Pharma Tips

Pharmacological Actions of Gymnema sylvestre R. Br.

By: Pharma Tips | Views: 3062 | Date: 01-May-2011

The Gymnema molecule’s affinity with sugar molecular acceptor is 20 times more than dextrose. The acceptor that can absorb sugar in the small intestine cannot absorb sugar when occupied by Gymnema. As the result, the blood sugar consistency plays down.2. As same reason, Gymnema can act on the taste buds in the tongue. The tongue feels no sweet taste when chewing Gymnema and candy at the same time.3. The blood sugar is controlled by insulin and the insulin is produced by β -cells in the pancreas. Us


            Blood sugar balance is made of the root and leaf of the plant Gymnema or its extraction. Its    functions    can    explain     as follow:

1.     The Gymnema molecule’s affinity with sugar molecular acceptor is 20 times more than dextrose. The acceptor that can absorb sugar in the small intestine cannot absorb sugar when occupied by Gymnema. As the result, the blood sugar consistency plays down.
2.     As same reason, Gymnema can act on the taste buds in the tongue. The tongue feels no sweet taste when chewing Gymnema and candy at the same time.
3.     The blood sugar is controlled by insulin and the insulin is produced by β -cells in the pancreas. Usually, in the adult diabetic, if the β -cell has been damaged, Gymnema can help the β -cell regenerate and thus lessen the diabetic symptoms. Therefore blood sugar balance and blood sugar balance II are effective for both dependent (infant) and adult diabetics.

[a] Blood Sugar Level
            Gymnema leaves, whether extracted or infused into a tea, suppress glucose absorption and reduce the sensation of sweetness in foods effects which may deliver important health benefits for individuals who want to reduce blood sugar levels or body weight. G. sylvestre is a woody climbing plant that grows in the tropical forests of central and southern India, Deccan peninsula, Assam, and some parts of Africa whose leaves are used in herbal medicine preparations65-69.
            Gymnema leaves raise insulin levels by regeneration of the cells in the pancreas that secrete insulin.  Other research has shown that Gymnema also improves uptake of glucose into cells by increasing the activity of the glucose utilizing enzymes, and prevents adrenaline from stimulating the liver to produce glucose, thereby reducing blood sugar levels70. The leaves are also noted for lowering serum cholesterol and triglycerides. It also abolishes the taste of sugar, which effectively suppresses and neutralizes the craving for sweets. The leaf extracts contain gymnemic acid which inhibits hyperglycemia and also acts as a cardiovascular stimulant71.
            The primary clinical application for this botanical is as an antidiabetic agent. Gymnema has been the subject of considerable research since the 1930s7, with promising results for types 1 and 2 diabetes. Gymnema has been successful in controlling the blood sugar level without reducing it to below the normal blood sugar level, an effect seen with the use of insulin or oral hypoglycemic sulphonylurea compounds. Gymnema provides a simple and effective method to help maintain healthy glucose levels. It works safely within your current regimen to promote proper pancreatic function. G. sylvestre significantly reduces the metabolic effects of sugar by preventing the intestines from absorbing the sugar molecules during the process of digestion. Because there is a change in the absorption of sugar, there is a consequent change in the blood sugar level.
 
[b] Diabetes
            As early as 1980s, researchers have started to study    the    anti-diabetic effects of G. sylvestre leaf extracts. G. sylvestre leave extract appears to have the benefits on supporting blood     glucose homeostasis of diabetic rats through     increased serum insulin levels via repair or regeneration of    the endocrine pancreas.72-82 In diabetic rabbits, dried leaf powder     of     G. sylvestre regulated the blood sugar levels by increasing  the enzyme activities affording the utilisation of glucose by insulin dependent pathways. Thus, G. sylvestre appears to     correct the metabolic defects in liver, kidney and muscle.

            In 1990, researchers started to conduct study of G.     sylvestre leaf extract on human beings. Researchers from India adminstered a water-soluble extract of the leaves of    Gymnema sylvestre to 27 patients with insulin-dependent diabetes    mellitus(IDDM) on therapy63. They found that the G.  sylvestre     leaves extract enhance endogenous insulin.  In another study     of     22 Type 2 diabetic patients on conventional oral anti-hyperglycaemic agents, researchers applied G. sylvestre leave extracts as supplements to these patients and five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with G. sylvestre leaf extract    alone83.

            In late 1990s, researchers reported that gymnemic    acid contributed    to    anti hyper-glycemic effect of G.  sylvestre     leaves. In a study of rats, high doses of gymnemic acids increased     fecal cholesterol and CA-derived bile acid excretion. While, other studies suggested that the stimulatory effects of     gymnemic     acid IV [or G. sylvestre leaves] on insulin release may     be     related to the increased cell permeability, rather than by stimulating exocytosis by regulated pathways. There are different kinds of gymnemic acids and related compounds.    Gymnemoside    b and gymnemic acids III, V, and VII exhibit a little inhibitory     activity     against glucose absorption, but the principal constituents,     gymnemic acid I and gymnemasaponin V, lack this activity35.

            Although G. sylvestre has been used to treat a number of conditions, it is best known for its apparent ability to lower blood sugar levels. Results from case reports and studies in humans and animals suggest that it may work in several ways to help control both type 1 and type 2 diabetes84. First, the acids contained in G. sylvestre seem to decrease the amounts of sugar that are absorbed from foods. As a result, blood sugar levels may not increase as much as usual after meals. Secondly, G. sylvestre may promote the production of insulin by the body. It is possible that G. sylvestre may even prompt the pancreas to develop more β cells, the source of insulin. It may also make body cells more responsive to the insulin that is available. Finally, several studies have shown that chewing on the leaves of G. sylvestre dulls the sense of taste for sweet foods. Participants in studies tended to consume fewer sweet-tastes in foods     and drinks after using G. sylvestre.

            Thousands of years ago, Type II diabetes was treated with Gymnema. The plant's sugar-destroying property was revealed when a person chewed one or two leaves. Gymnema was said to paralyze a person's tongue to the taste of sugar and bitter tastes. That taste-blocking reaction lasted for several hours85-90. During that time, leaves supposedly provided a slight block to the taste for salty foods, while the taste for acidic foods was not    affected. By blocking the taste buds from tasting sugar, Gymnema blocked sugar in the digestive system, resulting in a decrease in blood sugar, also known as a hypoglycemic effect. This medicinal action has been studied since the late    1930sR.

            In vivo studies have indicated that extracts of G. sylvestre containing gymnemic acid suppress the elevation of blood glucose levels by inhibiting glucose uptake in the intestine91 and by increasing insulin release from the pancreas. The major mode of action was proposed to be through increased permeability of the α -cell plasma membranes, leading to unregulated loss of insulin from the cells. The high saponin glycoside content of the extract is thought to be responsible for this action. In addition, a calcium 2 sensitive component is present; some degree of insulin release may occur through channel independent calcium influx into the β -cells, perhaps through the pores formed by plasma membrane disruption.

[c] Weight Loss
            Gymnema could also reduce and alter the taste of sugar, and it does just that. By placing the herb on your tongue or drinking the tea, the perception of sugar or aspartate is reduced or eliminated completely. That may come in handy if you want to deter a binge on chocolate cheesecake. Some articles state that this is not true so I tried it myself by breaking open a capsule and placing a small amount in my mouth. It did indeed eliminate the perception of sugar. The effect lasted for about 15 minutes as I sampled other foods and drinks. Sweet Relief gum is available which contains Gymnema. In a randomized, double-blind, placebo-controlled 8 week-study of 60 overweight subjects, combo of (-)-hydroxycitric    acid, niacin-bound chromium and G. sylvestre extract facilitated a reduction in excess    body    weight    and    BMI,    and    promoted healthy blood lipid levels92.

[d] Lipid Lowering
            Animal data: A dose-dependent increase in fecal cholesterol and cholic acid-derived bile acid excretion has been demonstrated in rats. A 3-week study showed a decrease in apparent fat digestibility and an increase in excretion of neutral sterols and acidic steroids in rats receiving an extract of G. sylvestre leaves and either a normal or high-fat diet. Total serum cholesterol and triglycerides also were decreased significantly. After 10 weeks, plasma triglycerides were lower in Gymnema-fed rats than in controls, but the difference in plasma total cholesterol levels was no longer    significant93-96.

            Clinical data: Reduction in plasma cholesterol, triglycerides, and free fatty acid levels was observed in 2 studies of diabetic patients who received supplements of Gymnema in addition to their usual antidiabetic medication (eg, insulin, glibenclamide, or tolbutamide). In contrast, these levels increased gradually from baseline in the control group patients not taking Gymnema. It should be noted that lipid lowering was a secondary endpoint in these studies, which were designed to demonstrate the antidiabetic effects    of    Gymnema97.


[e] Suppression of Sweet Taste
            Gymnema extract interferes with the ability of the taste buds to taste sweet and bitter flavors (such as sugar or quinine), but the ability to taste sour, astringent, or pungent substances    is maintained.
            Animal data: In rats, taste response to sucrose, fructose, lactose, and maltose was markedly suppressed by gurmarin, a protein extracted from G. sylvestre; response to saccharin sodium was weaker. Minimal response to sodium chloride, hydrochloric acid, and quinine hydrochloride was noted. Preference for sucrose recovered within 1 or 2 weeks    after    cessation    of    Gymnema     intake100.
            Clinical data: Research reveals no clinical data regarding the use of Gymnema for suppression of sweet taste. Gymnemic acid combined with the recognized site of sugar, and so it prevents sugar from combining.

[f] Inflammation
           Anti-inflammatory properties of Gymnema have been demonstrated. Biochemical markers of inflammation, such as α -glutamyl transpeptidase, superoxide dismutase, and lipid peroxides are enhanced, increasing protection against leukotrienes and free radicals and aiding     rapid    tissue        repair        and    remodeling.

            Animal data: Histamine release from mast cells was inhibited by extracts of G. sylvestre in vitro.103 Moderate inhibition of carrageenan-induced rat paw edema was induced by an aqueous extract of the leaves of G. sylvestre; naproxen produced superior inhibition of edema. However, efficacy of Gymnema was similar to naproxen in a peritoneal ascites model in mice. Unlike naproxen, Gymnema did not inhibit beneficial granuloma formation and the gastric mucosa was not irritated by high doses.
            Clinical data: Research reveals no clinical data regarding the use of Gymnema for inflammation.

[g] Antibacterial Effects
            Indian researchers demonstrated antimicrobial activity of     an     ethanolic extract of G.  sylvestre leaves against    Bacillus    pumilis, B. subtilis,    Pseudomonas    eruginosa and Staphylococcus    aureus.
            The ethanolic extract of G. sylvestre leaves demonstrated antimicrobial activity against Bacillus pumilis, B. subtilis, Pseudomonas aeruginosa and Staphylococcus aureus and inactivity against Proteus vulgaris and Escherichia coli.

[3.1] Mechanism of action
              Recent pharmacological and clinical studies have shown that G. sylvestre acts on two sites: First, on    the    taste    buds    in    the    oral    cavity; second, on the    absorptive     surface to the intestines.  The important active ingredient of G. sylvestre is an organic acid called "gymnemic acid." Those molecules fill the receptor locations on the taste buds for a period of one to two hours, thereby preventing the taste buds from being activated by any sugar molecules present in the food. Similarly, the gymnemic acid molecules fill the receptor locations in the absorptive external layers of the intestine, thereby preventing the intestine    from    absorbing    the    sugar    molecules.
            It has also been noted that G. sylvestre takes away the bitter taste of bitter substances, such as quinine, in much the same way that it affects the sense of sweetness associated with candies and other sweet foods. However, it has no effect on pungent, salty, astringent or acidic tastes. Therefore, if you are eating an orange within two hours after chewing G. sylvestre leaves, for instance, you would taste the sourness of it but not the sweetness. Gymnemic acid formulations have also been found useful against obesity, according to recent reports. This is attributed to the ability of gymnemic acids to delay the glucose absorption in the blood112. The atomic arrangement of gymnemic acid molecules is similar to that of glucose molecules. G. sylvestre leaves have been found to cause hypoglycemia in laboratory animals and have found a use in herbal medicine to help treat adult onset diabetes mellitus (NIDDM)64. When Gymnema leaf extract is administered to a diabetic patient, there is stimulation of the pancreas by virtue of which there is an increase in insulin release. These compounds have also been found to increase fecal excretion of cholesterol, but further studies to prove clinical significance in treating hypercholesterolemia (high serum cholesterol) are required113. Other uses for Gymnema leaf extract are its ability to act as a laxative, diuretic and cough suppressant114-118. These other actions would be considered adverse reactions when Gymnema is used for its glucose lowering effect in diabetes. Gymnema leaf extract, notably the peptide ‘Gurmarin’, has been found to interfere with the ability of the taste buds on the tongue to taste sweet and bitter. Gymnemic acid has a similar effect. It is believed that by inhibiting the sweet taste sensation, people taking it will limit their intake of sweet foods and this activity may be partially responsible for its hypoglycemic effect. There are some possible mechanisms by which the leaves and especially Gymnemic acids from G. sylvestre exert its hypoglycemic effects are:

1. It    increases    secretion    of        insulin.
2. It    promotes    regeneration    of    islet    cells.
3. It increases utilization of glucose: it is shown to increase the activities of enzymes     responsible for utilization of glucose by insulin-dependent pathways, an increase in phosphorylase activity, decrease in gluconeogenic enzymes and sorbitol dehydrogenase.
4. It causes inhibition of glucose absorption from intestine.
            The gymnemic acid components are believed to block the absorption of glucose in the small intestine, the exact action being unknown120. It could involve one or more mechanisms. One of the mechanisms responsible for adult onset diabetes mellitus is a form of insulin resistance, which is attributed to the inability of insulin to enter cells via the insulin receptor. Gymnema may overcome this resistance, but require further studies to confirm its validity and also whether the effect is clinically relevant. Should this effect be proven, Gymnema may prove useful in both adult onset (NIDDM) and juvenile onset diabetes mellitus (IDDM) to help insulin enter cells63. In the case of IDDM, the insulin is injected by syringe and is not secreted from the pancreas. The leaves are also noted for lowering serum cholesterol and triglycerides95. The primary chemical constituents of Gymnema include gymnemic acid, tartaric acid, gurmarin, calcium oxalate, glucose, stigmasterol, betaine and choline25. While the water-soluble acidic fractions reportedly provide the hypoglycemic action, it is not yet clear what specific constituent in the leaves is responsible for the same. Some researchers have suggested gymnemic acid as one possible candidate, although further research is needed. Both gurmarin (another constituent of the leaves) and gymnemic acid have been shown to block sweet taste in humans.
            The basic function of the gymnemic acids is to bind to the receptor on the intestine, and stop the glucose molecule from binding to the receptor. Thus, gymnemic acids prevent the absorption of excess glucose. Gymnema acts as a pancreatic trophorestorative by focusing on the β cells and the release of insulin. It seems to act by disrupting the absorption of sugar giving the β cells a rest121. It is used for hyperglycemia, diabetes, and sleep disturbance due to insulin resistance, sugar cravings and to assist weight loss by suppressing appetite. Our clients just won't stop taking this, even when their bodies no longer need it. When applied to the mouth directly in extract, it anesthetizes the sweet taste buds for several hours. The aqueous extract of Gymnema sylvestre leaves (GSE) tested on various inflammatory models showed anti-inflammatory activity by significantly inhibiting carrageenan-induced rat paw oedema and peritoneal ascites in mice122,123. GSE elevated liver enzymes (e.g. γ-glutamyl transpeptidase (γ-GT) and Superoxide dismutase (SOD)) showing a protective mechanism against the release of slow-reacting substances and free radicals124. GSE did not inhibit granuloma formation and related biochemical indices, such as hydroxyproline and collagen. GSE in high doses did not affect the integrity of the gastric mucosa and appears to be a less gastrotoxic anti-inflammatory agent when compared with other non-steroidal anti-inflammatory agents59-61. G. sylvestre significantly reduces the metabolic effects of sugar by preventing the intestines from absorbing the sugar molecules during the process of digestion116. Because there is a change in the absorption of sugar, there is a consequent change in the blood sugar level.

[3.2] Toxicological Study
            No adverse reactions were reported in a long-term study of insulin-dependent diabetic patients63. However, consider the possibility of hypoglycemia. Systolic blood pressure was raised in spontaneously hypertensive rats fed a high sucrose diet. The clinical significance    of    this    finding        is    unknown.
            The plant has not been associated with published reports of human toxicity; however, it is possible that as few as 12 tablets of some otc preparations could cause a demonstrable hypoglycemic reaction in humans. Blood urea, uric acid, and hemoglobin levels remained in the normal range in patients receiving Gymnema supplements in addition to their usual antidiabetic medication49, suggesting the absence of hepato- or nephrotoxicity at normal doses. In an acute toxicity study in mice, no gross behavioral, neurologic or autonomic effects were observed. The acute LD 50 was 3990 mg/kg. The safety ratio (LD 50 /ED 50)  was 11 and 16 in normal and diabetic rats, respectively.
The main side effect, as such, is that as it can reduce blood sugar levels, some caution may be necessary if you take it with other agents, such as herbs or pharmaceutical drugs, which might lower blood sugar. If blood sugar levels fall too low, side effects include shakiness, sweating, confusion, distorted speech and loss of muscle control may occur.
            Very little information is available on side effects of G. sylvestre relating to pregnancy or breast feeding, or its use for infants. Therefore, we advise caution in using Gymnema in these circumstances.
            Gymnema is a remarkable herb which, if used bearing in mind the above cautions, can be a huge benefit both to those who truly want to cut down their consumption of sweet foods and those with blood sugar issues52. Of course, if on medication you should consult your doctor before taking Gymnema: but if you have 'blood sugar lows' and are not on medication, try Gymnema.

[3.3] Side Effects
            Short-term uses of low doses of G. sylvesre may    have only un-noticeable side effects. Japanese researchers found    that     there was no toxic effect in rats treated with G. sylvestre     at up to 1.00% in the diet for 52 weeks.    The no-observable-effect level from this study is 1.00%     G. sylvestre, i.e., 504 mg/kg/day for male and 563 mg/kg/day  for the female as mean daily intake, for 52 weeks. In another study    of rats, long-term uses of the G. sylvestre leaves extract    did     not show any influence on hematological and blood chemical parameters125-130. However, one study suggests that G. sylvestre may raise systolic blood pressure R.    G.     sylvestre may lower blood sugar levels; individuals with diabetes  should consult with doctor before    use    this herb.

            People allergic to plants in the Asclepiadaceous (milkweed) family should avoid Gymnema. Gymnema may lower blood sugar levels131. Caution is advised if you are also taking prescription drugs that may lower blood sugar levels. Patients taking oral drugs for diabetes or using insulin should be monitored closely by their health care provider while using Gymnema. Dosing adjustments may be necessary. Gymnema may alter the ability to taste    sweet        foods.
            Pregnancy and Breast-Feeding: Gymnema cannot be recommended during pregnancy or breast-feeding because of a lack of information on safety and effectiveness.As of June 2000, Gymnema was believed to be free of side effects when taken at the recommended dosages. However, more research could reveal side effects.

            Although no side effects have been attributed to the use of G. sylvestre, its possible lowering effect on blood sugar may potentially result in hypoglycemia (blood sugar that is too low). Signs that blood sugar may be too low include shakiness, sweating, confusion, distorted speech, and loss of muscle control. If not corrected, low blood sugar can lead to unconsciousness and even death. Herbs whose side effects - or benefits, depending on your viewpoint - can include reducing blood sugar levels include134,135: Aloe Vera, Devil's Claw, Eleutherocccus senticosus (Siberian Ginseng), Fenugreek, Ginger (in high amounts), Jambul Seed, Panax ginseng, Psyllium Husks, Stevia, Turmeric. It must be stressed that there is little definitive research to show that these herbs definitely reduce blood sugar, and certainly not in every case; but it is best to be cautious if taking any of these herbs in addition to Gymnema. G.  sylvestre may increase the amount by which drugs for diabetes can lower blood sugar. As well as insulin, these drugs include: Actos, Avandia, Glimepiride, Glipizide, Glyburide, Glyset, Metformin, Prandin and Precose

[3.4] Precautions
            Because G. sylvestre is known to lower levels of blood sugar, individuals who have diabetes should use it with caution. If blood sugar levels fall too low, shakiness, sweating, confusion, distorted speech, and loss of muscle control may occur. If it is not corrected, low blood sugar can lead to unconsciousness and even death136-139.
            Very little information is available on how G. sylvestre might affect a developing fetus, an infant, or a small child140 Therefore, its use is not recommended during pregnancy,    while    breast-feeding,    or    during early    childhood. The United States Food and Drug Administration do not regulate Gymnema and other herbal remedies. That means that the remedies have not proven to be effective and that ingredients    are     not standard.
            In addition, the safety of Gymnema has not been established for use by children, pregnant women, nursing mothers and people with severe kidney and liver diseases. Before beginning any herbal treatment, people should consult a physician or health practitioner. Consulting a medical professional is particularly important before taking Gymnema because the remedy could potentially lower blood sugar too much, resulting in a    hypoglycemic  reaction.
            It is especially important for diabetics to consult with a doctor. Gymnema should not be regarded as a substitute for other medications47. If people diagnosed with Type I or Type II diabetes are taking insulin to control their blood sugar, they cannot replace the insulin with Gymnema.
            In addition, diabetes can go undetected for some time.48 It may not be diagnosed until a person goes to a doctor after experiencing symptoms such as frequent urination, dizziness, and fatigue. Diabetes must be treated medically since complications from untreated diabetes can include kidney failure, heart disease, blindness, and loss of limbs.
[3.5] Caution
            Gymnema has safely been used for decades in various countries. Careful long-term studies on its safety have not been done so far, however. Consult your doctor about your desire to supplement your diabetes regimen with Gymnema143.
            For most people using G. sylvestre, blood sugar goes down toward but not below normal blood sugar levels49. This can happen in a small number of patients, however, because the mechanisms of the diabetic syndrome vary with different patients. Remarkably, unlike insulin or oral hypoglycemic sulfonylurea compounds, the hypoglycemic effects of G. sylvestre are seen in only a small percentage of diabetic patients.


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