CLOVES

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Sy:ygini)i aromaticum L. (Cloves) is a native herb in Indonesia, Malaysia, Brazil, Mexico, India, Haiti, Madagascar, Sri Lanka, and Tanzania. Cloves are commonly used as spices for an aromatic flavor. Cloves contain essential oil, phenolic compounds, and hydrolyzable tannins [61]. Tahir et al. reported that the yield of essential oil in cloves was 8.5% with pale yellow color. It is soluble in alcohol and has a refractive index of 1.23 [103].

Quantity percentage of clove essential oil is determined by phenological state and agro-climatic conditions. Essential oils in cloves contain 2.93% of caryophyllene oxide, 3.36% of eucalyptol, 3.72% of citronellyl acetate, 3.84% of y-terpinene, 4.51% of methyl benzoate, 5.79% of geraniol, 8.12% of //-hexane, 8.84% of acetaldehyde, 15.3% of eugenyl acetate and 18.7% of eugenol. In addition, clove contains acetophenone, chromone glycosides, phenylpropanoids, 2,4,6-trihydroxy-3-methyl acetophenone-2- O-p-D-glucoside, sesquiteipenoids, triteipenoids, sterol, and tannin. Those mentioned compounds showed anticancer activity in human ovarian cancer cells (A2780) using MTT assay [63].

Clove oil reveals anti-diabetic benefit by reducing high blood sugar levels and lipid peroxidation, and recovering the antioxidant enzymes [90].

Alpha-amylase inhibition assay is commonly used to determine antidiabetic activity. According to the research, clove essential oil exhibits maximum anti-diabetic activity at 100 pg mL_1, whereas clove essential oil emulsion (essential oil (25%) + tween 80 (75%) + ethanol (25%) + water (25%)) shows a maximum anti-diabetic capability (as much as 95.30% inhibition of a-amylase activity) [103]. In addition, clove is an excellent functional food and is appropriate for alternative therapeutic of type-2 DM, because it can prevent activity of key enzymes in type-2 diabetic patients, such as: a-amylase and a-glucosidase [1].

Glycation is an attachment of excess sugar to the protein or lipid without enzymatic process. The free aldehyde or ketone group from this reducing sugar is able to adduct the alpha-amino group from N-tenninal or E-amino amine as on lysine, arginine, cysteine, and histidine. It fonns a cross-linking protein AGEs with other dipeptides having an N-terminal free side group (mainly on arginine and tryptophan). Advanced glycation end-products (AGEs) can induce pathogenesis and atherosclerosis in diabetic complications. A study reported that the antiglycation effect of some medicinal plants can be detected using the SDS-PAGE method [76].

Clove extracts demonstrated strong inhibition protein cross-linking formation at 25 pg mL'1 concentration. Therefore, clove has the ability as a glycation agent and to induce protein cross-linking inhibitory activity [76]. Another study reported that the aqueous extract of clove suppresses atherosclerosis and diabetes due to its strong antioxidant activity, anti- apolipoprotein A-I (apoA-I) glycation and phagocytosis prevention through inhibition of low-density lipoprotein (LDL) and cholesteryl ester transfer protein (CETP), and reducing hypolipidemic activity [44, 76].

CUMIN

Cumin (Cumimim cymimmi L.) originated from Southwest Asia and the Eastern Mediterranean region. It is cultivated in Europe, Egypt, the Middle East, India, and Iran. Cumin powder is used as a spice in various cuisines because of its unique flavor, strong, and warm aroma. The essential oil of cumin is also popular among traditional healers [56]. The different parts (roots, stems, leaves, and flowers) of the cumin plant have various bioactive compounds (phenolics, flavonoids, and tannins) with unique biological activities. The essential oil is produced from flowers (1.7%), leaves, and stems (0.1%), and roots (0.03%).

The main constituent in essential oil from roots is bornyl acetate (23%). However, a-terpinene is a major compound in the stem and leaves; and y-terpinene is abundant in the flower. Quercetin is a primary phenolic compound in the roots, while vanillic acid is present in a higher amount in the flowers. However, p-coumaric, rosmarinic, tran.s-2-dihydrocmnamic acids, and resorcinol are found predominantly in stems and leaves. Antioxidant activity assessment of the cumin plant parts has been checked using four types of assays, such as: 1,1 -diphenyl-2-piciylhydrazyl (DPPH), (3-carotene/ linoleic acid, reducing power and chelating power assays. The cumin flowers acetone extract has strong antioxidant activity, lipid peroxidation inhibitor, and reducing agent, whereas acetone extract of stem and leaves exhibits the highest chelating power. Nevertheless, the essential oil offers moderate antioxidant activity as shown by antioxidant assay [20].

Chemical distribution and cumin fruit antioxidant activity were determined by correlating harvesting time with plant maturity. Cumin fruit antioxidant activity in various growth levels is still lower than butylated hydroxytoluene (BHT) using both DPPH and FRAP assays. The ICJ0 value of BHT is about 27 times higher than the 13.59 mg mL'1 of IC.0 in immature cumin. On the other hand, intermediate, and premature cumin parts indicate the highest radical scavenging activity than the other growth stages, although their antioxidant activity is still lower than BHT.

FRAP assay can quantify the antioxidant compounds’ capability to diminish the ferric ion (Fe3+) to ferrous (Fe2_). FRAP assay studies reveal that BHT reducing power (602 mol Fe2+ per mass) is greater than immature, intermediate, premature, and fully mature cumin. The BHT values were 132, 121,106, and 89 moles of Fe2_ per mg of essential oil for immature, intermediate, premature, and fully mature cumin, respectively. In addition, phenolic contents (which enhance at intermediate and premature stages) have a positive correlation with their antioxidant capacity (AOC) of essential oils [65].

The essential oil from cumin can repair the metabolic condition and prevent the progression of diabetes. These biological activities are unique to cumin as an alternative adjuvant therapeutics for pre-diabetic subjects and support lifestyle alteration [41].

Dietaiy cumin seeds are known as an anti-diabetic agent to reduce blood glucose content and to decrease excretions of urea and creatinine in diabetic rats [108]. Cumin seed-derived peptides have radical scavenging activity; and therefore can be used as a substance in the functional food and pharmaceutical studies. Three novel cumin-seed peptides (CSPs) have successfully been extracted and identified as “a-amylase inhibitory peptide,” which plays an important role in retardation of carbohydrate digestion and glucose absorption. This process reduces the risks of DM development [93, 94]. Cumin improves metabolic index and anthropometric in overweight and/or type-2 diabetic subjects [42]. Furthermore, essential oil from cumin exhibits maximum anti-diabetic activity at a concentration of 100 pg mL-1. Cumin essential oil emulsion (essential oil (25%) + tween 80 (75%) + ethanol (25%) + water (25%)) demonstrates maximum anti-diabetic activity (95%) and a-amylase inhibition (83%). Inhibition of a-amylase activity delays the carbohydrate complex hydrolysis and glucose absorption in the intestinal tract, which reduces blood glucose levels [103].

The ethanolic seed extract of cumin exhibits good anti-hyperglycemic and anti-dyslipidemic activities. These have been validated with type-2 DM rat and male Syrian golden hamsters. Furthermore, the anti-dyslipidemic activity can be shown by declining of triglycerides, cholesterol, LDL-C in the serum, and enhancing of serum HDL-C. The ethanolic extract of cumin seeds also has aldose inhibitory activity. It can reduce secondaiy diabetic complications in the later stage [100].

GARLIC

Garlic (Allium sativum L.) is used as a common seasoning in almost every cuisine around the world. It is also used as a traditional therapeutic agent.

Scientific reports have documented that garlic can diminish the level of blood glucose (hypoglycemic activities) in diabetic annuals. Jain and Vyas [43] reported the hypoglycemic effects of garlic extracts (ethanol, 40-60° petroleum ether and diethyl ether) in diabetic rabbits induced by alloxan. The garlic ethyl extract offered maximum hypoglycemic activity (P < 0.001) [43].

Garlic extract offers anti-diabetic and hypoglycemic activities due to the enhancement of insulin-like activity in plasma. It influences the secretion of insulin from (3-cells, the release of bound insulin or increases insulin sensitivity. These processes liberate fixed insulin. The effect of garlic oil from fresh cloves has been studied on diabetic rats and mice (streptozotocin-induced and alloxan-induced) [73]. Treated annuals group and control were administrated (intra-gastrically) @ 50 mg per kg of body weight daily of garlic oil supplement for 28 days. Treated annual group exhibited a significant alleviation in red cell acid phosphatase (p<0.001), serum acid phosphatase and alkaline phosphatase (p<0.001), aminotransferases (p<0.001) and amylase (p>0.002) levels compared to the diabetic control rats.

Yang et al. [112] found that garlic diminishes concentrations of LDL cholesterol and total serum cholesterol in diabetic patients in a significant way as compared to a placebo, possibly due to the inhibition of reactive oxygen species (ROS) through the modulation of NADPH oxidase subunit expression and can restore erectile function in diabetic patients. Sheela et al. have reported that S-allyl cysteine sulfoxide from garlic provoked a reversal of diabetic conditions, such as, the depletion of liver glycogen, glucose tolerance, weight loss, etc., in alloxan-induced diabetic rats [87]. S-Allyl cysteine sulfoxide (isolated from garlic) rectified diabetic conditions in alloxan-induced diabetic rats and it was as effective as glibenclamide- and insulin-therapy [88]. S-Allyl cysteine sulfoxide can also control lipid peroxidation better than the glibenclamide and insulin. It also increased insulin secretion from pancreatic (3-cells [99].

Pandiya and Banerjee indicated that the beneficial effect of garlic in DM is attributed to the presence of volatile sulfur compounds, such as, alliin, allicin, diallyl disulfide, diallyl trisulfide, diallyl sulfide, S-allyl cysteine, ajoene, and allyl mercaptan. Allicin can enhance serum insulin by effectively combining with cysteine, which would spare insulin from SH group that is common cause of insulin inactivation [74].

GINGER

Ginger (Zingiber officinale Roscoe) is similar to turmeric and it is a popular ingredient in cooking due to a peculiar flavor, aroma, and pungent odors. Besides cooking, ginger is also well-known for its medicinal properties against gastrointestinal disorder, motion sickness, nausea relief, cold, and flu relief, pain, and inflammation (reduce muscle pain, knee, and elbow). Ginger contains several biochemical constituents, such as: gingerol, shogaol, paradol, and zingerone [23]. It may also reduce the risks of cardiovascular diseases (CVDs), blood clotting, and hyperglycemia.

A clinical trial was conducted by Shidfar et al. [89], who reported the impact of ginger on glycemic indices in patients with type 2-diabetes. The 45 patients with T2DM (20-60 years old), who did not receive insulin, were divided into control and treated groups. Patients in the treated group received 3 g of ginger supplement (capsule) daily for 3 months. The results of this study showed that ginger supplementation increased the glycemic indices, TAC, and PON-1 activity in patients with T2DM. It is reported that the phenolic compounds (such as: gingerol and shogaol) act as a-amylase and a-glucosidase inhibitors in carbohydrate metabolism and hyperglycemia. Ginger supplementation can enhance the homeostasis of glucose in T2DM patients by lowering insulin resistance and improving glucose tolerance. This study also reported that ginger supplementation significantly reduces the C-reactive protein (CRP) as an inflammation marker [89].

Khandouzi et al. [50] reported the effects of ginger on fasting blood sugar (FBS). Out of 41 patients with T2DM, 22 patients were assigned to the ginger group compared to 19 in the control group. The treated group received 2 g of ginger powder daily for 12 weeks. The results of this study exhibited that oral administration of ginger powder significantly reduced the levels of blood sugar, Hemoglobin Ale (HbAlc), Apolipoprotein B, Apolipoprotein B/Apolipoprotein A-I, and Malondialdehyde (MDA) [50]. Therefore, it is concluded that oral administration of ginger powder may relieve the risks of some chronic complications related to diabetes. These evidences are in agreement with results by Azimi et al. [13], who also reported the ability of ginger supplementation for decreasing the CRP concentration and reduction of the risk of Type 2 diabetes Mellitus (T2DM).

 
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