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Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats



Emeka. E.J. Iweala and Funmilayo D. Oludare
 
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ABSTRACT

The aim of this study was to evaluate the individual and synergistic hypoglycaemic and biochemical effects of the ethanolic extracts of seeds of Parinari polyandra and Spondias mombin in alloxan-induced diabetic rats. The ethanolic extracts of the seeds of Parinari polyandra and Spondias mombin were obtained by soxhlet extraction and administered to non-diabetic and alloxan-induced diabetic albino rats. Parameters including blood glucose, alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol, glutathione and total protein were checked using standard test kits and methods after administration of the extracts. Histological changes in the liver of the animal were also examined. The results obtained revealed that alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol and glutathione did not change significantly (p≤0.05) in the animals treated with the plant extracts. Glucose and total protein levels were significantly reduced (p≤0.05) in the animals treated with the plant extracts. The histological changes showed the presence of fatty cells in the liver of alloxan-induced diabetic control and non diabetic rats administered both Parinari polyandra and Spondias mombin extracts. The implications of the results obtained especially reduction of glucose by Parinari polyandra and Spondias mombin is their potential use in management of diabetes and apparent effects on the liver when administered together.

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Emeka. E.J. Iweala and Funmilayo D. Oludare, 2011. Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats. Journal of Pharmacology and Toxicology, 6: 101-112.

DOI: 10.3923/jpt.2011.101.112

URL: https://scialert.net/abstract/?doi=jpt.2011.101.112
 
Received: June 04, 2010; Accepted: July 15, 2010; Published: September 02, 2010



INTRODUCTION

Medicinal plants are widely used in management of diseases all over the world (Aliyu et al., 2007; Adewunmi and Ojewole, 2004). Historically, the use of medicinal plants is as old as mankind and medicine. In Nigeria, several thousands of plant species have been claimed to possess medicinal properties and employed in the treatment of many ailments (Okigbo and Mmeka, 2006).

Diabetes is a disease associated with glucose metabolism resulting from defects in insulin secretion and action (WHO, 1999). It is characterized by hyperglycemia, glucosuria and several microvascular and macrovascular complications (Brownlee, 2001; Virella-Lopes and Virella, 2003). The complications of diabetes are linked to oxidative stress induced by hyperglycemia which overcomes the body’s natural anti-oxidant system (Kikkawa et al., 2003; Udoh et al., 2007). In the later stages of diabetes, lipid metabolism is affected and seen as hyperlipidemia and hypercholesterolemia which are risk factors in artherosclerosis (Ross, 1999; Schwartz, 2006; Krishnakumar et al., 1999). There is also the possibility of liver damage in diabetes due to increased gluconeogenesis and ketogenesis (Felig et al.,1970). The incidence of diabetes is on the rise and is estimated to be over 150 million worldwide (Wild et al., 2004). There is yet no effective cure for diabetes and the available drugs and insulin currently used in managing the disease are associated with several undesirable side effects (Piedrola et al., 2001; Yaryura-Tobias et al., 2001; Gandhipuram et al., 2006). The undesirable side effects and high cost of anti-diabetic drugs has led to search for plants with hypoglycemic properties and their employment in the management of diabetes (Calixto, 2000; WHO, 2002). Several species of medicinal plants used in traditional treatment and management of diabetes worldwide have been evaluated (Brai et al., 2007; Gondwe et al., 2008). The hypoglycemic properties of plants used in management of diabetes are reported to be due to their content of flavonoids, glycosides, alkaloids terpenoids, plant polysaccharides and other bioactive compounds. The seeds of two medicinal plants namely Parinari polyandra and Spondias mombin are commonly employed in ethno medicine management of diabetic conditions in Nigeria. Parinari polyandra is a tropical plant belonging to the family, Rosaceae and widely used to enhance fertility and relieve painful and inflammatory conditions (Vongtau et al., 2004). Some species of Parinari have been claimed to be effective in the treatment of veneral diseases and erectile dysfunctions (Lans, 2007). Preliminary nutritional and phytochemical screening of the plant extracts revealed the presence of flavonoids, tannins, saponin and glycosides (Abolaji et al., 2007; Vongtau et al., 2004). Spondias mombin belongs to the tropical genus Anacardiaceae and its leaves and fruits are mostly used in treating various diseases including diarrhea, allegies, inflammatory conditions and microbial infections (Okolie et al., 2008; Ajao et al., 1985). It is also used in managing psychiatric disorders (Ayoka et al., 2005). Spondias mombin leaves contain tannins, flavonoids, saponins, alkaloids and phenols (Njoku and Akumefula, 2007). The hypoglycemic activity of the methanolic stem extract of Parinari polyandra has been reported (Vongtau et al., 2004). Also, the antidiabetic activity of the methanol leaf extract of Spondias mombin has been evaluated (Fred-Jaiyesimi et al., 2009). This study is designed to study the individual and synergistic hypoglycaemic and biochemical effects of the seeds of Parinari polyandra and Spondias mombin in view of their unorthodox use in the traditional management of diabetes in Nigeria.

MATERIALS AND METHODS

This study was carried out between November, 2009 to February, 2010 at the Department of Biological Sciences, Covenant University, Ota South West, Nigeria.

Collection, processing and extraction of seeds of Parinari polyandra and Spondias mombin: The seeds of Spondias mombin and Parinari polyandra were bought from a local market in Ogun State, Nigeria, identified, sorted, air-dried and ground to a coarse powdered form. Hundred grams of each of the plant seeds was extracted with 90% ethanol and the crude extracts concentrated to dryness.

Experimental design: Forty male albino rats aged six weeks old and with an average weight of 45 g were used for the experiment. They were housed in well ventilated cages and given normal rat chow and water ad libitum. The rats were randomly distributed into eight groups consisting of five animals each. Diabetes was induced in rats by administering 250 mg kg-1 of alloxan intraperitonally and then checking the fasting blood sugar for hyperglycemia after five days. Groups that were not administered alloxan for induction of diabetes were administered normal saline. Rats were orally administered plant extracts (100 mg kg-1) daily for ten days. Groups that were not given plant extracts were administered normal saline which was the vehicle. Group 1 and 2 were the non-diabetic and diabetic controls administered with vehicle. Group 3 and 4 were non-diabetic and administered Parinari polyandra and Spondias mombin extracts (100 mg kg-1 b.wt.), respectively. Group 5 were non-diabetic and co-administered Parinari polyandra and Spondias mombin extracts (100 mg kg-1 b.wt.). Group 6 and 7 were diabetic and administered Parinari polyandra and Spondias mombin extracts (100 mg kg-1 b.wt.), respectively. Group 8 were also diabetic and co-administered Parinari polyandra and Spondias mombin extracts (100 mg kg-1 b.wt.). The animals were weighed weekly throughout the period of the experiment.

All the animal experiments and handling were carried according to standard protocols approved by animal research ethics committee of the department of biological sciences, Covenant University, Ota, Nigeria.

Collection of blood, organs and tissue samples: At the end of the experimental period, four animals from each group were anesthetized and blood samples collected in heparinised sample bottles. Serum samples were collected in non-heparinized sample bottles and allowed to clot before being centrifuged at 5000 rpm for 10 min. The livers were quickly removed and stored in 10% formyl saline.

Biochemical determinations: Glucose, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined using Cypress diagnostic test kits. Total triglyceride and cholesterol were determined using test kits (Linear chemicals). Total protein was determined by the Lowry method (Lowry et al., 1951). Glutathione was determined using the method of Ellman (1959). Lipid peroxidation was determined by the thiobarbituric acid reactive substances (TBARS) method of Buege and Aust (1978).

Histological examination of liver tissue: Sections of liver tissue from all the groups were processed for histological examination according to procedures described by Disbrey and Rack (1970).

Statistical analysis: The results obtained were expressed as Mean±Standard deviation for triplicate determinations. Analysis of Variance (ANOVA) for a completely randomized design and Duncan’s multiple range tests were used to analyse data. Values were considered significant at p≤0.05.

RESULTS

The effect of administration of Parinari polyandra and Spondias mombin extracts on weight and the biochemical parameters in non diabetic rats are presented in Table 1. The results of the administration of Parinari polyandra and Spondias mombin extracts on weight and the biochemical parameters in alloxan-induced diabetic rats are provided in Table 2. Groups significant against the non-diabetic control (Positive control) are signified by (a) and the groups significant against alloxan-induced diabetic control (negative control) are signified by (b).

Table 1: Weight change and biochemical parameters in non-diabetic rats administered Parinari polyandra and Spondias mombin ethanolic extracts
Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats

Table 2: Weight change and biochemical parameters in alloxan-induced diabetic rats administered Parinari polyandra and Spondias mombin ethanolic extracts
Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats

Generally there were no significant percentage weight changes in all the experimental groups but the group administered Parinari polyandra and Spondias mombin extracts showed the highest percentage increase in weight while the alloxan-induced diabetic rats administered Parinari polyandra and Spondias mombin extracts had the lowest.

There were significant reductions (p≤0.05) in glucose concentration in all the groups administered Parinari polyandra and Spondias mombin extracts except the alloxan-induced diabetic group co-administered both extracts. The changes in total protein in most of the groups were not significant (p≤0.05) except the alloxan-induced diabetic control and the non-diabetic group administered Parinari polyandra and Spondias mombin extracts, respectively. There were no significant changes in glutathione, cholesterol, triglyceride and lipid peroxidation levels. The activities of the liver enzymes including AST and ALT were not significantly changed (p≤0.05) in all the groups.

The histological features of liver tissues of the animals administered Parinari polyandra and Spondias mombin extracts in all the groups are shown in Fig. 1-8. The liver of the rats in all the groups except those co-administered Parinari polyandra and Spondias mombin extracts and the alloxan-induced diabetic control (Fig. 4, 5) showed normal histological characteristics with preserved hepatic architecture and hepatocytes arranged in plates.

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 1: Photomicrograph of liver of non-diabetic control rats

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 2: Photomicrograph of liver of non-diabetic rats administered Parinari polyandra extracts

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 3: Photomicrograph of liver of non-diabetic rats administered Spondias mombin extracts

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 4: Photomicrograph of liver of non-diabetic rats co-administered Parinari polyandra and Spondias mombin extracts

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 5: Photomicrograph of liver of alloxan-induced diabetic control rats

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 6: Photomicrograph of liver of alloxan-induced diabetic rats administered Parinari polyandra extracts.

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 7: Photomicrograph of liver of alloxan-induced diabetic rats administered Spondias mombin extracts

Image for - Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Fig. 8: Photomicrograph of liver of alloxan-induced diabetic rats co-administered Parinari polyandra and Spondias mombin extracts

The normal liver was devoid of vascular congestions, necrosis, fibrosis, haemorrhage or fatty changes. The portal tracts contained the hepatic triads (artery, vein and bile duct) and scanty inflammatory cellular infiltrates.

DISCUSSION

The results showed a general increase in body weight of animals with no significant percentage weight changes, indicating that the plants generally were not toxic to the animals.

The oral administration of ethanolic extracts of Spondias mombin and Parinari polyandra caused a significant reduction in the blood glucose concentration of the diabetic rats. Alloxan induces diabetes by destroying the beta-cells of the Islets of Langerhans in the pancreas leading to reduction in synthesis and release of insulin (Szkudelski, 2001). This model has been used to study the anti diabetic effects of several plant products (Abdel-Barry et al.,1997; Babu et al., 2002). The hypoglycemic properties of numerous medicinal plants have been studied and reported (Adeneye and Agbaje, 2008; Rajagopal and Sasikala, 2008; Maroo et al., 2003; Vats et al., 2002). Reduction in blood glucose by most bioactive compounds from plants might act by one of several mechanisms including stimulation of insulin secretion, increased repair or proliferation of β-cells and enhancing the effects of insulin and adrenalin (Fayed et al., 1998). The possible mechanism by which the ethanolic extracts of Spondias mombin and Parinari polyandra reduced blood glucose concentration of the diabetic rats may be either by increasing the pancreatic secretion of insulin from the cells of islets of Langerhan’s or its release from bound insulin (Pari and Amarnath, 2004). This mechanism of action is suggested for other plants that have been studied (Chaude et al., 2001; Krishna et al., 2004; El-Demerdash et al., 2005; Alarcon-Aguilar et al., 2005).

There was also a decrease in total protein in the alloxan-induced diabetic control which could be attributed to the non-enzymatic glycation of proteins seen in diabetes and which contributes to the long-term complications of the disease (Vlassara et al., 1981). Oral administration of ethanolic extracts of Spondias mombin and Parinari polyandra significantly reduced total protein concentration in the non-diabetic animals.

Lipid peroxidation is one of the characteristic features of chronic diabetes and insulin secretion is also closely associated with lipoxygenase-derived peroxides (Metz, 1984). TBARS is the most commonly used indicator of lipid peroxidation (Lyons, 1991). Glutathione (GSH) is known to protect the cellular system against toxic effects of lipid peroxidation (Nicotera and Orrenius, 1986). Decreased level of GSH in the liver and kidney during diabetes represents its increased utilization due to oxidative stress (Anuradha and Selvam, 1993). In this study there was no significant difference in the lipid peroxidation and GSH levels in the tissues of all the test groups. This indicates that the extracts maintained the levels of GSH that are utilized during diabetes and hence also stabilized lipid peroxidation. This finding is similar to studies done on some antidiabetic plants (Ravikumar and Anuradha, 1999; Srinivasan et al., 2005; Adewole and Caxton-Martins, 2006).

High cholesterol levels and hyperlipidemia are associated consequences of diabetes (Mironova et al., 2000; Pepato et al., 2003; Odetola et al., 2006). In this study, cholesterol and triglyceride levels were not significantly changed following treatments with ethanolic extracts of Spondias mombin and Parinari polyandra. This result agrees with other cholesterol modulating effects of several other plants (Rajagopal and Sasikala, 2008; Iweala and Okeke, 2005; Dhandapani et al., 2002). The stabilization of triglyceride and cholesterol levels in the rats by ethanolic extracts of Spondias mombin and Parinari polyandra is related to their promotion of utilization of glucose and hence depressed mobilization of fat (Momo et al., 2006). This result implies that the plant extracts may be helpful in reducing the complications of hyperlipidemia and hypercholesterolemia which coexist quite often in diabetics (Sharma et al., 2003).

Aspartate transaminase (AST) and alanine transaminase (ALT) assay are important in the diagnosis of liver damage caused by drug toxicity or harmful chemicals (Nelson and Cox, 2005). In the present study, AST and ALT levels in the test groups did not significantly change. Increase in liver enzymes is an indication of liver damage. However, the histological changes in the liver of the diabetic rats and the non diabetic group co-administered both ethanolic extracts of Spondias mombin and Parinari polyandra indicated hepatic damage. This means that administration of alloxan and co-administration of the ethanolic extracts of Spondias mombin and Parinari polyandra alters liver function in diabetes. This suggests a possible harmful synergistic effect by both plants on the liver. This observation is similar to a study by Raji et al. (2006) and corroborates the claim that most medicinal preparations in traditional medicines contain a variety of synergistically acting phytochemicals that act on a variety of targets by various mechanisms (Tiwari and Madhusudana-Rao, 2002). The implication of this is the questionable safety especially on the liver associated with the traditional concurrent use of the seeds of Spondias mombin and Parinari polyandra in management of diabetes. However, the non significant changes in the liver enzymes in groups treated with the individual ethanolic extracts of Spondias mombin and Parinari polyandra suggests no apparent toxicity to the liver and hence improving its functions and enhancing transport of glucose to ameliorate diabetes (Bhandarkar and Khan, 2004). Several plants employed in the management of diabetes do not express liver toxicity (Muthulingam, 2010; Hossain and Bhattacharya, 2006).

Generally, the biological effects of ethanolic extracts of Spondias mombin and Parinari polyandra are not unconnected with their active principles including alkaloids, flavonoids, tannins, glycosides which have been reported to have hypoglycaemic, hypolipidemic, hypocholesterolemic, antioxidant properties amongst others (Oladele et al., 1995).

The results of the present study clearly indicate that the ethanolic extracts of seeds of Spondias mombin and Parinari polyandra have glucose lowering effects on alloxan-induced diabetic rats. It also reveals the possible hepatotoxic effect of co-administration of both S.mombin and P. polyandra extracts as commonly practiced in unorthodox traditional management of diabetes in Nigeria. Further studies are in progress to isolate the active principle and elucidate the exact mechanism of action of S. mombin and P. polyandra.

REFERENCES

  1. Abolaji, O.A., A.H. Adebayo and O.S. Odesanmi, 2007. Nutritional qualities of three medicinal plant parts (Xylopia aethiopica, Blighia sapida and Parinari polyandra) commonly used by pregnant women in the western part of Nigeria. Pak. J. Nutr., 6: 665-668.
    CrossRef  |  Direct Link  |  


  2. Adeneye, A.A. and E.O. Agbaje, 2008. Pharmacological evaluation of oral hypoglycemic and antidiabetic effects of fresh leaves ethanol extract of Morinda lucida benth. in normal and alloxan-induced diabetic rats. Afr. J. Biomed. Res., 11: 65-71.
    CrossRef  |  Direct Link  |  


  3. Adewole, S.O. and E.A. Caxton-Martins, 2006. Morphological changes and hypoglycemic effects of Annona Muricata Linn. (Annonaceae) leaf aqueous extract on pancreatic Β-cells of streptozotocin-treated diabetic rats. Afr. J. Biomed. Res., 9: 173-180.
    Direct Link  |  


  4. Adewunmi, C.O. and J.A.O. Ojewole, 2004. Safety of traditional medicines complementary and alternatives medicines in Africa. Afr. J. Trad. CAM, 1: 1-3.
    Direct Link  |  


  5. Ajao, O., O. Shonukan and B. Femi-onadeko, 1985. Antibacterial effect of aqueous and alcohol extracts of spondias mombin and alchornea cordifolia - two local antimicrobial remedies. Pharm. Biol., 23: 67-72.
    CrossRef  |  


  6. Alarcon-Aguilar, F.J., F. Calzada-Bermejo, E. Hernandez-Galicia, C. Ruiz-Angeles and R. Roman-Ramos, 2005. Acute and chronic hypoglycaemic effect of Ibervillea sonorae root extracts-II. J. Ethnopharmacol., 97: 447-452.
    CrossRef  |  PubMed  |  


  7. Aliyu, R., A.H. Adebayo, D. Gatsing and I.H. Garba, 2007. The effects of ethanolic leaf extract of Commiphora Africana (Burseraceae) on rat liver and kidney functions. J. Pharmacol. Toxicol., 2: 373-379.
    CrossRef  |  Direct Link  |  


  8. Anuradha, C.V. and R. Selvam, 1993. Effect of oral methionine on tissue lipid peroxidation and antioxidants in alloxan-induced diabetic rats. J. Nutr. Biochem., 4: 212-217.
    CrossRef  |  Direct Link  |  


  9. Ayoka, A.O., R.O. Akomolafe, E.O. Iwalewa and O.E. Ukponmwan, 2005. Studies on the anxiolytic effect of Spondias mombin L. (Anacardiaceae) extracts. Afr. J. Trad. C.A.M., 2: 153-165.
    Direct Link  |  


  10. Babu, V., T. Gangadevi and A. Subramanium, 2002. Antihyperglycemic activity of Cassia kleinii leaf extract in glucose feed normal rats and alloxan-induced diabetic rats. Indian J. Pharmacol., 34: 409-415.
    Direct Link  |  


  11. Brai, B.I.C., A.A. Odetola and P.U. Agomo, 2007. Hypoglycemic and hypocholesterolemic potential of Persea americana leaf extracts. J. Med. Food., 10: 356-360.
    CrossRef  |  PubMed  |  


  12. Brownlee, M., 2001. Biochemistry and molecular cell biology of diabetic complications. Nature, 414: 813-820.
    CrossRef  |  PubMed  |  Direct Link  |  


  13. Buege, J.A. and S.D. Aust, 1978. Microsomal Lipid Peroxidation. In: Methods of Enzymology, Fleischer, S. and L. Packer (Eds.). Academic Press, New York, pp: 302-310


  14. Calixto, J.B., 2000. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicine (phytotherapeutic agents). Braz. J. Med. Biol. Res., 33: 179-189.
    CrossRef  |  


  15. Chaude, M.A., O.E. Orisakwe, O.J. Afonne, K.S. Gamenial, O.H. Vongtau and E. Obi, 2001. Hypoglycemic effect of the aqueous extract of Boerrhavia diffusa leaves. Indian J. Pharmacol., 33: 215-216.
    Direct Link  |  


  16. Dhandapani, S., V.R. Subramanian, S. Rajagopal and N. Namasivayam, 2002. Hypolipidemic effect of Cuminum cyminum L. on alloxan-induced diabetic rats. Pharmacol. Res., 46: 251-255.
    CrossRef  |  Direct Link  |  


  17. Disbrey, B.D. and J.H. Rack, 1970. Histological Laboratory Methods. Livingstone, Edinburgh, ISBN-13: 9780443006944, pp: 56-128


  18. El-Demerdash, F.M., M.I. Yousef and N.I.A. El-Naga, 2005. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food Chem. Toxicol., 43: 57-63.
    CrossRef  |  PubMed  |  Direct Link  |  


  19. Ellman, G.L., 1959. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 82: 70-77.
    CrossRef  |  PubMed  |  Direct Link  |  


  20. Fayed, T., M.A. El-Missiry, H. Emara and N. El-Sayaad, 1998. Effect of Nigella sativa or fish oil supplementation in alloxan diabetic rats. J. Union. Arab. Biol., 9: 237-250.


  21. Felig, P., E. Marliss, J.L. Ohman and C.F. Cahill Jr., 1970. Plasma amino acid levels in diabetic ketoacidosis. Diabetes, 19: 727-728.
    PubMed  |  Direct Link  |  


  22. Fred-Jaiyesimi, A.A., M.R. Wilkins and K.A. Abo, 2009. Hypoglycaemic and amylase inhibitory activities of leaves of Spondias mombin Linn. Afr. J. Med. Med. Sci., 38: 343-349.
    PubMed  |  


  23. Gandhipuram, P.S.K., A. Palanisamy, S.K. Durairaj and P.S. Sorimuthu, 2006. Anti diabetic activity of fruits of Terminalia chebula on streptozotocin-induced diabetic rats. J. Health Sci., 52: 283-291.
    Direct Link  |  


  24. Gondwe, M., D.R. Kamadyaapa, M.A. Tufts, A.A. Chuturgoon, J.A.O. Ojewole and C.T. Musabayane, 2008. Effects of Persea americana Mill (Lauraceae) (Avocado) ethanolic extract on blood glucose and kidney function in streptozotocin- induced diabetic rats and on kidney cell lines of the proximal (LLCPK 1) and distal tubules (MDBK). Meth. Find. Exp. Clin. Pharmacol., 30: 25-35.
    Direct Link  |  


  25. Hossain, S.U. and S. Bhattacharya, 2006. Prevention of cadmium induced lipid peroxidation, depletion of some antioxidative enzymes and glutathione by a series of novel organoselenocyanates. Environ. Toxicol. Pharmacol., 22: 298-308.
    CrossRef  |  Direct Link  |  


  26. Iweala, E.E.J. and C.U. Okeke, 2005. Comparative study of the hypoglycemic and biochemical effects of Catharanthus roseus (Linn) g. apocynaceae (Madagascar periwinkle) and chlorpropamide (diabenese) on alloxan-induced diabetic rats. Biokemistri, 17: 149-156.
    Direct Link  |  


  27. Kikkawa, R., D. Koya and M. Haneda, 2003. Progress of diabetic neuropathy. Am. J Kidney Dis., 41: 19-21.


  28. Krishnakumar, K., K.T. Augustii and P.L. Vijayammal, 1999. Hypoglycaemic and anti-oxidant activity of Salacia oblonga Wall. extract in streptozotocin-induced diabetic rats. Indian J. Physiol. Pharmacol., 43: 510-514.
    Direct Link  |  


  29. Lans, C., 2007. Ethnomedicines used in Trinidad and Tobago for reproductive problems. J. Ethnobiol. Ethnomed., Vol. 3.
    CrossRef  |  


  30. Lowry, O.H., N.J. Rosebrough, A.L. Farr and R.J. Randall, 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem., 193: 265-275.
    CrossRef  |  PubMed  |  Direct Link  |  


  31. Lyons, T.J., 1991. Oxidized low density lipoproteins: A role in the pathogenesis of atherosclerosis in diabetes. Diabet Med., 8: 411-419.
    PubMed  |  


  32. Maroo, J., V.T. Vasu and S. Gupta, 2003. Dose dependent hypolycemic effect of aqueous extract of Enicostemma littorale blume in alloxan induced diabetic rats. Phytomedicine, 10: 196-199.
    CrossRef  |  Direct Link  |  


  33. Metz, S.A., 1984. Is phospholipase A2 a glucose sensor responsible for the phasic pattern of insulin release? Prostaglandins, 27: 147-151.
    CrossRef  |  PubMed  |  


  34. Mironova, M., R. Klein, G. Virella and M. Lopes-Virella, 2000. Anti-modified LDL antibodies, LDL-containing immune complexes and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes. Diabetes, 49: 1033-1041.
    PubMed  |  


  35. Momo, C.E.N., J.E. Oben, D. Tazoo and E. Dongo, 2006. Antidiabetic and hypolipemic effects of laportea ovalifolia (urticaceae) in alloxan induced diabetic rats. Afr. J. Trad. CAM, 3: 36-43.
    Direct Link  |  


  36. Muthulingam, M., 2010. Antidiabetic efficacy of leaf extracts of Asteracantha longifolia (Linn.) Nees. on alloxan induced diabetics in male albino wistar rats. Int. J. Pharm. Biomed. Res., 1: 28-34.
    Direct Link  |  


  37. Nelson, D.L. and M.M. Cox, 2005. Lehninger: Principles of Biochemistry. 4th Edn., W.H. Freeman and Company, New York, USA, ISBN-13: 9780716743392, Pages: 1119


  38. Nicotera, P. and S. Orrenius, 1986. Role of thiols in protection against biological reactive intermediates. Adv. Exp. Med. Biol., 197: 41-51.
    CrossRef  |  PubMed  |  Direct Link  |  


  39. Njoku, P.C. and M.I. Akumefula, 2007. Phytochemical and nutrient evaluation of Spondias mombin leaves. Pak. J. Nutr., 6: 613-615.
    CrossRef  |  Direct Link  |  


  40. Odetola, A.A., O. Akinloye, C. Egunjobi, W.A. Adekunle and A.O. Ayoola, 2006. Possible antidiabetic and antihyperlipidaemic effect of fermented Parkia biglobosa (JACQ) extract in alloxan-induced diabetic rats. Clin. Exp. Pharmacol. Physiol., 33: 808-812.
    CrossRef  |  PubMed  |  Direct Link  |  


  41. Oladele, S.B., J.O. Ayo and A.O. Adaudi, 1995. Medicinal and physiological properties of flavonoids, coumarin derivatives and anthraquinones of plant origin. W. Afr. J. Pharmacol. Drug Res., 11: 134-144.
    Direct Link  |  


  42. Okigbo, R.N. and E.C. Mmeka, 2006. An appraisal of phytomedicine in Africa. KMITL Sci. Technol. J., 6: 83-92.
    Direct Link  |  


  43. Okolie, U.V., C.E. Okeke, J.M. Oli and I.O. Ehiemere, 2008. Hypoglycemic indices of Vernonia amygdalina on postprandial blood glucose concentration of healthy humans. Afr. J. Biotechnol., 7: 4581-4585.
    Direct Link  |  


  44. Piedrola, G., E. Novo, F. Escober and R. Garcia-Robles, 2001. White blood cell count and insulin resistance in patients with coronary artery disease. Ann. Endocrinol., (Paris), 62: 7-10.
    PubMed  |  


  45. Pepato, M.T., A.M. Baviera, R.C. Vendramini, M.P. Perez, I.C. Kettelhut and I.L. Brunetti, 2003. Cissus sicyoides (Princess wine) in the long terme treatment of streptozotocin-diabetic rats. Biotchnol. Applied Biochem., 37: 15-20.
    PubMed  |  Direct Link  |  


  46. Rajagopal, K. and K. Sasikala, 2008. Antihyperglycaemic and antihyperlipidaemic effects of Nymphaea stellata in alloxan-induced diabetic rats. Singapore Med. J., 49: 137-141.
    PubMed  |  Direct Link  |  


  47. Raji, Y., M.A. Gbadegesin, O.A. Osonuga, R.A. Adisa and O.S. Akinsomisoye et al., 2006. Reproductive, haematologic and biochemical profile of male rats treated with aqueous extract of Spondias mombin bark. Int. J. Pharmacol., 2: 126-130.
    CrossRef  |  


  48. Ravikumar, P. and C.V. Anuradha, 1999. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats. Phytother. Res., 13: 197-201.
    CrossRef  |  Direct Link  |  


  49. Ross, R.N., 1999. Mechanisms of disease: Atherosclerosis- an inflammatory disease. New Engl. J. Med., 340: 115-126.
    Direct Link  |  


  50. Schwartz, S.L., 2006. Diabetes and dyslipidaemia. Diabetes Obes. Metab., 8: 355-364.
    PubMed  |  


  51. Sharma, S.B., A. Nasir, K.M. Prabhu, P.S. Murthy and G. Dev, 2003. Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits. J. Ethanopharmacol., 85: 201-206.
    CrossRef  |  Direct Link  |  


  52. Srinivasan, M., M. Padmanabhan and P.S. Prince, 2005. Effect of aqueous Enicostemma littorale blume extract on key carbohydrate metabolic enzymes, lipid peroxides and antioxidants in alloxan-induced diabetic rats. J. Pharm. Pharmacol., 57: 497-503.
    Direct Link  |  


  53. Szkudelski, T., 2001. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res., 50: 537-546.
    PubMed  |  Direct Link  |  


  54. Tiwari, A.K. and J.M. Rao, 2002. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: Present status and future prospects. Curr. Sci., 83: 30-38.
    Direct Link  |  


  55. Udoh, A.E., I. Ntu, O. Essien and M. Ndon, 2007. Red cell catalase activity in diabetics. Pak. J. Nutr., 6: 511-515.
    CrossRef  |  Direct Link  |  


  56. Vats, V., J.K. Grover and S.S. Rathi, 2002. Evaluation of anti-hyperglycemic and hypoglycemic effect of Trigonella foenum-graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabetic rats. J. Ethnopharmacol., 79: 95-100.
    PubMed  |  Direct Link  |  


  57. Vlassara, H., M. Brownlee and A. Cerami, 1981. Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. PNAS, 78: 5190-5192.
    PubMed  |  Direct Link  |  


  58. Virella-Lopes, M.F. and G. Virella, 2003. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes. Fron. Biosci., 8: 750-768.
    Direct Link  |  


  59. Vongtau, H.O. J. Abbah, I.E. Ngazal, O.F. Kunle, B.A. Chindo, P.B. Otsapa and K.S. Gamaniel, 2004. Anti-nociceptive and anti-inflammatory activities of the methanolic extract of Parinari polyandra stem bark in rats and mice. J. Ethnopharmacol., 90: 115-121.
    Direct Link  |  


  60. WHO., 1999. Definition Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes. WHO/NCD/NCS., Geneva, pp: 1-58


  61. WHO., 2002. WHO news: Traditional medicine strategy launched. Bull. World Health Organization, 80: 610-610.
    Direct Link  |  


  62. Wild, S., G. Roglic, A. Green, R. Sicree and H. King, 2004. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, 27: 1047-1053.
    CrossRef  |  PubMed  |  Direct Link  |  


  63. Yaryura-Tobias, J.A., A. Pinto and F. Neziroglu, 2001. Anorexia nervosa, diabetes mellitus, brain atrophy and fatty liver. Int. J. Eating Disorders, 30: 350-353.
    CrossRef  |  PubMed  |  Direct Link  |  


  64. Abdel-Barry, J.A., I.A. Abdel-Hassan and M.H. Al-Hakiem, 1997. Hypoglycaemic and anti hyperglycaemic effects of Trigonella foenum-graecum leaf in normal and alloxan induced diabetic rats. J. Ethnopharmacol., 58: 149-155.
    CrossRef  |  


  65. Bhandarkar, M.R. and A. Khan, 2004. Antihepatotoxic effect of Nymphaea stellata willd., against carbon tetrachloride-induced hepatic damage in albino rats. J. Ethnopharmacol., 91: 61-64.
    CrossRef  |  Direct Link  |  


  66. Murthy, B.K., S. Nammi, M.K. Kota, R.V.K. Rao, N.K. Rao and A. Annapurna, 2004. Evaluation of hypoglycemic and antihyperglycemic effects of Datura metel (Linn.) seeds in normal and alloxan-induced diabetic rats. J. Ethnopharmacol., 91: 95-98.
    CrossRef  |  Direct Link  |  


  67. Pari, L. and M.A. Satheesh, 2004. Antidiabetic activity of Boerhaavia diffusa L.: Effect on hepatic key enzymes in experimental diabetes. J. Ethnopharmacol., 91: 109-113.
    CrossRef  |  Direct Link  |  


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