**2.3.** *Piper betel*

**2.2.** *Momordica charantia*

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

arrows: connective tissue under Masson's Trichome stain (LM ×400) [17].

the plant.

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*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

**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

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.

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, LM ×200) [23].

countries [25]. It was observed that PB is enriched with antioxidant activity by investigating on DPPH scavenging assay [25, 26]. Researchers found the potent antioxidant property of PB suspension (75 mg/kg) in streptozotocin-induced diabetic animals. Eventually, it was believed that the antioxidant property of PB leaves plays a protective role in diabetes [27]. The topical application of PB 50 mg/kg for 10 days enhanced wound healing in diabetic rats [28].

Delayed wound healing is one of the critical complications in diabetes mellitus. Increased production of ROS and imbalance between oxidant and antioxidant enzymes contribute to impair healing process. In hyperglycemic condition, there is decreased superoxide dismutase (SOD) and increased malondialdehyde (MDA), a marker of lipid peroxidation and 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) enzyme, involving in the interconversion of cortisone and cortisol [29]. Increasing level of 11β HSD-1 enzyme has a negative influence on the fibroblasts proliferation. Less-responsive fibroblasts to growth factors in DM results in poor-wound tensile strength and decreased-wound closure rate [30]. Following 5 days of topical PB application to the diabetic wounds showed the fast wound closure rate (**Figure 7**) [7] as well as reduced 11β HSD-1 enzyme expression in wound tissue (**Figure 8**) [8]. This might be due to the presence of potent active compounds in PB extract, which act as a free radical scavenger increase the anti-oxidant activity [32].

#### **2.4. Common active antioxidant compounds for diabetes**

Each compound contains its own efficacy. Naringenin (4′,5,7-trihydroxyflavanone) is a highly potent natural antioxidant with high superoxide scavenging activity (**Figure 9**). Quercetin, an example of flavonoids, is also reported to improve the endothelial dysfunction by enhancing nitric oxide (NO) synthesis in human umbilical vein endothelial cells [16]. Tannins, the active potent anti-oxidant compounds, could increase the secretion of insulin and reduce hyperglycemia in experimental DM rats [34]. The mechanism of enhancing insulin secretion was clearly explained that the compounds contain an enzyme: a benzoic acid related molecules inhibited insulinase. This enzyme enhances the effect of insulin by inhibiting insulin degradation [34].

**Figure 8.** Expression of 11bHSD-1 by immunohistochemistry in wounded skin of diabetic rat model. Untreated diabetic group (Left) diabetic group treated with PB extract (Right). Decreased in expression was observed in the epidermal layer of the wounded skin of diabetic PB group compared to DM-Control (DM-Ctrl) and diabetic silver nitrate treated

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(DM-SN) groups [6].

**Figure 9.** Chemical structure of Naringenin [33].

**Figure 7.** Increase in wound healing following topical *piper betel* application for 5 days. Untreated diabetic group (Left) diabetic group treated with PB extract (Right). Red circle = wounded area [31].

**Figure 8.** Expression of 11bHSD-1 by immunohistochemistry in wounded skin of diabetic rat model. Untreated diabetic group (Left) diabetic group treated with PB extract (Right). Decreased in expression was observed in the epidermal layer of the wounded skin of diabetic PB group compared to DM-Control (DM-Ctrl) and diabetic silver nitrate treated (DM-SN) groups [6].

**Figure 9.** Chemical structure of Naringenin [33].

countries [25]. It was observed that PB is enriched with antioxidant activity by investigating on DPPH scavenging assay [25, 26]. Researchers found the potent antioxidant property of PB suspension (75 mg/kg) in streptozotocin-induced diabetic animals. Eventually, it was believed that the antioxidant property of PB leaves plays a protective role in diabetes [27]. The topical application of PB 50 mg/kg for 10 days enhanced wound healing

Delayed wound healing is one of the critical complications in diabetes mellitus. Increased production of ROS and imbalance between oxidant and antioxidant enzymes contribute to impair healing process. In hyperglycemic condition, there is decreased superoxide dismutase (SOD) and increased malondialdehyde (MDA), a marker of lipid peroxidation and 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) enzyme, involving in the interconversion of cortisone and cortisol [29]. Increasing level of 11β HSD-1 enzyme has a negative influence on the fibroblasts proliferation. Less-responsive fibroblasts to growth factors in DM results in poor-wound tensile strength and decreased-wound closure rate [30]. Following 5 days of topical PB application to the diabetic wounds showed the fast wound closure rate (**Figure 7**) [7] as well as reduced 11β HSD-1 enzyme expression in wound tissue (**Figure 8**) [8]. This might be due to the presence of potent active compounds in PB extract, which act as a free

Each compound contains its own efficacy. Naringenin (4′,5,7-trihydroxyflavanone) is a highly potent natural antioxidant with high superoxide scavenging activity (**Figure 9**). Quercetin, an example of flavonoids, is also reported to improve the endothelial dysfunction by enhancing nitric oxide (NO) synthesis in human umbilical vein endothelial cells [16]. Tannins, the active potent anti-oxidant compounds, could increase the secretion of insulin and reduce hyperglycemia in experimental DM rats [34]. The mechanism of enhancing insulin secretion was clearly explained that the compounds contain an enzyme: a benzoic acid related molecules inhibited insulinase. This enzyme enhances the effect of insulin by inhibit-

**Figure 7.** Increase in wound healing following topical *piper betel* application for 5 days. Untreated diabetic group (Left)

in diabetic rats [28].

114 Diabetes Food Plan

ing insulin degradation [34].

radical scavenger increase the anti-oxidant activity [32].

**2.4. Common active antioxidant compounds for diabetes**

diabetic group treated with PB extract (Right). Red circle = wounded area [31].
