|
 
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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 7
| Issue : 1 | Page : 72-78 |
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Antidiabetic effect of Borassus flabellifer L. extracts on streptozotocin-induced diabetic rats
Anitha Peter1, Nargis Begum Tajudheen2, Senthil Kumar Ramamoorthy3
1 Department of Biotechnology, Jamal Mohamed College (Autonomous), Affiliated to Bharathidasan University, Tiruchirappalli, Tamil Nadu, India
2 Department of Biochemistry, Shrimati Indira Gandhi College, Affiliated to Bharathidasan University
3 Department of Biochemistry, Thanthai Periyar Government Arts and Science College (Autonomous), Affiliated to Bharathidasan University, Tiruchirappalli, Tamil Nadu, India
| Date of Submission | 12-Nov-2022 |
| Date of Decision | 09-Dec-2022 |
| Date of Acceptance | 16-Jan-2023 |
| Date of Web Publication | 14-Mar-2023 |
Correspondence Address:
Anitha Peter
Department of Biotechnology, Jamal Mohamed College (Autonomous), Affiliated to Bharathidasan University, Tiruchirapalli - 620 020,Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/bbrj.bbrj_4_23
Background: Around the world, the number of people with diabetes is rising at an alarming rate, and experts have been using ancient drugs that are mostly made from plants as treatments.This study aimed to see if Borassus flabellifer L. palm sprout ethanolic extracts could help treat diabetes in rats made diabetic by streptozotocin (STZ). Methods: STZ (45 mg/kg bw) was injected once into the peritoneum of male albino Wistar rats. This caused them to get diabetes. For 60 days, intragastric intubation was used to give diabetic rats B. flabellifer palm sprout ethanolic extracts (400 mg/kg bw) and glibenclamide (1 mg/kg bw). Results: As a result, the rats lost a lot of weight, their blood sugar and glycosylated hemoglobin levels went up, and their total hemoglobin (Hb) levels went down. Furthermore, glucose-6-phosphatase and fructose-1,6-bis phosphatase were higher in rats made diabetic by STZ, while hexokinase and glycogen levels were lower. When diabetic rats were given ethanolic extracts of B. flabellifer palm sprouts and glibenclamide, their blood glucose and glycosylated Hb levels went down very well, and their Hb levels went up. Changes in how enzymes that break down carbohydrates and liver glycogen work were greatly improved. Conclusion: The results of the ethanolic extracts of B. flabellifer palm sprouts were similar to those of the standard drug glibenclamide. The results of this study back up the traditional use of plant extracts to treat diabetes.
Keywords: Borassus fabellifier L, carbohydrate metabolizing enzyme, in vivo antidiabetic activity, liver glycogen
How to cite this article:
Peter A, Tajudheen NB, Ramamoorthy SK. Antidiabetic effect of Borassus flabellifer L. extracts on streptozotocin-induced diabetic rats. Biomed Biotechnol Res J 2023;7:72-8 |
How to cite this URL:
Peter A, Tajudheen NB, Ramamoorthy SK. Antidiabetic effect of Borassus flabellifer L. extracts on streptozotocin-induced diabetic rats. Biomed Biotechnol Res J [serial online] 2023 [cited 2023 Jun 10];7:72-8. Available from: https://www.bmbtrj.org/text.asp?2023/7/1/72/371700 |
| Introduction | |  |
Diabetes mellitus (DM) can be a group of metabolic diseases that cause high blood sugar (hyperglycemia) due to problems with insulin production, insulin action, or both.[1] Chronic hyperglycemia has been linked to long-term damage and pathology that affects many organs.[2] It also makes you more likely to have dyslipidemia, high blood pressure, and be overweight. Insulin-dependent diabetes is caused by environmental factors that can trigger immune system responses in people who do not have a strong immune system because of their genes.[3] This can lead to the loss of pancreatic islet-cells, which causes insulin deficiency. A lack of insulin, obesity, insulin resistance, and a genetic predisposition in people over 40 causes noninsulin-dependent diabetes.[4] Langerhans' islets could be poisoned by streptozotocin (STZ), which causes bad diabetes. This condition is marked by a big rise in glucose levels in the blood and a big drop in insulin production. Hemoglobin (Hb) and frame glycosylated Hb react to the extra glucose in the blood glycosylated hemoglobin (HbA1c).[5] Reports from the past have shown that insulin makes glibenclamide work better, so it has been accepted as a qualified diabetes drug.[6] The best way to treat the polygenic disorder without affecting its symptoms is still debatable. Due to the growing interest in testing homegrown cures, these are seen as less dangerous and have small effects on the body.
The leaves of Borassus flabellifer L.(Arecaceae) are 0.9–1.5 m in diameter and palmately fan-shaped, while the petiole edges are covered in hard horny spinescent serratures; the flowers are unisexual; the male spadix is branched while the female spadix is simple, and the fruits are large, subglobose drupes on the greatly enlarged perian.[7] The herb was historically used for its stimulating, anti-leprotic, diuretic, and antiphlogistic properties. The fruit can be used as an aphrodisiac, laxative, sedative, or for upset stomachs. Roots and juice from the plant have anti-inflammatory effects.[8] The methanolic extract of B. flabellifer male flowers contains steroid saponins of the spirostane type, which have been shown to reduce the rise in serum glucose levels in rats fed sucrose. It has also been demonstrated to possess immunosuppressive properties. B. flabellifer Linn. has been used as an antidote, anti-inflammatory, wound healing, anthelmintic action, analgesic, and antipyretic, according to a review of the literature.[9] The effects of STZ-induced animal models on ethanolic extracts from Borassus flabellifer L. Palm sprouts (Bf-PSEt) have not yet been investigated. The current study aimed to investigate the antidiabetic effects of ethanolic extracts of B. flabellifer palm sprouts on STZ-induced diabetic rats.
| Methods | | |
Plant material
In November 2021, the fresh palm sprouts of B. fabellifier L. were harvested in the neighborhood of Tiruchirappalli, Tamil Nadu, India.
Plant extract
A soxhlet extractor was utilized to extract the chemical from 500 g of sprout powder using a variety of solvents, including hexane, chloroform, ethyl acetate, ethanol, and water. The crude extract was dried up in a rotary flash evaporator by condensing it at low pressure and controlled temperature. The extract was placed in vacuum desiccators to be employed in the next studies.
Experimental animals
Adult male albino Wistar rats weighing 150–200 g at birth were purchased from the BIOGEN Laboratory Animal Facility in Bangalore, India. They were housed in polypropylene enclosures and maintained in a typical environment (a 12-h cycle of light and dark at a temperature of (25°C ± 3°C). The rats were kept at the JJ College of Arts and Science in Pudukkottai and fed a conventional rat pellet diet provided by the BIOGEN Laboratory Animal Facility in Bengaluru, India. They also received unlimited access to water.
Experimental induction of diabetes
A single intraperitoneal injection of freshly produced STZ (45 mg/kg bw) in 0.1 M citrate buffer (pH 4.5) was used to induce diabetes in rats that had been fasted overnight.[10] To prevent the initial drug-induced hypoglycemia mortality, diabetic rats were allowed to consume a 20% glucose solution overnight. After 3 days, the blood glucose level was checked, and diabetic rats were those with glucose levels >250 mg/dL. The only injection to control rats throughout induction was 0.2 mL of vehicle (0.1 M citrate buffer, pH 4.5).
Experimental design
In this experiment, 24 rats (6 normal and 20 STZ diabetic existing rats) were used. They were separated into four groups of six rats each.
Group I: Control rats.
Group II: Diabetic group (STZ 45 mg/kg bw).
Group III: Diabetic rats were orally given Bf-PSEt (400 mg/kg bw) for 60 days.
Group IV: Diabetic rats were given glibenclamide (1 mg/kg bw) for 45 days
The animals were slaughtered by cervical decapitation and euthanized with ketamine (24 mg/kg/body) intramuscular injection toward the end of the trial (60 days). Blood was collected. The liver was quickly dissected to eliminate blood and cleaned with ice-cold saline. All experiments were carried out as per the guidelines of the Institutional Animal Ethical Committee (JJC/BC/AH/001/2022).
Biochemical analysis
Estimation of blood glucose
Using a reagent kit, the glucose oxidase/peroxidase method, as described by Trinder,[11] was used to measure the level of glucose in the plasma. In a nutshell, 1.0 ml of the enzyme was added, mixed, and incubated at 37°C for 15 min with 0.01 mL of plasma, standard, and distilled water (blank) in 3 test tubes. At 505 nm, the color created was compared to a reagent blank.
Determination of hemoglobin
The cyanmethemoglobin method of Drabkin and Austin measured the amount of Hb in the blood. The reaction mixture contains 0.02 ml of blood and 5.0 mL of Drabkin's reagent. To assure that the reaction would finish, the reaction mixture was left at room temperature for 5 min. The solution was read at 540 nm with the cyanmethemoglobin standard solution.[12]
Estimation of glycosylated hemoglobin
The Nayak and Pattabiraman approach was used to estimating the HbA1c level in the blood.[13] The 0.5 ml of erythrocytes that had been saline-washed were lysed with 5.5 ml of water, combined, and heated to 37°C for 15 min. After centrifuging the contents and removing the supernatant, 0.5 ml of saline was added, mixed, and processed for an estimate. Four milliliter of oxalate hydrochloric solution was added to 0.02 ml of the aliquot and stirred. The mixture was heated for 4 h at 100°C, cooled, and precipitated using 2 ml of 40% trichloroacetic acid (TCA). After centrifuging the mixture, 3.0 ml of concentrated H2SO4 and 0.05 ml of 80% phenol were added to 0.5 ml of the supernatant. After 30 min, the color formed was read at 480 nm.
Estimation of liver glycogen
The method used by Morales et al. to estimate hepatic glycogen content (1990).[14] After adding 5 ml of 30% potassium hydroxide to a known amount of the tissue, the alkali digestion process was carried out in a boiling water bath for 20 min. A drop of ammonium acetate and 3.0 ml of 100% ethanol were added once the tubes had been cooled. The tubes were next put in the freezer to precipitate the glycogen for an entire night. The precipitated glycogen was collected after a 10-min centrifugation at 3000 g. Following three alcohol washes, the residue was dissolved in 3 cc of water. Four milliliters of anthrone reagent were divided into aliquots and put into the tubes placed in an ice bath. After mixing, the tubes were heated for 20 min in a pot of boiling water. Six hundred and forty nanometer was used to read the green color that had emerged. A blank and the working standard glucose were handled the same way.
Assay of hepatic hexokinase (EC 2.7.1.1)
Brandstrup et al.'s method was used to measure the activity of hepatic hexokinase.[15] In a total volume of 5.3 ml, the reaction mixture contained the following ingredients: 1 ml of glucose solution, 0.5 ml of ATP solution, 0.1 ml of magnesium chloride solution, 0.4 ml each of potassium chloride, potassium dihydrogen phosphate, and sodium fluoride, as well as 2.5 ml of Tris-hydrochloride buffer (pH 8.0). The mixture underwent a 5-min preincubation at 37°C. Two milliliter of tissue homogenate was added to start the reaction. One milliliter of the reaction mixture was added to the tubes holding one milliliter of 10% TCA, which served as the reference point for time. After incubating at 37°C for 30 min, a second aliquot was taken out. Centrifugation was used to remove the protein precipitate, and the Trinder[11] method was used to determine the amount of remaining glucose in the supernatant (1969).
Activity of hepatic glucose-6-phosphatase (EC 3.1.3.9)
Glucose-6-phosphatase was measured using the Koide and Oda technique.[16] 0.7 ml of citrate buffer, 0.3 ml of the substrate, and 0.3 ml of tissue homogenate made up the incubation mixture. For 1 h, the reaction mixture was incubated at 37°C. The enzyme process was stopped by adding 1 ml of 10% TCA to the reaction tubes. The suspension was centrifuged, and the Fiske and Subbarow method was used to determine the phosphorus level of the tissue homogenate's supernatant (1925). A known volume of the supernatant was adjusted. 0.4 ml of amino napthol sulfonic acid (ANSA) was applied after 1 ml of ammonium molybdate. The absorbance was measured at 680 nm after 20 min.
Assay of fructose-1, 6-bisphosphatase activity (EC3.1.3.11)
The Gancedo and Gancedo method was used to assess the activity of fructose-1,6-bisphosphatase (1971).[17] 1.2 ml of Tris-HCl buffer (0.1 M, pH 7.0), 0.1 ml of the substrate (0.05 M), 0.25 ml of magnesium chloride (0.1 M), 0.0.1 ml of potassium chloride (0.1 M), 0.25 ml of ethylene diamine tetra acetic acid (0.001 M), and 0.1 ml of liver homogenate made up the assay mixture in a final volume of 2 m The incubation took place for 15 min at 37°C. The process was stopped by adding 1 ml of 10% TCA. The suspension was centrifuged, and Fiske and Subbarows phosphorus determination method was applied to the supernatant (1925). A known volume of the supernatant was adjusted. Then, 0.4 ml of ANSA was added, followed by 1 ml of ammonium molybdate. The absorbance was measured at 680 nm after 20 min.
Histopathological studies
The test rats' liver tissues were embedded in paraffin after being dried in an assessed arrangement of ethanol and 10% formaldehyde. The liver sections (5 m thick) were obtained using a rotating microtome and rehydrated. H and E staining was next applied to the sections, and they were photographed and studied under a light microscope.[18]
Statistical analysis
The mean standard deviation was used to express all values. Using SPSS Version 25 (SPSS Inc, 233 S Wacker Dr, Chicago, IL 60606) and Duncan's new multiple range test, a one-way analysis of variance was used to assess the statistical significance. The threshold for a significant difference between groups was set at P = 0.05.
| Results | | |
In this study, albino Wistar rats were given STZ (45 mg/kg bw) as a diabetogenic operator to induce diabetes. When STZ was used to induce diabetes in rats, significant weight loss was seen. [Figure 1] shows changes in body weight (15, 30, 45, and 60 days), [Figure 2] shows blood sugar levels, and [Figure 3] shows the Hb and HbA1c in normal and experimental rats. When STZ-induced untreated diabetic control rats were compared to normal rats, a significant decrease in body weight was observed. Compared to diabetic control rats, a significant increase in body weight was seen in the Bf-PSEt and glibenclamide-treated diabetic rats. The diabetic rats have greater blood glucose levels than the healthy rats. In diabetic rats treated with Bf-PSEt and glibenclamide, a significant increase in insulin was seen after the treatment period. A decrease in blood glucose level was seen starting on day 15 of treatment. When STZ-induced diabetic rats were treated with Bf-PSEt and glibenclamide, their Hb and HbA1C values dramatically improved compared to those of the control rats who did not have diabetes. The treatment outcomes for the diabetic rats with Bf-PSEt and glibenclamide were compared. | Figure 1: Effect of Bf-PSEt extracts on body weight in normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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 | Figure 2: Effect of Bf-PSEt extracts on blood glucose level of normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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 | Figure 3: The effect of Bf-PSEt extracts on heamoglobin and glycosylated hemoglobin levels in normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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When STZ-induced diabetic rats were compared to normal rats, a significant increase in glucose-6-phosphatase [Figure 4], fructose-1,6-bisphosphatase [Figure 5], and decreased hexokinase [Figure 6] activity was discovered. However, the treated groups tended to transmit these values to the control groups. Rats with diabetes caused by STZ had less liver glycogen. In STZ-induced diabetic rats, hepatic glycogen levels were markedly elevated by Bf-PSEt and glibenclamide. | Figure 4: Effect of Bf-PSEt extracts on glucose-6-phosphatase level of normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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 | Figure 5: Effect of Bf-PSEt extracts on fructose-1,6-bisphosphatase level of normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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 | Figure 6: Effect of Bf-PSEt extracts on hexokinase level of normal and experimental rats. Values are expressed as mean ± standard deviation (n = 6 rats in each group)
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The histopathological effects of normal and experimental rat liver are depicted in [Figure 7]. Compared to normal rats, the STZ-induced diabetes rat liver showed extensive vacuolization of degenerated nuclei. In contrast, diabetic rats treated with the Bf-PSEt group showed improved liver histology compared to the diabetic control group rats. The glibenclamide-treated group showed liver histopathology comparable to normal control rats. | Figure 7: Histopathology figure shows the photomicrographs of H and E 10X staining of liver tissues of control and experimental rats
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| Discussion | | |
STZ was often used at the lowest dose possible to induce Type I diabetes.[19] Type 2 diabetes is caused by the partial destruction of the beta cells by STZ, which results in insufficient insulin release.[20] It is the most widely utilized animal model for research on diabetes.[21] Reduced body weight in diabetic rats indicates that the disease has harmed basic proteins.[22] The loss of muscle mass observed in STZ-induced diabetic control rats may cause a body weight deficit.[23] In STZ-induced diabetic rats, oral treatment of Bf-PSEt and glibenclamide cause weight increases.
Over 15 days of treatment, Bf-PSEt demonstrated a propensity to lower the blood glucose level in STZ-induced diabetic rats.[24] According to the findings, it can now be hypothesized that elevated pancreatic insulin release could increase glucose uptake by peripheral tissues of diabetic rats or else inhibit hepatic gluconeogenesis in addition to lowering blood glucose levels.[25] The significant increase in insulin levels in the extract-treated rats suggests that one possible mechanism by which extracts exert their antidiabetic effects is by potentiating pancreatic release of insulin from existing B-cells of islets.[26]
HbA1c concentrations are a valuable and reliable measure of glycemic management in people with diabetes.[27] Our result also supports a prior study that found that in diabetic control rats, total Hb exhaustion and HbA1c levels were elevated. Diabetes-prone rats treated with Bf-PSEt and glibenclamide had significantly lower HbA1c levels and higher levels of total Hb. This might be a direct outcome of the extract's framework initiating glycogen synthesis. HbA1c significantly decreased, demonstrating the extract's effectiveness in managing diabetes.[28] Previous studies with similar findings discovered that Plectranthus esculenthus reversed the blood glucose, Hb, and HbA1c levels in STZ-induced diabetic rats.[29]
In diabetics, the liver is crucial for preserving a balanced glucose level.[25] Reduced glycolysis, hindered glycogenesis, and enhanced gluconeogenesis are all progressive aspects of glucose production in the diabetic liver.[30] Hexokinase, the initial enzyme in glycolysis, aids in the energy-producing conversion of glucose to G6P.[31] Diabetes and decreased adenosine triphosphate (ATP) production are caused by decreased hexokinase activity, which weakens glucose oxidation through glycolysis.[32] Since a shortage of insulin characterizes diabetes, lower insulin levels in the STZ-induced diabetic rats eventually prevent hexokinase from performing its function.[33] In diabetic rats, hexokinase levels were decreased, although Bf-PSEt and glibenclamide increased hexokinase activity. The results can be a result of higher insulin levels.
Gluconeogenic enzymes, including G6P and F1,6BP, and carbohydrate metabolic enzymes are controlled by insulin.[34] In STZ-induced diabetic rats, increased hepatic glucose synthesis and reduced hepatic glucose utilization may be mediated by dysregulation of G6P activity.[35] In the current work, diabetic rats induced with STZ had elevated levels of gluconeogenic enzymes. In a diabetic state, the liver produces more glucose, which has been proven to be directly related to G6P and F1,6BP's inadequate suppression.
cAMP stimulates G6P activity while insulin inhibits it; maintaining glucose homeostasis may largely depend on reduced endogenous glucose synthesis, which links insulin to the gluconeogenic flow.[36] A lack of insulin 37 may cause these gluconeogenic enzyme increases in diabetic rats' livers. The G6P and F1,6BP in diabetic rats treated with Bf-PSEt and glibenclamide changed to levels that were close to normal, which may have been caused by increased insulin emission.
Glycogen, a tissue reserve for glucose, is stored as glucose in intracellular areas.[37] The presence of insulin is necessary for converting glucose to glycogen; insulin stimulates glycogen synthesis by elevating glycogen levels and inhibiting glycogen phosphorylase.[38] DM disables the normal liver limit for incorporating glycogen. Glycogen synthase is stimulated by synthase phosphatase, leading to glycogenesis.[25] In this investigation, liver glycogen content was much lower in diabetic rats. Bf-PSEt with glibenclamide restored normal liver glycogen levels in diabetic rats. Reduced cell glycogen content, hormone signaling, sub-cell restriction, phosphatase concentrating, and allosteric activation by G6P all affect glycogen synthase activity.[39] The extract partially improved the diabetic condition's faulty glycogen concentration.[6]
The primary source of natural antioxidants is planted secondary metabolites.[40] Alkaloids, coumarins, flavonoids, and steroids, among other phytochemicals, may be present and have antidiabetic properties.[41] The total phenol and flavonoid contents of Bf-PSEt appear to be high, and both extracts demonstrated strong in vitro free radical scavenging activity. In STZ-induced diabetic rats, Bf-PSEt can restore the tissue glycoprotein components. Therefore, these phytochemical components may be responsible for the antidiabetic effects of Bf-PSEt.
| Conclusion | | |
Our research has shown that Bf-PSEt has antidiabetic activity in STZ-induced diabetic rats. This effect may be caused by an increase in plasma insulin levels, which would be the cause of the recovery of liver glycogen and enzymes that break down carbohydrates. Bf-PSEt produces results that are superior to those of the common medication glibenclamide. A new anti-diabetogenic drug could be developed due to additional investigation into the molecular mechanism and the isolation of the chemical that causes this action.
Financial support and sponsorship
Nil.
Conflicts of interest
The authors declare that none of the authors have any competing interests.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
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