**7. Inhibition of α-amylase and** α**-glucosidase enzymes.**

α-Amylase and α-glucosidase are carbohydrate hydrolyzing enzymes located in the digestive tract. α- amylase in the duodenum initiates digestion and catalyzes the hydrolysis of α-1, 4 glycosidic linkages in starch resulting into sugars such as maltose, maltotriose and branched oligosaccharides. Then, α-glucosidase present in the brush border of the intestinal epithelium (enterocytes) is responsible for the final step of carbohydrates digestion, prior to their absorption. This enzyme cleaves

**17**

*Antidiabetic Principle in* Cucumis sativus *L. DOI: http://dx.doi.org/10.5772/intechopen.96393*

humans [42, 43].

terminal non-reducing 1, 4 linkages and converts the disaccharides and oligosaccharides into glucose, which is then transported by sodium/glucose co-transporter 1 (SGLT1) from the intestinal lumen to the cytosol of enterocytes. In turn, glucose transporter 2 (GLUT2), found in the basolateral membrane of enterocytes, trans-

by the inhibition of carbohydrate hydrolyzing enzymes in the digestive tract of

kaempferol lowers blood glucose and inhibit α-amylase and α -glucosidase.

inhibition of α -amylase and α -glucosidase through kaempferol.

sis by targeting the glucose production and metabolic pathways.

**8. Maintaining glucose homeostasis**

**9. Modulation of antioxidant profile**

**10. Reversal of lipid profile alterations**

induced diabetic rats [29].

One of the approaches to managing diabetes is to delay the absorption of glucose

Controlling the activity of these enzymes slows glucose production in the postprandial stage and this could be a therapeutic approach for people with diabetes. Hence, the search for inhibitors from medicinal plants is a great development [44]. Ibitoye et al. identified that kaempferol from *Cucumis sativus L*. lowers blood glucose and inhibited the activity of α -amylase and α glucosidase at IC50 of 51.24 and 29.37 μg/mL respectively [29]. This inhibition means reduction in blood glucose in the postprandial stage of alloxan-induced diabetic rats when given 165 mg/kg body weight of kaempferol from *Cucumis sativus* fruits. This evidently supports that

It may be possible that the glucose lowering activity of *C. sativus* fruits is through

Diabetes features dysregulated glucose metabolism characterized by increased

hepatic glucose production and decreased glucose oxidation. This eventually leads to deterioration in glucose control. Alkhalidy *et al* reported that kaempferol ameliorate hyperglycemia and enhance glucose tolerance in insulin deficient mice [45]. Diabetic mice displayed significantly higher pyruvate carboxylase activity. Kaempferol treatment suppressed the elevated pyruvate carboxylase activity and glucose-6 phosphatase activity in the liver suggesting that kaempferol may improve glycemic control in diabetes in part through suppressing gluconeogenesis in the liver via the regulation of pyruvate carboxylase, the first and critical step in gluconeogenesis [45]. It could therefore be a strategy for maintaining glucose homeosta-

Generation of reactive oxygen species and free radicals contributes to the pathogenesis of diabetes [46]. This increased ROS production overruns the cellular antioxidant defense system leading to oxidative stress and damage [47]. Some diabetes research confirm this phenomenon in different diabetes model [48, 49]. Catalase, superoxide dismutase and glutathione are reduced significantly in diabetes [50]. Kaempferol reversed the alterations on oxidative stress markers in alloxan-

One of the complications in diabetes is dyslipidemia, where the lipid profile is disturbed. It is usually presented with elevated levels of total cholesterol TC, triacylglycerol TAG, and low-density lipoprotein cholesterol LDLc and a reduction of high density lipoprotein cholesterol HDLc [51]. These alterations could predispose to developing

ports glucose from cytosol to blood via facilitated diffusion.

#### *Antidiabetic Principle in* Cucumis sativus *L. DOI: http://dx.doi.org/10.5772/intechopen.96393*

*Cucumber Economic Values and Its Cultivation and Breeding*

Intestinal permeability study of kaempferol shows it undergoes significant biotransformation, with only a small fraction of the unchanged kaempferol able

broccoli, cabbage, grapes, strawberries, tomatoes, apples and grapefruit [37].

Kaempferol has been reported to lower blood glucose [40], inhibit α -amylase and α -glucosidase [41]. This section addresses the mechanism of action of

α-Amylase and α-glucosidase are carbohydrate hydrolyzing enzymes located in the digestive tract. α- amylase in the duodenum initiates digestion and catalyzes the hydrolysis of α-1, 4 glycosidic linkages in starch resulting into sugars such as maltose, maltotriose and branched oligosaccharides. Then, α-glucosidase present in the brush border of the intestinal epithelium (enterocytes) is responsible for the final step of carbohydrates digestion, prior to their absorption. This enzyme cleaves

It has been isolated from tea as well as common vegetables and fruits like beans,

Kaempferol has anti-inflammatory and anti-cancer properties, protects the liver and prevent metabolic diseases (**Figure 3**). The most well-known of its properties are its anti-inflammatory effects by decreasing lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) expression and also by increasing the number of activated macrophages [38]. Kaempferol is a dietary flavonoids that occur in fruits, vegetables, beverages, chocolates, herbs and plants [39]

to cross the intestinal barrier [36].

**Figure 3.**

*Biological roles of Kaempferol.*

and reported to possess anti-diabetic property.

Kaempferol under the following headings.

**6. Mechanism of antidiabetic action of kaempferol**

**7. Inhibition of α-amylase and** α**-glucosidase enzymes.**

**16**

terminal non-reducing 1, 4 linkages and converts the disaccharides and oligosaccharides into glucose, which is then transported by sodium/glucose co-transporter 1 (SGLT1) from the intestinal lumen to the cytosol of enterocytes. In turn, glucose transporter 2 (GLUT2), found in the basolateral membrane of enterocytes, transports glucose from cytosol to blood via facilitated diffusion.

One of the approaches to managing diabetes is to delay the absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes in the digestive tract of humans [42, 43].

Controlling the activity of these enzymes slows glucose production in the postprandial stage and this could be a therapeutic approach for people with diabetes. Hence, the search for inhibitors from medicinal plants is a great development [44].

Ibitoye et al. identified that kaempferol from *Cucumis sativus L*. lowers blood glucose and inhibited the activity of α -amylase and α glucosidase at IC50 of 51.24 and 29.37 μg/mL respectively [29]. This inhibition means reduction in blood glucose in the postprandial stage of alloxan-induced diabetic rats when given 165 mg/kg body weight of kaempferol from *Cucumis sativus* fruits. This evidently supports that kaempferol lowers blood glucose and inhibit α-amylase and α -glucosidase.

It may be possible that the glucose lowering activity of *C. sativus* fruits is through inhibition of α -amylase and α -glucosidase through kaempferol.
