Antileishmanial Activity of Lignans, Neolignans …
145
atheroprotective properties, and hence may help to reduce the risks associated with
chronic diseases [288–291].
3.3.7 Antidiabetic and Antiobesity Effects
Diabetes is a group of metabolic diseases caused by defects in insulin production,
insulin regulation, or a combination of both, which results in hyperglycemia or
chronic hyperglycemia. Both these diseases have unpleasant consequences, sometimes inclusive of the failure of the eyes, kidneys, nervous system, blood vessels, or
heart. Pathological processes that lead to such consequences vary from autoimmune
destruction of β-cells to abnormalities linked with insulin resistance. Hyperglycemia
is a causative agent of polyuria, polydipsia, weight loss, polyphagia, or blurred vision.
The acute symptoms are life threatening and include ketoacidosis or nonketotic
hyperosmolar syndrome. Chronic hyperglycemia relates to retinopathy and loss of
vision, nephropathy and renal failure, peripheral neuropathy, and dysfunction of the
intestinal and urinary tracts and the cardiovascular system [292]. In general, if a
patient suffers from insulin resistance and type 2 diabetes, obesity is also evident.
Obesity may trigger coronary heart diseases, certain forms of cancer, sleep-breathing
disorders, and complicate the treatment of other diseases due to the inflammation of
metabolic tissues [293, 294].
In the case of plant phenolic compounds, some have proven to be valuable in
ameliorating the symptoms of diabetes type 2. Flavonoid derivatives such as various
anthocyanins, and catechin (45), epicatechin (32), and kaempferol (49) and/or their
glycosides, as well as procyanidins, may have a preventive role and can be used
in nutrition-based cotreatments during the stabilization of diabetes symptoms [101,
295]. Their general mechanisms of action are based on the protection of β cells against
glucose toxicity and on the regulation of glucose transport (glycemic management)
[122, 295–297]. Another well-studied compound is the flavonol diglycoside, rutin
(105), which possesses antioxidant, anticarcinogenic, antihypertensive, and antihypercholesterolemic activity, which makes it a compound of interest in influencing
the progression of obesity and diabetes [298, 299]. Interestingly, its biological activities are not dependent on one single mechanism. Clinical studies suggest that 105
increases HDL (high-density lipoprotein), VLDL (very-low density lipoprotein),
TGL (triglycerides), and TC (total cholesterol) levels, while decreasing LDL (lowdensity lipoproteins) levels. Rutin (105) also increases the secretion of insulin, and
therefore decreases glucose levels (in hyperglycemic rats) and moderates the Ca
+2
uptake (in rat pancreatic islets) [299, 300].
The stilbenoid, resveratrol (31), in laboratory animals and humans, may improve
glycemic control. It affects the energy metabolism and mitochondrial function, and
in animal models acts as a calorie restriction mimetic. Compound 31 can activate 5
-adenosine monophosphate-activated protein kinase (AMPK), increase SIRT1
expression, and modulate peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha protein levels, and also it increases citrate synthase activity
145
atheroprotective properties, and hence may help to reduce the risks associated with
chronic diseases [288–291].
3.3.7 Antidiabetic and Antiobesity Effects
Diabetes is a group of metabolic diseases caused by defects in insulin production,
insulin regulation, or a combination of both, which results in hyperglycemia or
chronic hyperglycemia. Both these diseases have unpleasant consequences, sometimes inclusive of the failure of the eyes, kidneys, nervous system, blood vessels, or
heart. Pathological processes that lead to such consequences vary from autoimmune
destruction of β-cells to abnormalities linked with insulin resistance. Hyperglycemia
is a causative agent of polyuria, polydipsia, weight loss, polyphagia, or blurred vision.
The acute symptoms are life threatening and include ketoacidosis or nonketotic
hyperosmolar syndrome. Chronic hyperglycemia relates to retinopathy and loss of
vision, nephropathy and renal failure, peripheral neuropathy, and dysfunction of the
intestinal and urinary tracts and the cardiovascular system [292]. In general, if a
patient suffers from insulin resistance and type 2 diabetes, obesity is also evident.
Obesity may trigger coronary heart diseases, certain forms of cancer, sleep-breathing
disorders, and complicate the treatment of other diseases due to the inflammation of
metabolic tissues [293, 294].
In the case of plant phenolic compounds, some have proven to be valuable in
ameliorating the symptoms of diabetes type 2. Flavonoid derivatives such as various
anthocyanins, and catechin (45), epicatechin (32), and kaempferol (49) and/or their
glycosides, as well as procyanidins, may have a preventive role and can be used
in nutrition-based cotreatments during the stabilization of diabetes symptoms [101,
295]. Their general mechanisms of action are based on the protection of β cells against
glucose toxicity and on the regulation of glucose transport (glycemic management)
[122, 295–297]. Another well-studied compound is the flavonol diglycoside, rutin
(105), which possesses antioxidant, anticarcinogenic, antihypertensive, and antihypercholesterolemic activity, which makes it a compound of interest in influencing
the progression of obesity and diabetes [298, 299]. Interestingly, its biological activities are not dependent on one single mechanism. Clinical studies suggest that 105
increases HDL (high-density lipoprotein), VLDL (very-low density lipoprotein),
TGL (triglycerides), and TC (total cholesterol) levels, while decreasing LDL (lowdensity lipoproteins) levels. Rutin (105) also increases the secretion of insulin, and
therefore decreases glucose levels (in hyperglycemic rats) and moderates the Ca
+2
uptake (in rat pancreatic islets) [299, 300].
The stilbenoid, resveratrol (31), in laboratory animals and humans, may improve
glycemic control. It affects the energy metabolism and mitochondrial function, and
in animal models acts as a calorie restriction mimetic. Compound 31 can activate 5
-adenosine monophosphate-activated protein kinase (AMPK), increase SIRT1
expression, and modulate peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha protein levels, and also it increases citrate synthase activity