Hypoglycemic and Antihyperglycemic Prospective of marketed and Herbal Resilient Mediators

 

Mr. Aniket Garud ^1*, Dr. N S Vyawahare²

¹Department of Pharmacy, Ponnaiyah Ramajayam Institute of Science and Technology (PRIST University) Vallam, Thanjavur, Tamil Nadu, India

²Department of Pharmacy, Dr. D. Y. Patil College of Pharmacy, Pune, Maharashtra, India.

 

ABSTRACT:

Diabetes is drumming worldwide to not only developed countries but developing countries too. Many combinations and Antidiabetic drugs are available in the market which claims effective management of blood glucose levels. One must study how the effectively and accuracy of the same scientifically. Ayurveda is the longest and strongest mother source for all treatments of numerous ailments. In Ayurveda a separate section called as Rasayana Chikista is meant for antiaging as well as rejuvenation. Curcumin is the major conqueror molecule which has shown the promising effect toward various ailments. Ginger is also Rasayana Herb. Allium sativum that is Garlic is best known for its antibacterial activity as well as lipid lowering activity. Here we would like to test and evaluate comparative status of various marketed and herbal Antidiabetic drugs. Different animal models claim different mechanism which is quite comparable to several diabetic conditions of patient.

 

 

 

INTRODUCTION:

Diabetes is a complex disease and measure meager to be treated smartly. Diabetes is playing with public health from decades. Diabetes is drumming worldwide to not only developed countries but developing countries too [1-4]. There are total four types of diabetes mellitus. All are distinct from each other but it achieves severe damage to health. First one is insulin dependent diabetes in which pancreas is damaged due enormous reasons. In second type its non- insulin dependent due resistance to insulin by the cells [5-7]. Third and fourth type is reversible as due gestation that is pregnancy and change in hormonal levels & drug induced respectively. [7-9]. Hur, Kyu Yeonet, al. very precisely mentioned the metabolic disorders its characteristics and causes. When anomalous biochemical replies in the body modifies the typical metabolic processes.

 

It can also be demarcated as hereditary solitary gene incongruity, maximum of which are autosomal ebbing. [10] So many combinations and antidiabetic drugs are available in the market which claims effective management of blood glucose levels. One must study how the effectively and accuracy of the same scientifically.

 

Ayurveda is the longest and strongest mother source for all treatments of numerous ailments. In Ayurveda a separate section called as Rasayana Chikista is meant for antiageing as well as rejuvenation. [11,12] Turmeric is one of the Ayurveda Rasayana herb. Turmeric is mainly known as Haldi, Curcuma Longa scientifically and Haridra Spiritually [13,14,15]. This plant is basically from Zinger family and contains many enchanted molecules which can do wonders in the future. Curcumin is the major conqueror molecule which has shown the promising effect toward various ailments.

 

Ginger is the folk medicine scientifically known as Zingiber officinale. Turmeric and Ginger are from same family widely known as Zingiberaceae [16,17]. Ginger is effective against many bacteria’s so its majorly used for the treatment of fever and stomach infections as mention in ancient texts [18]. Ginger also helps in preventing nausea; vomiting in recent studies it has seen promising effect as antidiabetic agent [19]. Ginger is also Rasayana Herb. Allium sativum that is Garlic is best known for its antibacterial activity as well as lipid lowering activity [20]. Major role played by garlic is to lower the lip levels from the body which is best suited action for cardiac patients [21]. Many diabetics face cardiac issues [22]. Many paper claim garlic can prevent as well as sojourn the various carcinomas [23,24].

 

Here we would like to test and evaluate comparative status of various marketed and herbal drugs. Different animal models claim different mechanism which is quite comparable to several diabetic conditions of patient.

 

MATERIAL AND METHODS:

Experimental Animals:

Wistar rats weighing 160-200 gm were selected. Animals of either sex were housed under standard laboratory conditions of temperature 22±3⁰C and relative humidity of 44-56% with free access to standard pellet diet and water ad libitum. Has received ethical approval by the Institutional Animal Ethical Committee & number is CPCSEA/IAEC/2017/015.

 

Chemicals:

Marketed drugs were purchased from local market, Glucose diagnostic kit (Bio lab India), Nano Curcumin and Allicin were received as gift sample by Konark Herbals Pvt. Ltd and Alllusure, Allimax Pvt. Ltd. The Great Britain United Kingdom, and Supercritical fluid extract of Zingiber Officinalewas kindly provided by Nisarg Biotech Pvt. Ltd. Bangalore.

 

Acute toxicity:

Acute oral toxicity studies were performed for Super critical fluid extract of Gineger [25,26, 27] according to the OECD (Organization for Economic Co-operation and Development) guidelines. Male Rat (n = 6/each dose) were selected for acute toxicity study. The animals were fasted overnight with free access to water. Extract (suspended in 0.6% carboxy methyl cellulose) was administered orally at a dose of 5 mg/kg. The general behaviors such as motor activity, tremors, convulsions, straub reaction, aggressiveness, piloerection, loss of lighting reflex, sedation, muscle relaxation, hypnosis, analgesia, ptosis, lacrimation, diarrhea and skin colour were observed for 3 days. If mortality observed in 4/6 or 6/6 animals, the dose administered was considered as toxic dose. However, if the mortality was observed in only one rat, then the dose was repeated with higher doses such as 100, 200, 500, 1000 and 2000 mg/kg. All combinations were found to be safe at 2000 mg/kg, p.o.

 

 

Effect on Normal glucose levels: Hypoglycemic study in normal fasted rats. [28,29,30]

The effect of all groups on fasting blood glucose was studied in normal rats. Animals were divided into eleven groups of six rats each as mentioned in Table No 1. All groups received respective treatment mentioned in the table. At the 0^th, 60^th, 120^th and 180^th min after drug administration blood was collected by puncturing retro-orbital plexus under light ether anesthesia by using fine glass capillary in epindroff. Plasma glucose levels will be estimated by GOD/POD method.[32]

 

Oral Glucose Tolerance Test [28-31].

The Wistar albino rats weighing 160-230 g were used. The overnight fasted animals were divided into eleven groups (n=6) as mentioned in Table No 1. After 30 min of drug administration, the rats of all groups were orally treated with 2 g/kg of glucose. Blood samples were collected retro-orbital plexus just prior to glucose administration and at 30, 90 and 150 min after glucose loading. Serum was separated and blood glucose levels will be measured immediately by GOD/POD method [32].

 

Table 1: Selected Groups and Dose respectively.

Sr No	Group and Drug	Drug Dose
1.	Group I: Normal (NC)
2.	Group II: Metformin (M)	100 mg/kg PO
3.	Group III: Metformin + Glibenclamide(GM)	100+0.6=106 mg/kg, P.O.
4.	Group IV: Metformin + Sitagliptine (JM)	120 mg/kg metformin P.O.+ 11.67 mg/kg Sitagliptin P.O.
5.	Group V: Metformin + Glimepride (GLM)	Metformin 120 mg/kg, + Glimepiride 1 mg/kg, P.O.
6.	Group VI: Metformin + Pioglitazone + Glimepride (Tri)	120 mg/kg Metformin 1.25 mg/kg Pioglitazone 0.7 mg/kg Glimepiride P.O.
7.	Group VII: Metformin + Nano Curcumin (MC)	100 mg/kg P.O. + 100 mg/kg P.O.
8.	Group VIII: Metformin + Allicin (MA)	100 mg/kg P.O. + 16mg/kg i.p.
9.	Group IX: Metformin + Ginger CO2 Extract (MG50)	100 mg/kg P.O. + 50 mg/kg P.O.
10.	Group X: Metformin + Ginger CO2 Extract (MG100)	100 mg/kg P.O. + 100 mg/kg P.O.
11.	Group XI: Metformin + Ginger CO2 Extract (MG200)	100 mg/kg P.O. + 200 mg/kg P.O.

 

STATISTICAL ANALYSIS:

Data obtained were subjected to one way ANOVA followed by the student’s t-test to determine the level of significance at P<0.05 probability level. The results were expressed as Mean±SD/SEM. The data was statistically analyzed using Prism version 6.01. Mean values were considered statistically significant when p<0.05, p<0.01 and p < 0.001. [33]

RESULT AND DISCUSSION:

Acute toxicity:

As per the OECD 425 guidelines acute oral toxicity was done and shown that supercritical fluid extract is safe up to the extreme dose of 2000 mg/kg body weight. The extract administration neither triggered any significant change in the behavior’s nor the death of animals. 1/10^th, 1/20^th and 1/40^th of the determined dose was fixed for further analyses. The animals were divided into 11 groups of six animals each.

 

 

Effect on Normal glucose levels: Hypoglycemic study in normal fasted rats

 

Fig.01. Effect on Effect on Normal glucose levels

Results are presented as mean ± SEM (n=6), data analysed by ANNOVA followed by student’s t-test. **p<0.01, * p<0.05 compared with normal control. control 1% CMC (1 ml/kg, p.o.).

 

 

Oral Glucose Tolerance Test

 

Fig.02 Effect on Oral Glucose Tolerance Test

Results are presented as mean ± SEM (n=6), data analysed by ANNOVA followed by student’s t-test. **p<0.01,* p<0.05 compared with normal control. control 1% CMC (1 ml/kg, p.o.).

 

 

Metformin is claimed to be first line agent in the management of diabetes. By decreasing gluconeogenesis metformin also act by stimulation of AMPK (AMP-activated protein kinase), inhibition of complex I that is the mitochondrial respiratory chain, by increasing levels of cAMP (cyclic adenosine monophosphate) along with decreased activation of PKA (protein kinase-A) [34-38].

 

Sitagliptin is a novel compound which is Antihyperglycemic in nature. It mainly inhibits DPPIV Enzyme which inhibits gluconeogenesis and improves insulin secretion. Major side effect when combined with Metformin is Upper respiratory tract infection, kidney problem and low blood glucose levels [39-42]. Glibenclamide also known as glyburide is used and considered as standard Antidiabetic drug but due to its hypoglycemic nature it has to use with observation and precaution. Patient must be counseled properly before using these kinds of drugs. Marked hypoglycemia and cholestatic jaundice are major side effects. In the pancreatic beta cell it inhibits the KATP (ATP-sensitive potassium channels) inhibitory regulatory SUR1 (subunit sulfonylurea receptor1). This cell membrane depolarization, opening voltage-dependent calcium channels by mean of which causes insulin release [43,44,59]. Glimepiride Though act as secretogouge and decreases blood glucose levels by stimulating the release of insulin by pancreatic beta cells. It is less preferred than Metformin. [45,46] Pioglitazone is mostly used with Metformin. It improves tissue sensitivity to insulin. It preferentially stimulates the nuclear receptor PPAR-γ (peroxisome proliferator-activated receptor gamma).It causes transcription of various genes involved in the control of lipid and glucose metabolism in muscles, adipose tissue and mainly in the liver. Due to this magical behavior pioglitazone reduces insulin resistance and glycation of blood hemoglobin [47-50].

 

Curcumin is a wonder molecule. Its major drawback was absorption due to its nonpolar nature. Curcumin exhibited various activities like Antidiabetic, anticancer, antibiotic etc. Curcumin is a potent Protein Kinase C Inhibitor. Protein Kinase C activation is major cause of various diabetic complications like Dementia, Alzheimer’s disease, and Immune dysfunction, Diabetic Cardiomyopathy, Diabetic Nephropathy and Response to vaccines is also dwindled due to conceded immune system [51-58, 70-72]. Ginger and its active analogues have been tried in the various animal models like Alloxan, streptozotocin and steroid induced diabetes. Ginger is strong cardio protective and wound healing property [59-64]. Garlic is the golden drug from Ayurveda which has been proven for various activities like cardio protective, lipid lowering, Immuno boosting, antidiabetic, and antihypertensive, hepato as well as neuroprotective [65-69].

 

CONCLUSION:

The major dictum of the study was to verify whether combination of marketed and herbal leads will work or not. Further detailed study is required to extend the degree of effectiveness of such concept. No doubt as many researchers are working to achieve the common goal, the rising sun of health will come in the life of Indian patients.

 

ACKNOWLEDGEMENT:

The authors are thankful to Dr. Pralhad Wangikar (Prado Preclinical Pvt. Ltd.) and Dr. S R Chaudhari, Principal SJVPM’S Rasiklal M Dhariwal Institute of Pharmaceutical Education and Research Chinchwad Pune for providing Infrastructure.

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Received on 19.03.2019          Modified on 18.04.2019

Accepted on 20.05.2019        © RJPT All right reserved