Medicinal Plants Classification Biosynthesis and ... - Index of

Gastroprotective Triterpenoids: Pharmacological Mechanism
to yield PGH2 [31]. The latter is a relatively unstable compound that has a half-life of seconds
and is a common intermediate that is converted to biologically active products such as
thromboxane (TXA2), prostacyclin (PGI2), PGD2, PGE2 and PGF1α, by thromboxane
synthase, prostacyclin synthase, PGD2 isomerase, PGE2 isomerase and PGF reductase
respectively. The synthesis of each kind of prostaglandin depends of the cell and enzyme
present in each tissue.
In gastric tissue, mainly are synthesized PGE2 and PGI2. Prostaglandins derived from
COX-1 in gastric mucosa mediate many of the components of gastric mucosa defense, such
as the maintenance of gastric blood flow by PGI2 and bicarbonate and mucus secretion by
PGE2; in addition it retards the ability of acid and pepsin to penetrate mucus [22, 32]. When
COX-1 is inhibited, COX-2 expression is induced to protect or heal gastric damage. COX-2
synthesizes PGs from arachidonic acid and their functions in gastric mucosa healing are due
to the inhibition of leukocyte adherence and the increment on epithelial proliferation [32].
Prostaglandins generally act in an autocrine or paracrine manner and have short half-lives
(seconds to minutes) in the circulation.
COX-1 is the predominant form expressed in the normal gastrointestinal tract, but COX-
2 can be detected and has been shown to be rapidly up-regulated in response to a number of
stimuli, such as aspirin or indomethacin administration [33].
Besides, COX-1 and COX-2 inhibition is required for the development of gastric
erosions after NSAID administration [34, 35]. It has been reported that SC-560, a COX-1
selective inhibitor, did not elicit gastric damage, even SC-560 decreased gastric blood flow
and did not increase leukocyte adherence in mesentery. Furthermore, celecoxib, a selective
COX-2 inhibitor, did not induce gastric damage by itself. However, celecoxib increase
leukocyte adherence, while did not produce any significant changes in gastric blood flow.
Celecoxib and SC-560 administered concomitantly induced a decreased on gastric blood flow
and an augmented leukocyte adherence, and then this combination produced gastric erosions
[35].
Moreover, mice in which the gene for COX-1 was disrupted did not exhibit spontaneous
gastric damage despite negligible gastric PG synthesis. However, these mice did developed
erosions when indomethacin was given (a dual COX-1/COX-2 inhibitor) [34].
Furthermore about mucosal defense role of COX-2, this enzyme derived prostaglandins
also make an important contribution to the repair of ulcers. COX-2 is strongly expressed in
cells at the ulcer margin, which is where epithelial proliferation primarily occurs, allowing
for reestablishment of glands. COX-2 is also strongly expressed in endothelial cells in the
ulcer bed, where is the site of new vessel growth (angiogenesis) [36].
3.2.2. Nitric oxide (NO)
Nitric oxide is a small molecule synthesized from the terminal guanidine nitrogen atom
of L-arginine. Its synthesis is carried out by a nitric oxide synthase (NOS) through a five
electron oxidation reaction using as cofactors flavin mononucleotide, flavin adenine
dinucleotide, tetrahydrobiopterin and protoporphyrin IX heme. There are three different
isoforms of NOS, its distributions depends on cell kind. Two of them are Ca 2+ /calmodulindependent
constitutive enzymes (cNOS); neuronal (nNOS) and endothelial (eNOS). The third
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