mechanisms: blockage of PTP1B to enhance leptin and insulin sensitivity to exhibit
synergistic effects on glucose and lipidic metabolism and modulation of GLUT4
translocation via activating PI3K/AKT pathway in the liver and muscle. Finally, the
amelioration of glucose and lipidic metabolism and insulin level through the
functional enzymes, insulin-related oxidant stress, and inflammatory factors are also
implicated in the antidiabetic action of some natural bioactive compounds.
15.3 a-Amilase Inhibitors
Since ancient times, plants have been considered as a source of compounds for the
treatment of various diseases. Currently, given the availability of these compounds,
their low cost, ease of preparation and/or minimal side effects have increased their
use throughout the country world (Sachithanandam et al. 2019), as well as the
interest in discovering new antidiabetic drugs.
Several studies have focused on plants that have been attributed to antidiabetic
activity by inhibiting carbohydrate-degrading enzymes (Trinh et al. 2020) also
called glucosidases. Glucosidases are a group of digestive enzymes that break down
the dietary carbohydrates into simple monosaccharides. One of these glucosidases
is a-amylase. The a-amylase is one of the major secretory products of the pancreas
and salivary glands, catalyze the hydrolysis of starch via a double displacement
mechanism involving the formation and hydrolysis of a covalent-glycosyl enzyme
intermediate by using active site carboxylic acids for it (Sales et al. 2012).
Glucosidases inhibitor enzymes reduce the rate of carbohydrate digestion and delay
the carbohydrate absorption from the digestive tract; therefore, they have the
potential to prevent the development of diabetes by lowering the after-meal glucose
levels (Miao et al. 2015). a-Amylase inhibitors are also called starch blockers since
they prevent or slow down the absorption of starch into the body mainly by
blocking the hydrolysis of 1,4-glycosidic linkages of starch and other oligosaccharides into maltose, maltotriose, and other simple sugars.
Plants have a wide diversity of compounds including polyphenols than are good
inhibitors of enzymes responsible for carbohydrate digestion. The inhibition of
a-amylase by a polyphenol is highly related to its molecular structure, as the
inhibition results from binding interactions between polyphenols and the enzyme
(Sun et al. 2019). Hydroxyl groups, galloyl substituents, and conjugated systems
are some of the important characteristics of polyphenols for effective inhibition of
the enzyme (Table 15.1).
There are other compounds such as oligosaccharide inhibitors of the trestatin
family, proteinaceous inhibitors isolated from plant tissues. Acarbose is obtained
from this type of compound. Acarbose is a compound used in the clinical treatment
of diabetes mellitus, it is a competitive a-Amylase inhibitor. Terpenoids (oleanane,
ursane, and lupane) have been linked to a-Amylase inhibition although their
mechanism is not yet known (Sales et al. 2012).
538
S. N. Jimenez-Garcia et al.
synergistic effects on glucose and lipidic metabolism and modulation of GLUT4
translocation via activating PI3K/AKT pathway in the liver and muscle. Finally, the
amelioration of glucose and lipidic metabolism and insulin level through the
functional enzymes, insulin-related oxidant stress, and inflammatory factors are also
implicated in the antidiabetic action of some natural bioactive compounds.
15.3 a-Amilase Inhibitors
Since ancient times, plants have been considered as a source of compounds for the
treatment of various diseases. Currently, given the availability of these compounds,
their low cost, ease of preparation and/or minimal side effects have increased their
use throughout the country world (Sachithanandam et al. 2019), as well as the
interest in discovering new antidiabetic drugs.
Several studies have focused on plants that have been attributed to antidiabetic
activity by inhibiting carbohydrate-degrading enzymes (Trinh et al. 2020) also
called glucosidases. Glucosidases are a group of digestive enzymes that break down
the dietary carbohydrates into simple monosaccharides. One of these glucosidases
is a-amylase. The a-amylase is one of the major secretory products of the pancreas
and salivary glands, catalyze the hydrolysis of starch via a double displacement
mechanism involving the formation and hydrolysis of a covalent-glycosyl enzyme
intermediate by using active site carboxylic acids for it (Sales et al. 2012).
Glucosidases inhibitor enzymes reduce the rate of carbohydrate digestion and delay
the carbohydrate absorption from the digestive tract; therefore, they have the
potential to prevent the development of diabetes by lowering the after-meal glucose
levels (Miao et al. 2015). a-Amylase inhibitors are also called starch blockers since
they prevent or slow down the absorption of starch into the body mainly by
blocking the hydrolysis of 1,4-glycosidic linkages of starch and other oligosaccharides into maltose, maltotriose, and other simple sugars.
Plants have a wide diversity of compounds including polyphenols than are good
inhibitors of enzymes responsible for carbohydrate digestion. The inhibition of
a-amylase by a polyphenol is highly related to its molecular structure, as the
inhibition results from binding interactions between polyphenols and the enzyme
(Sun et al. 2019). Hydroxyl groups, galloyl substituents, and conjugated systems
are some of the important characteristics of polyphenols for effective inhibition of
the enzyme (Table 15.1).
There are other compounds such as oligosaccharide inhibitors of the trestatin
family, proteinaceous inhibitors isolated from plant tissues. Acarbose is obtained
from this type of compound. Acarbose is a compound used in the clinical treatment
of diabetes mellitus, it is a competitive a-Amylase inhibitor. Terpenoids (oleanane,
ursane, and lupane) have been linked to a-Amylase inhibition although their
mechanism is not yet known (Sales et al. 2012).
538
S. N. Jimenez-Garcia et al.