F.; Anjum, F.M.; Afzaal, M.; Tufail, T.; Bashir, M.S.; Ishtiaq, A.; Hussain, S.; Suleria, H.A.R. Natural Polyphenols: An Overview. Int. J. Food Prop. 2017, 20, 1689–1699. [Google Scholar]
- Filosa, S.; Di Meo, F.; Crispi, S. Polyphenols-Gut Microbiota Interplay and Brain Neuromodulation. Neural Regen. Res. 2018, 13, 2055–2059. [Google Scholar]
- Rasouli, H.; Farzaei, M.H.; Khodarahmi, R. Polyphenols and their benefits: A review. Int. J. Food Prop. 2017, 20, 1700–1741. [Google Scholar]
- Adebooye, O.C.; Alashi, A.M.; Aluko, R.E. A Brief Review on Emerging Trends in Global Polyphenol Research. J. Food Biochem. 2018, e12519. [Google Scholar]
- Bohn, T. Dietary Factors Affecting Polyphenol Bioavailability. Nutr. Rev. 2014, 72, 429–452. [Google Scholar] [CrossRef] [PubMed]
- Carmody, R.N.; Turnbaugh, P.J. Host-Microbial Interactions in the Metabolism of Therapeutic and Diet-Derived Xenobiotics. J. Clin. Invest. 2014, 124, 4173–4181. [Google Scholar]
- Cueva, C.; Gil-Sánchez, I.; Ayuda-Durán, B.; González-Manzano, S.; González-Paramás, A.M.; Santos-Buelga, C.; Bartolomé, B.; Moreno-Arribas, M.V. An Integrated View of the Effects of Wine Polyphenols and Their Relevant Metabolites on Gut and Host Health. Molecules 2017, 22, 99. [Google Scholar]
- Van Duynhoven, J.; Vaughan, E.E.; Jacobs, D.M.; Kemperman, R.A.; van Velzen, E.J.J.; Gross, G.; Roger, L.C.; Possemiers, S.; Smilde, A.K.; Doré, J.; et al. Metabolic Fate of Polyphenols in the Human Superorganism. Proc. Natl. Acad. Sci. USA 2011, 108, 4531–4538. [Google Scholar]
- Chiu, H.F.; Fang, C.Y.; Shen, Y.C.; Venkatakrishnan, K.; Wang, C.K. Efficacy of Probiotic Milk Formula on Blood Lipid and Intestinal Function in Mild Hypercholesterolemic Volunteers: A Placebo-Control, Randomized Clinical Trial. Probiotics Antimicrob. Proteins 2021, 1–9. [Google Scholar] [CrossRef]
- Wan, M.L.Y.; Co, V.A.; El-Nezami, H. Dietary Polyphenol Impact on Gut Health and Microbiota. Crit. Rev. Food Sci. Nutr. 2021, 61, 690–711. [Google Scholar] [CrossRef]
- Woting, A.; Blaut, M. The Intestinal Microbiota in Metabolic Disease. Nutrients 2016, 8, 202. [Google Scholar]
- Catinean, A.; Neag, M.A.; Muntean, D.M.; Bocsan, I.C.; Buzoianu, A.D. An Overview on the Interplay between Nutraceuticals and Gut Microbiota. PeerJ 2018, 6, e4465. [Google Scholar]
- Louis, P.; Flint, H.J. Formation of Propionate and Butyrate by the Human Colonic Microbiota. Environ. Microbiol. 2017, 19, 29–41. [Google Scholar]
- Moorthy, M.; Chaiyakunapruk, N.; Jacob, S.A.; Palanisamy, U.D. Prebiotic Potential of Polyphenols, Its Effect on Gut Microbiota and Anthropometric/Clinical Markers: A Systematic Review of Randomised Controlled Trials. Trends Food Sci. Technol. 2020, 99, 634–649. [Google Scholar]
- Kumar Singh, A.; Cabral, C.; Kumar, R.; Ganguly, R.; Kumar Rana, H.; Gupta, A.; Rosaria Lauro, M.; Carbone, C.; Reis, F.; Pandey, A.K. Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency. Nutrients 2019, 11, 2216. [Google Scholar]
- Ma, G.; Chen, Y. Polyphenol Supplementation Benefits Human Health via Gut Microbiota: A Systematic Review via Meta-Analysis. J. Funct. Foods 2020, 66, 103829. [Google Scholar] [CrossRef]
- Gupta, A.; Kagliwal, L.D.; Singhal, R.S. Biotransformation of Polyphenols for Improved Bioavailability and Processing Stability. Adv. Food Nutr. Res. 2013, 69, 183–217. [Google Scholar]
- Carding, S.; Verbeke, K.; Vipond, D.T.; Corfe, B.M.; Owen, L.J. Dysbiosis of the Gut Microbiota in Disease. Microb. Ecol. Health Dis. 2015, 26, 26191. [Google Scholar]
- Roberts, F.A.; Darveau, R.P. Microbial Protection and Virulence in Periodontal Tissue as a Function of Polymicrobial Communities: Symbiosis and Dysbiosis. Periodontol. 2000 2015, 69, 18–27. [Google Scholar]
- Nagao-Kitamoto, H.; Kitamoto, S.; Kuffa, P.; Kamada, N. Pathogenic Role of the Gut Microbiota in Gastrointestinal Diseases. Intest. Res. 2016, 14, 127–138. [Google Scholar]
- Zhang, H.; Tsao, R. Dietary Polyphenols, Oxidative Stress and Antioxidant and Anti-Inflammatory Effects. Curr. Opin. Food Sci. 2016, 8, 33–42. [Google Scholar]
- Kim, C.H.; Park, J.; Kim, M. Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, and Inflammation. Immune Netw. 2014, 14, 277–288. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chiu, H.-F.; Lin, T.-Y.; Shen, Y.-C.; Venkatakrishnan, K.; Wang, C.-K. Improvement of Green Tea Polyphenol with Milk on Skin with Respect to Antioxidation in Healthy Adults: A Double-Blind Placebo-Controlled Randomized Crossover Clinical Trial. Food Funct. 2016, 7, 893–901. [Google Scholar] [CrossRef] [PubMed]
- Adami, G.R.; Tangney, C.; Schwartz, J.L.; Dang, K.C. Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans. Molecules 2020, 25, 4753. [Google Scholar] [CrossRef]
- Lambert, J.D.; Sang, S.; Yang, C.S. Biotransformation of Green Tea Polyphenols and the Biological Activities of Those Metabolites. Mol. Pharm. 2007, 4, 819–825. [Google Scholar]
- Yan, Z.; Zhong, Y.; Duan, Y.; Chen, Q.; Li, F. Antioxidant Mechanism of Tea Polyphenols and Its Impact on Health Benefits. Anim. Nutr. 2020, 6, 115–123. [Google Scholar] [CrossRef]
- Afzal, M.; Safer, A.M.; Menon, M. Green Tea Polyphenols and Their Potential Role in Health and Disease. Inflammopharmacology 2015, 23, 151–161. [Google Scholar]
- Almatroodi, S.A.; Almatroudi, A.; Khan, A.A.; Alhumaydhi, F.A.; Alsahli, M.A.; Rahmani, A.H. Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer. Molecules 2020, 25, 3146. [Google Scholar]
- Yang, C.; Du, W.; Yang, D. Inhibition of Green Tea Polyphenol EGCG ((−)-Epigallocatechin-3-Gallate) on the Proliferation of Gastric Cancer Cells by Suppressing Canonical Wnt/β-Catenin Signalling Pathway. Int. J. Food Sci. Nutr. 2016, 67, 818–827. [Google Scholar] [CrossRef]
- Du, G.J.; Zhang, Z.; Wen, X.D.; Yu, C.; Calway, T.; Yuan, C.S.; Wang, C.Z. Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea. Nutrients 2012, 4, 1679–1691. [Google Scholar] [CrossRef]
- Kim, H.S.; Kim, M.H.; Jeong, M.; Hwang, Y.S.; Lim, S.H.; Shin, B.A.; Ahn, B.W.; Jung, Y.D. EGCG Blocks Tumor Promoter-Induced MMP-9 Expression via Suppression of MAPK and AP-1 Activation in Human Gastric AGS Cells. Anticancer Res. 2004, 24, 747–753. [Google Scholar]
- Zhang, Z.; Zhang, S.; Yang, J.; Yi, P.; Xu, P.; Yi, M.; Peng, W. Integrated Transcriptomic and Metabolomic Analyses to Characterize the Anti-Cancer Effects of (−)-Epigallocatechin-3-Gallate in Human Colon Cancer Cells. Toxicol. Appl. Pharmacol. 2020, 401, 115100. [Google Scholar]
- Negri, A.; Naponelli, V.; Rizzi, F.; Bettuzzi, S. Molecular Targets of Epigallocatechin-Gallate (EGCG): A Special Focus on Signal Transduction and Cancer. Nutrients 2018, 10, 1936. [Google Scholar]
- Park, J.S.; Khoi, P.N.; Joo, Y.E.; Lee, Y.H.; Lang, S.A.; Stoeltzing, O.; Jung, Y.D. EGCG Inhibits Recepteur d’origine Nantais Expression by Suppressing Egr-1 in Gastric Cancer Cells. Int. J. Oncol. 2013, 42, 1120–1126. [Google Scholar] [CrossRef] [PubMed]
- Jiang, J.; Cao, D.; Jia, Z.; You, L.; Tsukamoto, T.; Hou, Z.; Cao, X. The Green Tea Polyphenol Epigallocatechin-3-Gallate Effectively Inhibits Helicobacter Pylori-Induced Gastritis in Mongolian Gerbils. Int. J. Clin. Exp. Med. 2016, 9, 2479–2485. [Google Scholar]
- Ruggiero, P.; Rossi, G.; Tombola, F.; Pancotto, L.; Lauretti, L.; Del Giudice, G.; Zoratti, M. Red Wine and Green Tea Reduce H Pylori-or VacA-Induced Gastritis in a Mouse Model. World J. Gastroenterol. WJG 2007, 13, 349. [Google Scholar]
- Stoicov, C.; Saffari, R.; Houghton, J. Green Tea Inhibits Helicobacter Growth in Vivo and in Vitro. Int. J. Antimicrob. Agents 2009, 33, 473–478. [Google Scholar]
- Yee, Y.K.; Koo, M.W. Anti-Helicobacter Pylori Activity of Chinese Tea: In Vitro Study: Anti-H. Pylori activity of Chinese tea. Aliment. Pharmacol. Ther. 2000, 14, 635–638. [Google Scholar] [CrossRef]
- Raj, R.; Agarwal, N.; Raghavan, S.; Chakraborti, T.; Poluri, K.M.; Pande, G.; Kumar, D. Epigallocatechin Gallate with Potent Anti-Helicobacter Pylori Activity Binds Efficiently to Its Histone-like DNA Binding Protein. ACS Omega 2021, 6, 3548–3570. [Google Scholar] [CrossRef]
- Dias, R.; Pereira, C.B.; Pérez-Gregorio, R.; Mateus, N.; Freitas, V. Recent Advances on Dietary Polyphenol’s Potential Roles in Celiac Disease. Trends Food Sci. Technol. 2021, 107, 213–225. [Google Scholar] [CrossRef]
- Unno, T.; Sakuma, M.; Mitsuhashi, S.E. Effect of Dietary Supplementation of (-Epigallocatechin Gallate on Gut Microbiota and Biomarkers of Colonic Fermentation in Rats. J. Nutr. Sci. Vitaminol 2014, 60, 213–219. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- **, J.S.; Touyama, M.; Hisada, T.; Benno, Y. Effects of Green Tea Consumption on Human Fecal Microbiota with Special Reference to Bifidobacterium Species: Effects of Green Tea on Fecal Microbiota. Microbiol. Immunol. 2012, 56, 729–739. [Google Scholar] [CrossRef] [PubMed]
- Barbalho, S.M.; Bosso, H.; Salzedas-Pescinini, L.M.; de Alvares Goulart, R. Green Tea: A Possibility in the Therapeutic Approach of Inflammatory Bowel Diseases?: Green Tea and Inflammatory Bowel Diseases. Complement. Ther. Med. 2019, 43, 148–153. [Google Scholar]
- Rahman, S.U.; Li, Y.; Huang, Y.; Zhu, L.; Feng, S.; Wu, J.; Wang, X. Treatment of Inflammatory Bowel Disease via Green Tea Polyphenols: Possible Application and Protective Approaches. Inflammopharmacology 2018, 26, 319–330. [Google Scholar]
- Nakachi, K.; Matsuyama, S.; Miyake, S.; Suganuma, M.; Imai, K. Preventive Effects of Drinking Green Tea on Cancer and Cardiovascular Disease: Epidemiological Evidence for Multiple Targeting Prevention. Biofactors 2000, 13, 49–54. [Google Scholar]
- Shimizu, M.; Fukutomi, Y.; Ninomiya, M.; Nagura, K.; Kato, T.; Araki, H.; Suganuma, M.; Fujiki, H.; Moriwaki, H. Green Tea Extracts for the Prevention of Metachronous Colorectal Adenomas: A Pilot Study. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 3020–3025. [Google Scholar]
- Zhu, M.Z.; Lu, D.M.; Ouyang, J.; Zhou, F.; Huang, P.F.; Gu, B.Z.; Tang, J.W.; Shen, F.; Li, J.F.; Li, Y.L.; et al. Tea Consumption and Colorectal Cancer Risk: A Meta-Analysis of Prospective Cohort Studies. Eur. J. Nutr. 2020, 59, 3603–3615. [Google Scholar] [CrossRef] [PubMed]
- Wada, K.; Oba, S.; Tsuji, M.; Goto, Y.; Mizuta, F.; Koda, S.; Uji, T.; Hori, A.; Tanabashi, S.; Matsushita, S.; et al. Green Tea Intake and Colorectal Cancer Risk in Japan: The Takayama Study. Jpn. J. Clin. Oncol. 2019, 49, 515–520. [Google Scholar] [CrossRef]
- Okubo, T.; Ishihara, N.; Oura, A.; Serit, M.; Kim, M.; Yamamoto, T.; Mitsuoka, T. In Vivo Effects of Tea Polyphenol Intake on Human Intestinal Microflora and Metabolism. Biosci. Biotechnol. Biochem. 1992, 56, 588–591. [Google Scholar]
- Boyanova, L.; Ilieva, J.; Gergova, G.; Vladimirov, B.; Nikolov, R.; Mitov, I. Honey and Green/Black Tea Consumption May Reduce the Risk of Helicobacter Pylori Infection. Diagn. Microbiol. Infect. Dis. 2015, 82, 85–86. [Google Scholar]
- Dryden, G.W.; Lam, A.; Beatty, K.; Qazzaz, H.H.; McClain, C.J. A Pilot Study to Evaluate the Safety and Efficacy of an Oral Dose of (−)-Epigallocatechin-3-Gallate–Rich Polyphenon E in Patients with Mild to Moderate Ulcerative Colitis. Inflamm. Bowel Dis. 2013, 19, 1904–1912. [Google Scholar]
- ** Faecal Gut Microbiota Composition by the Intake of Trans-Resveratrol and Quercetin in High-Fat Sucrose Diet-Fed Rats. J. Nutr. Biochem. 2015, 26, 651–660. [Google Scholar]
- Askari, G.; Ghiasvand, R.; Feizi, A.; Ghanadian, S.M.; Karimian, J. The Effect of Quercetin Supplementation on Selected Markers of Inflammation and Oxidative Stress. J. Res. Med. Sci. 2012, 17, 637–641. [Google Scholar]
- Ekström, A.M.; Serafini, M.; Nyrén, O.; Wolk, A.; Bosetti, C.; Bellocco, R. Dietary Quercetin Intake and Risk of Gastric Cancer: Results from a Population-Based Study in Sweden. Ann. Oncol. 2011, 22, 438–443. [Google Scholar]
- Reyes-Farias, M.; Carrasco-Pozo, C. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int. J. Mol. Sci. 2019, 20, 3177. [Google Scholar]
- Li, H.; Christman, L.M.; Li, R.; Gu, L. Synergic Interactions between Polyphenols and Gut Microbiota in Mitigating Inflammatory Bowel Diseases. Food Funct. 2020, 11, 4878–4891. [Google Scholar] [CrossRef] [PubMed]
- Roudsari, N.M.; Lashgari, N.-A.; Momtaz, S.; Farzaei, M.H.; Marques, A.M.; Abdolghaffari, A.H. Natural Polyphenols for the Prevention of Irritable Bowel Syndrome: Molecular Mechanisms and Targets; a Comprehensive Review. Daru 2019, 27, 755–780. [Google Scholar]
- Kaulmann, A.; Bohn, T. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases-Promises, Perspectives, and Pitfalls. Oxid. Med. Cell. Longev. 2016, 2016, 9346470. [Google Scholar]
- Pei, R.; Liu, X.; Bolling, B. Flavonoids and Gut Health. Curr. Opin. Biotechnol. 2020, 61, 153–159. [Google Scholar] [CrossRef] [PubMed]
- Adhami, V.M.; Malik, A.; Zaman, N.; Sarfaraz, S.; Siddiqui, I.A.; Syed, D.N.; Afaq, F.; Pasha, F.S.; Saleem, M.; Mukhtar, H. Combined Inhibitory Effects of Green Tea Polyphenols and Selective Cyclooxygenase-2 Inhibitors on the Growth of Human Prostate Cancer Cells Both in Vitro and in Vivo. Clin. Cancer Res. 2007, 13, 1611–1619. [Google Scholar]
- Suganuma, M.; Okabe, S.; Kai, Y.; Sueoka, N.; Sueoka, E.; Fujiki, H. Synergistic Effects of (−)-Epigallocatechin Gallate with (−)-Epicatechin, Sulindac, or Tamoxifen on Cancer-Preventive Activity in the Human Lung Cancer cell Line PC-9. Cancer Res. 1999, 59, 44–47. [Google Scholar]
Polyphenol | Source | Active Metabolites/Phenolic Acids and Its Derivatives |
---|---|---|
Green tea polyphenols (GTP) | Green tea leaves (Camellia sinensis)-Rich in Catechins | 1. Methylated Metabolites: 4′-O-methyl-epigallocatechin (4′-MeEGC); 4′,4″-di-O-methyl-epigallocatechin-3-gallate (4′,4″-di MeEGCG) 2. Sulfated Metabolites: EGCG-sulfate; EGC-sulfate 3. Glucuronidase Metabolites: 5-(3,4′,5′-trihydroxyphenyl)-γ-valerolactone; 5-(3,4′-dihydroxyphenyl)-γ-valerolactone; [Valeric acid derivatives] 4. Phenolic acids: Gallic acid; coumaric acid, caffeic acid |
Resveratrol (Resv) | Grape, wine, peanut, cranberry | 1. Methylated Metabolites: 7′,8′-dihydro-methyl-resveratrol 2. Glucuronidase Metabolites: Resveratrol-3′-O-glucuronide, resveratrol-4′-O-glucuronide 3. Sulfated Metabolites: Resveratrol-3′-O-sulfate, resveratrol-4′-O-sulfate, 7′,8′-dihydro resveratrol-3-sulfate 4. Phenolic acids: Cinnamic acid; coumaric acid |
Quercetin | Onion, apple grape, citrus fruits (glucoside form-Rutin and aglycons) | 1. Methylated Metabolites: 3′-O-methyl-quercetin, 4′-O-methyl-quercetin 2. Glucuronidase Metabolites: Quercetin-3′-O-glucuronide, Quercetin-4′-O-glucuronide, Quercetin-3′-4′-di-O-glucuronide 3. Sulfated Metabolites: Quercetin-3′-O-sulfate Lots of lactic and benzoic acid derivatives like dihydro-phenylacetic acid/propionic acid/benzoic acid). |
Curcumin | Turmeric (Curcuma longa)(Curcuminoid) | 1. Methylated Metabolites: Desmethoxycurcumin; bisdesmethoxycurcumin 2. Glucuronidase Metabolites: Curcumin-O-glucuronide, Di/tetra/hexa/octa-hydro-curcumin glucuronide 3. Sulfated Metabolites: Curcumin-O-sulfate, Di/tetra/hexa/octa-hydro-curcumin sulfate 4. Phenolic acid: Ferulic and vanillic acid as well as dimethyl form. |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chiu, H.-F.; Venkatakrishnan, K.; Golovinskaia, O.; Wang, C.-K. Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence. Molecules 2021, 26, 2090. https://doi.org/10.3390/molecules26072090
Chiu H-F, Venkatakrishnan K, Golovinskaia O, Wang C-K. Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence. Molecules. 2021; 26(7):2090. https://doi.org/10.3390/molecules26072090
Chicago/Turabian StyleChiu, Hui-Fang, Kamesh Venkatakrishnan, Oksana Golovinskaia, and Chin-Kun Wang. 2021. "Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence" Molecules 26, no. 7: 2090. https://doi.org/10.3390/molecules26072090