**2.1.** *Piper sarmentosum*

*Piper sarmentosum* (P.s), locally referred to as "daun kadok," is a member of the Piperaceae family which closely resembled the features of a betel leaf (**Figure 3**). Its leaves and roots are commonly used for experimental purposes [15]. P.s possesses high antioxidant compounds such as naringenin (75.7%), hesperetin (91.7%), taxifolin/dihydroquercetin (90.9%), and quercetin (98.1%) from its leaves [15].

compounds that are present in the leaves of P.s. Quercetin present in P.s has a positive role in reducing blood sugar levels, promoting the regeneration of the pancreatic islets and increas-

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Moreover, antioxidant compounds present in P.s prevent the morphological changes of diabetic cardiac and aortic tissues following 28 days of treatment (**Figure 4**). The antioxidant activity of quercetin controls the glucose uptake and increased levels of mitochondrial reactive oxygen species (ROS) linked to hyperglycemia [16]. This would protect the excess collagen deposition in cardiac tissues by inhibiting the metabolic disturbances of DM. Another antioxidant compound, naringenin, also improves endothelial function that reduces the risk of developing coronary heart disease [15]. The authors suggested that P.s could modify the cellular deteriorations in hyperglycemic condition. It was presumed that the mechanism by which P.s exerts its cardio-protective and vascular-protective effects might be due to the pres-

ing insulin release with high superoxide scavenging activity [16].

ence of antioxidant compounds [11].

**Figure 3.** Photograph of *Piper sarmentosum* leaves [14].

During the past few years, our research group observed that type 1 diabetic rat treated with P.s groups showed a significant decrease (P < 0.05) in fasting blood glucose level, urine glucose level [11], and blood pressure level [14] compared to untreated diabetic group in experimental Sprague-Dawley rats. The decrease in fasting blood and urine glucose level following P.s administration (0.125 g/kg) is probably due to the underlying action of the antioxidant

**Figure 3.** Photograph of *Piper sarmentosum* leaves [14].

which is enriched with antioxidant properties. We agreed the fact that there are plenty of natural products which have antioxidant property; however, only a few are highlighted in this chapter. Herein with, we present some common herbs and active compounds that are

The decreased antioxidant level is found in the diabetic patient. In a previous study, the total antioxidant capacity in the plasma of type 1 DM was shown to be 16% lower than that of normal subjects. Antioxidants counter the action of free radicals via several mechanisms such as degradation of free radicals, regulating the metals that stimulate the production free radicals, and scavenging the free radical. Lately, researchers found out the beneficial use of antioxi-

Among the natural resources, data from laboratory studies showed that plants contain a large amount of antioxidant properties. Antioxidants occur in all parts of any higher plants (wood, bark, stems, pods, leaves, fruit, roots, flowers, pollen, and seeds). Plants with high levels of antioxidant have a significant role in improving oxidative stress disorders like DM. A number of findings showed the protective effect of the antioxidant ingredients against DM and achieved good results [10]. Hence, classical antioxidant could regulate the process and progress of DM and its complications. The good impact antioxidant activity toward DM and its associated complications has highly gained attention in the recent therapeutic society. Plenty of plants are rich in antioxidant property. To name it few, the plant or natural herbs such as *Piper sarmentosum* [11], *Momordica charantia* (bitter gourd) [12], and *Piper betel* [6], the common herbs used in improving the diabetic status enriched with antioxidant compounds. Noticeable active compounds like naringenin and quercetin are also important in managing hyperglycemic condition as well as regulating the oxidative stress–induced complication in DM. Vitamin C and E are well-known antioxidant agents for DM [13]. The antioxidant-enriched herbs not only increase the antioxidant level but also reduce the serum glucose level as well as improve

*Piper sarmentosum* (P.s), locally referred to as "daun kadok," is a member of the Piperaceae family which closely resembled the features of a betel leaf (**Figure 3**). Its leaves and roots are commonly used for experimental purposes [15]. P.s possesses high antioxidant compounds such as naringenin (75.7%), hesperetin (91.7%), taxifolin/dihydroquercetin (90.9%), and quer-

During the past few years, our research group observed that type 1 diabetic rat treated with P.s groups showed a significant decrease (P < 0.05) in fasting blood glucose level, urine glucose level [11], and blood pressure level [14] compared to untreated diabetic group in experimental Sprague-Dawley rats. The decrease in fasting blood and urine glucose level following P.s administration (0.125 g/kg) is probably due to the underlying action of the antioxidant

enriched with antioxidant activity.

the deteriorative changes in DM.

cetin (98.1%) from its leaves [15].

**2.1.** *Piper sarmentosum*

dants from natural resources to replace synthetic ones.

**2. Antioxidants**

110 Diabetes Food Plan

compounds that are present in the leaves of P.s. Quercetin present in P.s has a positive role in reducing blood sugar levels, promoting the regeneration of the pancreatic islets and increasing insulin release with high superoxide scavenging activity [16].

Moreover, antioxidant compounds present in P.s prevent the morphological changes of diabetic cardiac and aortic tissues following 28 days of treatment (**Figure 4**). The antioxidant activity of quercetin controls the glucose uptake and increased levels of mitochondrial reactive oxygen species (ROS) linked to hyperglycemia [16]. This would protect the excess collagen deposition in cardiac tissues by inhibiting the metabolic disturbances of DM. Another antioxidant compound, naringenin, also improves endothelial function that reduces the risk of developing coronary heart disease [15]. The authors suggested that P.s could modify the cellular deteriorations in hyperglycemic condition. It was presumed that the mechanism by which P.s exerts its cardio-protective and vascular-protective effects might be due to the presence of antioxidant compounds [11].

Charantins from MC increase the glucose transporter (GLUT4), thus increases glucose utilization in the liver and muscle [18]. Increasing body weight that was observed in MC-treated experimental rats was due to the increase in glucose metabolism as compared to DM group [21]. Moreover, it was found out that the active compound present in MC fruit extract, leptin, lowered the blood pressure in diabetes. In the rural African communities, leptin is used in the management and control of DM-associated hypertension. Leptin reduces blood pressure by increasing the anti-oxidant and nitric oxide efficiency [22]. Our previous findings also showed significant decrease in systolic, diastolic, and mean blood pressure in experimental diabetic

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In the diabetic state, there is a decrease in the activities of superoxide dismutase (SOD), glutathione, and catalase due to the increase production of ROS. Supplementation with MC extract restores anti-oxidant levels of SOD, glutathione, and catalase by regulating the deleterious effects of free radicals in diabetic state due to the presence of charantosides [24]. Moreover, supplementation with MC fruit extract also reverted the histological deteriorations of aortic tissue in diabetic rats (**Figure 6**). Apart from this, antioxidant compounds, luteolin, in the MC extract is observed to improve diabetic cardiac tissue morphology in experimental animals [12]. Previous study showed that MC fruit extract exerts positive effect on plasma MDA level in alloxan-induced diabetic. MC regulates membrane lipid peroxidation and reduces the thickness of diabetic aortic tissue with the presence of anti-

Betel vine or scientifically known as *Piper betel* (PB), which belongs to *Piperaceae* family, is commonly found in South East Asia. PB is commonly found in South East Asian

**Figure 6.** Photomicrograph showing transverse sections of the thoracic aorta under Alcian blue staining. Untreated diabetic group (Left) diabetic group treated with *Momordica charantia* fruit extract (Right). Note: TM = Tunica Media,

rats treated with MC [23].

oxidant effect [23].

**2.3.** *Piper betel*

LM ×200) [23].

**Figure 4.** Photomicrograph showing the longitudinal section of cardiac tissues of untreated diabetic group (Left) diabetic group treated with 0.125 g/kg *Piper sarmentosum* (Right). Note: N: nuclei of cardiomyocytes, MF: myofibers, white arrows: connective tissue under Masson's Trichome stain (LM ×400) [17].

#### **2.2.** *Momordica charantia*

*Momordica charantia* (MC) belongs to the family of *Cucurbitaceae* (**Figure 5**) and is commonly known as bitter gourd or bitter melon [18]. The immature fruits of MC are a good source of Vitamin C and A. Several active compounds such as momorcharins, momordin, charantin, and goyasaponins are found in MC extract [19]. These are reported to present in all parts of the plant.

The leaf and fruit extract of MC are enriched with carbohydrate and protein. The supplementation with MC extract is a source of energy and nutrients for the body metabolic activities [20]. MC stimulates the number of pancreatic beta cells and promotes the insulin secretion.

**Figure 5.** Fruits of *Momordica charantia*.

Charantins from MC increase the glucose transporter (GLUT4), thus increases glucose utilization in the liver and muscle [18]. Increasing body weight that was observed in MC-treated experimental rats was due to the increase in glucose metabolism as compared to DM group [21]. Moreover, it was found out that the active compound present in MC fruit extract, leptin, lowered the blood pressure in diabetes. In the rural African communities, leptin is used in the management and control of DM-associated hypertension. Leptin reduces blood pressure by increasing the anti-oxidant and nitric oxide efficiency [22]. Our previous findings also showed significant decrease in systolic, diastolic, and mean blood pressure in experimental diabetic rats treated with MC [23].

In the diabetic state, there is a decrease in the activities of superoxide dismutase (SOD), glutathione, and catalase due to the increase production of ROS. Supplementation with MC extract restores anti-oxidant levels of SOD, glutathione, and catalase by regulating the deleterious effects of free radicals in diabetic state due to the presence of charantosides [24]. Moreover, supplementation with MC fruit extract also reverted the histological deteriorations of aortic tissue in diabetic rats (**Figure 6**). Apart from this, antioxidant compounds, luteolin, in the MC extract is observed to improve diabetic cardiac tissue morphology in experimental animals [12]. Previous study showed that MC fruit extract exerts positive effect on plasma MDA level in alloxan-induced diabetic. MC regulates membrane lipid peroxidation and reduces the thickness of diabetic aortic tissue with the presence of antioxidant effect [23].
