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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 35  |  Issue : 4  |  Page : 207-211

Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice


1 Department of Kayachikitsa, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India
2 Department of Rasashastra and Bhaishajya Kalpana, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India
3 Department of Pharmacology, Pharmacology Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India

Date of Web Publication10-Aug-2016

Correspondence Address:
Ankush Gunjal
Department of Kayachikitsa, IPGT and RA, Gujarat Ayurved University, Jamnagar - 361 008, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0257-7941.188177

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  Abstract 

Background: Triphalādi kvātha is well known herbal Ayurvedic formulation used in Prameha (~type 2 diabetes mellitus). In the present study, kvātha was converted into granules and assessed for its hypoglycemic and anti-hyperglycemic effects in albino mice.
Materials and Methods: Triphalādi granules (650 mg/kg, p.o.) were administered in normal albino mice for assessment of hypoglycemic activity. Anti-hyperglycemic activity of Triphalādi granules was assessed in glucose (5 g/kg, p.o.) solution overloaded mice. The blood sugar level (BSL) was measured with the help of one touch easy glucometer.
Results: Triphalādi granules produced significant decrease in blood glucose level after one hour in comparison to initial values while decreasing BSL by 27.92% in comparison to control group in normal albino mice. In hyperglycemic study, Triphalādi granules produced significant decrease the BSL after 2 hr. of administration compared to control group.
Conclusion: Triphalādi granules have significant hypoglycemic and anti-hyperglycemic activity in mice with minimal effect on BSL below normal range. The studies suggest the potential role of Triphalādi granules as an alternative adjuvant therapy in diabetic individuals for the control of the blood glucose level.

Keywords: Anti-hyperglycemic activity, diabetes mellitus, hypoglycemic activity, Triphalādi granules


How to cite this article:
Gunjal A, Walunj M, Aghera H, Nariya M, Goyal MR. Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice. Ancient Sci Life 2016;35:207-11

How to cite this URL:
Gunjal A, Walunj M, Aghera H, Nariya M, Goyal MR. Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice. Ancient Sci Life [serial online] 2016 [cited 2019 May 21];35:207-11. Available from: http://www.ancientscienceoflife.org/text.asp?2016/35/4/207/188177


  Introduction Top


Diabetes mellitus, a metabolic disorder, is a major global health concern with a projected rise in prevalence from 171 million in 2000 to 366 million in 2030.[1] The disease is caused due to an insufficiency of insulin secretion, insulin action or both. While type 1 diabetes can be easily managed with regulated insulin administration, repeated administration of insulin prior to every meal is not desirable. Insulin treatment, if not managed properly, occasionally can result in severe hypoglycemia, a life-threatening situation. Further, continued administration of therapeutics such as sulfonylureas, biguanides, thiazolidinediones and alpha glucosidase inhibitors used for the treatment of type 2 diabetes is also known to cause undesirable effects.[2]

Currently there is an increased interest among diabetics for complementary and alternative medicine involving the use of traditional medicinal herbs and their products, and other dietary supplements.[3] In Ayurvedic practice, there is a need of easily accessible and more efficient therapeutically potential herbal drugs. Administration of drugs in various dosage forms provides an opportunity to the physician to choose better options. In the present study, Triphalādi kvātha [4] a known Ayurvedic formulation used in Prameha (~type 2 diabetes mellitus), was converted into granule form using Rasakriyā (method involving making the kvātha into a semi solid mass) to increase the shelf life, make it palatable, easy to dispense, and aid dose fixation. The granules were assessed for their hypoglycemic and anti-hyperglycemic effects in animals.


  Materials and Methods Top


Drugs

The authenticated drugs were collected from the Pharmacy Division, Gujarat Ayurved University, Jamnagar. Equal proportions of dried raw materials [Table 1] were crushed to prepare coarse powder separately and mixed with eight parts of water in a stainless steel container. Continuous mild heat was applied until it was reduced to one fourth of its initial quantity. During heating process, continuous stirring was done to facilitate the evaporation and avoid any deterioration due to burning of materials. Kvātha (decoction) was filtered through single folded cotton cloth and collected into a separate vessel. Subsequently, the kvātha was boiled again over low heat, maintaining the temperature between 90°C and 95°C till a semisolid consistency was obtained. As the water evaporated, the viscosity of the extract increased, resulting in solid mass (ghana).[5] The Ghana was mixed with 10% of the fine powder which is used to make Triphalādi kvātha . The solid mass (ghana) was passed through a sieve no. 8 to prepare granules and were then dried at 50°C in a hot air oven for 5 hr.[6]
Table 1: Ingredients of Triphalādi granules

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Animals

Swiss albino mice weighing between 30 ± 5 g of either sex were used for the study. The animals were maintained under ideal husbandry conditions and reared under standard conditions of (23 ± 2°C), humidity (50 to 70%) and exposed to 12 h light and dark cycles. All animals were exposed to the same environmental conditions and were maintained on standard diet and water ad libitum. They were fed with Amrut brand rat pellet feed supplied by Pranav Agro Industries and drinking water ad libitum . All the selected animals were kept under acclimatization for seven days before experimentation. The experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC/12/2012/06) in accordance with the guidelines formulated by CPCSEA, India.

Dose fixation

Dose of Triphalādi granules was calculated by extrapolating the human dose to animal dose based on the body surface area ratio using the table of Paget and Barnes (1964).[7] The test drug suspensions were made by suspending in lukewarm water and administered orally with the help of oral rat feeding cannula. Based on therapeutic dose, mice dose was fixed as 650 mg/kg body weight.

Hypoglycemic activity

Swiss albino mice of either sex were selected and randomly divided into three groups with six mice per group. Group (I) was normal control and received distilled water (10 ml/kg, p.o.). Group (II) was test drug treated group and received Triphalādi granules (650 mg/kg, p.o.). Group (III) served as standard control group treated with glibenclamide (0.65 mg/kg, p.o.).

The animals were fasted overnight prior to the experimentation. On the next morning, initial fasting blood sugar level (BSL) was measured with the help of Touch Ez Smart Glucometer (CE0537), by using one touch EzGluco test strips as per user guidelines. Blood was collected from mice tail vein under light ether anesthesia following aseptic conditions. Then distilled water, test drug and standard drug were administered to respective groups of animals as per the body weight. Again, blood sugar level was recorded after 1 hr., 3 hr. and 5 hr. of the test drug administration for assessing the hypoglycemic effect of test drugs.[8]

Anti-hyperglycemic activity

Swiss albino mice of either sex were selected and randomly divided into three groups with six mice per group. Group (I) kept as normal control and received distilled water (10 ml/kg, p.o.). Group (II) kept as hyperglycemic control and received distilled water (10 ml/kg, p.o.). Group (III) of mice kept as test drug treated group and received Triphalādi granules (650 mg/kg, p.o.). Group (IV) served as standard control group treated with glibenclamide (0.65 mg/kg, p.o.).

The animals were fasted overnight prior to the experimentation. In the next day morning, initial fasting blood sugar level (BSL) was measured with the help of Touch Ez Smart Glucometer (CE0537), by using one touch EzGluco test strips as per user's guidelines. Blood was collected from mice tail vein under light ether anesthesia following aseptic conditions. Then distilled water, test drug and standard drug were administered to respective groups of animals as per the body weight. One hour after test drug administration, mice of Group (II) to (IV) were administered orally with glucose (5 g/kg) solution in distilled water. Thereafter BSL was again recorded for all mice at 30 min, 60 min and 120 min of post glucose overload for accessing the anti-hyperglycemic activity of test drug.[8]

Statistical analysis

The data are expressed as mean ± standard error of mean for six mice per experimental group. The data generated during the study were subjected to Student's t -test for paired and unpaired data to assess the statistical significance between the groups at P < 0.05.


  Results Top


Hypoglycemic activity

Data of test drugs on blood sugar level in normal overnight fasted mice reveals that Triphalādi granules and glibenclamide both resulted in a significant decrease in blood sugar levels at all-time intervals in comparison to respective initial values. However, normal control group shows significant decrease in blood sugar level at 3 hr. and 5 hr. in comparison to their initial values. Further, Triphalādi granules produced non-significant decrease (27.92%) in blood sugar level after one hour and did not produce any effect at 3 and 5 hr. intervals when compared to normal control group [Table 2].
Table 2: Effect of Triphalādi granules on blood sugar level in albino mice during hypoglycemic study

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Antihyperglycemic activity

The effect of Triphalādi granules on blood glucose level in glucose overloaded mice was noted at 30 min., 60 min. and 120 min [Table 3]. Glucose overload leads to significant increase in blood sugar levels in hyperglycemic control group when compared to normal control group. Triphalādi granules produced non-significant decrease in BSL after 30 min. (8.08%) and statistically significant decrease (P < 0.05) after 120 min. interval in comparison to hyperglycemic control group. Standard drug, Glibenclamide produced 28.95%, 40.31% and 24.66% decrease in BSL at 30 min, 60 min and 120 min. respectively compared to hyperglycemic control group which was statistically significant at 60 and 120 min.
Table 3: Effect of Triphalādi granules on blood glucose level in glucose overloaded albino mice during anti-hyperglycemic study

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  Discussion Top


In the fasting state, low insulin level increases glucose production by promoting hepatic gluconeogenesis and glycogenolysis. Glucagon also stimulates glycogenolysis and gluconeogenesis by the liver and renal medulla. Postprandially, the glucose load triggers a rise in insulin and fall in glucagon. The major portion of postprandial glucose is utilized by skeletal muscles, an effect of insulin-stimulated glucose uptake. Decreased peripheral utilization due to target tissue defects or increased hepatic production of glucose can lead to hyperglycemia. A good anti-diabetic agent is that which would not lower the blood glucose level below the normal level in normoglycemics and should have a good blood glucose lowering effect in hyperglycemic subjects. Hypoglycemia is an abnormally diminished content of glucose in the blood.[9]

Triphalādi granules have shown hypoglycemic effect in mice after one hour, the values are still within normal range. In the control group and standard treated group, blood sugar level decreased progressively from initial to 5 hr. due to fasting but the Triphalādi granules treated group shows minimal effect after three hours in decreasing sugar level. In the hyperglycemic study, Triphalādi granules produced non-significant decrease in BSL after 30 min. and statistically significant decrease in BSL after 120 min. interval in comparison to control group. The results of this study suggest hypoglycemic effect of Triphalādi granules in hyperglycemic state in mice.

According to some reports the active principle of T. chebula [10] and T. bellerica [10] i.e., chebulinic acid has been reported to possess alpha glucosidase inhibitory action. Mixture of turpenoids in C. rotundus [11] stimulates glucose uptake, whereas H. antidysenterica [12] retards the carbohydrate absorption from intestine. Earlier Pharmacological studies reveals marsupsin and pterostilbene in P. marsupium [13] significantly lowered the blood glucose level of hyperglycemic rats, causing lesser absorption of glucose from intestine and increasing peripheral utilization of glucose. Epicatechin, its active principle, has been found to be insulinogenic, enhancing insulin release and conversion of proinsulin to insulin in vitro . Just as insulin, epicatechin stimulates oxygen uptake in fat cells and tissue slices of various organs and increases glycogen content of rat diaphragm in a dose dependent manner.[14]

E. officinalis has been reported for antioxidant and hypoglycaemic activities.[15]T. bellerica [10] also contains gallic acid which helps in regeneration of β cells of pancreas, similar action is observed in flavonoid, epicatechin found in P. marsupium. [16] Berberine in B. aristata promotes regeneration and functional recovery of β cells, thus Triphalādi granules help in relieving the signs and symptoms of diabetes mellitus type 2 in chronic stages where β cells play a major role in pathology.[17] The important Ayurvedic ingredients which have potential anti-hyperglycemic effects may be responsible for the observed therapeutic effect in Triphalādi granules in the present study. However, further studies are required to ascertain the exact mechanism of action of Triphalādi granules.


  Conclusion Top


From the present study, it is concluded that Triphalādi granules have significant hypoglycemic activity after one hour, the values are still within normal range and has minimal effect on BSL below normal range in mice. Further, Triphalādi granules have significant anti-hyperglycemic activity after 2 hr. of administration. Thus, it can be suggested that Triphalādi granules can be used by diabetic individuals and that it can help in the control of the blood glucose levels if taken as an alternative adjuvant therapy.

Acknowledgement

Authors express their sincere grattitude Prof. P.K. Prajapati, Director, IPGT and RA, Gujarat Ayurved University, Jamnagar for their valuable technical inputs and encouragement for this work.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.  Back to cited text no. 1
    
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Matthaei S, Stumvoll M, Kellerer M, Häring HU. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 2000;21:585-618.  Back to cited text no. 2
    
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Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabet Med 2001;18:242-5.  Back to cited text no. 3
    
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Tripathi I, Tripathi DS. Yoga Ratnakar with Vaidyaprabha Hindi commentary, Pramehachikitsa/73. Varanasi: Chowkhamba Krishnadas Academy; 2008. p. 531.  Back to cited text no. 4
    
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Shastri P. Sharangadhara Samhita. 4th ed. Varanasi: Chowkhamba Orientalia; 2000. p. 206.  Back to cited text no. 5
    
6.
Gupta AK. Introduction to Pharmaceutics – I. New Delhi: CBS Publishers and Distributors; 2002. p. 254.  Back to cited text no. 6
    
7.
Paget GE, Barnes JM. Evaluation of drug activities. In: Laurence DR, Bacharach AL, editors. Pharmacometrics. Vol. 1. London: Academic Press; 1964. p. 50.  Back to cited text no. 7
    
8.
Pilkhwal SS, Sah ML, Juyal V, Pandey S. Hypoglycemic activity of aqueous extract of Urtica parviflora Roxb. innormoglycemic rats. Int J Phytomed 2010;2:47-51.  Back to cited text no. 8
    
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Available from: http://www.en.wikipedia.org/wiki/Hypoglycemia. [Last retrieved on 2105 Jul 13].  Back to cited text no. 9
    
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Anam K, Widharna RM, Kusrini D. α-glucosidase inhibitor activity of Terminalia species. Int J Pharmacol 2009;5:277-80.  Back to cited text no. 10
    
11.
Hakky IS. Composition for and Method of, Treatment of Diabetes United States Patents, 1989, US4826684; 1989.  Back to cited text no. 11
    
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Keshri U, Chandra S, Sharma J. Antidiabetic efficacy of ethanolic extract of Holarrhena antidysenterica seeds in streptozotocin – Induced diabetic rats and its influence on certain biochemical parameters. J Drug Deliv Ther 2012;2:159-62.  Back to cited text no. 12
    
13.
Manickam M, Ramanathan M, Jahromi MA, Chansouria JP, Ray AB. Antihyperglycemic activity of phenolics from Pterocarpus marsupium . J Nat Prod 1997;60:609-10.  Back to cited text no. 13
    
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Shukla A, Shukla HM. Antidiabeticherbal drugs: A review. Int Ayurvedic Med J 2015;3:134-47.  Back to cited text no. 14
    
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Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 2007;40:163-73.  Back to cited text no. 15
    
16.
Chakravarthy BK, Gupta S, Gambhir SS, Gode KD. Pancreatic beta cell regeneration – A novel antidiabetic mechanism of Pterocarpus marsupium Roxb. Indian J Pharmacol 1980;12:123-7.  Back to cited text no. 16
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Yanxia N, Liu A, Gao Y, Wang W, Song Y, Wang L, et al . Therapeutic effect of berberine on 60 patients with non-insulin dependent diabetes mellitus and experimental research. Chin J Integr Tradit West Med 1995;1:91-5.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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