A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression

Abstract Background Intestinal epithelial barrier dysfunction predisposes to many gastrointestinal, metabolic, and psychological disorders. A flavonoid rich extract of Glycyrrhiza glabra (FREG) has previously been reported to possess anti-inflammatory, antioxidant, and antiulcer properties. Aim To i...

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Main Authors: Sasi Kumar Murugan, Bharathi Bethapudi, Subramanian Raghunandhakumar, Divya Purusothaman, Muruganantham Nithyanantham, Deepak Mundkinajeddu, Muralidhar Srinivasaih Talkad
Format: Article
Language:English
Published: BMC 2022-02-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-021-03500-1
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author Sasi Kumar Murugan
Bharathi Bethapudi
Subramanian Raghunandhakumar
Divya Purusothaman
Muruganantham Nithyanantham
Deepak Mundkinajeddu
Muralidhar Srinivasaih Talkad
author_facet Sasi Kumar Murugan
Bharathi Bethapudi
Subramanian Raghunandhakumar
Divya Purusothaman
Muruganantham Nithyanantham
Deepak Mundkinajeddu
Muralidhar Srinivasaih Talkad
author_sort Sasi Kumar Murugan
collection DOAJ
description Abstract Background Intestinal epithelial barrier dysfunction predisposes to many gastrointestinal, metabolic, and psychological disorders. A flavonoid rich extract of Glycyrrhiza glabra (FREG) has previously been reported to possess anti-inflammatory, antioxidant, and antiulcer properties. Aim To investigate the effect of FREG (GutGard®) on restoring intestinal barrier function in tumor necrosis factor-alpha (TNF-α) stimulated human colonic adenocarcinoma cell monolayer (Caco-2) and 2,4,6-Trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rats. Methods In in vitro, human intestinal Caco-2 cell monolayers were treated with TNF-α in the presence or absence of FREG and the paracellular permeability to FITC-conjugated 4-kD dextran (FD4) was measured to evaluate protection against the barrier dysfunction. In in vivo, intestinal barrier dysfunction was induced in male albino Wistar rats via intrarectal instillation of TNBS. Subsequently, the rats were treated orally with either FREG at 6.25, 12.5, and 25 mg/kg body weight, or Mesacol (250 mg/kg) for 5 days. On day 5, intestinal epithelial permeability was assessed with FD4 leakage into the serum. Also, colonic inflammation, colon morphology, histology and macroscopic score, weight to length ratio were evaluated. The activity of myeloperoxidase (MPO), TNF- α, secretory IgA levels and tight junction proteins expression were evaluated in rat’s colon. Results FREG protected the intestinal epithelial barrier integrity in human intestinal Caco-2 cells in vitro. FREG administration significantly improved the intestinal epithelial barrier function as evident from significant reduction in FD4 leakage. The colon morphology, histology score, macroscopic score, colon weight to length ratio also indicates beneficial effects of FREG on barrier function. In addition, FREG regulated the tight junction proteins, and markedly decreased TNF-α, MPO levels and significantly increased the secretory IgA levels in TNBS induced colitis rats. Conclusion The study findings support the protective action of FREG on intestinal epithelial barrier integrity indicating its potential in protecting from implications of leaky gut.
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spelling doaj.art-21ec959981d84749b49c7ad33885c1142022-12-21T17:26:29ZengBMCBMC Complementary Medicine and Therapies2662-76712022-02-0122111410.1186/s12906-021-03500-1A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expressionSasi Kumar Murugan0Bharathi Bethapudi1Subramanian Raghunandhakumar2Divya Purusothaman3Muruganantham Nithyanantham4Deepak Mundkinajeddu5Muralidhar Srinivasaih Talkad6Department of Pharmacology & Toxicology, R&D Centre, Natural Remedies Private LimitedDepartment of Pharmacology & Toxicology, R&D Centre, Natural Remedies Private LimitedDepartment of Pharmacology, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS)Department of Pharmacology & Toxicology, R&D Centre, Natural Remedies Private LimitedDepartment of Pharmacology & Toxicology, R&D Centre, Natural Remedies Private LimitedDepartment of Pharmacology & Toxicology, R&D Centre, Natural Remedies Private LimitedDepartment of Animal Health Science, R&D Centre, Natural Remedies Private LimitedAbstract Background Intestinal epithelial barrier dysfunction predisposes to many gastrointestinal, metabolic, and psychological disorders. A flavonoid rich extract of Glycyrrhiza glabra (FREG) has previously been reported to possess anti-inflammatory, antioxidant, and antiulcer properties. Aim To investigate the effect of FREG (GutGard®) on restoring intestinal barrier function in tumor necrosis factor-alpha (TNF-α) stimulated human colonic adenocarcinoma cell monolayer (Caco-2) and 2,4,6-Trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rats. Methods In in vitro, human intestinal Caco-2 cell monolayers were treated with TNF-α in the presence or absence of FREG and the paracellular permeability to FITC-conjugated 4-kD dextran (FD4) was measured to evaluate protection against the barrier dysfunction. In in vivo, intestinal barrier dysfunction was induced in male albino Wistar rats via intrarectal instillation of TNBS. Subsequently, the rats were treated orally with either FREG at 6.25, 12.5, and 25 mg/kg body weight, or Mesacol (250 mg/kg) for 5 days. On day 5, intestinal epithelial permeability was assessed with FD4 leakage into the serum. Also, colonic inflammation, colon morphology, histology and macroscopic score, weight to length ratio were evaluated. The activity of myeloperoxidase (MPO), TNF- α, secretory IgA levels and tight junction proteins expression were evaluated in rat’s colon. Results FREG protected the intestinal epithelial barrier integrity in human intestinal Caco-2 cells in vitro. FREG administration significantly improved the intestinal epithelial barrier function as evident from significant reduction in FD4 leakage. The colon morphology, histology score, macroscopic score, colon weight to length ratio also indicates beneficial effects of FREG on barrier function. In addition, FREG regulated the tight junction proteins, and markedly decreased TNF-α, MPO levels and significantly increased the secretory IgA levels in TNBS induced colitis rats. Conclusion The study findings support the protective action of FREG on intestinal epithelial barrier integrity indicating its potential in protecting from implications of leaky gut.https://doi.org/10.1186/s12906-021-03500-1Leaky gutGlycyrrhiza glabraIntestinal permeability2,4,6-Trinitrobenzenesulfonic acidTNF-alphaTight junction proteins
spellingShingle Sasi Kumar Murugan
Bharathi Bethapudi
Subramanian Raghunandhakumar
Divya Purusothaman
Muruganantham Nithyanantham
Deepak Mundkinajeddu
Muralidhar Srinivasaih Talkad
A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
BMC Complementary Medicine and Therapies
Leaky gut
Glycyrrhiza glabra
Intestinal permeability
2,4,6-Trinitrobenzenesulfonic acid
TNF-alpha
Tight junction proteins
title A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
title_full A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
title_fullStr A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
title_full_unstemmed A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
title_short A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression
title_sort flavonoid rich standardized extract of glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight junction proteins expression
topic Leaky gut
Glycyrrhiza glabra
Intestinal permeability
2,4,6-Trinitrobenzenesulfonic acid
TNF-alpha
Tight junction proteins
url https://doi.org/10.1186/s12906-021-03500-1
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