Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-trinitrobenzene sulphonic acid.
BACKGROUND
Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis and, thus, surgery remains the only available strategy in the management of fibrostenotic enteropathies, especially Crohn's disease. The aim of this study was to evaluate the efficacy of a combined therapy of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts on the development of colonic fibrosis in rats.


METHODS
Chronic colonic inflammation-associated fibrosis was induced in rats by intracolonic administration of 2,4,5-trinitrobenzene sulphonic acid (TNBS). Sixty-four healthy male Sprague-Dawley rats were assigned to five groups: 8 controls, 14 TNBS, 14 TNBS orally treated with Boswellia extracts (50 mg kg(-1) day(-1)), 14 TNBS orally treated with Scutellaria extracts (150 mg kg(-1) day(-1)), and 14 TNBS orally treated with both Boswellia (50 mg kg(-1) day(-1)) and Scutellaria extracts (150 mg kg(-1) day(-1)). The colon was removed after 21 days of treatment and assessed by macroscopic, histological, morphometric and immunohistochemical analyses. For immunohistochemical analysis, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1), Smad3, Smad7 and CD3 antibodies were used.


RESULTS
Combined oral administration of Boswellia and Scutellaria significantly improved the course and macroscopic findings of TNBS-induced chronic colitis assessed by disease activity index, colon weight, length, adhesions, strictures, dilatation, thickness, oedema, ulcerations and extension of damage. The histological severity of the colonic fibrosis was also notably improved by the treatment and associated with a significant reduction in the colonic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7.


CONCLUSIONS
These data demonstrate that the prophylactic administration of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts is effective in preventing colonic fibrosis in TNBS-induced colitis. Their antifibrotic mechanism of action seems to be mediated by the inhibition of TGF-beta1/Smad3 pathway.
Latella
G
G
Dipartimento di Medicina Interna e Sanità Pubblica, University of L'Aquila, L'Aquila, Italy. giolatel@tin.it
Sferra
R
R
Vetuschi
A
A
Zanninelli
G
G
D'Angelo
A
A
Catitti
V
V
Caprilli
R
R
Gaudio
E
E
D000199:Actins / Q000032:analysis; D000818:Animals; D029743:Boswellia; D017252:CD3 Complex / Q000032:analysis; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D003106:Colon / Q000737:chemistry / Q000473:pathology*; D055513:Connective Tissue Growth Factor; D003424:Crohn Disease / Q000628:therapy; D005355:Fibrosis; D017874:Immediate-Early Proteins / Q000032:analysis; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D023421:Models, Animal; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D031363:Scutellaria; D051900:Smad3 Protein / Q000032:analysis; D051906:Smad7 Protein / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014302:Trinitrobenzenesulfonic Acid
D000199:Actins; C526316:CCN2 protein, rat; D017252:CD3 Complex; D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010936:Plant Extracts; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D014302:Trinitrobenzenesulfonic Acid