About Authors:
Mr. Satyanand Tyagi
President, Tyagi Pharmacy Association & Scientific Writer,
Chattarpur, New Delhi, India.
Prof. Satyanand Tyagi is a life time member of various pharmacy professional bodies like IPA, APTI and IPGA. He has published various research papers and review articles. His academic works include 50 Publications (42 Review Articles and 08 Research Articles of Pharmaceutical, Medicinal and Clinical Importance, published in standard and reputed National and International Pharmacy journals; Out of 50 publications, 11 are International Publications).
sntyagi9@yahoo.com, +91-9871111375 / 9582025220
ABSTRACT:
Diabetic nephropathy is one of the most serious complications related to diabetes, often leading to end-stage kidney disease. Purple corn grown in Peru and Chile is a relative of blue corn, which is readily available in the U.S. The maize is rich in anthocyanins (also known as flavonoids), which are reported to have anti-diabetic properties. Scientists from the Department of Food and Nutrition and Department of Biochemistry at Hallym University in Korea investigated the cellular and molecular activity of purple corn anthocyanins (PCA) to determine whether and how it affects the development of diabetic nephropathy (DN). Their findings suggest that PCA inhibits multiple pathways involved in the development of DN, which may help in developing therapies aimed at type 2 diabetes and kidney disease. The aim of present article is to provide in depth knowledge about Purple Corn, their clinical and biological utility as well as their role in treatments of type 2 diabetes and kidney disease. An attempt is also made to focus on compounds found in purple corn which may aid in developing future treatments for type 2 Diabetes as well as kidney disease.
REFERENCE ID: PHARMATUTOR-ART-1476
INTRODUCTION
Purple corn (Fig 1.) or purple maize, a variety of zea mays, is a corn grown in the Andes region of South America. Especially common in Peru, it is used in chicha morada (a drink made by boiling purple corn with pineapple, cinnamon, clove, and sugar) and mazamorra, a type of pudding.
The kernels of Purple Corn have long been used by the people of the Peruvian Andes to color foods and beverages, a practice just beginning to become popularized in the industrialized world. Purple corn is a Peruvian super food cultivated in coastal areas, as well as in mountains of almost ten thousand feet. Besides its use as food and dye, purple corn is thought to have many health benefits [1].
FIG. 1: PURPLE CORNS
The purple corn contains phenolic acid and anthocyanins. Purple corn is a maize variety that contains higher amounts of phytonutrients, especially anthocyanins and phenolics, than its golden and blue cousins. Anthocyanins have both antioxidant and anti-inflammatory properties and increasingly are being studied for their effect on various health challenges ranging from cancer to aging, heart disease, and diabetes. The purple corn has anti-aging, anti-tumoral as well as anti-cancer (especially colon cancer) activity. Researches suggest that purple corns have also been used to control obesity, to reduce cholesterol level, reduce blood clots as well as to reduce high blood pressure [2, 3].
It protects against atherosclerosis as well as it also elevates anti-oxidant capacity of the blood as well as also sustain weight when ingested with a high fat diet. Purple corn contains a variety of phytonutrients (plant nutrients) including massive amounts of phenolics and anthocyanins. Research shows that crops with the highest phenolic and anthocyanin content also have the highest antioxidant activity. Anthocyaninins are a type of complex flavonoid that produces blue, purple or red colors. Anthocyaninins are anti-inflammatory and encourage connective tissue regeneration. As well as being powerful antioxidants that keep us looking young and protected from disease, they promote blood flow and reduce cholesterol. It appears that anthocyaninins may stabilize and protect capillaries and blood vessels from free radical damage, and they have been shown to promote collagen formation (which is great for our skin) and improve circulation. Purple Corn has a higher antioxidant capacity than blueberries, making it one of the most exciting new super foods of our time.
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DIABETES MELLITUS AND TYPE 2 DIABETES
Diabetes Mellitus is, by definition, a risk factor for eye and kidney disease. It is also, on the basis of many epidemiologic studies, a risk factor for many other serious adverse health outcomes; the risk for all of these other outcomes may, however, not be confined just to the diabetic range of hyperglycemia. In people with diabetes mellitus, the plasma glucose level is a continuous risk factor for all of these diabetes related chronic illness and has been shown to be a modifiable risk factor for most of them. Often referred to by doctors as diabetes mellitus, describes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both.
Patients with high blood sugar will typically experience polyuria (frequent urination); they will become increasingly thirsty (polydipsia) and hungry (polyphagia). In summary, diabetes mellitus is metabolic disorder characterized by hyperglycemia, which is associated with a high subsequent risk of eye and kidney disease, although it is also associated with a high subsequent risk of neurologic, cardiovascular, and other adverse health outcomes. Diabetes mellitus is a metabolic disorder characterized by a fasting plasma glucose ≥ 7.0 mmol/l or a 2-hour plasma glucose level ≥ 11.1 mmol/l; these numbers clearly differentiate people at high and low risk for subsequent retinopathy and nephropathy [4]. Type 2 diabetes is a lifelong (chronic) disease in which there are high levels of sugar (glucose) in the blood. Type 2 diabetes is the most common form of diabetes.
The presence, severity and number of symptoms vary from person to person. Symptoms that may be experienced include, but aren't limited to:
* Blurred vision
* Fatigue
* Slow-healing infections
* Increased thirst
Type 2 diabetes usually develops gradually and may not have any noticeable symptoms.
DIABETIC NEPHROPATHY (DN)
Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis [5] and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime indication for dialysis in many Western countries. Kidney failure provoked by glomerulosclerosis leads to fluid filtration deficits and other disorders of kidney function. There is an increase in blood pressure (hypertension) and fluid retention in the body plus a reduced plasma oncotic pressure causes edema. Other complications may be arteriosclerosis of the renal artery and proteinuria. Diabetic nephropathy is defined as the presence of a persistently positive urine dipstick for albumin or > 0.3 gm /d of albumin excretion in a person with diabetes, in the absence of other renal disease [6, 7].
Throughout its early course, diabetic nephropathy has no symptoms. They develop in late stages and may be a result of excretion of high amounts of protein in the urine or due to renal failure:
* edema: swelling, usually around the eyes in the mornings; later, general body swelling may result, such as swelling of the legs
* foamy appearance or excessive frothing of the urine (caused by the proteinuria)
* unintentional weight gain (from fluid accumulation)
* anorexia (poor appetite)
* nausea and vomiting
* malaise (general ill feeling)
* fatigue
* headache
* frequent hiccups
The first laboratory abnormality is a positive microalbuminuria test.
Most often, the diagnosis is suspected when a routine urinalysis of a person with diabetes shows too much protein in the urine (proteinuria). The urinalysis may also show glucose in the urine, especially if blood glucose is poorly controlled. Serum creatinine and BUN may increase as kidney damage progresses. A kidney biopsy confirms the diagnosis, although it is not always necessary if the case is straightforward, with a documented progression of proteinuria over time and presence of diabetic retinopathy on examination of the retina of the eyes.
TREATMENT OF DIABETIC NEPHROPATHY
The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment, once proteinuria is established, is ACE inhibitor drugs, which usually reduces proteinuria levels and slows the progression of diabetic nephropathy. Several effects of the ACEIs that may contribute to renal protection have been related to the association of rise in Kinins which is also responsible for some of the side effects associated with ACEIs therapy such as dry cough. The renal protection effect is related to the antihypertensive effects in normal and hypertensive patients, renal vasodilatation resulting in increased renal blood flow and dilatation of the efferent arterioles.
Many studies have shown that related drugs, angiotensin receptor blockers (ARBs), have a similar benefit. However, combination therapy, according to the ONTARGET study [8], is known to worsen major renal outcomes, such as increasing serum creatinine and causing a greater decline in estimated glomerular filtration rate (eGFR). Blood-glucose levels should be closely monitored and controlled. This may slow the progression of the disorder, especially in the very early ("microalbuminuria") stages.
Medications to manage diabetes include oral hypoglycemic agents and insulin injections. As kidney failure a progress, less insulin is excreted, so lesser doses may be needed to control glucose levels. Diet may be modified to help control blood-sugar levels. Modification of protein intake can affect hemodynamic and nonhemodynamic injury. High blood pressure should be aggressively treated with antihypertensive medications, in order to reduce the risks of kidney, eye, and blood vessel damage in the body. It is also very important to control lipid levels, maintain a healthy weight, and engage in regular physical activity.
Patients with diabetic nephropathy should avoid taking the following drugs:
* Contrast agents containing iodine
* Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, or COX-2 inhibitors like celecoxib, because they may injure the weakened kidney.
Urinary tract and other infections are common and can be treated with appropriate antibiotics. Dialysis may be necessary once end-stage renal disease develops. At this stage, a Kidney transplantation must be considered. Another option for type 1 diabetes patients is a combined kidney-pancreas transplant. C-peptide, a by-product of insulin production, may provide new hope for patients suffering from diabetic nephropathy [9]. Currently, several compounds are in development for diabetic kidney disease. These include, but are not limited to, bardoxolone methyl [10], olmesartan medoxomil, sulodexide, and avosentan [11].
ROLE OF PURPLE CORN IN TREATMENT OF DIABETES AND KIDNEY DISEASE
In a pre-clinical study, Tsuda & col. (2003) [3] studied the effects of purple corn on obesity and diabetes, compared two sample groups. They consumed a diet rich in fats during 12 weeks, but one of the groups also received purple corn pigments.
Compared with the control group the group consuming anthocyaninins did not gain any weight, nor suffered hypertrophy in the adiposites of the fat tissues, didn’t not show hyperglycemia, hyperinsulinemia, hyperleptinemia, or increase in levels of the genetic codes that produce the factor or tumoral necrosis or the enzymes related to the synthesis of fatty acids and triglicerol. In comparison, the group that didn’t receive the extract and ate only a fat rich diet, showed an increase of more then 100% in all those parameters. Thus, there are good nutritional and biochemical reasons to use the anthocyanins present in purple corn, with obvious benefits for the prevention of obesity and diabetes. Diabetic nephropathy (DN) is one of the most serious complications related to diabetes, often leading to end-stage kidney disease. Purple corn grown in Peru and Chile is a relative of blue corn, which is readily available in the U.S. The maize is rich in anthocyanins (also known as flavonoids), which are reported to have anti-diabetic properties.
Scientists from the Department of Food and Nutrition and Department of Biochemistry at Hallym University in Korea investigated the cellular and molecular activity of purple corn anthocyanins (PCA) to determine whether and how it affects the development of diabetic nephropathy. Their findings suggest that PCA inhibits multiple pathways involved in the development of DN, which may help in developing therapies aimed at type 2 diabetes and kidney disease. The study is entitled "Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration." It appears in the online edition of the American Journal of Physiology -- Renal Physiology, published by the American Physiological Society [12].
Methodology
Researcher Min-Kyung Kang and colleagues performed a two-part study, an in vitro experiment investigating the effects of PCA on human endothelial cells cultured under hyperglycaemic kidney conditions and an in vivo study that investigated the effects of PCA on kidney tissue in diabetic mice. In the in vitro experiment, cultured cells were exposed to 1-20 µg/ml of PCA for six hours (control cells were not exposed), then assessed for level of monocyte-endothelial cell adhesion, a major factor in the development of diabetic glomerulosclerosis. In the in vivo experiment, diabetic and control mice were dosed with PCA for eight weeks, then changes in kidney tissue were assessed and immuno histological analyses were performed. Kidney tissue was further analyzed for levels of inflammatory chemokines, which are key components in DN.
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Results
Researchers found that in human endothelial cells cultured in hyperglycaemic kidney conditions, induction of endothelial cell adhesion molecules decreased in a dose-dependent manner with PCA exposure, meaning that the PCA likely interfered with cell-cell adhesion in glomeruli. PCA also appeared to interfere with leukocyte recruitment and adhesion to glomerular endothelial cells.
In diabetic mice, PCA exposure slowed mesangial expansion and interrupted the cellular signaling pathway that may instigate glomerular adhesion and infiltration of inflammatory cells responsible for diabetic glomerulosclerosis. Finally, PCA inhibited levels of macrophage inflammatory protein-2 and monocyte chemotactic protein-1 in kidney tissue, demonstrating that it may inhibit macrophage infiltration, which is closely related to renal inflammation.
Importance of the Findings
The research suggests that anthocyanins may be the main bio-functional compound in purple corn and could protect against mesangial activation of monocytes and infiltration of macrophages in glomeruli -- the two major contributors to DN. The research further suggests that renoprotection by PCA against mesangial activation may be specific therapies targeting diabetes-associated diabetic glomerulosclerosis and renal inflammation. Finally, PCA supplementation may be an important strategy in preventing renal vascular disease in type 2 diabetes. "PCA may be a potential renoprotective agent treating diabetes-associated glomerulosclerosis," wrote the researchers [13].
OTHER STUDIES
In one experiment, the researchers evaluated the effect of purple corn anthocyanins on human cells while the other looked at the effect on kidney tissue in diabetic mice who were dosed with the phytonutrient for eight weeks. They found that: Exposure of the human cells to purple corn anthocyanins for six hours resulted in a reduction of adhesion of endothelial cells. This suggests the anthocyanins helped prevent the cells from sticking to glomeruli, structures that are responsible for filtering blood in the kidneys and thus play a significant role in the development of diabetic kidney disease. Diabetic mice treated with purple corn anthocyanins showed several promising responses, including interruption of activity that may lead to cell adhesion and infiltration of cells responsible for diabetic kidney disease. Anthocyanins also inhibited levels of certain proteins in kidney tissue, suggesting they may help fight kidney inflammation.
DIABETIC KIDNEY DISEASE
Diabetic kidney disease, also known as diabetic glomerulosclerosis, nephropathy, and diabetic nephropathy, develops when the nephrons (structures in the kidneys that filter blood and remove waste) become thick and scarred over time. Eventually the kidneys begin to leak protein (albumin) into the urine (proteinuria). Not everyone who had diabetes develops diabetic kidney disease. According to the National Kidney Foundation, about 30% of people with type 1 and 10 to 40% of those with type 2 diabetes eventually develop kidney failure. Risk factors for diabetic nephropathy include poor glucose management, high blood pressure, smoking, being African-American, Hispanic or American Indian, and development of type 1 diabetes before age 20. The earliest indication of kidney disease in diabetics is protein in the urine.
PURPLE CORN AND DIABETES
Several previous studies have indicated that purple corn has potential in fighting diabetes. In 2009 in the Journal of Medicinal Food, scientists evaluated 10 Peruvian Andean grains for potential type 2 diabetes antihyperglycemia and antihypertension activity. They found that purple corn had high antioxidant activity and the highest total phenolic (similar to anthocyanins) content of all the grains examined. In a subsequent study, scientists evaluated the effect of purple corn anthocyanins in both human cells and diabetic mice and concluded that "purple corn may be a potent therapeutic agent for the treatment of diabetes-associated glomerulosclerosis accompanying proteinuria and kidney filtration dysfunction." Now the results of this latest study have provided scientists with more information on the potential use of purple corn anthocyanins in the prevention of kidney disease associated with diabetes. They note that supplementation with purple corn anthocyanins may be an important approach to help prevent kidney disease in type 2 diabetes [14].
CONCLUSION
Purple corn has been discovered as a potential new treatment option for those who have type 2 diabetes and kidney disease. Scientists from Korea’s Hallym University Department of Food and Nutrition and Department of Biochemistry investigated the cellular and molecular activity of purple corn anthocyanins (PCA) to determine how it affects the development of diabetic nephropathy. Nephropathy is a scientific term meaning damage or disease of the kidney and anthocyanins are pigments that are responsible for the color of a plant or vegetables. These pigments also tend to have health benefits or are used as dietary antioxidants and in this case purple corn. The findings from the study suggest that PCA inhibits pathways of the development of DN, which may lead to new discoveries in the development of therapies for treating type 2 diabetes and kidney disease (DN).
ACKNOWLEDGEMENT
The corresponding author, Prof. Satyanand Tyagi is highly thankful to his Parents, wife Pooja, and daughter Tanisha for their moral support and encouragement.
REFERENCES
1. Jones, Kenneth. “Purple Corn: Ancient Healing Food”. Purple Corn Science (2012).
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3. Tsuda T, Horio F, Osawa T, et al, Dietary Cyanidin 3-O-?-D-glucoside-rich purple corn colour prevents obesity and ameliorates hyperglycaemia in mice, J Nutr, 2003, 133(7), 2125-2130.
4. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Diabetes Care, 1997, 20, 1183-1197.
5. Berkman James and Rifkin Harold, “Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson): Report of a Case, Metabolism (Elsevier Inc.), 1973, 22(5), 715-722.
6. Breyer JA, Diabetic Nephropathy in insulin-dependent patients, Am J Kid Dis, 1992, 20, 533-547.
7. Ritz E, Stefansky A, Diabetic Nephropathy in Type 2 Diabetes, Am J Kid Dis, 1996, 27,167-194.
8. The ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al, “ Telmisartan, Ramiprl, or Both in Patients at High Risk for Vascular Events” , 2008, 358(15), 1547-1559.
9. Wahren J, Ekberg K, Jornvall H, “C-peptide is a bioactive peptide”, Diabetologia, 2007, 50(3), 503-509.
10. medscape.com/viewarticle/590644.
11. medicalnewstoday.com/articles/139028.php
12. M.-K. Kang, J. Li, J.-L. Kim, J.-H. Gong, S.-N. Kwak, J. H. Y. Park, J.-Y. Lee, S. S. Lim, Y.-H. Kang, Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration, AJP: Renal Physiology, 2012, 10, 1152.
13. Compound found in purple corn may aid in developing future treatments for type-2 diabetes, kidney disease, Science daily, 2012, (Sciencedaily.com/releases/2012/09/120918184756.htm).
14. whatsonningbo.com/wine_msg.php?titleid=399.
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