Anti-diabetic potential of a traditional Polyherbal Formulation – A Review

 

Kumudhaveni B*, Radha R

 Department of Pharmacognosy, College of Pharmacy, Madras Medical College, Chennai, Tamilnadu, India

 

ABSTRACT:

Diabetes mellitus is caused by decreased insulin secretion. The people throughout the world increasingly affected by diabetes mellitus, a global problem. Due to side effects and other reasons usage of oral hypoglycemic agents is reduced. Globally, there will be an increase in the usage of herbal medicines for treating various diseases was reported. According to WHO all herbal medicines should be scientifically evaluated for their activities. In India from ancient time onwards herbal medicines were used to cure many diseases.  Diabetes mellitus is cured by many medicinal plants. Many formulations were also formulated to treat diabetes mellitus but there is a lack of scientific validation so, the aim of this study is to select and scientifically validate a traditional polyherbal formulation. This review work is a small step towards scientifically studying the traditional polyherbal antidiabetic formulation, so as to standardize and improve the formulation for the benefit of humankind.

 

 

 

 

 

1. INTRODUCTION:

Diabetes mellitus is a chronic metabolic disorder associated by hyperglycemia with depleted insulin secretion with altered metabolism of carbohydrates, lipids, and proteins. When pancreatic beta cells are unable to secrete insulin or the cells of the body does not respond to the secreted insulin will also leads to diabetes mellitus ¹.

 

Diabetes is a growing epidemic disease found along the world which affects 10% of the population². Recent estimates indicate that 171 million people with diabetes in 2000 were projected to rise to 366 million by 2030, worldwide³. In India, it is estimated that 51 million of people with diabetic in 2010 will rise to 87 million in 2030⁴.

 

Three major types of diabetes mellitus are Insulin-dependent diabetes mellitus (IDDM) / Type 1, Non-insulin-dependent diabetes mellitus (NIDDM) / Type 2, Gestational diabetes mellitus (GDM). IDDM / Type 1- beta cells of the islets of Langerhans in the pancreas produce very little or no insulin leading to insulin deficiency and hence these types of patients are dependent on injected insulin to prevent ketosis and sustain their life. NIDDM / Type 2- characterized by insulin resistance or with reduced insulin secretion, a condition in which cells fail to respond to insulin properly. Gestational diabetes mellitus (GDM) - Onset or detection of glucose intolerance occurs during pregnancy. GDM is associated with older age, family history of diabetes, obesity and resembles type 2 DM with both inadequate insulin secretion and responsiveness.

 

In India, from Rig Veda (5600 BC) onwards medicinal plants were used for treating various diseases. In Rig Veda 67 medicinal plants were recorded. Out of 2,50,000 higher plants, more than 80000 plants have medicinal value. Tribal people lived in ancient cultures, collected information on herbs and also developed a well-defined herbal pharmacopeias ⁵.

 

Many medicinal plants in ancient Indian medicine have been used to control the hyperglycemic condition and effectively maintain normal glucose levels⁶.

 

Many medicinal plants have recently been evaluated for antihyperglycemic property and have been proven for their effects. Many polyherbal formulations having antidiabetic activity were also been evaluated⁷.

Some commonly used medicines are

1.    Madhumegha churna

2.    Triphala churna

3.    Naval churna

4.    Seenthil churna

5.    Avarai kudineer

6.    Vilva kudineer

7.    Abarga parpam

8.    Abraka chendooram

 

Selection of the polyherbal formulation

Based upon the literature survey a new polyherbal formulation with six different plants having significant antidiabetic activity was selected. This formulation was not scientifically proven so, it was thought worthy to study about this traditional antidiabetic polyherbal formulation to create scientific evidence. The individual ingredients were already proven for having antidiabetic activity. The polyherbal formulation contains the following ingredients

 

Kadalazhinjil pattai (Salacia reticulate, Hippocrateaceae)

Avarai verpattai (Cassia auriculata, Fabaceae)

Nelli mulli (Phyllanthus emblica, Phyllanthaceae )

Tanrikkai (Terminalia bellirica, Combretaceae)  

Parankip-pattai (Smilax china Linn, Liliaceae)

Thetrankottai (Strychnos potatorum, Loganiaceae)

 

Antidiabetic studies on individual ingredients

Cassia auriculata

Praveenkumar JS et al., studied about the Cassia auriculata flower extract articulate its antidiabetic effects by regulating antioxidant levels in plasma, liver and pancreas in T2DM rats and evaluated that the Cassia auriculata extract showed significant improvement in the glucose, insulin, lipid levels in plasma and have significant antioxidant activity⁸. Guruprasad CN et al studied about the hypoglycemic effect of Talapotaka Churna in streptozotocin-induced hyperglycemia in rats. Talapotaka Churna produced a significantly lowering of fasting blood glucose with various doses in STZ-induced diabetic rats⁹. Sivaraj A et al evaluated anti-hyperglycemic and anti-hyperlipidemic effect of combined plant extract of Cassia auriculata and Aegle marmelos in streptozotocin (STZ) induced diabetic albino rats. a 4-week study, Talapotaka Churna produced a significant reduction in blood glucose compared to glibenclamide. The combined plant extracts treated animals revealed restoration of β-cells¹⁰.

 

The effect of aqueous and ethanol extracts of Cassia auriculata L. flowers on diabetes using alloxan induced diabetic rats was revealed by Hakkim FL et al and reported that the water soluble fraction of the ethanol extract showed a more efficient antihyperglycemic effect compared to the aqueous extract¹¹. Aruna P et al studied about the evaluation of antidiabetic activity of Cassia auriculata Linn seeds for alloxan induced diabetes in rats and found that petroleum ether and ethyl acetate extract treated diabetic groups showed significant anti diabetic activity. Reduction in pancreatic TBARS levels in ethyl acetate extract treated diabetic rats is attributed to the flavoniods¹².

 

The polyherbal formulations based on Indian medicinal plants as antidiabetic phytotherapeutics was reviewed by Srivastava S. This review focuses on the potential of different polyherbal formulation in the treatment of diabetes and also reviews their pharmacological investigations¹³. Anti-hyperglycemic and antioxidant properties of Cassia auriculata leaves and flowers on alloxan induced diabetic rats was evaluated by Kalaivani A et al. The present study proved that the Cassia auriculata leaves and flowers possess significant anti-diabetic activity along with potent antioxidant potential in diabetic conditions¹⁴. The antihyperglycemic activity of various fractions of Cassia auriculata Linn. in alloxan diabetic rats was studied. The n-butanol fraction exhibited significant reduction in blood glucose level¹⁵.

 

The anti-oxidative effect of Cassia auriculata on streptozotocin induced diabetic rats were evaluated. The antioxidative effect of 200 mg/kg bw was significantly better than 100 mg/kg bw of C. auriculata and the reference drugs used were tolbutamide and metformin¹⁶. The in vitro antiglycation activity of some medicinal plants used in diabetes mellitus were evaluated. The results showed that among the Phyllanthus emblica and Cassia auriculata, Phylanthus emblica has significant anti glycation activity¹⁷. Nilam Y et al., evaluated the carbohydrate hydrolyzing enzyme inhibitor property, antioxidant and phytochemical analysis of Cassia auriculata, Delonix regia and Vinca rosea Linn: an in vitro study and concluded that the methanol extract of C. auriculata flowers exhibited high  carbohydrate hydrolyzing enzyme inhibitor activity and antioxidant activity¹⁸.

 

 

 

Phyllanthus emblica

Sultana Z et al investigated antidiabetic effect of ethanolic extract of Phyllanthus emblica Linn. fruits in experimental animal models. Study showed significant inhibition of intestinal disaccharidase activity results in reduction of sucrose absorption¹⁹. Arijit C et al studied about the evaluation of antidiabetic activity of polyherbal formulation in streptozotocin- induced diabetic rats. The varied concentration of formulation significantly lowers the blood glucose level, total cholesterol, triglycerides and low density lipoprotein²⁰. Krishnaveni M et al studied about the antidiabetic and antihyperlipidemic properties of Phyllanthus emblica Linn. (Euphorbiaceae) on streptozotocin induced diabetic rats. This study   shows about the antidiabetic and its beneficial effects on lipid profile²¹. Arunvanan M et al reviewed about the overview on anti diabetic activity of siddha medicinal plants which reveals its antidiabetic activity through pancreatic and extra pancreatic mechanism²².

 

Anti-diabetic activity studies of herbomineral formulation for treatment of diabetes were evaluated. This study evaluate the antidiabetic activity of the formulation containing five different herbs and two minerals in streptozotocin (STZ 50 mg/Kg ip single dose) induced diabetic rats. The two formulations F1 (500 mg/Kg) and F2 (1000mg/Kg) had showed significant reduction in blood glucose level²³. The development of an antidiabetic formulation and its inhibitory activity against α -amylase and α– glucosidase were performed. The results showed that the formulation had a significant inhibitory activity on α-amylase and α-glucosidase and was less than that of acarbose. The plants that are formulated possess potent antidiabetic activity²⁴.

 

The nano-encapsulated form of Phyllanthus emblica extract increases its therapeutic effects as antidiabetic and antioxidant in rats. The results showed significantly decreased blood glucose alterations in the expression of glycolytic and gluconeogenic genes, DNA damage and increased the activity of glutathione peroxidase enzyme²⁵.

 

The anti-diabetic activity of commercially available extracts of phyllanthus emblica in streptozocin induced diabetic rats was performed. The results showed that commercially available Phyllanthus emblica extracts have significant hypo glycemic activity²⁶. Mali PR. Performed a study of antidiabetic activity of Phyllanthus emblica linn and Curcuma longa Linn on alloxan induced mice. The extracts were effective in regulating the bio chemical indices associated with diabeties mellitus such as glycogen content and the activities of glucokinase and glucose-6- phosphate²⁷. Hamid KS et al evaluated a systematic review of the antioxidant, anti-diabetic and anti-obesity effects and safety of triphala herbal formulation. This study showed activities like anti-diabetic, antioxidant and lowers cholesterol²⁸. An investigation of antidiabetic effect of ethanolic extract of Phyllanthus emblica Linn fruits in experimental animal models were studied and results showed that ethanolic extract has significant antidiabetic effects²⁹.

 

Terminalia bellerica

On oral administration of various crude extracts of Terminalia bellerica fruits decreases the blood glucose level in STZ-induced diabetic rats. The decrease in blood glucose was greater in the methanol extract treated diabetic rats. The gallic acid (GA) and octyl gallate (OG) present in the methanol extract are responsible for the antihyperglycemic activity which was proved from the biochemical, histopathological and molecular studies³⁰.  The methanolic extract of T. chebula had a significant hypoglycemic activity in normal and glucose induced hyperglycemic rats than that of T. bellerica and T. arjuna and also the three plants exhibit antioxidant activity. These activities were evaluated by Arya A et al in antioxidant and hypoglycemic activities of leaf extracts of three popular Terminalia species³¹. A study was conducted to formulate a suitable dosage form with Eugenia jambolana, Gymnema sylvestre, Tinospora cordifolia, Pterocarpus marscipum, Terminalia bellerica which was used traditionally to treat diabetes mellitus. This study was done by Arora R et al³².

 

Latha et al isolated Octyl gallate for the first time from the fruit rind of T. bellerica has potential antidiabetic effect as it augments insulin secretion and normalizes the altered biochemical parameters in experimental diabetic rat models³³. The different extracts such as hexane, chloroform, ethanol, aqueous at the dose of 200mg/kg were administered to high fat diet associated with alloxan induced diabetic hyperlipidemic rats. It was found that the fruit extracts significantly reduce the total cholestrol, LDL, VLDL levels and significant increase in HDL levels. Aqueous extract of Terminalia bellerica fruit extracts, have more significant activity on reducing the total cholestrol, LDL, VLDL levels and significantly increase in HDL levels³⁴.

 

The effect of methanol extract of fruits of Terminalia belerica was studied in alloxan induced hyperglycemia and antioxidant defense mechanism in rats. Decrease in glutathione peroxidase by alloxan administration was found to be increased significantly in the blood and liver from 9^th day. Glutathione reductase also was found to be increased in blood and liver³⁵. Manila et al studied about the in vitro antidiabetic properties of the fruits and leaves of Terminalia bellerica. The acetone extract of both the fruits and leaves of Terminalia bellerica shows strong inhibitory activity against alpha amylase and the aqueous extract of fruits and leaves of Terminalia bellerica were found to exhibit highest alpha glucosidase activity³⁶.

 

Salacia reticulata

Medagama demonstrated the in vitro studies of Salacia to inhibit intestinal alpha glucosidase. In mouse mesenteric fat it enhances the mRNA expression for hormone sensitive lipase (HSL) and adiponectin; thus increasing lipolysis and reducing insulin resistance respectively. Thus S. reticulata effectively improves insulin resistance, glucose metabolism and reduces obesity³⁷. The extracts from the roots and stem of S. reticulata, S. oblonga, and S. chinensis that have been used as a remedy for diabetes showed substantial inhibitory effects in increase in oral sucrose- and maltose loaded rats and inhibitory effects on intestinal α- glucosidase³⁸. Mangiferin was found to inhibit carbohydrate metabolize enzymes sucrase, isomaltase, and aldose reductase from rat with IC50 values of 87, 216 and 1.4 mg/ml, respectively. The inhibitory activities of mangiferin are competitive for sucrase and isomaltase with inhibitor constant (Ki) 55 mg/ml and 70 mg/ml, respectively³⁹.

 

Hiromi et al isolated a novel 13-membered ring thiocyclitol, from an aqueous extract of Kothala-himbutu (Salacia reticulata) inhibited α -glucosidase in vitro. The inhibitory activity was performed on maltose- and sucrose loaded wistar rats. This study  found significant lowering of postprandial glucose levels and the potency of 13-membered ring thiocyclitol was confirmed in vivo⁴⁰. Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α-glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator-activated receptor-α, glucose transporter-4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities⁴¹. Salacia extract has remarkable potential to prevent obesity and associated metabolic disorders including the development of metabolic syndrome⁴².

 

Smilax chinensis

Dried aqueous, alcoholic, and petroleum ether extracts of roots of Smilax china were subjected for hypoglycaemic activity in wistar rats. Blood sugar level was determined using digital glucometer. The oral administration of root extracts at doses of 200 mg/ kg lead to a significant blood glucose reduction⁴³.

 

The anti‐diabetic effects of the methanol extracts of the Smilax chinensis L. (MESC) on alloxan‐induced diabetes were evaluated on albino wistar rats. MESC (200 and 400 mg/kg) treated groups showed significant reduction in the serum levels of Total cholesterol and triglycerides. The results suggested that the methanolic extract of Smilax chinensis L. possesses a potential hypoglycaemic effect with potential hypolipidemic effect⁴⁴.

 

Strychnos potatorum

The antidiabetic effect of seeds of Strychnos potatorum Linn. was evaluated in a model of diabetes mellitus using streptozotocin. The antidiabetic effects were compared with glipizide. Strychnos potatorum significantly reduce the fasting blood sugar. It also increase the body weight along with decreased food and water intake in streptozotocin-induced diabetic rats⁴⁵.

Hydro alcoholic extract of Strychnos potatorum Linn were analyzed for glucose uptake activity and found to be significantly active at 200 μg/ml dose comparable with insulin and metformin. Elevation of glucose uptake by Strychnos potatorum Linn in association with glucose transport supported the up regulation of glucose uptake. It was concluded that hydro alcoholic extract of Strychnos potatorum Linn activate glucose uptake in L-6 cell line of rat skeletal muscles⁴⁶.

 

CONCLUSION:

In the traditional medicinal practice, more number of herbal drugs and formulations were used to treat diabetic disease. They were given according to the patients need, but many of the herbal drugs and formulations are not scientifically proven. The above reviewed traditional polyherbal formulation were prescribed for diabetes mellitus but not standardized by scientific methods. Development of scientific evidence for these formulations may have a greater use and the usage can be increased globally due to their safety and non-toxic.

 

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Accepted on 12.06.2017        © RJPT All right reserved