Phytochemical screening and evaluation of Anti-Diabetic activity of CARICA PAPAYA extracts:

Abstarct

Anti-Diabetic activity of Carica Papaya extracts –  Diabetes is one of the major global public health problems and rapidly getting worse particularly in the developing nations. In addition, the use of plants herbal remedies against diseases that constitutes economic problems such as diabetes. C.Papaya Extract was shown to have mild anti diabetic activity as it is a fruit there is possibility to take this fruit along with anti diabetic drug Glibenclamide. So the present study was conducted to evaluate the influence of CPAE and CPHAE on anti diabetic activity of glibenclamide Carica papaya belongs to the family of Caricaceae and several species of Caricaceae have been used as remedy against a variety of diseases.

Hydro Alcoholic and alcohlic extracts of C.Papaya were prepared and were subjected to phyto chemical evaluation and acute toxity studies following OECD guidelines. Phytochemical evaluation reveals that it contains Alkaloids, Glycosides, Flavonoids, Saponins, Tannin, Terpanoids and Polyphenols acute toxicity studies indicated that upto 1000mg/kg in mice and upto 2000mg/kg in rats. No toxity was observed.

To study the influence of  anti-diabetic-activity-of-carica-papaya-extracts of Glybenclamide albino rats weighing 135 to 190gms were randomly distributed into 8 groups each group containng 6 rats. Diabetic was induced in all rats with Alloxan 150mg/kg interpretonially. Group I served as diabetic control. Group II was given Glibenclamide 10mg/kg body weight, Group III, IV and V were given CPHAE 200mg, 300mg and 400mg/kg. Group VI, VII and VIII were given CPAE 200mg, 300mg and 400mg/kg respectively.

All the drugs were gven orally and blood samples were collected before and after drug administration at 0,1,2,4 and 6 hour from Rats tail vein and blood glucose levels at each time interval was estimated by glucometer. Results were expressed as Mean+SEM and percentage blood glucose reduction was estimated.

It was observed that CPHAE and CPAE enhanced the anti diabetic activity of Glibenclamide with 300 and 400 mg/kg which is statistically significant at P<0.05 and P<0.01. As C.Papaya was shown mild anti diabetic activity when it was given with Glibenclamide it enhanced the anti diabetic activity of glibenclimide.

Anti-Diabetic activity of Carica Papaya extracts can be seen here.

AIM AND OBJECTIVE:

 Since there are reports that papaya decrease the nitrite – nitrate in the body, decreased nitrite –nitrate and increased potassium levels in diabetes mellitus increases the effect of insulin on control of blood sugar. Hence, the present study was conducted.

  1. To study the influence of Alcoholic Extract of C.Papaya (CPAE) on the and diabetic activity of Glibenclamide in Alloxan induced diabetic rats.
  2. To study the influence of Hydro Alcoholic Extract of C.Papaya (CPHAE) on the and diabetic activity of Glibenclamide in Alloxan induced diabetic rats.

Carica Papaya

Papaya tree and fruit, from Koehler’s Medicinal-Plants (1887)
Scientific classification
Kingdom:Plantae
(unranked):Angiosperms
(unranked):Eudicots
(unranked):Rosids
Order:Brassicales
Family:Caricaceae
Genus:Carica
Species:C. papaya
Binomial name
Carica papaya

Glibenclamide:

 Mechanism of action

The drug works by inhibiting the sulfonylurea receptor 1 (SUR1), the regulatory subunit of the ATP-sensitive potassium channels (KATP) in pancreatic beta cells[44]. This inhibition causes cell membrane depolarization opening voltage-dependent calcium channel. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release.

After an cerebral ischemic insult the blood brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.

Medical uses

It is used in the treatment of type 2 diabetes. As of 2011, it is one of only two oral antidiabetics in the World Health Organization Model List of Essential Medicines (the other being metformin).[5] As of 2003, in the United States, it was the most popular sulfonylurea.[6]

INFLUENCE OF C.PAPAYA EXTRACT ON ANTI DIABETIC ACTIVITY OF GLIBENCLAMIDE

Alcoholic and Hydro Alcoholic extracts of  Carica Papaya were prepared and subjected to

  1. Phyto chemical evaluation
  2. Acute toxicity studies in rats
  3. To Study the influence of Alcoholic extract of C.Papaya (CPAE)
  4. To Study the influence of Hydro Alcoholic extract of C.Papaya (CPHAE)

PREPARATION OF CARICA PAPAYA EXTRACT:

 Papaya fresh fruit was taken and dried in the shade for few days then dried fruit was powdered finely ,the fine powder was macerated for 72 hours with the composition of  70%  water and 30% alcohol  (hydro alcoholic  extract) was made then it was evaporated to dryness and was kept in the dessicator for 24 hours  for the prevention of growth of micro-organisms . That adduct was weighed and used for the experiment

Actual powder : 2500gms

Dry powder  :1325 gms

For the preparation of Alcoholic extract Papaya fresh fruit was taken and dried in the shade for few days then dried fruit was powdered finely ,the fine powder was macerated for 72 hours with Absolute Alcohol and was evaporated to dryness was kept in the dessicator for 24 hours  for the prevention of growth of micro-organisms . That adduct was weighed and used for the experiment

Actual powder : 1200gms

Dry powder  : 850 gms

As discussed in literature C.Papaya Extract was shown to have mild ant diabetic activity as it is a fruit there is possibility to take this fruit along with anti diabetic drug glibenclamide so the present study was conducted to evaluate the influence of CPAE and CPHAE on anti diabetic activity of glibenclamide

In this study diabetics was induced in rats by given 150mg per kg of Alloxan. To prevent the death of animal due to hypoglycaemia every 6 hours 10% of glucose solution was given intra peritonially upto 24 hours Blood glucose level is estimated periodically and the rats showing blood glucose level above 250mg per100 ml were considered  as diabetic about 48 diabetic rats were selected and randomly distributed in to 8 groups each containing 6 animals.

All drugs were given orally and treat schedule is as follows:-

Group 1          –           Diabetic Control (0.25% Sodium Carboxy Methyl Cellulose)

Group 2          –           Glibeclamide 10mg/kg.

Group 3          –           CPHAE 200mg+Glibencamide 10mg /kg.

Group 4          –           CPHAE 300mg+ Glibencamide 10mg /kg.

Group 5          –           CPHAE 400mg+ Glibencamide 10mg /kg.

Group 6          –           CPAE 200mg+ Glibencamide 10mg /kg.

Group 7          –           CPAE 300mg+ Glibencamide 10mg /kg.

Group 8          –           CPAE 400mg+ Glibencamide 10mg /kg.

 All Drugs were given orally and blood samples (0.5ml) were collected from tail and vein of  0,1,2,4 and 6 hours. Glucose was estimated in all blood samples using Glucometer and percentage blood glucose reduction was calculated at each Time Interval –‘t’ is calculated by using the formulae

t=A-B/A X 100

 A is Blood Glucose concentration at time 0

B is Blood Glucose concentration at time t

 And results were expressed as Mean + SEM

And were represented in tables (Table Number) and were graphically represented in figure (Image number)

Diabetic Control
HoursR1R2R3R4R5Mean+SEM%reduction in blood glucose
0 Hour3353383373403453390%
1 Hour337339340342343340.2-0.29
2 Hour3363383393403423390%
4 Hour340342344345346343.4-1.30
6 Hour342343346349360348-2.65
Glibenclamide 10mg/kg
HoursR1R2R3R4R5Mean+SEM% reduction in blood glucose
0 Hour320335339340340334.80.00
1 Hour3293203213303053214.12
2 Hour29528028029029028714.28
4 Hour230254258245240245.426.70
6 Hour206208210214226212.836.44
CPHAE 200 mg+ Glibenclamide 10mg/kg
HoursR1R2R3R4R5Mean+SEM% reduction in blood glucose
0 Hour328330331338345334.40.00
1 Hour310312312310300308.87.66
2 Hour290285275269272278.216.81
4 Hour240235240249235239.828.29
6 Hour215210185196190199.240.43
CPHAE 300 mg+ Glibenclamide 10mg/kg
HoursR1R2R3R4R5Mean+SEM% reduction in blood glucose
0 Hour320319318317319318.60.00
1 Hour2952982902872802908.98
2 Hour270275272269220261.218.02
4 Hour20221220520020120435.97
6 Hour180173164152120157.850.47
CPHAE 400 mg+ Glibenclamide 10mg/kg
HoursR1R2R3R4R5Mean+SEM% reduction in blood glucose
0 Hour345349335350350345.80.00
1 Hour310305310309320310.810.12
2 Hour290292280270255277.419.78
4 Hour20320219519518019543.61
6 Hour168160165150130154.655.29

CONCLUSIONS:

  Results for anti-diabetic-activity-of-carica-papaya-extracts: Serum blood glucose was measured in all groups and %blood glucose reduction was estimated.

Glibenclamide 10mg/kg showed 37%blood glucose level reductionat 6th hour.

When glibenclamide  10mg/kg was given with CPHAE 200mg, 300mg, 400mg/kg the blood glucose reduction was enhanced to 40%, 50%, 55% respectively.

Discussion: All results were statistically significant at **P<0.05 **P<0.01

When Glibenclamide 10mg/kg was given with CPAE 200mg, 300mg, 400mg/kg the blood glucose reduction was enhanced to 38, 43, 51 respectively.

This indicated C.Papaya extracts is shown to influence the antidiabetic activity.

CPHAE is shown have more effect than CPAE.

In presence of study As per the literature C.Papaya was shown to have mild anti disbetic activity. As it is a fruit there is possible for taking along with antidiabetic drugs such as insulin, sulfonylUreas etc. In present study results indicate that CPHAE and CPAE enhanced antidiabetic activity of Glibenclamide in dose dependent manner.

This  results suggest that concomitant administration of Glibenclamide and papaya is safe in diabetes at lower dose and with higher dose hypoglycemia is more due to enhancement of antidiabetic activity of Glibenclamide.  The patient should be conscious while taking papaya the dose of Glibenclamide can be adjusted accordingly.

This results indicate that papaya might be influencing the absorption of Glibenclamide as shown by the enhancement of peak effect induced by Glibenclamide. So it can be concluded that papaya appears to interfere with the insulin resistance in pancreases their by further enhancing the reduction of blood glucose shown Glibenclamide.

Conclusion: C.papaya higher dose interfering with pharmacodynamics of Glibenclamide. Anti-diabetic-activity-of-carica-papaya-extracts can be seen.

References

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