Figure 2.

Physiological regulation of gastric mucosa and key factors involved in the gastroprotective effect of propolis against NSAIDs-induced gastric ulcers. Black arrows and slashes show the relationship between the cells that are present in gastric mucosa. The ganglion cell of the enteric nervous system (ENS) that secretes histamine interacts with parietal cells and epithelial cells to regulate the acid and mucus secretion, respectively; additionally, it induces the secretion of histamine in the enterochromaffin-like cells (ECL), and, together with the gastrin, induces acid secretion in parietal cells. COX isoenzymes (COX-1 and COX-2) and their localization in the gastric mucosa cells are presented, as well as the production of prostaglandin E₂ (PGE₂), which is a key molecule that regulates mucus production in epithelial cells and acid suppression in parietal cells; moreover, it is implicated in the pro-inflammatory response exerted by leucocytes as a response to the increase in the prostaglandin secretion by COX-2, as well as the reduction in blood flow in the gastric mucosa. The COX suppressor activity of NSAIDs and their adverse effects in the gastric mucosa cells, such as the capacity for generating COX-independent damage in epithelial cells by inducing reactive oxygen species (ROS) production, are shown by red arrows and slashes. On the other hand, green arrows and slashes show the key factors implicated in the gastroprotection of propolis in the gastric mucosa, as well as its antioxidant and anti-inflammatory effects in the gastric tissue. Finally, membrane receptors and their agonists are included in the figure according to their cellular localization and physiological function in the gastric mucosa. Additionally, are shown some secondary metabolites identified in propolis samples that display gastroprotective effects and the cell types in which they have their activity. In the yellow section are named secondary metabolites that have antacid activities; the blue section is listed secondary metabolites that stimulate gastric mucus secretion; the red section is shown secondary metabolites that own antioxidant activity, and the purple section is shown secondary metabolites that displays anti-inflammatory activities related to gastric ulcer disease. It should be noted that the blue arrows and slashes are shown specific activity of some secondary metabolites as the baicalein that display their suppressive activity of acid secretion in parietal cells by means of H2 receptors. Quercetin inhibits the proton pump ATPase activity of parietal cells. On the other hand, epicatechin has cytoprotective activity in epithelial cells of the gastric mucosa; and formononetin (an inhibitor of TNF-α and IL-6), chrysin (that is an immunomodulator), and CAPE (an inhibitor of NF-κB) display their activities on leukocytes of gastric mucosa in the ulcerative process.