3-epi-oleanolic acid
6. Summary and Conclusions
In summary there are several mechanisms that mediate gastric injury, all of them work together. PGs are the basis for mucosa gastric defense, they regulate gastric blood flow and gastric mucus secretion and bicarbonate throw the activation of COX-1; moreover, PGs regulate leukocyte adherence and reepithelization with COX-2. However, when both cyclooxygenases are inhibited another mechanism emerges to compensate this lack in PGs synthesis. NO and H2S are gaseous mediators and it has been elucidated their role in gastric mucosa defense. Both gases could be synthesized to reduce the damage caused by PGs inhibition; they share roles with PGs such as the increment in gastric blood flow and the inhibition on leukocyte adherence.
Ethanol- and NSAIDs-induced gastric injuries are the most common experimental models for the study of gastroprotective drugs. Ethanol induces mucosa necrosis and NSAIDs inhibit PGs synthesis to stimulate damage. Furthermore, both increment TNF-α to induce injury. Several natural products have exhibited a significant contribution in the field of gastroprotective substances. Triterpenes are compounds with gastroprotective properties; they play this role by PGs, NO and/or -SH stimulation. There are many reports about the role that LTB4 plays on gastric damage, however there is not much information about those levels after administration of gastroprotective triterpenoids.
Moreover, a lack on leukocyte adherence may play a role in the gastroprotective properties of some triterpenoids. Moreover, there are an unexplored field in the role of annexins, lipoxins and H2S generation after gastroprotective triterpenoid administration.
TNF-α is another inflammatory mediator that a lack on it should help to the healing of the endothelium.
In relationship with the chemical structure requirement for triterpenoids to exhibit gastroprotective properties, it has been found that a hydroxyl group in the C-3 position is related with its gastroprotective activity.
In conclusion, triterpenoid exhibit gastroprotective properties by PGs, NO and/ or -SH stimulation. There is another mechanism that remains unexplored such as H2S generation mainly. Pharmacokinetic studies need to be done about active triterpenoids. It should help to explain its properties in the organism. Derivatives from natural triterpenes should be a strategy to improve the gastroprotective effect of this kind of natural products.
7. Acknowledgements
The authors acknowledge to Dirección General de Asuntos del Personal Académico (DGAPA IN 205008) and Consejo Nacional de Ciencia y Tecnología (CONACYT 82613) for partial support to study the pharmacology of Mexican natural products. A. Chavez acknowledges postdoctoral fellowship from DGAPA.
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