Dr. Daniel’s Terogena.
Terogena is a formulation, developed by the well-known phytochemist, Prof. M. Daniel and his teamin Dr. Daniel’s Laboratories after extensive research, of well-known scientifically proved plants in the most effective combination. Along with the proven antidiabetic plants, other medicinal plants which are rich in antioxidants and protect the heart, liver and kidney as well as increasing stamina are added in this combination. The plants used in Terogena, their active principles and their clinically proven activities are summarized below.
- Amala (Emblica officinalis Gaertn) fruit is a rich source of gallic acid and gallotannins like emblicanin which is vitamin C like in action. The extract of this fruit, which is very rich in antioxidants, is found to reduce serum glucose levels, prevents cancer and is hypolipidaemic, antiaging, hepatoprotective and cardioprotective (Sukhdev, 2006)
- Gudmaar (Gymnema sylvestre R.Br.) is the well-known ‘Madhunaashi’ containing triterpenoid glycosides such as gymnemic acids, gymnemosides and gymnema saponins. The leaf extracts are found to reduce blood glucose, and corrects abnormal lipid levels (cholesterol, triglycerides etc) caused by diabetes. This plant is sold in markets of USA, Japan and Germany as a health food. This plant prevents tooth decay and obesity.
- Sariva (Hemidesmus indicus R.Br.) This is one of the rasayana drugs used to revitalise human body. The roots contain coumarino-lignoids such as hemidesminine. Sariva possesses great antioxidant activities and is a blood thinner. It has proven anti-inflammatory as well as hepatoprotective activities (Prabhakaran and Co-workers, 2000).
- Arjuna ( Terminalia arjuna W.& A. ). Arjuna bark contains a number of triterpenoids such as arjunic acid and arjunolic acid. This drug takes care of all the problems of lipid profile caused by diabetes and keeps the heart healthy. It is also anticancer and antioxidant in nature.
- Vijaysar (Pterocarpus marsupium Roxb.). This plant is rich in flavonoidal glycosides marsupin and pterosupin and kinotannin. The drug is found to reduce blood glucose levels, hypolipidaemic and reduces blood pressure (Sharma, 1986).
- Galo ( Tinospora cordifolia Miers) This is the famous ‘Amruta’, which is a well known Rasayana drug. It contains diterpenoids like columbin and chasmanthin as also an ecdysteroid. Galo exhibits hypoglycemic (reducing blood and urine sugar), antioxidant, immunomodulatory, antiarthritic and anticancer properties (Prince and Co-workers, 2001).
- Jamun beej (Syzygium cuminii L.). The seeds yield phenolics like guaiacol, veratrol and gallic acid. They are antidiabetic in nature increasing insulin levels in blood serum and reducing fasting glucose levels (Grover and co-workers, 2002). The drug is found to increase muscle and liver glycogen content also. Seeds are found to reduce serum cholesterol and LDL and raised HDL (Sharma and co-workers, 2003)
This formulation of plants (Terogena) was subjected to a critical study in Botany Department of the Maharaja Sayajirao University of Baroda, Vadodara by Prof. Daniel and his team (Remya, 2009) for: 1). Its efficacy in reducing blood and urine sugar in diabetic rats, 2).Hypoglycemic activity (to check the lowering of blood glucose in normal rats), 3). effect of the extracts on enzymatic (SOD, CAT, and GPX) and non-enzymatic antioxidants, 4).Effect of the extracts on lipid peroxidation (TBARS, GSH, vitamin C and vitamin E), 5) Effect of the extracts on carbohydrate metabolizing enzymes (hexokinase, glucose-6-phosphatase and fructose-1, 6-bisphosphatase), 6).Effect to retrieve the renal toxicity caused due to diabetes (urea, uric acid, creatinine and blood urea nitrogen – BUN) and 7). Antihyperlipidaemic effect (cholesterol, free fatty acids, triglycerides, phospholipids, LDL, VLDL and HDL).
Terogena caused up to 65.2% reduction in the blood glucose level. It also improved the body weight by 30.1%.The levels of TBARS were decreased in plasma, liver, kidney, and in brain. The level of GSH and vitamin C was increased in plasma, liver, kidney and in brain. There was a decrease in the plasma vitamin E while its level was increased in liver, kidney and brain. Terogena also caused increased activities of SOD, CAT and GPX. The formulation reduced levels of urea, uric acid and creatinine in plasma.
Due to the administration of Terogena, the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase were reduced but the activity of hexokinase increased. Lipid levels such as cholesterol, triglycerides, free fatty acids, phospholipids, LDL and VLDL were decreased while increased level of HDL was observed. When given to normal rats this formulation did not reduce sugar level indicating that it is a safe drug. All these results are published in the book “Studies on some Indian antidiabetic plants” written by Prof. Daniel in 2012.
In conclusion, it is experimentally proved that Terogena reverses the changes of diabetic complications thereby acting as a potent antidiabetic, antioxidant and antilipidaemic herbal formulation. It also reverses the changes of carbohydrate metabolizing enzymes by increasing the activity of hexokinase which can decrease the level of blood glucose. Terogena possesses hypolipidaemic effect and increased haemoglobin content. The formulation also protects the body from oxidative stress by increasing the antioxidants. Apart from that, it also protected the diabetic induced renal damage by decreasing the level of urea, uric acid and creatinine in the blood. The formulation shows better effect than the standard drug glibenclamide.
Diabetes mellitus is a group of metabolic diseases characterized by increased levels of sugar in blood (plasma) and urine (hyperglycemia) resulting from defects in insulin secretion, action or both. In Diabetic cases, insulin deficiency is due to destruction of islet cells in the pancreas, so that pancreas does not produce enough insulin, or cells do not respond to the insulin that is produced. In such cases, glucose in blood is not removed (oxidized) and the sugar content in blood increases. Along with this, the liver does not convert all the glucose available to glycogen. When the blood glucose level exceeds about 160 – 180 mg/dl, the renal tubules of kidney become overwhelmed and begin to excrete glucose in the urine. People with diabetes are 25 times more likely to develop blindness, 17 times more likely to develop kidney disease, 30-40 times more likely to undergo amputation, two to four times more likely to develop heart problems and twice as likely to suffer a stroke when compared to non-diabetics
Diabetes is of two main subtypes: type-I or insulin-dependent diabetes (IDDM), and type-II or non-insulin-dependent diabetes (NIDDM). Type 1 diabetes is caused by the absence of insulin due to pancreatic islet beta cell destruction and more prone to ketoacidosis. This is seen mostly in children and is an autoimmune process. Type 2 diabetes (formerly named non-insulin-dependent-the most common form) which results from defect(s) in insulin secretion, almost always with a major contribution from insulin resistance, the body’s inability to respond properly to the action of insulin. Type 2 diabetes is much more common and accounts for around 90% of all diabetes cases worldwide. It occurs most frequently in adults, but is being noted increasingly in adolescents as well.
Diagnostic criteria for diabetes mellitus
Fasting plasma sugar (FPS), postprandial plasma sugar (PP2
PS) and oral glucose tolerance test (OGTT) are the golden criteria for the diagnosis of diabetes mellitus.
Normal type – FPS below 100 mg/dl and 2-hBG < 7.7 mmol/L (140 mg/dl)
Borderline type – FPS > 110 mg/dl) PP2PS> 7.0 mmol/L (150mg/dl)
Diabetic type – FPS > 7.0 mmol / L (126 mg/dl) and PP2PS > 11.1 mmol/L (200 mg/dl)
- The A1C test
– at least 6.5% means diabetes
– between 5.7% and 5.99% means prediabetes
– less than 5.7% means normal
- The FPG (fasting plasma glucose) test
– at least 126 mg/dl means diabetes
– between 100 mg/dl and 125.99 mg/dl means prediabetes
– less than 100 mg/dl means normal
An abnormal reading following the FPG means the patient has impaired fasting glucose (IFG)
The OGTT (oral glucose tolerance test)
– at least 200 mg/dl means diabetes
– between 140 and 199.9 mg/dl means prediabetes
– less than 140 mg/dl means normal
An abnormal reading following the OGTT means the patient has impaired glucose tolerance (IGT)
Long Term Complications of diabetes
- Heart: Blood vessels: Atherosclerotic plaque builds up and blocks large or medium-sized arteries in the heart, brain, legs and penis. The walls of small blood vessels are damaged and may leak. Poor circulation causes wounds to heal poorly and can lead to heart disease, stroke, gangrene of the feet and hands, impotence and infections
- Blood: WBC get impaired; susceptibility to infection, especially of the urinary tract and skin increases.
- Eyes: The small blood vessels of the retina become damaged leading to diabetic retinopathy, temporary blurring and cataracts
- Kidney: Blood vessels in the kidney thicken; protein leaks in to the urine; Poor kidney function; kidney failure
- Nerves: Nerves are damaged because glucose is not metabolized normally due to inadequate blood supply. Sudden or gradual loss of body weight; reduced sensations, tingling and pain in the hands and feet, chronic damage to nerves
- Autonomous nervous system: Swings in blood pressure, swallowing difficulties and altered gastrointestinal function with bouts of diarrhoea.
- Skin: Poor blood flow to the skin and loss of feeling resulting in repeated injury. Sores, deep infections (diabetic ulcers; poor healing)
- Connective tissue: tissues to thicken or contract. Carpal tunnel syndrome; Dupuytrens’s contractive.
Role of insulin in carbohydrate metabolism
One of the major effects of insulin is to enhance overall glucose utilization (for the body energy and metabolism) and this is achieved by stimulation of glucose uptake into the target tissues. Insulin increases all the activities of glucose oxidation such as activity of glucokinase (which attaches phosphate to glucose to produce glucose 6-phosphate), phosphofructokinase (which attaches phosphate to fructose 6-phospahate to produce fructose I, 6-bisphospahate) and pyruvate kinase (which removes phosphate from phosphoenol pyruvate to produce pyruvate) so that the products are processed further in respiration. Insulin also decreases the activity of glucose-6-phosphatase in liver (which adds phosphate to glucose to produce glucose 6-phosphate to initiate glycogen synthesis in liver), resulting in retardation of glycogen synthesis and retention of glucose within the liver cell.
In skeletal muscles, insulin promotes the activity of hexokinase, which phosphorylates glucose and initiates glucose metabolism. Other than this, it also stimulates lipogenesis in the adipose tissue by providing acetyl-CoA and NADPH which are required for fatty acid synthesis. The final action of insulin is the conversion glucose-6-phosphate to glucose-1-phosphate which is incorporated in to glycogen by the enzyme glycogen synthase.
Thus, insulin deficiency leads to increased amounts of glucose in blood and urine and the excess glucose is carried in blood to all parts of body and this initiates secondary reactions leading to other complications.
Diabetes mellitus – other consequences
With severe insulin deficiency, plasma fatty acid levels increase in response to enhanced lipolysis and plasma triglyceride levels may increase because of a decrease in lipoprotein lipase activity. Deficiency of insulin or increase in counter-insulin hormones is sufficiently severe to increase glycogen, protein and lipid catabolism which lead to the elevation of free fatty acids, triglycerides, cholesterol, VLDL, ketone bodies, etc. in plasma. All these consequences lead to oxidative stress, lipid peroxidation there by resulting in diabetic complications.
Increased oxidative stress and accelerated atherosclerosis are the most common conditions associated with Diabetes mellitus. The autoxidation and glycoxidation reactions of glucose are sources of free radicals. Glycosylated protein, reduced superoxide dismutase enzyme and ascorbic acid and lack of reduced glutathione are other causes for oxidative stress. Both high glucose levels and protein glycation enhance LDL oxidation by metal ions, and these reactions also yield advanced glycosylation end (AGE) products. The high blood glucose level and the high lipid content of the adipose tissues during obesity also leads to the increase in the size of adipocytes and thus leading to the generation of phospholipase A2. The activation of phospholipase A2 finally leads to the process of the lipid peroxidation. Increased levels of lipid peroxides and diminished antioxidant vitamin status also are the chronic complications of diabetes.
Antioxidant Defense System
The increased levels of glucose in plasma and increased free radicals mainly from lipid peroxidation, alter the antioxidant status and defense system of diabetic patients. To counter the harmful effects of the oxidants formed thus, antioxidant defense mechanism operates to detoxify or scavenge these free radicals. This defense line consists of antioxidant enzymes like – superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymatic molecules like – reduced glutathione (GSH), vitamin C, vitamin E etc.
Therapies for Diabetes mellitus
A. Hypoglycemic Drugs
- Sulfonylureas (Sulpha group containing drug like Tollbutamide, Chlorpropamide, Glibenclamide, Glipizide, Gliclazide)
Hypoglycemia is the most difficult side effect of the sulfonylureas. Diabetic patients who take drugs called sulfonylureas (glyburide and glipizide) as an initial therapy have a higher risk of death (58 percent more) than those who take the diabetes drug metformin(Glucophage and Fortamet), a new study says.
- Meglitinides (Repaglinide -Prandin)
- Biguanides ( Metformin) Metformin causes gastrointestinal problems such as nausea, stomach pain, bloating, diarrhea and malabsorption of vitamin B12 and folic acid.
- Alpha-glucosidase inhibitors (Acarbose –Precose, and miglitol – Glycet) The most bothersome side effects observed with these agents are gastrointestinal, including abdominal discomfort, bloating, flatulence and diarrhoea but are reversible with discontinuation. Therapy with acarbose has been linked to elevations in serum transaminase levels and the use of this agent is contraindicated in patients with liver cirrhosis.
Insulin administration is also associated with some side effects like hypoglycemic shock, weight gain and an increased risk of atherogenesis.
The Ayurvedic approach to diabetes
Ayurvedic remedies for diabetes are usually mixed formulations containing blood sugar lowering herbs in combination with immunomodulators, diuretics and detoxicants. The rationale behind such formulations is provided by modern research, which documents that immune processes play a predominant role in the destruction of beta cells and that free radicals feature predominantly in the progression of the disease and its secondary complications. The inclusion of immunomodulators and detoxifying antioxidants in mixed formulations is therefore beneficial. Some traditional formulations also contain cholesterol- reducing agents and adaptogens such as Emblica officinalis.