HYPONIDD combination rationale HYPONIDD is a herbomineral combination for the treatment of Type II diabetes and Polycystic Ovarian Syndrome

(PCOS) its action comparable to Metformin. Hyponidd is an insulin sensitizer that works very well for women with insulin-resistance. 1-2 tablets twice a day, half an hour before meals decreases gastrointestinal absorption of glucose from the meals, regulates the insulin response of the pancreas and increases peripheral utilization of glucose in the muscles and processing in the liver. Hirsutism, acne, alopecia and obesity improve with decreased insulin levels and so does the frequency of ovulation and the menstrual cycle. A treatment protocol with Hyponidd lasting for 3-4 months supported by uterine tonics such as M2-Tone restores ovulation in a large percentage of women. Hyponidd can safely be used as an adjuvant therapy to sulphonylurea and metformin in secondary OHAs failure cases to postpone insulin therapy. In clinical trials, for cases of newly diagnosed diabetes, HbA1c fell from 9.08% at baseline to 8.14% at the end of 3 months and again from 9.69% to 8.08% at the end of 90 days. In combination with ADAs in the management of patients with secondary failure, Hyponidd was associated with significantly greater reductions in HbA1c (8.31% to 7.01% and also from 9.08% at baseline to 8.14 at the end of three months, a decrease of 10.4%. Known as Tibb-Diabetes Plus in South Africa and is marketed by Tibb Health Sciences, this herbal formula Hyponidd is proven to have a definite beneficial effect not only in lowering blood sugar levels, but also in lowering lipids to reduce LDL cholesterol. In South Africa it is used for the treatment of severe diabetes under the Tibb-Unani system of traditional medicine where it minimizes long-term diabetic complications. Pharmacological Group: Combined preparation for Type 2 diabetes mellitus, PCOS, Border line diabetes, [Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)] and as an OHA that can be added to sulphonylurea and metformin to postpone insulin therapy. Insulin Sensitizer; action is comparable to Metformin but better tolerated. Benefit to Risk Ratio: Metabolic Axis: Corrects hyperinsulinemia Reduces waist-hip ratio Reduces body weight Reproductive Axis: Improves ovulatory function Superior rate of ovulation

Steroidogenic Axis: Decreases free testosterone levels Ensures rapid suppression of insulin and androgen levels

Lowers free estrogen levels Reduces fasting glucose: fasting insulin ratio

Regularizes menstruation Promotes efficient intracellular & peripheral glucose utilization

Hyponidd is useful in the treatment of Type II Diabetes and PCOS and its action is equally efficacious but better tolerated than Metformin. As an insulin sensitizing agent, Hyponidd (IHMDCI) is as efficacious as and better tolerated than metformin. In PCOS, it leads to rapid suppression of Insulin and androgen levels as well as improved menstrual frequency. The post-receptor insulin mediator signaling process by D-chiroinositol promotes efficient intracellular glucose utilization and is fundamental to the correction of pathophysiology of PCOS. Hirsutism, acne, alopecia and obesity improve with decreased insulin levels and so does the frequency of ovulation and the menstrual cycle. A treatment protocol with Hyponidd lasting for 3-4 months supported by uterine tonics such as M2-Tone restores ovulation in a large percentage of women. Hyponidd can safely be used as an adjuvant therapy to sulphonylurea and metformin in secondary OHAs failure cases to postpone insulin therapy. Hyponidd will also simplify the treatment protocol for patients with Type II diabetes/insulation resistance and high cholesterol and will therefore result in improved compliance since there are fewer tablets to take. In clinical trials, for cases of newly diagnosed diabetes, HbA1c fell from 9.08% at baseline to 8.14% at the end of 3 months and again from 9.69% to 8.08% at the end of 90 days. In combination with ADAs in the management of patients with secondary failure, Hyponidd was associated with significantly greater reductions in HbA1c (8.31% to 7.01% and also from 9.08% at baseline to 8.14 at the end of three months, a decrease of 10.4%. In newly diagnosed, mild to moderate diabetes, Hyponidd has been proven to be very beneficial: a 20-30% reduction in HbA1c in a 6 month period. In patients with diabetes for 2-5 years we find a 10-15% reduction in HBA1c levels within 3-6 months. In patients with very chronic diabetes for more than 10 years the reduction of HBA1c is much less and in these cases Hyponidd may be taken as an adjunct therapy until a satisfactory response is achieved and then the dosage of Insulin/OHAs may then be reduced slowly until the patient is on Hyponidd alone or until homeostasis is reached . Because Hyponidd is an excellent Insulin sensitizer, Type II Diabetes patients need to be sensitized about the symptoms of hypoglycemia and therefore close monitoring, regulation of the dosage of OHAs or insulin is absolutely vital.

THERAPEUTIC RATIONALE (For Type II diabetes): HYPONIDD is a combination of herbs and minerals for diabetes treatment. The ingredients are proven to have a definite beneficial effect not only in lowering blood sugar levels but also in lipid lowering effect. Pterocarpus marsupium is an insulin sensitiser; Emblica officinalis is an antioxidant. Momordica charantia, Melia azadirachta and Gymnema sylvestre are potent anti-diabetic ingredients. The cumulative pharmacological action of HYPONIDD is insulin sensitising, antihyperglycemic, hypolipidemic and antioxidant. HYPONIDD minimizes the chances of diabetic complications, if started sufficiently early.

THERAPEUTIC RATIONALE (For PCOS): HYPONIDD is also used for the treatment of Polycystic Ovarian Syndrome (PCOS) on account of its role as an herbal insulin sensitiser with d-chiro-inositol edge. PCOS affects 6-10 % of women population and it is very often associated with insulin resistance. PCOS leads to amenorrhoea, anovulation, oligomenorrhoea, hirsutism etc. HYPONIDD in PCOS improves ovulatory function and several metabolic derangements associated with insulin resistance. In cases of PCOS, Hyponidd was better tolerated than Metformin, lowered Insulin resistance and hyperandrogenemia. HYPONIDD decreases insulin resistance and thereby corrects the three axes namely metabolic, reproductive and steroidogenic. Flavonoid constituents of Pterocarpus marsupium like marsupin, pterosupin and epicatechin are insulinogenic because of post-receptor intracellular mediation by d-chiro-inositol. Curcuma longa has antiandrogenic, hypolipidemic, anti-obesity and antioxidant properties. Gymnema sylvestre, Emblica offincinalis, Tinospora cordifolia, Enicostemma littorale and Cassia auriculata possess antidiabetic, hypolipidemic, cardioprotective and antioxidant properties. Momordica charantia and Eugenia jambolana suppress overstimulation of androgen receptors in the pilosebaceous units in the skin and thus disrupt the pathophysiology of acne in PCOS patients. Thus HYPONIDD is a safe and effective insulin sensitizer.

Indications: In PCOS associated with adolescent infertile women on oral contraceptive pills: As insulin sensitizer. Long-term management of PCOS. Border line diabetes, [Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)]

 Adult stable mild to moderate Non Insulin Dependent Diabetes Mellitus (NIDDMType 2 DM) Newly discovered maturity onset diabetes (NIDDM-Type 2) As an adjuvant therapy with existing oral hypoglycemic agents in secondary OHAs failure cases to prevent further complications. Along with any integrated diabetes control program

Compositon: Powders: Yashad bhasma Zinc 37.5mg Suddha shilajit Purified Asphaltum ..37.5 mg Mormordica charantia Cerasee 12 mg

Extracts: Curcuma longa - Turmeric 300 mg Cassia auriculata Senna/Tanners Cassia.. 225 mg Emblica oficinalis Indian Gooseberry ...150 mg Eugenia jambolana Java Plum ..150 mg Enicostemma littorale Indian Whitehead112.5 mg Gymnema sylvestre Australian Cow Plant.112.5 mg Pterocarpus marsupium Indian Kino Tree ..75 mg Tinospora cordifolia - Heart Leaved Moonseed 75 mg Melia azadirachta Neem 75 mg Swertia chirata Indian Gentian .15 mg

Therapeutic Rationale: Hyponidds Active Ingredients Zinc English Name Reason for Inclusion Deficiency causes insulin resistance Regulates blood sugar, improves metabolism, antidepressant, promotes longevity. The most well researched MC mechanism is its blood sugar lowering effect. Extracts of MC also enhance cellular uptake of glucose, promote insulin release and potentiate its effect, Leatherdale BA, Panesar RK, Singh G, et al. Improvement in glucose tolerance due to Momordica charaantia (Karela). Br Med J 1981; 282(6279):1823 1824. Welihinda J, Karunanayake EH, Sheriff MHR, et al. Effect of Momordica charantia on the glucose tolerance In maturity onset diabetes. J Ethnopharmacol 1986;17(3):277 282. Momordica charantia contains a polypeptide known as Polypetptide-P or plant insulin along with other hypglycemic compouds which activate the enzyme AMPK, a protein well known for regulating fuel metabolism and

Purified Asphaltum

Momordica charantia

Cerasee

enabling glusose uptake; the pharmacokinetics of Polypetptide-P is similar to bovine insulin onset between 30 and 40 minutes and peak effect at about 4 -12 hours; Reports of synergistic effects in Type II diabetes patients who consumed Bitter Melon curry while taking chlorpromide (Diabenese); Dosage of Insulin or other OHAs must be reduced in order to prevent hyperglycemia and patients monitored closely. The first clinical study into the influence of the powder of bittergourd in the management of DM was by Akhtar, This suggested the intervention would effectively treat all symptoms of diabetes including polyuria, polydipsia, and polyphagia. Urinary excretion of sugar was also reduced and insulin injections were stopped. (Akhtar MS. Trial of Momordica charantia Linn (Karela) powder in patients with maturity-onset diabetes. J Pak Med Assoc 1982; 32:106-107.) Bitter melon can be used as a dietary supplement herbal medicine for the management of diabetes and/or metabolic syndromes (Cefalu WT, Ye J, Wang ZQ: Efficacy of dietary supplementation with

botanicals on carbohydrate metabolism in humans. Endocr Metab Immune Disord Drug Targets. 2008, 8(2):76-81). Curcumoids are antioxidant; Curcumin is antiinflammatory, a COX inhibitor, antiandrogenic, hypolipidemic, and antiobesity. According to recent research Curcumin also helps to prevent diabetes among those with prediabetes. Turmeric and curcumin have been shown in previous research to also fight inflammation and oxidative damage two processes which help a number of diseases to appear and develop, including type 2 diabetes. One study published in the journal Nutrition shows how turmeric normalizes insulin and triglyceride levels while boosting antioxidant defenses; keeping triglyceride and insulin levels low effectively reduces your risk for numerous health conditions like metabolic syndrome, heart disease, and you guessed it diabetes. Regulates glucose and lipid levels. It establishes good control on sugar levels and reduces symptoms like Polyurea and thirst in Diabetics

Curcuma longa

Turmeric

Cassia auriculata

Senna/Tanners Cassia

Emblica officinalis

Indian Gooseberry

Eugenia jambolana

Java Plum

Antioxidant, Vitamin C (ascorbic acid) concentration 160-fold than those of apple; extract was shown to inhibit cholesteremia at a higher level than the anticholesterol drug Probucol. Juice with turmeric powder and honey is prescribed in diabetes insipidus; cardioprotective, hypolipidemic Exhibits normoglycemia and better glucose tolerance & reduces the amount of sugar present in urine in a very brief space of time (Potters Cyclopedia) Decrease glycosated Hb & glucose 6 phosphatase. Indian Whitehead is taken in combination with other herbs, especially for diabetes (Upadhyay and Goyal 2004). Gymnema has 5 triterpene glycosides: gymnemic acids I-IV and gymnemasporin V an insulin mimetic that lowers blood plasma level. "This herbal therapy (GSE Gymnema sylvestre Extract) appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas." Clincally proven to reduce insulin requirements.

Enicostemma littorale

Indian Whitehead

Gymnema sylvestre

Australian Cow Plant

Pterocarpus marsupium

Indian Kino Tree

Phenolics Marsupen, Pterosupin and pterostilbene of the heartwood is comparable to metformin; Insulin sensitizer (it increases the effectiveness of insulin in metabolizing glucose), it acts as an insulinlike agents through the stimulation of d-chiro inositol.

Tinospora cordifolia

Heart Leaved Moonseed

Hypolipidemic, anti-obesity and antioxidant Neem leaf and certain extracts of the leaf and seed oil are effective in reducing insulin requirements. Found to lower blood sugar by over 50% in twenty weeks and maintained thereafter (Saraf, 1993). Neem leaf extracts have been shown to reduce insulin requirements of diabetics without apparent effect on blood glucose levels (Dixit, 1986). Neem leaf reduces blood glucose level by regeneration of cells (Chatopadhyay et al,1996). Neem-based tablets significantly improved the effectiveness of standard hypoglycemic drugs when taken together. Neem oil is effective in secondary diabetes i.e. relief in itching, dyspepsia, tiredness, muscular pain and wound healing. Neem leaf extract

Melia azadirachta

Neem

can cause the blood vessels to dilate, allowing for increased circulation to the extremities. Stimulates insulin from the islets of Langerhans by depleting Aldehyde-fuchsin stained beta-granules and immunostained Insulin

Swertia chirayita

Indian Gentian

Combination Rationale According to the Canadian Diabetes Association Clinical Practice Guidelines [8, 29], a newly diagnosed type 2 diabetic will be prescribed up to five different drugs. These include (1) oral hypoglycemic drugs, alone or in combination, to reduce blood sugar; (2) lipid-lowering drugs, especially to reduce LDL-cholesterol; (3) antihypertensive drugs to reduce blood pressure or prevent hypertension; (4) low-dose aspirin to reduce the risk of thrombosis; (5) insulin, in more advanced stages of the disease. The oral hypoglycemic drugs contain several classes that point to the various targets that can be useful in restoring glucose homeostasis. Major formulations used in Ayurveda are based on herbs used as decoctions, infusion, tinctures and powders. Drug formulation in Ayurveda (As mentioned in Ayurvedic treatise like Charaka Samhita, Sushruta Samhita) is based on two principles: (a). Use as single drug, and (b). Use of more than two drugs. When two or more herbs are used in formulation they are known as polyherbal formulations. Sometimes herbs are combined with mineral preparation. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial. The concept of polyherbalism is peculiar to Ayurveda although it is difficult to explain in term of modern parameters. Sarandghar Samhita highlights the concept of synergism behind polyherbal formulations. Ayurveda has fundamental aspects for drug formulation. The herbs are selected according to disease other herbs are used to prevent side effect arising from the chief herb. It is evident that there are many herbal formulations of varying potency and since these preparation act by different mechanisms, it is theoretically possible that different combination of these extracts will do better job in reducing blood glucose. In practice, in the traditional system of plant

medicine it is usual to use plant formulations and combined extract of plants are used as a drug of choice rather than individual ones (Kumar, 2010), to get the benefit of synergism and to find suitable antidiabetic and antioxidant combination therapy. Scientific Basis for using Mixed Formulations & Synergy Ayurvedic remedies for diabetes are usually mixed formulations containing blood sugar lowering herbs, in combination with immunomodulators, diuretics and detoxicants, with the rationale behind such formulations being provided by modern research which documents that, immune process plays a predominant role in the destruction of beta cells and features predominantly in the progression of the disease and its secondary complications [6]. The inclusion of immunomodulators such as Tinospora cordifolia, and detoxifying antioxidants such as Emblica officinalis in mixed formulations is therefore beneficial. Some traditional formulations also contain cholesterol reducing agents and adaptogens such as Emblica officinalis. Vascular inflammation is now regarded by medical researchers as the key underlying cause for several chronic disease conditions, including diabetes. Anti-inflammatory approaches such as Turmeric root (contains curcuminoids that help in inhibiting COX-2 enzymes), Commiphora mukul (Guggul) extract (contains guggulsterones and ferulates, that help in reducing markers of inflammation such as C-reactive protein CRP in the plasma), and other healthful medicinal plants from Ayurveda, are therefore integrated into diabetes support formulations. These healthful herbs also support cardiovascular health through their beneficial effects against vascular inflammation. 59 . Polyherbal formulations have plant-based pharmacological agents which may exert synergistic, potentiative, agonistic antagonistic actions by virtue of its diverse active principles within themselves. These pharmacological principles work together in a dynamic way to produce maximum therapeutic efficiency with minimum side effects. Hyponidd can be used alone or in combination with oral hypoglycemic drugs.

Risks: Adverse Drug Reactions (ADR) The addition of actives in any formulation is generally done as per Ayurvedic principle of VRIDDHI SAMANAHI---, which means that medicines with similar properties even though added in less quantity give good result. Therefore in practice instead of using single drug in therapeutic dosage it is always preferred to use combination of more than one herb in sub-therapeutic dosage, this not only provides good result, but also chances of ADR is also substantially reduced. Contraindications:

Insulin Dependent Diabetes Juvenile Diabetes Ketoacidosis Terminal stage diabetes complications Patients with severe cardiovascular disorders Gestational Diabetes Pregnancy and lactation Traditional texts do not recommend use of the contents of HYPONIDD during pregnancy and lactation. Precautions for diabetics Cautious use is recommended in patients on oral hypoglycemic drugs/Insulin. Dosage has to be adjusted and regular monitoring of blood sugar is required. It is extremely important to follow physicians instruction regarding diet and exercise. HYPONIDD, like any other antidiabetic medication, requires routine monitoring of blood/urine sugar levels, especially when HYPONIDD is prescribed as an add-on medication with existing OHAs. HYPONIDD, again, like the OHAs will achieve a better control of disease when integrated with dietary discipline and controlled physical activity. In the event that the patient exhibits symptoms of hypoglycemia, a lollypop or sweet should be sucked on and the patient should return to the clinic or ones physician as soon as possible to have the dosage of OHAs adjusted. Drug interactions HYPONIDD can safely be used as an adjuvant therapy to sulphonylurea and metformin in secondary OHAs failure cases to postpone insulin therapy. In Type II patients already on oral hypoglycemic drugs (OHAs) or insulin, 2 tablets per day may be added initially for a week. Once satisfactory response is achieved, the dosage of OHA may be slowly reduced and that of the HYPONIDD increased to 4 tablets a day. Adverse effects: Hyponidd did not cause any side effects during clinical trials in India. Significant glycemic control was achieved by HYPONIDD in patients who showed glycemic levels uncontrolled even by maximum permissible dosage of OHAs, without any adverse event including hypoglycemia or weight gain during the study. All patients reported a sense of wellbeing during the trials. Because Hyponidd is an excellent Insulin sensitizer, Type II Diabetes patients need to be sensitized about the symptoms of hypoglycemia and therefore close monitoring, regulation of the dosage of OHAs or insulin is absolutely vital.

Herbal medicine Hyponidd is as effective as metformin in reducing insulin resistance, hyperandrogenemia and in increasing ovulation rate in anovulatory PCOS women with added advantage of almost no side effect of gastric disorders as found in metformin. As an insulin-sensitizing agent, Hyponidd (IHMDCI) is as efficacious as and better tolerated than metformin. Overdosage Hypoglycemia, nausea, vomiting, general fatigue, vertigo are the symptoms of overdosage. In the event that the patient exhibits symptoms of hypoglycemia, a lollypop or sweet should be sucked on or a sweet drink administered and symptomatic treatment followed. The patient should return to the clinic or ones physician as soon as possible to have the dosage of OHAs adjusted. Individual Ingredients: activities & Rationale for inclusion: Momordica charantia or cerasee/bitter melon powder The first clinical study into the influence of the powder of bittergourd in the management of DM was by Akhtar, This suggested the intervention would effectively treat all symptoms of diabetes including polyuria, polydipsia, and polyphagia. Urinary excretion of sugar was also reduced and insulin injections were stopped. (Akhtar MS. Trial of Momordica charantia Linn (Karela) powder in patients with maturity-onset diabetes. J Pak Med Assoc 1982; 32:106-107.) Bitter melon can be used as a dietary supplement herbal medicine for the management of diabetes and/or metabolic syndromes (Cefalu WT, Ye J, Wang ZQ: Efficacy of dietary supplementation with botanicals on carbohydrate metabolism in humans. Endocr Metab Immune Disord Drug Targets. 2008, 8(2):76-81). Contains many active chemicals including charantin (a steroid glycoside), polypeptide "p" or plant insulin similar in structure to bovine insulin (a 166 residue insulin mimetic peptide) including Quercetin and gallic acids. Quercetin has been demonstrated to inhibit adipogenesis and induce Apoptosis in 3T3-L1 mouse adipocytes[54,55], while gallic acid is known to increase the number of early and late apoptotic 3T3-L1 cells in culture via loss of mitochondrial membrane potential[56].We therefore speculate that insulinmimetic peptides as well as polyphenols such as quercetin and gallic acid may in part be responsible for anti-adi-pogenic properties of Bitter Melon Juice. Polypeptide - P was found to decrease blood sugar levels when injected subcutaneously into type 1 diabetic patients. Oleanolic acid glycosides, compounds from bitter melon, improved glucose tolerance in Type II diabetics by preventing sugar from being absorbed into intestines. The oral administration of Bitter Melon preparations has also shown satisfactory results in clinical trials in type 11 diabetic patients. Recent studies indicate that cucurbutanoid compounds are the active principals of BMJ which possess

hypoglycemic properties [57], but the exact active ingredients possessing hypolipidemic properties are unknown. Momordica charantia or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. Bitter melon has a synergistic effect with other glucose lowering agents. Leatherdale BA, Panesar RK, Singh G, et al. Improvement in glucose tolerance due to Momordica charaantia (Karela). Br Med J 1981; 282(6279):1823 1824. Bitter melon is used to treat diabetes and its complications in traditional Chinese and Ayurvedic medicine and by traditional Sri Lankan practitioners. Welihinda J, Karunanayake EH, Sheriff MHR, et al. Effect of Momordica charantia on the glucose tolerance In maturity onset diabetes. J Ethnopharmacol 1986;17(3):277 282. The researchers concluded that the results nonetheless gave some scientific validity to the use of bitter melon as an oral hypoglycemic agent by traditional Sri Lankan practitioners.

NEEM Scientific studies show neem leaf and certain extracts of the leaf and seed oil are effective in reducing insulin requirements. 85 diabetics aged over 35 years participated in a trial of neem oil in the treatment of diabetes. Since it is bitter, neem oil was given in gelatin capsules, in a dose of 5 to 10 drops each day in 2 doses. Dietary control comprised of restricting pure sugars. There was a significant fall in both fasting and postprandial blood sugars following the use of neem oil (Table 1). The requirements of insulin or oral antidiabetic agents fell by 25 to 50%. Different studies show insulin requirement reductions of between 20- 50 % for those who take five grams of dried neem leaf capsules daily. There are even anecdotal reports of diabetics chewing a single neem leaf daily that have been able to eliminate hypoglycemic drugs completely. Found to lower blood sugar by over 50% in twenty weeks and maintained thereafter (Saraf, 1993). Neem leaf extracts have been shown to reduce insulin requirements of diabetics without apparent effect on blood glucose levels (Dixit, 1986). Neem leaf reduces blood glucose level by regeneration of cells (Chatopadhyay et al,1996). Based on the many studies of neems effect on diabetes, the Indian government approved neem-based tablets for sale by a pharmaceutical company as a treatment for diabetes. One study of the product published in The Journal of General Medicine showed the tablets alone significantly lowered blood glucose levels. Tests were also performed on the effect of taking the tablets along with standard hypoglycemic drugs. These tests showed that the neem-based tablets significantly improved the effectiveness of standard hypoglycemic drugs when taken together. Secondary Diabetes

The decoction of tender leaves, oil from seeds nimbin from oil of seed produced hypoglycaemic effect ranging from 24 % to 26 %. Within 7 to 10 days of intake of neem oil hyperglycaemic patients reported relief in itching, dyspepsia, tiredness and muscular pain and wound healing started fast after therapy. These results suggest that the oil is effective in secondary diabetes. It was most suitable for mild and moderate diabetes and 50% effective in severe diabetes (lndian Med. J. 1990, 84, 331). Circulation problems are a frequent cause of amputations for diabetics. Neem leaf extracts cause the blood vessels to dilate, allowing for increased circulation to the extremities. Neem leaf extract can cause the blood vessels to dilate, (Thompson and Anderson, 1978) allowing for increased circulation to the extremities. Ingesting neem leaf extract several times a week will enhance poor circulation and oxidize the blood. It has been observed that compound nimbidin from neem leaves cause blood vessels to dilate and may be responsible for reducing blood pressure (Arivazhagan et al. 2000). Polyherbal formulations based on Indian Medicinal Plants as Antidiabetic Phytotherapeutics - Shikha Srivastava, Vijay Kumar Lal, Kamlesh Kumar Pant

Activities Neem Leef: Beta-sitosterol: Hepatoprotective, Hypoglycemic, Hypolipidemic 2-6 g/day Quercetin: Anticataract, Antidiabetic, Antihepatotoxic, Antihypertensive, Antiinflammatory 20-150 mg/kg, Hepaprotective, Hypoglycemic, Insulinogenic, Quercitrin: Anticataract, Antihepatotoxic, Antiinflammatory, Antioxidant, Hypoglycemic Rutin: Anticataract, Antidiabetic, Antihepatotoxic, Antihypertensive, Antiinflammatory, Antioxidant, Hepaprotective 20 mg/kg rat, Hypoglycemic Magnesium: Antiretinopathic 400 mg/day, Insulinogenic 400 mg/day - A deficiency of Magnesium is significantly more common in type 2 diabetics than in the general population. Magnesium deficiency has been associated with complications of diabetes, retinopathy in particular. One study found patients with the most severe retinopathy were also lowest in Magnesium.

Source: Multiple Activities Menus: Dr. Dukes Phytochemical & Ethnobotanical Database

PTEROCARPUS MARSUPIUM / Indian kino tree

The Phenolics Marsupen, Pterosupin and Pterosilbene of the heartwood are comparable to metformin.

Pterocarpus Marsupium is one of the drugs used in the treatment of diabetes mellitus by Ayurvedic physicians in India. An aqueous infusion of the heartwood has been found to reduce glucose-absorption from the gastrointestinal tract and improve insulin and pro-insulin levels. It is effective in beta cell regeneration (stimulates the Beta-cells of the Islets of Langerhans to create more insulin, thus enabling the pancreas to function at its normal and optimum capacity) and has also been found to have a hypocholesteremic effect (that is, reducing hypercholesterolemia. It has been found to reduce FBS (fasting blood sugar), PBS (post-prandial blood sugar, that is, blood sugar level 2 hours after a meal), and Glycosylated Hemoglobin levels. It prevents development of long-term complications of diabetes. It is well documented in clinical trials. Activities Pterocarpus Heartwood: Gallic Acid: Insulin sparing Isoliquiritigenin: Antidiabetic Pectin: Antidiabetic 10 g/man/day/orl, Hypoglycemic Epicatechin: Antidiabetic, Antihyperglycemic, Antioxidant, Cardiotonic, Hypocholesterolemic, Hypoglycemic, Insulinogenic

Source: Multiple Activities Menus: Dr. Dukes Phytochemical & Ethnobotanical Database GYMNEMA SYLVESTRE 5 triterpene glycosides gymnemic acids I-IV and gymnemasporin V

The plant is known for reducing the taste of sweet, and in humans, gymnema reduced the taste stimuli of sweetness by an average of 77% regardless of the type of sweetener used (acesulfame K, aspartame, sodium cyclamate, fructose, glucose, sucrose, stevia, and xylitol were tested).52 Gymnema also has a reputation for aiding in weight reduction.53,54 Gymnema sylvestre extract (GSE) - Clinical Findings In 1990 a series of published studies on GSE lifted this herb from interesting to revolutionary. To begin with, it was shown that the administration of GSE to diabetic animals not only resulted in improved glucose homeostasis, this improvement was accompanied by a regeneration of beta cells in the pancreas.(5) In the words of the authors, "This herbal therapy appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas." To my knowledge, this is the only compound that has shown the ability to lessen indicators of diabetes by directly repairing/regenerating the pancreas cells responsible for producing insulin. As abnormalities in beta cell number and/or function are directly related to both Type I (insulin dependent) and Type II diabetes mellitus, it appeared that GS and GSE was a major discovery in the battle against one of the most common disorders in the world. Also in 1990, this same research team published results on their treatment of both Type I and Type II diabetics with GSE over a period of more than 2 years. In the case of Type II diabetics, GSE resulted in significant reductions in blood glucose, glycosylated hemoglobin, glycosylated plasma proteins, and conventional drug dosage.(6) At the beginning of the study all participants were taking oral antidiabetic medication, and treatment with GSE resulted not only in a lowering of oral medication necessity, but almost 25% of the participants were able to discontinue conventional oral medication and maintain blood glucose homeostasis with GSE alone. Additionally, GSE significantly improved cholesterol, triglyceride, and free fatty acid levels that were elevated in the study participants. The fact that GSE lowered conventional medication requirements, increased serum insulin levels, and required months to obtain optimal effects, led the authors to speculate that, "These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GSE supplementation." The control group used in this study not only didn't improve during the study period, they actually worsened. An additional study in Type 1 diabetics showed equally impressive results.(7) Insulin requirements came down together with blood glucose, glycosylated hemoglobin and glycosylated plasma protein levels. Serum lipids returned to near normal levels with GSE therapy. This may help prevent cardiovascular disease, a common complication in diabetics. Most impressively, an increase in C-peptide levels was found in these participants. This is strong indication of a restoration of insulin production, presumably due to regeneration/repair of beta cells in the pancreas. A control group showed none of these improvements, and actually worsened over the study period. Importantly, none of the participants in either of these studies presented any adverse side effects, although many patients developed

hypoglycemia (low blood glucose) and required a lowering of their dose of conventional oral medication or insulin. Thus, any diabetic that uses GSE must carefully monitor blood glucose levels and adjust their medication, in consultation with their physician, to maintain desired blood glucose levels. This is because improved insulin production and release during GSE supplementation may result in over-medication, and thus low blood glucose levels, unless the dosage of conventional oral medication or insulin is lowered. Since most diabetics monitor their blood glucose levels on a daily basis, this shouldn't present a problem. References: 1. K.G. Gharpurey, Indian Medical Gazette 1926; 61: 155 (Abstr). 2. K.S. Mhaskar, J.G. Caius, Indian Medical Research Memoirs 1930; 16: 2-75. 3. K.R. Shanmugasundaram, C. Panneerselvam, P. Samudram, et al, Pharmacological Research Communications 1981; 13: 475-486. 4. E.R.B. Shanmugasundaram, M. Venkatasubramanyam, M. Vijendran, et al, Ancient Science of Life 1988; 8: 183-194. 5. E.R.B. Shanmugasundaram, K.L. Gopinath, K. Rhada Shanmugasundaram, et al, Journal of Ethnopharmacology 1990; 30: 265-279. 6. K. Baskaran, B. Kizar Ahamath, K. Radha Shanmugasundaram, et al, Journal of Ethnopharmacology 1990; 30: 295-300. 7. E.R.B. Shanmugasundaram, G. Rajeswari, K. Baskaran, et al, Journal of Ethnopharmacology 1990; 30: 281-294. Clinical Studies and Validation: In one controlled study, a standardized gymnema extract was given to 50 people with Type I diabetes, all receiving a dosage of 400 mg daily for periods ranging from 6 months to 2 and years. 50 of the other people in the study continued to take the usual insulin therapy without the addition of gymnema. Among those who took the herbal extract, researchers found that insulin requirements fell off dramatically. In addition, there was a statistically significant decrease in the blood sugar markers that tests long-term blood sugar. Those in the control group showed no significant decreases in blood sugar or insulin requirements. In a second study, 55 people with Type II diabetes were given 400mg of gymnema extract every day for 18 to 20 months while they also continued to get their usual medication for hypoglycemia. Average blood sugar levels improved significantly in the group, along with another sugar related factor (glycosylated hemoglobin). Results also showed that there was an increase in pancreatic release of insulin among the people who got gymnema. People in the study were able to reduce their medication, and five were able to discontinue their drugs completely. ENICOSTEMMA LITTORALE / HEART LEAVED MOONSEED

A perennial herb found throughout India. Available commercially as a botanical extract. Pills prepared from Enicostemma littorale were administered to 84 human patients with Type II Diabetes for three months (1). Estimation of various biochemical parameters showed that E. littorale reduced blood glucose as well as serum insulin levels and prevented the progression of complications in diabetic patients. Significant improvement in kidney function, lipid profile and blood pressure was observed suggesting that E. littorale is an effective herbal antidiabetic (1). 1.Upadhyay U.M. & Goyal R.K. (2004) Efficacy of Enicostemma littorale in Type 2 diabetic patients. Phytother Res., 18(3): 233-235. TURMERIC (CURCUMA LONGA) SPICE, COX-2 INHIBITOR, CHOLESTEROL LOWERING, HEPAPROTECTIVE & ANTIOXIDANT Biological Targets: Aryl hydrocarbon receptor, Cytochrome P450 enzymes,
Glutathione, S-transferase, kinases, COX, iNOS, MMP

Therapeutic Class: Cancer, inflammation, Diabetes and Chemoprevention Curcumoids - antioxidants, hypolipedemic action of curcumin Action: Anti-inflammatory, cholagogue, hepatoprotective, blood-purifier, antioxidant, detoxifier and regenerator of liver tissue, antiasthmatic, anti-tumour, anticutaneous, antiprotozoal, stomachic, carminative. Reduces high plasma cholesterol. Antiplatelet activity offers protection to heart and vessels. Chinese clinical trials in 1987 indicate that turmeric lowers cholesterol levels. Curcumins cholesterol-lowering actions include interfering with intestinal cholesterol uptake, increasing the conversion of cholesterol into bile acids and increasing the excretion of bile acids via its choleretic effects. Curcuminoids prevent the increases in liver enzymes, SGOT and SGPT; this validates the use of turmeric as a hepatoprotective drug in liver disorders. Curlone, obtained from the dried rhizome, is used against hepatitis. Rhizome: Activities Chromium Rhizome 6 ppm: Antidiabetic 200-1,000 ug; Antiobesity, Cardioprotective, Hypocholesterolemic 20 ug/day, Hypoglycemic, Insulinogenic

Curcumin: Anticataract Dosage: 75 mg/kg orl rat, Antiinflammatory Dosage: 1,200 mg/man/day, Antioxidant Dosage: 1/3 BHA, COX-2-Inhibitor Dosage: 10-20 uM, Hepatoprotective Dosage: 30 ppm; Dosage: 30 mg/kg/day, Hypocholesterolemic Dosage: 0.15% diet 7 wks, Hypolipidemic Dosage: 0.15% diet 7 wks EMBLICA OFFICINALES SYN. PHYLLANTHUS EMBLICA OR INDIAN GOOSEBERRY Chemical Composition The major chemical constituents of Amla consist of polyphenols. The fruit and most other parts of the plant contain gallic acid, phyllemblin, phyllemblic acid, emblicol, ellagic acid, chebulagic acid, glucogallin, corilagin, 3,6-digalloyl glucose, putranjivin A, emblicanin A and B, punigluconin, pedunculagin and quercetin. The cytokinins zeatin, zeatin riboside and zeatin nucleotide have been isolated from the Amla fruit. The fatty acids arachidic and behenic acids have been isolated from the seed oil.5 Action _ Fruitantianaemic, anabolic, antiemetic, bechic, astringent, antihaemorrhagic, antidiarrhoeal, diuretic, antidiabetic, carminative, antioxidant. Used in jaundice, dyspepsia, bacillary dysentery, eye trouble and as a gastrointestinal tonic. Juice with turmeric powder and honey is prescribed in diabetes insipidus. Two of its most exciting effects are its ability to reduce cholesterol and LDL (bad cholesterol) levels, and improve glucose tolerance and blood sugar regulation. This is especially important because both high blood cholesterol and high blood sugar are risk factors for the development of cardiovascular disease. A study just published in March 2003 suggests that the tannins in Emblica inhibit the production of aldose reductase, an enzyme implicated in the development of diabetic cataracts. (Suryanarayana P, Kumar PA, Saraswat M, Petrash JM, Reddy GB. Inhibition of aldose reductase by tannoid principles of Emblica officinalis: implications for the prevention of sugar cataract. Mol Vis. 2004 Mar 12; 10:148-54.) The fruit is an important source of vitamin C, minerals and amino acids. The edible fruit tissue contains protein concentration threefold and vitamin C (ascorbic acid) concentration 160-fold than those of apple. The fruit also contains considerably higher concentration of most minerals and amino acids than apple. The fruit gave cytokinine-like substances identified as zeatin, zeatin riboside and zeatin nucleotide; suspension culture gave phyllembin. Phyllembin exhibits CNS depressant

and spasmolytic activity, potentiates action of adrenaline and hypnotic action of Nembutal. The fruit contains superoxide dismutase 482.14 units/g fresh weight and exhibits antisenescent (anti-aging) activity. Juice with turmeric powder and honey is prescribed in diabetes insipidus EtOH (50%) extractantiviral. Preliminary evidence suggests that the fruit and its juice may lower serum cholesterol, LDL, triglycerides and phospholipids without affecting HDL levels and may have positive effect on atherosclerosis. (Eur J clin Nutr, 42, 1988, 939-944; Phytother Res, 14, 2000, 592595.)

Hyper-cholesterolemic activity In a human pilot study, blood cholesterol levels were reduced in both normal and hypercholesterolemic men. In this clinical study, the diet of normal and hypercholesterolemic men aged 35-55 years was supplemented with raw Amla fruit for 28 days. Men in both study groups showed decreases in total serum cholesterol levels. When the Amla supplements were discontinued, the subjects cholesterol levels reverted to near their initial values after two weeks. 11 Amlas effects on low-density lipoprotein oxidation and cholesterol levels were studied in vitro and in vivo. Low-density lipoprotein oxidation was induced in study animals fed a high cholesterol diet. Amla extract was shown to inhibit cholesteremia at a higher level than the anti-cholesterol drug Probucol.

Rats fed Amla extract along with a high cholesterol diet for 20 days showed significantly reduced levels of total, free and LDL cholesterol. Oxidized LDL levels in the animals blood serum was also reduced by the Amla extract. Serum TBA-reactive substance levels were decreased after oral administration of Amla. These results suggest that Amla may be effective for hypercholesterolemia and prevention of atherosclerosis.10 Hypo-lipidemic activity The lipid-lowering and anti-atherosclerotic actions of Amla fruits were evaluated in rabbits fed a high cholesterol diet. The fresh juice of Amla fruits for 60 days at a dose of 5 ml/kg per rabbit per day for 60 days lowered serum cholesterol, triglycerides, phospholipids and low-density lipoprotein levels. Concentration of lipids in animal tissues decreased significantly, along with levels of aortic plaque. Analysis of the animals urine showed increased amounts of cholesterol and phospholipids, suggesting that Amla may have affected the mode of absorption.12 A separate study revealed that Amla also reduces serum, aortic and hepatic cholesterol in rabbits.13 Hypoglycemic activity Amla and Curcuma longa in a combined extract caused a marked reduction in blood sugar levels in both normal fasting and alloxan-induced diabetic rats, with a good response in the glucose tolerance test.15 SYZYGIUM CUMINII SKEELS SYN. S. JAMBOLANUM OR EUGENIA JAMBOLANA OR JAVA PLUM Part Used: Seed Kernels Action: hypoglycaemic, astringent and diuretic. This drug has been found very useful in Diabetes, as it reduces the amount of sugar present in urine in a very brief space of time. Although not a specific in all cases of diabetes, it promises to be of the greatest value and should be tried whenever an occasion presents itself. Van Noorden recommends large doses in cases of diabetes mellitus, and says ounce of the fluid extract in 8 ounces of hot water should be taken 1 hour before breakfast and last thing at night. (Potters Cyclopaedia of Botanical Drugs & Preparations by R.C. Wren & E.M. Holmes).

Chemical Composition The Ayurvedic Pharmacopoeia of India recommends the seed in hyperglycaemia and polyuria. The seeds contain tannin (about 19%), ellagic acid, gallic acid (12%), beta-

sitosterol, 0.05% essential oil; myricyl alcohol is present in the unsaponifiable matter. Analysis by Mr. W. Elborne (1888) showed the presence of a trace of essential oil, fat, chlorophyll, gallic acid (1.65 per cent), colored extractive soluble in water, albumen, and resin soluble in ether and alcohol, all in small amounts, together with a large proportion of insoluble matter (Pharm. Jour. Trans., Vol. XVIII, p. 921). The fluid extract of the seeds is administered in doses of from 30 minims to 1 fluid drachm a day, beginning with 10-drop doses 3 times a day at first, and gradually increasing each day. (Indian Medicinal Plants & Henriettes Herbal.com) Powdered seeds of Eugenia Jambolana in a clinical trial were given in the dose of 12g daily in 3 divided doses for 3 months to 30 patients of non-insulin dependent diabetes. Initial fasting blood sugar in mg % SE was 163.00 (14.83), after 1 month 129.61 (12.03), after 2 months 99.64 (9.49), after 3 months 130.11 (18.87). The reduction in blood sugar was found significant after 1 month and 2 months. It was less after 3 months. (CCRAS) In a clinical trial, 10 patients of type 2 diabetes mellitus with no previous medication, 1o patients of type 2 diabetes mellitus taking oral glycemic agents with history of inadequate control and six control subjects were administered low (2 g thrice daily) and high (4 g thrice daily) of powdered part, aqueous extract and alcoholic extract of seeds of Eugenia jambolana for 14 days after assaying fasting plasma and urinary glucose. On 15th day blood and urine samples for glucose were taken. Based on results obtained it was found that EJ has significant hypoglycemic activity in both low and high doses. (Pak J Pharmacol Jan 2007; 24(1); 13-7) A 6 month parallel designed open labeled randomized, controlled trial was conducted in 30 newly diagnosed type 2 diabetes mellitus. Patients were enrolled to: Group 1 (n = 15) received Madhuhara churna [AVA Trust Regd] (a household remedy of Eugenia jambolana seed based drug); Group 2 (n= 5) received metformin and Group 3 (n=10) were on diet restriction and exercise therapy only. They were followed up each month for 6 months with detailed clinical examination; assessment of compliance to drug intake, diet adherence and exercise; a complete history of adverse events; different parameters to measure the efficacy were done. There was no significant difference in the baseline characteristics of patients in each of the three groups enrolled for study. The results showed a significant decrease in fasting blood glucose at 3rd (152.0 mg/dl 22.5 to 140.7 mg/dl 26.6, P=0.016) and 6th (152.0 mg/dl 22.5 to 134.0 21.3, P=0.043) month, homeostatic model assessment for insulin resistance at 3rd (10.3 4.7 to 6.5 4.1, P=0.027) month and a highly significant rise in high density lipoprotein value at 3rd (39.7 9.6 to 47.3 6.8, P= 0.001) month was seen in group 1 when compared to baseline values. Madhuhara churna [AVA Trust Regd] treatment in type 2 diabetic patients for 6 months has a beneficial effect in improving the glycemic profile (reducing postprandial plasma glucose, insulin resistance and elevating HDL-C levels) in newly diagnosed

type 2 diabetics. (Sahana D.A et al. / Journal of Pharmacy Research 2010, 3(6),12681270) SWERTIA CHIRATA / INDIAN GENTIAN Swerchirin, xanthone from Swertia chirayita (Roxb ex. Flem) Karst] (Gentianaceae) has hypoglycemic activity. Researchers compared the effects of mode of action of three different hypoglycemic agents; centipiperalon, tolbutamide and swerchirin in normal as well as diabetic rats. Except in rats with severe pancreatic damage, swerchirin showed better glucose lowering effect compared to tolbutamide (Saxena AM, Murthy PS, Mukherjee 1996).

ACTIONS AND PHARMACOLOGY COMPOUNDS Iridoide monoterpines as bitter substances (1.3%): chief components swertiamarin (0.4%), sweroside (0.2%), including as well gentiopicrin. amarogentin, amaroswerin Xanthone derivatives: including mangiferin (0.12%), swerchirin (methyl bellidifoline), swertianin, 7-O-methyl swertianin, chiratol, swertiapunicoside, chiratanin EFFECTS Chiretta stimulates the secretion of gastric juices. In animal experiments, an anticholinergic (due to swertiamarin), antiphlogistic, hypoglycemic (due to xanthone derivatives), and centrally suppressing effect has been described. Activities Plant: Gentianine: Hypoglycemic Lupeol: Antihyperglycemic, Antiinflammatory 1/3 Indomethacin Antioxidant Mangiferin: Antidiabetic, Antihepatotoxic, Antiinflammatory, Antioxidant, Cardiotonic Swerchirin: Antihepatotoxic, Hypoglycemic Oleic-Acid: Antiinflammatory, Hypocholesterolemic Stearic-Acid: Hypocholesterolemic Suddah Shilajit or purified asphaltum

Shilajit, also known as silajit, mumijo, and momia,[1] is a thick, sticky tar-like substance with a colour ranging from white to dark brown (the latter is more common), sometimes found in Caucasus mountains, Altai mountains, and Tibet mountains.[2] It is used in Ayurveda, the traditional Indian system of medicine. The composition of Shilajit has been investigated numerous times in both India and the former USSR, and depends on the location where it is found. It has been reported to contain at least 85 minerals in Ionic form, including triterpenes and aromatic carboxylic acid, as well as humic acid and fulvic acid.[3][4][5] A similar substance from the Caucasus Mountains, and Altai mountains is called Mumijo (Russian).[6] ENICOSTEMMA LITTORALE OR INDIAN WHITEHEAD A perennial herb found throughout India. Available commercially as a botanical extract. Pills prepared from Enicostemma littorale were administered to 84 human patients with Type II Diabetes for three months (1). Estimation of various biochemical parameters showed that E. littorale reduced blood glucose as well as serum insulin levels and prevented the progression of complications in diabetic patients. Significant improvement in kidney function, lipid profile and blood pressure was observed suggesting that E. littorale is an effective herbal antidiabetic (1). This herbs potent antidiabetic properties have also been well demonstrated in experiments with rats (eg. 2,3). Note: this scientific name is under review. E. littorale is taken in combination with other herbs, especially for diabetes (Upadhyay and Goyal 2004). 1.Upadhyay U.M. & Goyal R.K. (2004) Efficacy of Enicostemma littorale in Type 2 diabetic patients. Phytother Res., 18(3): 233-235. 2.Srinivasan M., Padmanabhan M. & Prince P.S. (2005) Effect of aqueous Enicostemma littorale Blume extract on key carbohydrate metabolic enzymes, lipid peroxides and antioxidants in alloxan-induced diabetic rats. J Pharm Pharmaco7l., 57(4): 497-503. 3.Maroo J., Vasu V.T. & Gupta S. (2003) Dose dependent hypoglycemic effect of aqueous extract of Enicostemma littorale blume in alloxan induced diabetic rats. Phytomedicine, 10(2-3): 196-199. Cassia auriculata OR TANNERS CASSIA Name : Cassia auriculata - A herb that controls blood sugar and rejuvenates Parts Used : Roots, Leaves, Flowers, Bark Uses : This shrub is specially famous for its attractive yellow flowers, which are used in treatment of skin disorders, body odour. The decoction of the flower may be taken internally. The dried flowers can be used as an external scrub for body odours.

Kalpa drug The five parts of the shrub(Root, leaves, flowers, bark and unripe fruits) are taken in equal quantity, dried and then powered, to give Avarai Panchaga Choornam which gives a good effect in treatment of Diabetes. It establishes good control on sugar levels and reduces symptoms like Polyurea and thirst in Diabetics. Dosage: About 4-5 gms/ day Diabetics and 2-2.5 gms for non-diabetics. It also helps in rejuvenation and maintenance of health as a kalpa drug