Medicinal Plants Classification Biosynthesis and ... - Index of

108
Aracely E. Chávez-Piña and Andrés Navarrete
by vagal and spinal afferent neurons innervating the rodent and human GI tract [72, 73].
Capsaicin, the main active ingredient on hot chilli peppers, activates TRPV1 [74]. In humans,
capsaicin decreased stomach injury caused by ethanol and microbleeding induced by
indomethacin administration was reversed by co-administration with capsaicin [75].
Capsaicin induces its gastroprotective action by the induction of the increment on gastric
blood flow, but in contrast to this statement capsaicin reverts gastroprotection induced by
tumoral growth factor-α (TGF-α) [76]. Then, capsaicin exerts its gastroprotective effect at
low doses, while higher doses of capsaicin induce injury. Taken those results together, appear
that capsaicin is involved in adaptative cytoprotection induced by mild irritants. Adaptative
cytoprotection is the ability that gastric mucosa possesses to induce damage by prolonged
exposure to low doses of an irritant.
3.4. Other Gastroprotective Mechanism.
3.4.1. Cytokines
Cytokines are substances released from the immune system to cause injury or healing.
IL-1β is produced in various types of cells such as monocytes, macrophages, neutrophils,
endothelial cells and fibroblasts [77]. IL-1β inhibits migration of neutrophils and leukotriene
B4 in a dose-dependently manner after the injection of the noxious stimulus. IL-1β also
protected the mucosa against indomethacin-induced injury in gastric tissue [78]. This
interleukin also reduced acid gastric secretion induced by aspirin treatment [79] and inhibited
the release of platelet-activating factor, a potent pro-inflammatory substance, from peritoneal
mast cells through stimulating NO release [80].
3.4.2. Annexin-1
Annexin-1 is a protein of 37 kDa, which used to be named as lipopocortin-1. Annexin-1
is member of annexin family of proteins that bind to and activate ―formyl-peptide‖ receptors
(FPR) [81, 82]. Glucocorticoids can modulate this protein expression. It was found that
annexin-1 possesses calcium and phospholipids binding properties and was actively involved
in the inhibition of eicosanoid synthesis and PLA2 [83].
Furthermore, glucocorticoid treatment increases annexin-1 content in circulating
neutrophils in humans and rodents [84, 85]. Annexin-1 promotes leukocyte detachment, and
then inhibits cell extravasation. Besides, dexamethasone, a glucocorticoid, protects the
mucosa against indomethacin-induced injury. This effect was reverted by the administration
of formyl-peptide receptor antagonist. Dexamethasone decreases leukocyte adherence in
mesentery induced after indomethacin treatment, throw the expression of annexin-1; besides,
annexin-1 is expressed constitutively in rat stomach [86]. Annexin-1 has been related to act
throw the same receptor than lipoxin A4 and 15-epi-LXA4.
Annexin-1 also participates on gastric ulcer healing; annexin-1 expression is strongly
induced in ulcerated gastric tissue. Furthermore, annexin-1 knockout mice show similar
susceptibility to indomethacin-induced gastric damage. For this result Martin proposes the
hypothesis that annexin-1 contributes to the healing of gastric mucosal damage [83].