Elsevier

Journal of Ethnopharmacology

Volume 228, 10 January 2019, Pages 1-10
Journal of Ethnopharmacology

Effects of Parkia biglobosa aqueous seed extract on some biochemical, haematological and histopathological parameters in streptozotocin induced diabetic rats

https://doi.org/10.1016/j.jep.2018.09.016Get rights and content

Abstract

Ethnopharmacological relevance

Parkia biglobosa seeds are used to treat diabetes and complications hence this study.

Aim

This study investigated the effects of Parkia biglobosa aqueous seed extract on some biochemical, haematological and histopathological indices in streptozotocin-induced diabetic rats.

Materials and methods

Wistar rats of either sex (180–300 g) were fasted overnight and diabetes mellitus induced using streptozotocin 40 mg/kg IP. Diabetes mellitus (fasting blood glucose ≥ 200 mg/dl) was confirmed 48 h later. The rats were randomly grouped into six groups (n = 5): Group 1 (diabetic untreated control), group 2 (Parkia biglobosa 200 mg/kg), group 3 (Parkia biglobosa 400 mg/kg). group 4 (Parkia biglobosa 800 mg/kg), group 5 (glibenclamide 5 mg/kg as standard drug control) and group 6 (normoglycaemic control). They were treated daily. Acute toxicity study and phytochemical screening were also performed. Fourteen days later, they were sacrificed under chloroform anaesthesia. Vital organs (kidneys, liver and pancreas) and blood samples were obtained for histopathological, biochemical and haematological analysis.

Results

Parkia biglobosa aqueous seed extract at the various doses caused significant (P < 0.05) elevations in red blood cell parameters in comparison to the diabetic control. The mean cell volume did not differ significantly from the diabetic control while 200 mg/kg and 400 mg/kg doses of the extract did not significantly modify the HCT levels. Treatment with Parkia biglobosa significantly (P < 0.05) lowered white blood cell and platelet counts in comparison to the diabetic control. Liver enzymes and total bilirubin levels were significantly (P < 0.05) reduced while total protein increased in the treated diabetic rats in comparison to controls. Treatment with Parkia biglobosa extract significantly (P < 0.05) increased bicarbonate and sodium ion levels while decreasing potassium ion levels. Chloride levels were not significantly different from the diabetic control.

Conclusion

These data suggest that Parkia biglobosa ameliorates biochemical, haematological and histopathological changes associated with diabetes mellitus.

Introduction

Diabetes mellitus is a heterogenous group of metabolic disorders characterized by persistent hyperglycaemia (Neelesh et al., 2010) and dysfunctional metabolism of carbohydrates, fats and proteins due to defects in insulin secretion and/or insulin action (Maritim et al., 2003). Derangements in biochemical, haematological and histopathological parameters have been associated with diabetes (Oyedemi et al., 2011). These can however be mitigated through good glycaemic control. Drugs currently used in the management of diabetes include insulin, amylin analogues, Insulin secretagogues such as sulphonylureas, meglitinides and incretin mimetics, insulin sensitizers such as biguanides and thiazolidinediones, alpha glucosidase inhibitors, inhibitors of sodium glucose co-transporter 2, dopamine agonists and bile acid resins (Powers and D’Alessio, 2011).

Newer strategies are being proposed for the management of diabetes mellitus. Glucokinase activators are molecules which have been used to activate glucokinase, an enzyme which determines the rate of glucose metabolism, hepatic glycogen production and the formation of cholesterol, phospholipids and triacylglycerol (Gianluca, 2010). Inhibitors of 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD 1) has been shown to be a promising target (Peng et al., 2016). 11-β-HSD 1 converts cortisone to the biologically active cortisol. Defects in glucocorticoid metabolism and action have been shown to promote insulin resistance, glucose intolerance, dyslipidemia and obesity (Peng et al., 2016). Therefore, the inhibition of 11-β-HSD 1 improves insulin sensitivity with a resultant amelioration of derangements in glucose and lipid metabolism (Peng et al., 2016, Courtney et al., 2008). The activation of a subtype of sirtuins (SIRT1) has also been proposed as a therapeutic strategy for managing type-2 diabetes mellitus (Powers and D’Alessio, 2011). SIRT1 is a nutrient sensor which improves insulin sensitivity and hence regulates glucose and lipid metabolism (Carafa et al., 2016). Resveratrol, a natural polyphenol has been shown to activate SIRT1 (Jing et al., 2007). Other strategies involving nutrient sensors which have been shown to improve insulin sensitivity and are hence considered useful include AMP-activated protein kinase (AMPK) activation (Kim et al., 2016), diacylglycerol acyl transferase (DGAT) inhibition (Roe et al., 2018) and acetyl co-A carboxylase (ACC) inhibition (Harriman et al., 2016). Immunomodulatory approaches have been considered for type-1 diabetes mellitus. These have however not been fully accepted because of the long-term toxicity associated with this strategy (Powers and D’Alessio, 2011). Free radicals have also been implicated in the pathophysiology of diabetes and the complications therefrom. Antioxidants have therefore been proposed to be useful in managing this condition (Dal and Sigrist, 2016)

Despite the progress made in the treatment of diabetes, several challenges are still encountered. These include the side effects associated with these medications, the high cost of most of these drugs and their mechanisms of action which address symptomatology rather than underlying pathophysiology (Akinmoladun et al., 2014). There is therefore a need to evaluate plants for their antidiabetic effects with a view to developing new and more effective strategies for managing diabetes.

Parkia biglobosa (Jacq) is a perennial deciduous tree found in a wide range of environments in Africa. It is known as dawadawa (Hausa), ogiri (Igbo) and Iru (Yoruba) in some Nigerian languages. It is primarily grown for its pods which contain a sweet pulp and valuable seeds (Ntui et al., 2012). The fermented seeds of Parkia. biglobosa are used in all parts of Nigeria and the west African coast to season traditional soups (Ajaiyeoba, 2000, Assane et al., 1993). In Nigerian folkloric medicine, Parkia biglobosa is used in the management of diabetes mellitus. The Igbo and Yoruba people use it in their traditional systems to treat diabetes (Lawal et al., 2010, Erakhrumen et al., 2010). Various parts are used for this purpose including the seeds, leaves and bark (Ajaiyeoba, 2000, Assane et al., 1993). The seeds either in their unprocessed or fermented form are soaked in a vehicle which is normally water and left overnight to allow for extraction by maceration. The next morning this is filtered and the extract consumed (Erakhrumen et al., 2010) to treat diabetes mellitus. Parkia biglobosa is also used in folkloric medicine in the treatment of leprosy, hypertension, wound healing, bacterial infections and diarrhoea (Assane et al., 1993).

The hypoglycaemic and hypolipidemic effects of the fermented seeds of Parkia biglobosa have been established in various studies including that done by Odetola et al. (2006). Studies have shown the protective effects of Parkia biglobosa protein isolate on the testes and the liver of diabetic rats (Ogunyinka et al., 2016, Ogunyinka et al., 2017). No study has demonstrated the effects of Parkia biglobosa seeds on the electrolyte levels, some renal and hepatic function parameters and histopathological indices in streptozotocin-induced diabetic rats hence this study.

Sodium citrate (JHD, China), citric acid (JHD, China), buffers 4 and 7 (Loba Chem, India), distilled water, streptozotocin (Santa Cruz Biotechnology, USA), methylated spirit (Nomagbon Pharmaceutical Industries, Nigeria), glibenclamide (Sigma Aldrich, USA), chloroform (Fharmtrends Nigeria limited, Nigeria), 1% hydrochloric acid (BDH chemicals, England), neutral buffer formalin (Thermo Scientific, USA), 70% and 96% ethanol (Fharmtrends Nigeria limited, Nigeria), haematoxylin-eosin dye (BDH Chemicals, England),

Hetich centrifuge (Rotofix 32A, Germany), human automated haematology system analyzer (ERMA PCE 210, ERMA, Japan), optical photomicroscope (Leica MC170HD Biosystems, Germany), measuring cylinder, test tubes, beaker, spatula, plastic cages, 1 ml syringes, 2 ml syringes, 5 ml syringes, surgical dissecting kits, plain sample bottles, EDTA bottles, cotton wool, surgical gloves, weighing balance, electric burner, orogastric tube, Whatman filter paper.

Parkia biglobosa aqueous seed extract.

Wistar rats of either sex weighing between 180 and 300 g were obtained and kept in the animal house of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin city, Edo state, Nigeria. They were allowed to acclimatize for a period of two weeks and provided with standard pellet feed (Top feed finisher pellet, Ibadan, Nigeria) and water ad libitum while maintaining high sanitary and normal lighting conditions. All experimental protocols were performed in tandem with the National Institute of Health Guidelines for the Care and Use of laboratory animals (NIH Publications No. 80-23) revised in 2002.

Ethical approval was obtained from the Research and Ethics Committee of the Faculty of Pharmacy, University of Benin with the reference number: EC/FP/017/04.

Unprocessed Parkia biglobosa seeds were purchased from the herbs’ market in Federal Capital Territory, Abuja and a sample deposited in the herbarium of the National Institute of Pharmaceutical Research and Development with voucher number NIPRD/H/6847. The name of the plant was checked on www.theplantlist.org.

The unprocessed seeds were pounded lightly to enable the fleshy aspect to be removed from the shell after which the fleshy part was pulverized to obtain a powder. Extraction was carried out using cold water maceration for 24 h after which the solution was filtered using a Whatman filter paper to obtain the extract. The extract was mildly dried on a hot water bath at a constant temperature and the yield determined. The extract was put into a beaker, covered with foil paper and kept in the freezer at − 20 °C until needed.

Phytochemical analysis was performed using standard procedures as given by Sofowora (2008) and Evans (2002).

Determination of acute toxicity of the extract was done by using a modification of the method described by Lorke (1983). For phase 1, nine (9) rats were randomly divided into three groups of three rats. The rats in the three groups were administered with the aid of an orogastric tube, single doses (10, 100 and 1000 mg/kg body weight respectively) of the Parkia biglobosa aqueous seed extract orally. These were observed for signs of toxicity. In the absence of toxicity, the second phase was carried out.

In Phase 2, based on the results of the phase 1 study, three rats (One rat per group) were orally administered single doses of 1600, 2900 and 5000 mg/kg body weight of Parkia biglobosa. For the two phases of the study, the rats were kept under the same conditions and observed for signs of toxicity and mortality for 24 h. The LD50 was calculated based on the results of the final phase as the square root of the product of the lowest lethal dose and the highest non-lethal dose, i.e. the geometric mean of the consecutive doses where 0% and 100% survival rates were recorded. Where the extracts at doses above 5000 mg/kg did not cause any visible toxicity or mortality, the extracts were regarded as safe. A last group served as control and was administered 1 ml distilled water orally. All the rats used for the acute toxicity study were observed daily for any signs of toxicity over a period of two weeks.

Wistar rats of either sex weighing between 180 g and 300 g were randomly selected and put into cages. They were fasted for a period of 24 h. The rats were weighed using a sensitive weighing balance to calculate appropriate doses of streptozotocin to be administered. Two beakers, each containing 100 ml of potable water were obtained. A tablet of buffer 7 was dissolved in one of the beakers and a tablet of buffer 4 dissolved in the other. These were used to calibrate the pH meter by initially dipping the pH meter into the buffer solution (and watching the pH rise to 7.0) and then into the buffer 4 solution (and watching the pH fall to 4.0) (Deeds et al., 2011). The pH meter cleaned with a dried piece of cotton wool. Two clean and dried sample bottles were gotten and 0.29 g and 0.21 g of sodium citrate and citric acid respectively weighed into them. In each case, 100 ml of distilled water was used to dissolve them in a beaker. The 100 ml solution of 0.21 g citric acid was titrated against a 100 ml solution of 0.29 g sodium citrate. This was continued until a pH of 4.5 was obtained as indicated by the pre-calibrated pH meter (Deeds et al., 2011). Diabetes mellitus was then induced using a single 40 mg/kg dose of streptozotocin ip dissolved in freshly prepared citrate buffer (pH = 4.5) (Srinivasan and Ramarao, 2007). To prevent hypoglycaemia associated mortality seen within the first few hours following the administration of streptozotocin, a 5% w/v solution of glucose was given to the rats (Eleazu et al., 2013). Diabetes (Fasting blood glucose > 200 mg/dl) was confirmed after 48 h with the aid of an ‘ACCUCHECK’ glucometer (Roche) and glucose test strips (Roche) and expressed in mg/dl (Rheney and Kirk, 2000).

The method of Owolabi and Omogbai (2012) which was adopted from Szkudelski (2001) was used for the study. The rats were grouped into six groups of five rats each (n = 5) according to the intervention to be instituted and treated daily for two weeks as follows:

  • Group 1: Diabetic rats treated with 200 mg/kg Parkia biglobosa aqueous seed extract using 1 ml of water as vehicle.

  • Group 2: Diabetic rats treated with 400 mg/kg Parkia biglobosa aqueous seed extract using 1 ml of water as vehicle.

  • Group 3: Diabetic rats treated with 800 mg/kg Parkia biglobosa aqueous seed extract using 1 ml of water as vehicle.

  • Group 4: Diabetic rats receiving 1 ml distilled water (untreated diabetic control).

  • Group 5: Diabetic rats treated with 5 mg/kg glibenclamide (Standard drug control) using 1 ml of water as vehicle.

  • Group 6: Non-diabetic rats receiving 1 ml distilled water (Normoglycaemic control).

The weights of the rats were taken on a weekly basis using a sensitive weighing balance and the changes in weight determined (Igbe et al., 2009).

After two weeks of treatment, animals were sacrificed under chloroform anaesthesia and blood samples gotten from the abdominal aorta into ethylene diamine tetra-acetic acid and plain sample bottles and taken to the laboratory for haematological and biochemical analysis respectively (Ogbera et al., 2007).

Organs (Liver, kidneys and pancreas) were excised under chloroform anaesthesia and fixed in neutral buffered formalin. The fixed organs were completely dehydrated using absolute ethanol followed by 96% ethanol, 70% ethanol and then rinsed with distilled water. A 4 µm section was prepared in each case and stained using haematoxylin-eosin dye and the stained tissues were viewed using an optical photomicroscope (Leica MC170 HD, LeicaBiosystems, Germany) at × 400 magnification (Ogbera et al., 2007). The analysis and interpretation of the results were done by a histopathology expert.

Data were expressed as mean ± standard error of mean (SEM). Statistical analysis was carried out using one-way analysis of variance followed by Dunnett's post-hoc test (Graphpad Prism® San Diego, USA). P < 0.05 was considered significant.

The aqueous extract of Parkia biglobosa seeds was a partially sticky, light brown solid mass which was soluble in water. It gave a yield of 10.2%.

Phytochemical analysis of Parkia biglobosa revealed the presence of carbohydrates, alkaloids, flavonoids, tannins, saponins, anthraquinones and the absence of glycosides.

The acute toxicity study revealed no mortality when Parkia biglobosa was administered even at doses as high as 5000 mg/kg. No mortality was also reported over the two-week observation period

The weights of rats treated with Parkia biglobosa 200 mg/kg, 400 mg/kg and 800 mg/kg were not significantly different from the normal control at the end of weeks 1 and 2. Table 1 provides details.

The various doses of Parkia biglobosa caused significant elevations (P < 0.05) in red blood cell count and haemoglobin levels in comparison to the diabetic control. Parkia biglobosa 800 mg/kg showed a significant (P < 0.05) in HCT levels in comparison to the diabetic control. MCH and MCHC levels were significantly (P < 0.05) greater than the diabetic control. The extract at the various doses significantly (P < 0.05) reduced platelet and WBC levels in comparison to the diabetic controls. Treatment with the extracts did not significantly modify differential white blood cell count and mean cell volume in comparison to the controls. Table 2, Table 3 provide details.

The various doses of Parkia biglobosa significantly (P < 0.05) increased serum bicarbonate and sodium ion levels while decreasing potassium levels in comparison to the diabetic control. Chloride levels were not significantly different between the treated and untreated groups. The extract significantly (P < 0.05) lowered liver enzymes. Parkia biglobosa 400 mg/kg and 800 mg/kg significantly (P < 0.05) increased total protein levels however albumin and globulin levels were not significantly different from the diabetic control. Parkia biglobosa 400 mg/kg and 800 mg/kg significantly (P < 0.05) lowered total bilirubin levels but did not significantly alter direct bilirubin levels. Table 4, Table 5, Table 6 provide details.

Control normoglycemic liver section reveals prominent histological feature showing portal vein (arrow) with well fenestrated sinusoids and hepatocytes with distinct nucleus. Hyperglycaemic liver section reveals prominent histological feature showing portal vein (arrow) appearing slightly congested with inflammatory cells surrounding it with visible fatty hydropic changes (arrow head). Liver of rat administered with Parkia biglobosa 200 mg/kg reveals prominent central vein (long arrow) and mild fatty changes (short arrow). Liver of rat treated with Parkia biglobosa 400 mg/kg reveals prominent centriole (long arrow) with visible hepatocytes that have a remarkable pyknotic nucleus (short arrow). Liver of Parkia biglobosa 800 mg/kg treated rat reveals prominent histological features. Portal vein (Long arrow) is surrounded by focal inflammatory cells with scanty fatty hydropic changes (Short arrow). Liver of rat treated with glibenclamide 5 mg/kg reveals prominent histological feature showing portal vein (long arrow) with mild hydropic nucleus changes (short arrow) (Fig. 1).

Normoglycaemic kidney section shows normal histological features with detailed cortical parenchyma and the renal corpuscles appearing as dense rounded structures (arrow). Untreated diabetic kidney section shows detailed cortical parenchyma with the renal corpuscles appearing as atrophied dense rounded structures (arrow) bounded by prominent inflammatory infiltrates (arrow head). Kidney of rat treated with Parkia biglobosa 200 mg/kg reveals atrophied glomerulus with clearing to the corpuscles (long arrow) and mild focal tubular necrosis (short arrow). Kidney of rat treated with Parkia biglobosa 400 mg/kg shows cortical parenchyma and focal necrosis of the tubules (short arrow) with the renal corpuscles appearing as dense rounded enlarged structures (long arrow). Kidney of rat given Parkia biglobosa 800 mg/kg shows prominent histology with visible renal corpuscles (Long arrow). The glomerulus has clearing to the corpuscles. There is mild tubular necrosis (short arrow). Kidney section of rat treated with glibenclamide 5 mg/kg shows normal histological features with detailed cortical parenchyma (short arrow) and the renal corpuscles appearing as dense rounded structures (long arrow) (Fig. 2).

Pancreas of normoglycaemic control reveals acinar pattern structure with the nuclei of some acinar cells appearing. The acinar cells which stained strongly are arranged in lobules with prominent nuclei. The islet cells are seen embedded within the acinar cells and surrounded by a fine capsule (arrow head). Pancreas of hyperglycaemic control reveals some acinar cells with islet cells showing congested pyknotic nuclei and visible lymphocytic infiltrates (arrow). Pancreas of rat treated with Parkia biglobosa 200 mg/kg reveals secretory acini (long arrow) with mild atrophic pancreatic islet with pyknotic nuclei (arrow head). Pancreas of rat treated with Parkia biglobosa 400 mg/kg reveals prominent secretory acini arranged in lobules (long arrow) with mild congestion (short arrow). Pancreas of rat treated with Parkia biglobosa 800 mg/kg reveals secretory acini with bulky pancreatic islet (short arrow). The histology reveals intralobular duct at low power with evidence of mild congestion (arrow head). Pancreas of rat treated with glibenclamide 5 mg/kg reveals acinar pattern structure with pyknotic nuclei of some acinar cells appearing. The acinar cells which stained strongly are arranged in lobules with prominent nuclei (long arrow) ( Fig. 3).

Section snippets

Discussion

Diabetes mellitus is a metabolic condition characterized by myriads of complications with associated morbidity and mortality. Poorly controlled diabetes could lead to conditions such as non-alcoholic fatty liver disease, retinopathy, neuropathy, nephropathy, cardiovascular complications, anaemia, diabetic foot ulcers, infection and inflammation. These complications necessitate timely and proper intervention with medications. In Nigeria, orthodox medical care is not accessible to all due to

Conclusion

Phytochemical screening of Parkia biglobosa seed extract revealed the presence of carbohydrates, flavonoids, saponins, alkaloids, anthraquinones and tannins. The extract gave a yield of 10.2% Parkia biglobosa prevented changes in weight in comparison to the untreated diabetic group. Parkia biglobosa ameliorated changes in some haematological indices in comparison to the untreated diabetic group. Some biochemical parameters were also ameliorated. Administration of Parkia biglobosa provided some

Acknowledgements

The authors are grateful to Mr. Kelvin Odega, of the histopathology unit, Department of Pathology, University of Benin Teaching Hospital for his assistance with the analysis and interpretation of the photomicrographs. The authors are also grateful to Mr. Otobong Ibe of the Animal house, Department of Pharmacology and Toxicology and Mr. Kingsley Ugwu of the Department of Pharmacognosy for their support during the course of the research.

Declaration of interest

None.

Author contributions

Conceptualization: Ekperikpe Ubong S and Omonkhelin J Owolabi

Diabetes Induction: Ekperikpe Ubong S and Bolanle I Olapeju

Animal Daily Treatment: Ekperikpe Ubong S

Preparation of samples for biochemical and histopathological analysis: Ekperikpe Ubong S and Bolanle I Olapeju

Data Generation and Analysis: Ekperikpe Ubong S

Resources: Ekperikpe Ubong S and Omonkhelin J Owolabi

Writing (Original Draft): Ekperikpe Ubong S

Writing (Review and Editing): Omonkhelin J Owolabi

Ekperikpe Ubong Stephen: He conceptualized the study and largely executed the methodology including diabetes induction, daily treatment of the diabetic rats and the preparation of samples for biochemical, haematological and histopathological analysis. He solely took charge of data generation and analysis and the writing of the draft manuscript. He provided resources needed for the study. He can be reached on [email protected].

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    Ekperikpe Ubong Stephen: He conceptualized the study and largely executed the methodology including diabetes induction, daily treatment of the diabetic rats and the preparation of samples for biochemical, haematological and histopathological analysis. He solely took charge of data generation and analysis and the writing of the draft manuscript. He provided resources needed for the study. He can be reached on [email protected].

    Omonkhelin Josephine Owolabi: She conceptualized the study, proofread the manuscript and provided resources for the study. Generally, she supervised the entire experimental protocol. She can be reached on [email protected].

    Bolanle Israel Olapeju: He executed the methodology especially with respect to the induction of diabetes mellitus and the preparation of samples for biochemical, haematological and histopathological analysis. He can be reached on [email protected].

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