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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Cell+Physiol
2017 ; 312
(4
): C438-C445
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Curcumin improves intestinal barrier function: modulation of intracellular
signaling, and organization of tight junctions
#MMPMID28249988
Wang J
; Ghosh SS
; Ghosh S
Am J Physiol Cell Physiol
2017[Apr]; 312
(4
): C438-C445
PMID28249988
show ga
Association between circulating lipopolysaccharide (LPS) and metabolic diseases
(such as type 2 diabetes and atherosclerosis) has shifted the focus from high-fat
high-cholesterol containing Western-type diet (WD)-induced changes in gut
microbiota per se to release of gut bacteria-derived products (e.g., LPS) into
circulation due to intestinal barrier dysfunction as the possible mechanism for
the chronic inflammatory state underlying the development of these diseases. We
demonstrated earlier that oral supplementation with curcumin attenuates
WD-induced development of type 2 diabetes and atherosclerosis. Poor
bioavailability of curcumin has precluded the establishment of a causal
relationship between oral supplementation and it is in vivo effects. We
hypothesized that curcumin attenuates WD-induced chronic inflammation and
associated metabolic diseases by modulating the function of intestinal epithelial
cells (IECs) and the intestinal barrier function. The objective of the present
study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and
HT-29 were used for these studies and modulation of direct as well as indirect
effects of LPS on intracellular signaling as well as tight junctions were
examined. Pretreatment with curcumin significantly attenuated LPS-induced
secretion of master cytokine IL-1? from IECs and macrophages. Furthermore,
curcumin also reduced IL-1?-induced activation of p38 MAPK in IECs and subsequent
increase in expression of myosin light chain kinase involved in the
phosphorylation of tight junction proteins and ensuing disruption of their normal
arrangement. The major site of action of curcumin is, therefore, likely the IECs
and the intestinal barrier, and by reducing intestinal barrier dysfunction,
curcumin modulates chronic inflammatory diseases despite poor bioavailability.