The present study was undertaken to scientifically validate the antidiabetic activity of aqueous fruit extract of
Diabetes mellitus and its complications are becoming a global burden and have to be dealt with firmly. Hypercholesterolemia associated with this dreaded disease [
Fresh unripe fruits (6 kg) of
Experiments were performed in 6–8-week-old, healthy, male albino Wistar rats, of body weight 150–200 g. Animals obtained from National Institute of Communicable Diseases (NICD) New Delhi, India were housed under standard environmental conditions (
Diabetes was induced by a single intraperetonial injection of freshly prepared Streptozotocin (STZ) (purchased from Sigma Aldrich Chem. Co., St. Louis, USA) at a standard dose of 55 mg kg−1 bw [ Mild diabetic (MD): FBG 150–250 mg dL−1 Severely diabetic (SD): FBG > 250 mg dL−1.
Blood samples were collected from the tail vein from the afore mentioned overnight fasted rats, and the BGL were estimated by glucose oxidase method [
Initial screening of the aqueous extract for the hypoglycemic activity was done with a range of variable doses in overnight fasted normal healthy rats by conducting FBG and glucose tolerance test (GTT) studies. The antidiabetic effect was assessed in mild-diabetic models fasted overnight with the same range of doses by studying their effect on FBG and GTT levels. The results were compared with a reference drug, Tolbutamide, for positive control. Severely diabetic animals were used for evaluating the antidiabetic and hypolipidemic potential of the most effective dose identified in case of normal and mild-diabetic animals. Effect of this dose was also studied on TC, TG, HDL, TP, Hb, US, and bw of severely diabetic rats.
Five groups of six rats each were used in the experiment. Group I served as untreated control received vehicle (distilled water only), and animals of groups II, III, IV, and V received aqueous fruit extract suspended in distilled water at doses 500, 750, 1000, and 1250 mg kg−1 bw, respectively. Blood samples were collected from tail vein at 1.5, 3, 4.5, and 6 h after administering the extract.
The antidiabetic effect of aqueous extract of
Three groups of 6 rats each were used in the experiment. Groups I and II served as normal and severely diabetic control, whereas group III was treated once daily for 4 weeks with the dose of 1000 mg kg−1 bw identified as the most effective dose in case of normal and mild-diabetic rats. Various biochemical parameters such as FBG, PPG, TC, TG, HDL, LDL, VLDL, TP, Hb, US, and bw were taken into consideration and were estimated initially and then weekly up to 4 weeks.
Toxic effect of the aqueous extract was also studied by LD50 experiment. Two groups of rats of both the sexes (6 animals per group, 3 females and 3 males), weighing about 180–200 g were orally administered ten and fifteen times the most effective dose of 1000 mg kg−1 bw by a single dose of 10.0 g and 15.0 g. of the aqueous extract of
Data were statistically evaluated using one-way ANOVA (Analysis of Variance), followed by a post hoc Newman-Keuls Multiple Comparison Test. The values were expressed as mean ± S.D. and considered significant at
Table
Effect of graded dose of
Experimental Groups | Treatment (mg kg−1 bw) | Blood glucose levels (mg dL−1) | ||||
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Pretreatment | Post treatment (hours) | |||||
FBG | 1.5 | 3.0 | 4.5 | 6.0 | ||
Control (I) | Distilled water |
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Extract (II) | 500 |
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Extract (III) | 750 |
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Extract (IV) | 1000 |
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Extract (V) | 1250 |
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Table
Effect of graded doses of
Experimental Groups | Treatment (mg kg−1 bw) | Blood glucose levels (mg dL−1) | ||||
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Pretreatment | Post treatment (hours) | |||||
FBG | 0 | 1 | 2 | 3 | ||
Control (I) | Distilled water |
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Extract (II) | 500 |
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Extract (III) | 750 |
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Extract (IV) | 1000 |
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Extract (V) | 1250 |
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Tolbutamide (VI) | 250 |
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Tables
Effect of most effective dose of
Experimental animals | Treatment (aqueous extract) | Pretreatment levels | Posttreatment levels | |||
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7 days | 14 days | 21 days | 28 days | |||
FBG (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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PPG (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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Effect of most effective dose of
Experimental animals | Treatment (aqueous extract) | Pretreatment levels | Posttreatment levels | |||
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7 days | 14 days | 21 days | 28 days | |||
Total cholesterol (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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HDL cholesterol (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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Triglycerides (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg/kg |
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LDL and VLDL cholesterol (mg dL−1) were calculated with Friedwald’s formula.
Tables
Effect of most effective dose of
Experimental animals | Treatment (aqueous extract) | Pre-treatment levels | Post-treatment levels | |||
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7 days | 14 days | 21 days | 28 days | |||
Total protein (mg dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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Total hemoglobin (g dL−1) | ||||||
Normal (control I) | D W |
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SD (control II) | D W |
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SD (treated III) | 1000 mg kg−1 |
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Effect of most effective dose of
Experimental animals | Treatment (aqueous extract) | Pre-treatment levels | Post-treatment levels | |||
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7 days | 14 days | 21 days | 28 days | |||
Urine Sugar | ||||||
Normal (control I) | D W | Nil | Nil | Nil | Nil | Nil |
SD (control II) | D W | +++ | +++ | ++++ | ++++ | ++++ |
SD (treated III) | 1000 mg kg−1 | ++++ | ++++ | +++ | ++ | + |
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Body weight (g) | ||||||
Normal (control I) | D W | 200 | 200 | 210 | 210 | 210 |
SD (control II) | D W | 190 | 190 | 180 | 180 | 180 |
SD (treated III) | 1000 mg kg−1 | 200 | 200** | 210* | 210* | 210** |
Experiment was carried out on normal healthy rats. The behavior of the treated rats appeared normal. No toxic effect was reported at doses up to 10 and 15 times of the identified most effective dose of the aqueous extract as no mortality was observed in any of these groups.
Fruits of
The results obtained with the dose of 250 mg kg−1 bw of the reference drug, Tolbutamide, taken as standard are comparable with the results of the most effective dose of 1000 mg kg−1 bw of the extract indicating thereby the possible similar mechanism of action [
Generally, it has been observed that hyperlipidemia is a complication associated with hyperglycemia [
Results reveal that
A number of lectins have been reported from
In conclusion, the relevance and significance of this pioneer study cannot be ignored as it reconfirms the ethnobotanical profile of
Blood glucose level
Body weight
Distilled water
Fasting blood glucose
Glucose tolerance test
Hours
Haemoglobin
High density lipoprotein
Kilogram
Lethal dose 50%
Low density lipoprotein
Milligram
Postprandial glucose
Standard deviation
Streptozotocin
Total cholesterol
Total protein
Triglycerides
Urine sugar.
The authors are thankful to Indian Council of Medical Research (ICMR), New Delhi, India and National Medicinal Plants Board (NMPB), New Delhi, India for providing financial assistance to carry out the present study.