Elsevier

Bioresource Technology

Volume 99, Issue 8, May 2008, Pages 2981-2988
Bioresource Technology

In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension

https://doi.org/10.1016/j.biortech.2007.06.035Get rights and content

Abstract

National Diabetes Education Program of NIH, Mayo Clinic and American Diabetes Association recommend eggplant-based diet as a choice for management of type 2 diabetes. The rationale for this suggestion is the high fiber and low soluble carbohydrate content of eggplant. We propose that a more physiologically relevant explanation lies in the phenolic-linked antioxidant activity and α-glucosidase inhibitory potential of eggplant which could reduce hyperglycemia-induced pathogenesis. Results from this study indicate that phenolic-enriched extracts of eggplant with moderate free radical scavenging-linked antioxidant activity had high α-glucosidase inhibitory activity and in specific cases moderate to high angiotensin I-converting enzyme (ACE) inhibitory activity. Inhibition of these enzymes provide a strong biochemical basis for management of type 2 diabetes by controlling glucose absorption and reducing associated hypertension, respectively. This phenolic antioxidant-enriched dietary strategy also has the potential to reduce hyperglycemia-induced pathogenesis linked to cellular oxidation stress. These results provide strong rationale for further animal and clinical studies.

Introduction

Diabetes mellitus (DM) is a major chronic disease caused by an improper balance of glucose homeostasis (Rosetti et al., 1990). DM is a serious chronic metabolic disorder that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. At least 171 million people worldwide have diabetes; this figure is likely to be more than double by 2030 and around 3.2 million deaths every year are attributable to complications of diabetes; six deaths every minute (WHO, 2007).

Two types of DM are currently known, one being insulin-dependent diabetes mellitus, IDDM and the other being type 2 non-insulin-dependent diabetes mellitus, NIDDM (Harris and Zimmer, 1992). The most common acute complications of NIDDM due to the hyperglycemia-induced pathogenesis are metabolic problems and infection (Nishikawa et al., 2000). Hyperglycemia, a condition characterized by an abnormal postprandial increase of blood glucose level, has been linked to the onset of NIDDM and associated oxidation-linked vascular complications (Dicarli et al., 2003, Haffner, 1998). Recent studies have shown that the glucose-induced increased levels of mitochondrial reactive oxygen species (ROS) produced by the mitochondrial electron transport chain seems to be the causal link between elevated levels of glucose and the pathways responsible for hyperglycemia-induced vascular complications (Kawamura and Heinecke, 1994).

Studies indicate that hyperglycemia triggers the generation of free radicals and oxidative stress in capillary endothelial cells in the retina, mesangial cells in the renal glomerulus and neuron cells in the peripheral nerves (Brownlee, 2005). Therefore, it is essential to regenerate critical cellular antioxidant responses to manage cellular redox status for preventing these diabetic complications resulting from hyperglycemia (Heilig et al., 1995, Lee and Chung, 1999). Effective dietary strategies can contribute to solutions for managing both hyperglycemia and proper cellular redox status.

α-Amylase and α-glucosidase are key enzymes involved in starch breakdown and intestinal absorption, respectively. It is now believed that inhibition of these enzymes involved in the digestion and uptake of carbohydrates can significantly decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet and therefore can be an important strategy in the management of hyperglycemia linked to type 2 diabetes (Puls et al., 1977). A main drawback of currently used α-glucosidase and α-amylase inhibitors such as acarbose is side effects such as abdominal distention, flatulence, meteorism and possibly diarrhea (Bischoff et al., 1985). It has been suggested that such adverse effects might be caused by the excessive inhibition of pancreatic α-amylase resulting in the abnormal bacterial fermentation of undigested carbohydrates in the colon (Bischoff, 1994, Horii, 1987). Therefore, natural inhibitors from dietary plants have shown to have lower inhibitory effect against α-amylase activity and a stronger inhibitory activity against α-glucosidase and can be used as effective therapy for postprandial hyperglycemia with minimal side effects (Kwon et al., 2006).

One of the long-term complications of diabetes is hypertension, or high blood pressure. Angiotensin I-converting enzyme (ACE) is an important enzyme involved in maintaining vascular tension. ACE activates a histidyl-leucine dipeptide called angiotensin I, into a potent vasoconstrictor called angiotensin II (Skeggs et al., 1956). Angiotensin II also stimulates the synthesis and release of aldosterone, which increases blood pressure by promoting sodium retention in the distal tubules (Lieberman, 1975). Inhibition of ACE is considered a useful therapeutic approach in the treatment of high blood pressure in both diabetic and non-diabetic patients (Erdos and Skidgel, 1987).

Phenolic compounds or phenolic phytochemicals are secondary metabolites of plant origin and are important parts of the diet (Bravo, 1998; Paganga et al., 1999, Urquiaga and Leighton, 2000) providing potential antioxidant benefits for managing oxidation stress-related chronic diseases such as diabetes and cardiovascular disease (Serdula et al., 1996). Vegetables such as eggplant, pepper and tomato of the Solanaceae family have high phenolic content and specifically eggplants are a rich source of phenolic phytochemicals having high free radical scavenging-linked antioxidant activity (Luthria and Mukhopadhyay, 2006). Further, understanding the health benefits of eggplant has merit when considering the cholesterol-lowering effects of a portfolio diet, which has eggplant as an important fiber source (Jenkins et al., 2003). The food recipes of the National Diabetes Education Program of NIH (National Institute of Health), Mayo Clinic and American Diabetes Association (ADA) recommend eggplant as a part of the diet for management of type 2 diabetes (NIH, 2007, MAYOCLINIC, 2007, ADA, 2007). Our hypothesis is that the biochemical rationale behind this recommendation lies in the phenolic-enriched antioxidant activity and α-glucosidase inhibitory potential of eggplant, which has the potential to reduce hyperglycemia-induced pathogenesis. Any dietary management of hyperglycemia linked to type 2 diabetes and related complications from oxidative dysfunction can benefit from specific enzyme inhibitory activity combined with antioxidant activity in the same whole food extracts. This approach has potential for high compliance and less side-effects. Therefore, the objective of this research was to evaluate several types of commonly available eggplant varieties for α-amylase, α-glucosidase and ACE inhibitory activities using different enzyme sources such as yeast α-glucosidase, rat intestinal α-glucosidase and porcine pancreatic α-amylase and rabbit lung ACE. These in vitro inhibitory activities were compared to total phenolic content and antioxidant activity in the water extracts of these readily available eggplant varieties.

Section snippets

Extract preparation

Fresh and well-ripened eggplant (Solanum melongena); Purple, White, Graffiti, Italian were purchased from Big Y supermarket, Hadley, MA. After peeling of each type of eggplant with a knife, 15 g of pulp and skin were added to 10 ml of distilled water separately and homogenized for 1 min using a Waring laboratory blender (Winsted, CN) set on “HIGH”. The homogenate was centrifuged (Eppendorf 5415D, Brinkmann Instruments Inc., Westbury, NY) at 9300g for 10 min. The supernatant was vacuum filtered

Total phenolics and antioxidant activity

The skin extract of Italian, which had 94.7 ± 13.3 μg/ml of total soluble phenolics and was highest among all the eggplant extracts evaluated (Fig. 1). The pulp extract of Graffiti, pulp extract of White and skin extract of Purple eggplant had 59.7 ± 0.9 μg/ml, 56.7 ± 5.1 μg/ml and 44.7 ± 12.3 μg/ml of soluble phenolics, respectively (Fig. 1).

The antioxidant activity of the extracts was monitored using the DPPH radical inhibition (DRI) assay. The ability of phenolics in eggplant extracts to inhibit the

Discussion

Hyperglycemia, a condition characterized by an abnormal postprandial increase of blood glucose level, has been linked to the onset of type 2, non-insulin-dependent diabetes mellitus and associated vascular complications (Dicarli et al., 2003, Haffner, 1998). Recent studies have indicated that hyperglycemia-induced vascular complications are likely from oxidative dysfunction from reactive oxygen species (ROS) produced by the mitochondrial electron transport chain (Kawamura and Heinecke, 1994,

Conclusion

Although this is an in vitro study and the sample size (varieties) evaluated is not extensive, the results indicate the positive effect of the two eggplant types, such as White and Graffiti on hyperglycemia risk factors and the biomarker of hypertension (ACE). It is clear from these in vitro assays that White and Graffiti eggplant types have moderate antioxidant activity and good inhibitory profile against carbohydrate modulating enzyme such as α-glucosidase related to glucose absorption in the

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