Anti-Inflammatory and Antioxidant Effects Induced by Allium sativum L. Extracts on an Ex Vivo Experimental Model of Ulcerative Colitis

Inflammatory bowel diseases (IBDs) are chronic and multifactorial inflammatory conditions of the colonic mucosa (ulcerative colitis), characterized by increased and unbalanced immune response to external stimuli. Garlic and its bioactive constituents were reported to exert various biological effects, including anti-inflammatory, antioxidant and immunomodulatory activities. We aimed to evaluate the protective effects of a hydroalcoholic (GHE) and a water (GWE) extract from a Sicilian variety of garlic, known as Nubia red garlic, on an ex vivo experimental model of ulcerative colitis, involving isolated LPS-treated mouse colon specimens. Both extracts were able to counteract LPS-induced cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, nuclear factor-kB (NF-kB), and interleukin (IL)-6 gene expression in mouse colon. Moreover, the same extracts inhibited prostaglandin (PG)E2, 8-iso-PGF2α, and increased the 5-hydroxyindoleacetic acid/serotonin ratio following treatment with LPS. In particular, GHE showed a better anti-inflammatory profile. The anti-inflammatory and antioxidant effects induced by both extracts could be related, at least partially, to their polyphenolic composition, with particular regards to catechin. Concluding, our results showed that GHE and GWE exhibited protective effects in colon, thus suggesting their potential use in the prevention and management of ulcerative colitis.

[1]  A. Hayes,et al.  A review of the protective effects of chlorogenic acid against different chemicals. , 2022, Journal of food biochemistry.

[2]  C. Ghelardini,et al.  Anti-Inflammatory Effects Induced by a Polyphenolic Granular Complex from Olive (Olea europaea, Mainly Cultivar coratina): Results from In Vivo and Ex Vivo Studies in a Model of Inflammation and MIA-Induced Osteoarthritis , 2022, Nutrients.

[3]  C. Ruiz,et al.  Biological properties and therapeutic applications of garlic and its components. , 2022, Food & function.

[4]  A. Schally,et al.  Antagonist of growth hormone-releasing hormone MIA-690 attenuates the progression and inhibits growth of colorectal cancer in mice. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[5]  Ningyang Li,et al.  In vitro Prebiotic Properties of Garlic Polysaccharides and Its Oligosaccharide Mixtures Obtained by Acid Hydrolysis , 2021, Frontiers in Nutrition.

[6]  A. Cataldi,et al.  Phenolic Characterization and Neuroprotective Properties of Grape Pomace Extracts , 2021, Molecules.

[7]  A. Schally,et al.  Effects of growth hormone-releasing hormone receptor antagonist MIA-602 in mice with emotional disorders: a potential treatment for PTSD , 2021, Molecular Psychiatry.

[8]  Dan Wang,et al.  Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease , 2021, Frontiers in Pharmacology.

[9]  A. Cama,et al.  Protective Effects Induced by a Hydroalcoholic Allium sativum Extract in Isolated Mouse Heart , 2021, Nutrients.

[10]  P. Calder,et al.  Effects of Citrus Fruit Juices and Their Bioactive Components on Inflammation and Immunity: A Narrative Review , 2021, Frontiers in Immunology.

[11]  J. Mathew,et al.  Protective effect of (+)–catechin against lipopolysaccharide-induced inflammatory response in RAW 264.7 cells through downregulation of NF-κB and p38 MAPK , 2021, Inflammopharmacology.

[12]  A. Schally,et al.  Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice , 2021, Scientific Reports.

[13]  Y. Zhang,et al.  Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[14]  A. Camargo,et al.  Multi-phytochemical determination of polar and non-polar garlic bioactive compounds in different food and nutraceutical preparations. , 2020, Food chemistry.

[15]  K. Faber,et al.  Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease. , 2020, Trends in molecular medicine.

[16]  F. Köktürk,et al.  Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats: Garlic oil and experimental colitis. , 2020, Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES.

[17]  Y. Elewa,et al.  Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review , 2020, Nutrients.

[18]  G. Zengin,et al.  Multidirectional Pharma-Toxicological Study on Harpagophytum procumbens DC. ex Meisn.: An IBD-Focused Investigation , 2020, Antioxidants.

[19]  A. Schally,et al.  Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice , 2020, Scientific Reports.

[20]  H. Suleria,et al.  LC-ESI-QTOF/MS Characterisation of Phenolic Acids and Flavonoids in Polyphenol-Rich Fruits and Vegetables and Their Potential Antioxidant Activities , 2019, Antioxidants.

[21]  Xiaozhen Tang,et al.  Effects and mechanism of free amino acids on browning in the processing of black garlic. , 2019, Journal of the science of food and agriculture.

[22]  C. Ghelardini,et al.  Protective Effects Induced by Two Polyphenolic Liquid Complexes from Olive (Olea europaea, mainly Cultivar Coratina) Pressing Juice in Rat Isolated Tissues Challenged with LPS , 2019, Molecules.

[23]  R. Venanzoni,et al.  Protective effects induced by alcoholic Phlomis fruticosa and Phlomis herba‐venti extracts in isolated rat colon: Focus on antioxidant, anti‐inflammatory, and antimicrobial activities in vitro , 2019, Phytotherapy research : PTR.

[24]  H. Corke,et al.  Bioactive Compounds and Biological Functions of Garlic (Allium sativum L.) , 2019, Foods.

[25]  G. Zengin,et al.  New pharmacological targets of three Asphodeline species using in vitro and ex vivo models of inflammation and oxidative stress , 2018, International journal of environmental health research.

[26]  A. Mollica,et al.  Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control , 2018, Molecules.

[27]  N. Tinari,et al.  Effects of repurposed drug candidates nitroxoline and nelfinavir as single agents or in combination with erlotinib in pancreatic cancer cells , 2018, Journal of Experimental & Clinical Cancer Research.

[28]  R. Mariani-Costantini,et al.  Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells , 2018, Scientific Reports.

[29]  Lingtao Jin,et al.  Naringenin as a potential immunomodulator in therapeutics. , 2018, Pharmacological research.

[30]  L. Barros,et al.  Antimicrobial and antioxidant properties of various Greek garlic genotypes. , 2018, Food chemistry.

[31]  Yuchuan Wang,et al.  Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice , 2018, Pharmaceutical biology.

[32]  B. Jiang,et al.  Resveratrol and inflammatory bowel disease , 2017, Annals of the New York Academy of Sciences.

[33]  L. Gómez-Gómez,et al.  Tissue-Specific Accumulation of Sulfur Compounds and Saponins in Different Parts of Garlic Cloves from Purple and White Ecotypes , 2017, Molecules.

[34]  Jinhua Zhang,et al.  Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies , 2017, Oxidative medicine and cellular longevity.

[35]  M. A. Nazareno,et al.  Cooked garlic and antioxidant activity: Correlation with organosulfur compound composition. , 2017, Food chemistry.

[36]  M. Jiang,et al.  Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease , 2017, Molecules.

[37]  M. Vacca,et al.  An Hydroalcoholic Chamomile Extract Modulates Inflammatory and Immune Response in HT29 Cells and Isolated Rat Colon , 2016, Phytotherapy research : PTR.

[38]  F. Chu,et al.  Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon , 2016, Mediators of inflammation.

[39]  Hailin Qin,et al.  The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-κB pathway , 2016, Pharmacological reports : PR.

[40]  S. Giofrè,et al.  Statistical Analysis of Mineral Concentration for the Geographic Identification of Garlic Samples from Sicily (Italy), Tunisia and Spain , 2016, Foods.

[41]  Yulong Yin,et al.  Quercetin, Inflammation and Immunity , 2016, Nutrients.

[42]  Walaa M. Elwan,et al.  Garlic oil inhibits dextran sodium sulfate-induced ulcerative colitis in rats. , 2016, Life sciences.

[43]  P. Paolicelli,et al.  Infant Milk Formulas: Effect of Storage Conditions on the Stability of Powdered Products towards Autoxidation , 2015, Foods.

[44]  L. Carrera-Quintanar,et al.  Immunomodulation and Anti-Inflammatory Effects of Garlic Compounds , 2015, Journal of immunology research.

[45]  Hui-Yi Lin,et al.  Lotus leaf (Nelumbo nucifera) and its active constituents prevent inflammatory responses in macrophages via JNK/NF-κB signaling pathway. , 2014, The American journal of Chinese medicine.

[46]  Sang Joon Lee,et al.  Ethyl linoleate from garlic attenuates lipopolysaccharide-induced pro-inflammatory cytokine production by inducing heme oxygenase-1 in RAW264.7 cells. , 2014, International immunopharmacology.

[47]  M. Vacca,et al.  Peripheral chemerin administration modulates hypothalamic control of feeding , 2014, Peptides.

[48]  Jaykaran Charan,et al.  How to calculate sample size in animal studies? , 2013, Journal of pharmacology & pharmacotherapeutics.

[49]  Min‐Jung Kang,et al.  Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[50]  M. Lappas,et al.  Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium. , 2013, Molecular human reproduction.

[51]  M. Vacca,et al.  Orexigenic effects of omentin-1 related to decreased CART and CRH gene expression and increased norepinephrine synthesis and release in the hypothalamus , 2013, Peptides.

[52]  A. Ciobica,et al.  Different Profile of Peripheral Antioxidant Enzymes and Lipid Peroxidation in Active and Non-active Inflammatory Bowel Disease Patients , 2013, Digestive Diseases and Sciences.

[53]  S. Heuskin,et al.  Analysis of the diastereoisomers of alliin by HPLC. , 2012, Talanta.

[54]  M. Vasson,et al.  Aloysia triphylla infusion protects rats against dextran sulfate sodium-induced colonic damage. , 2012, Journal of the science of food and agriculture.

[55]  S. Westphal,et al.  Green tea polyphenol epigallocatechin-3-gallate shows therapeutic antioxidative effects in a murine model of colitis. , 2012, Journal of Crohn's & colitis.

[56]  S. Chen,et al.  Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: an ex vivo approach. , 2012, Journal of agricultural and food chemistry.

[57]  G. Poli,et al.  Polyphenol supplementation as a complementary medicinal approach to treating inflammatory bowel disease. , 2011, Current medicinal chemistry.

[58]  C. Lii,et al.  Effect of garlic oil on neutrophil infiltration in the small intestine of endotoxin-injected rats and its association with levels of soluble and cellular adhesion molecules. , 2011, Journal of agricultural and food chemistry.

[59]  F. Mansilla,et al.  Changes in Phenolic Compounds in Garlic (Allium sativum L.) Owing to the Cultivar and Location of Growth , 2011, Plant foods for human nutrition.

[60]  S. M. H. Sohi,et al.  Antioxidant activity of methanolic and hydroalcohlic extracts of garlic plant , 2011 .

[61]  J. K. Kim,et al.  Carotenoid accumulation and characterization of cDNAs encoding phytoene synthase and phytoene desaturase in garlic (Allium sativum). , 2011, Journal of agricultural and food chemistry.

[62]  L. Peyrin-Biroulet,et al.  Recent advances in cytokines: therapeutic implications for inflammatory bowel diseases. , 2011, World journal of gastroenterology.

[63]  E. El-Sayed,et al.  L-arginine augments the antioxidant effect of garlic against acetic acid-induced ulcerative colitis in rats. , 2009, Pakistan journal of pharmaceutical sciences.

[64]  N. Mimica-Dukić,et al.  Phenolics as antioxidants in garlic (Allium sativum L., Alliaceae) , 2008 .

[65]  T. Seki,et al.  Thermostability of Allicin Determined by Chemical and Biological Assays , 2008, Bioscience, biotechnology, and biochemistry.

[66]  R. Orlando,et al.  Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes , 2008, Nutrition & metabolism.

[67]  T. Seki,et al.  Biological and chemical stability of garlic-derived allicin. , 2008, Journal of agricultural and food chemistry.

[68]  G. Yue,et al.  Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats. , 2007, World journal of gastroenterology.

[69]  M. Samsom,et al.  Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[70]  M. Abdollahi,et al.  Oxidative Stress and Pathogenesis of Inflammatory Bowel Disease: An Epiphenomenon or the Cause? , 2007, Digestive Diseases and Sciences.

[71]  M. Lejeune,et al.  Prostaglandin E2 receptor distribution and function in the gastrointestinal tract , 2006, British journal of pharmacology.

[72]  E. Schnug,et al.  Influence of Nitrogen and Sulfur Fertilization on the Alliin Content of Onions and Garlic , 2005 .

[73]  E. Castanas,et al.  Decreased Total and Corrected Antioxidant Capacity in Patients with Inflammatory Bowel Disease , 2004, Digestive Diseases and Sciences.

[74]  M. Crowell,et al.  Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. , 2004, Gastroenterology.

[75]  T. Sasaoka,et al.  Identification of six phenylpropanoids from garlic skin as major antioxidants. , 2003, Journal of agricultural and food chemistry.

[76]  Inder M. Verma,et al.  NF-κB regulation in the immune system , 2002, Nature Reviews Immunology.

[77]  S. Hodge,et al.  Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. , 2002, Cytometry.

[78]  M. Gulubova,et al.  Mast cells and inflammatory mediators in chronic ulcerative colitis. , 2002, Acta histochemica.

[79]  L. Fitzpatrick,et al.  Caffeic acid phenethyl ester, an inhibitor of nuclear factor-kappaB, attenuates bacterial peptidoglycan polysaccharide-induced colitis in rats. , 2001, The Journal of pharmacology and experimental therapeutics.

[80]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[81]  J.-J. Lee,et al.  Changes In Endogenous Monoamines In Aged Rats , 2001, Clinical and experimental pharmacology & physiology.

[82]  Dongman Kim,et al.  Storage quality of chopped garlic as influenced by organic acids and high-pressure treatment , 2001 .

[83]  G. Sivam.  Protection against Helicobacter pylori and other bacterial infections by garlic. , 2001, The Journal of nutrition.

[84]  R. Spiller,et al.  Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acuteCampylobacter enteritis and in post-dysenteric irritable bowel syndrome , 2000, Gut.

[85]  J. Trojanowski,et al.  Increased F2‐isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[86]  D. Perrett,et al.  Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study , 1998, Gut.

[87]  D. Waterer,et al.  Influence of variety and cultural practices on garlic yields in Saskatchewan , 1994 .

[88]  J. Coyle,et al.  Effect of Sodium Benzoate and Sodium Phenylacetate on Brain Serotonin Turnover in the Ornithine Transcarbamylase-Deficient Sparse-Fur Mouse , 1988, Pediatric Research.