Pharmacognosy Research. Dec/31/2016; 9(1): 80-86

PMID: 28250659

PMC: 5330109

Antidiabetic Effects of Aqueous and Dichloromethane/Methanol Stem Bark Extracts of Pterocarpus soyauxii Taub (Papilionaceae) on Streptozotocin-induced Diabetic Rats

Marie Claire Tchamadeu

Paul Désiré Djomeni Dzeufiet

Abstract

Aim of the Study:

The aim is to evaluate the hypoglycemic and antidiabetic effects of aqueous and CH₂Cl₂/CH₃OH stem bark extracts of Pterocarpus soyauxii Taub in normal and diabetic rats.

Materials and Methods:

Streptozotocin (STZ)-induced diabetic and normal adult Wistar rats were orally administered with aqueous and CH₂Cl₂/CH₃OH plant extracts of P. soyauxii at various doses (38–300 mg/kg) in a single administration. In addition, STZ-induced diabetic rats received prolonged daily administration for 14 days. Glibenclamide (GB) (10 mg/kg) was used as reference treatment. In acute test, fasting blood glucose was followed for 5 h. In subacute test, body weight, food and water intakes, and blood glucose were followed weekly and serum biochemical parameters evaluated after 14 days treatment.

Results:

Acute administration of aqueous and CH₂Cl₂/CH₃OH stem bark extracts moderately decreased fasting blood glucose compared to GB, significantly in normal rats (P < 0.05 to P < 0.01) but, as GB, not significantly in diabetic rats. Prolonged treatments in diabetic rats with aqueous and CH₂Cl₂/CH₃OH extracts reduced blood glucose to an extent, respectively, superior or similar to GB. Moreover, P. soyauxii also significantly (P < 0.01) reduced weight loss, and diabetes increased serum triglycerides, total cholesterol, and transaminases (alanine aminotransferase/aspartate aminotransferase) elevations.

Conclusion:

P. soyauxii Taub stem bark extracts have possible value for antidiabetic oral medication.

SUMMARY

Aqueous and Dichloromethane/Methanol stem bark extracts of Pterocarpus soyauxii Taub have potent (compared to Glibenclamide) antidiabetic effects in STZ-diabetic rats, with specific kinetics and dose-responses.
Moderate hypoglycemia effects upon acute P. soyauxii administration.
Potent anti-hyperglycemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats.
Potent anti-hyperlipidemic effects of sub-acute P. soyauxii administration in STZ-diabetic rats.
Improved hepatic and renal serum parameters after sub-acute P. soyauxii administration in STZ-diabetic rats.
P. soyauxii extracts may be useful for oral treatment of diabetes and related metabolic disorders.

Abbreviations Used: CH2Cl2/CH3OH: Dichloromethane/Methanol; STZ: Streptozotocin; GB: Glibenclamide; AE: Aqueous extract; OE: Organic extract; FeCl3: Iron (III) chloride; NaCl: Sodium chloride; K3Fe(CN)6: Potassium ferricyanide; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; H: Hour; BW: Body weight, W1 and W2: Weeks 1 and 2; CHOD: Cholesterol oxidase; GPO: Glycerol-3 Phosphate oxidase; PAP: Phenol + Aminophenazone

INTRODUCTION

Diabetes mellitus, a chronic metabolic disorder characterized by high glucose level in blood and altered metabolism, is a growing health problem. Diabetes affected 387 million (8.3%) people worldwide in 2014, with an increasing high percentage in poor and developing countries.[1] In Africa (including Cameroon), almost 5% of the population is diabetic and a high number could be undiagnosed.[2] In addition to common Type 1, Type 2, and gestational diabetes, ketosis-prone atypical diabetes is mostly seen in populations from African origin.[3] Type 1 diabetes in Africa may somewhat differ from typical European, with later age at onset. Costs of modern therapies, associated with well-known side effects, orient most patients of poor countries toward traditional medicine.[4]

Validation of alternative therapies is of great interest.[5] Medicinal plants provide exciting new therapeutic opportunities,[6] and a number of medicinal plants were reported to show antidiabetic potential.[4] Phytochemicals with antidiabetic properties include saponins,[7] flavonoids,[8] phenolics,[9] and other antioxidant compounds.[10] African medicinal plants are evaluated for their antidiabetic potentials,[11 12] with paucity studied in Cameroon.[13 14] In that context, after an ethnobotanical survey in the central region of Cameroon, we chose to study Pterocarpus soyauxii Taub, a medicinal plant used in traditional medicine.

P. soyauxii Taub (Papilionaceae) is a deciduous rain forest tree of the genus Pterocarpus belonging to the family of Fabaceae or Papilionaceae, in the branch of spermaphytes. Leaves, wood, stem bark, seeds, and flours are used in African, especially Cameroonian pharmacopeia, to treat various diseases including hypertension, diabetes, gastrointestinal parasites, and renal and cutaneous diseases. Leaves of P. soyauxii added to food were reported to normalize hematological alterations associated with diabetes mellitus.[15]

Despite knowledge on medicinal potential of P. soyauxii, there is a lack of experimental reports on pharmacological activities, particularly in diabetes mellitus. Besides, hypoglycemic and antidiabetic activities of crude extracts of other species of the genus Pterocarpus are largely investigated, i.e. for Pterocarpus marsupium[4 16] and Pterocarpus santalinus.[17 18] Recently, aqueous P. soyauxii plant extracts were shown devoid of toxic effects after oral administration to rodents.[19]

The main goal of the present study was to evaluate P. soyauxii for hypoglycemic and antidiabetic activities in normal and diabetic rats. We assessed oral administration of aqueous extraction (noted AE) and dichloromethane/methanol (CH₂ Cl₂/CH₃ OH) (noted organic extraction [OE]) stem bark extracts of P. soyauxii Taub on glycemia, either after acute administration in normal and streptozotocin (STZ)-induced diabetic rats or after subacute (14 days) treatment in STZ-induced diabetic rats. Glibenclamide (GB) was used as reference antidiabetic treatment (positive control).[8] In addition, we investigated subacute impacts on body parameters (weight, food and water intakes) and serum biochemical parameters (total proteins, creatinine, total cholesterol, triglycerides, and alanine aminotransferase/aspartate aminotransferase [ALT/AST] activities).

MATERIALS AND METHODS

Chemicals

GB was obtained from Mylan Laboratory. STZ was purchased from Sigma Chemical Co. (Saint Louis, MO, USA). Blood glucose test strips were Accu-chek PLUS from Roche Diagnostics (Mannheim, Germany). All other reagents and chemicals used in the study were extra pure analytical grade obtained from common commercial suppliers.

Plant material

P. soyauxii (Papilionaceae) barks were collected in March 2002 in Nkolbibanda village (Central Region, Cameroon) by Dr. Louis Zapfack (Botany Department, University of Yaounde 1). The plant was identified at the National Herbarium of Yaounde where a voucher specimen was deposited (HNC/2427).[19]

Preparation of aqueous and organic extracts of Pterocarpus soyauxii

Stem barks were dried at room temperature and ground into powder. For AE, dry powder (200 g) was macerated in 2 L of boiling distilled water for 10 min and then kept 24 h at room temperature before filtering. The filtrate was concentrated in a drying room at 40°C, yielding 24.10 g (w/w 12%) red well-dried aqueous residue, and stored at −20°C until use as previously reported.[19]

For dichloromethane/methanolic extraction (OE), 2 kg of dried stem bark powder was macerated 24 h at room temperature in 5 L CH₂Cl₂/CH₃ OH (1:1) and filtered. The filtrate was concentrated using a rotary evaporator, yielding 459.60 g (w/w 23%) of red dried residue, and stored at room temperature.

For each series of experiments, the AE and OE were weighed and dissolved in distilled water to obtain 30 mg/ml stock solutions. Fixation of plant dosing for administration to rats was based on usual dosage by traditional healer (i.e. around 20 mg/kg dried stem barks/body weight [BW]) and on previous animal studies with P. marsupium,[16] P. santalinus,[20] and P. soyauxii.[19] Plant materials were extracted separately in two solvents (water and CH₂Cl₂/CH₃ OH); however, dissolution of the two dried filtrates being well done in water, we only performed water control vehicle.

Phytochemical screening

Qualitative phytochemical screenings of the aqueous (AE) and CH₂Cl₂/CH₃ OH (OE) stem bark extracts of P. soyauxii were carried out following standard procedures as previously described[21] to reveal the presence of alkaloids (Mayer and Dragendorff's test), tannins (FeCl₃ test), saponins (frothing test), lipids (Whatman paper test), flavonoids (Shinoda's test), glycosides and polyoses (NaCl and Fehling's solutions A and B), anthraquinones (ether–ammoniac), phenols (FeCl₃ test), polyphenols (FeCl₃ and K₃ Fe (CN)₆ test), and terpenoids (Liebermann–Burchard test), as previously used to screen the aqueous P. soyauxii extract.[19]

Animals

Adult male albino Wistar rats (3-month-old weighing 200–250 g) were used. They were raised in the animal core facility of the Faculty of Science, University of Yaoundé 1. They were housed in colony cages (5 rats per cage), at controlled room temperature (23°C ± 0.5°C) and humidity (75% ±5%), on a 12 h light/dark cycle and allowed free access to tap water and standard rat diet. Before testing for blood glucose level, the rats were fasted overnight for 12 h, with free access to water. All animal experiments were conducted in accordance with the International Guidelines for Care and Use of Laboratory Animals as described in the European Community Guidelines (EEC Directive 2010/63/EU of the September 22, 2010).

Induction of diabetes mellitus

Diabetes was induced by a single intravenous injection (caudal vein) of STZ (55 mg/kg freshly prepared in ice cold 0.9% saline solution)[22] in overnight-fasted rats anesthetized by ketamine and xylazine (50 mg/kg, 10 mg/kg, i.p.) to avoid pain and stress.[21] Procedure was performed in darkness to avoid degradation of STZ. Control rats received the vehicle alone. Three days after STZ injection, rats with a fasting blood glucose level of at least 250 mg/dL were considered diabetic and used in the experiments.

Measurement of fasting blood glucose level

Blood drop sample was collected from overnight-fasted rats and determination of blood glucose was carried out by glucose-peroxidase method using test strips (Accu-chek PLUS) and an appropriate glucose meter (Accu-chek, Roche Diagnostics, USA). More precisely, for fasting blood glucose determination (at 0, 1, 2, 3, and 5 h for acute experiment and at 0, 8, and 15 days for subacute experiment), the rat was covered with a clean cloth, the tail tip was slightly injured, and the released blood drop deposited on the reactive zone of a strip connected to the glucometer. Repeated bleeding was feasible in the short term by removing the clot.[23]

Experimental design for evaluating acute effects of Pterocarpus soyauxii extracts in normal and diabetic rats

A total of 100 rats were used.

Fifty nondiabetic rats randomly divided into ten groups (five rats each):

Group 1: Nondiabetic control (NC) rats received distilled water (10 mL/kg)
Groups 2–5: Nondiabetic rats administered with aqueous P. soyauxii extract at different doses (AE 38, 75, 150, and 300 mg/kg, respectively)
Groups 6–9: Nondiabetic rats administered with dichloromethane/methanol extract at different doses (OE 38, 75, 150, and 300 mg/kg, respectively)
Group 10: Nondiabetic positive control rats administered with GB (10 mg/kg).

Moreover, fifty STZ-diabetic rats randomly assigned into ten groups (five rats each):

Group 11: Diabetic control (DC) rats received distilled water (10 mL/kg)
Groups 12–15: Diabetic rats administered with the aqueous extract at different doses (AE 38, 75, 150, and 300 mg/kg, respectively)
Groups 16–19: Diabetic rats administered with the dichloromethane/methanol extract at different doses (OE 38, 75, 150, and 300 mg/kg, respectively)
Group 20: Diabetic positive control rats administered with GB (10 mg/kg).

All groups of rats received a single oral administration of the treatments by gavage. Blood glucose levels were measured before treatment administration (0 h) and 1, 2, 3, and 5 h after.

Experimental design for evaluating subacute effects of Pterocarpus soyauxii extracts in diabetic rats

A total number of 55 rats were used, fifty diabetic rats randomly assigned into ten diabetic groups (5 rats in each) and a group of five nondiabetic rats. Rats were daily treated by gavage for 14 days beginning 3 days after STZ treatment with the respective drug or vehicle as follows:

Group 1: NC rats received 10 mL/kg of distilled water
Group 2: DC rats received 10 mL/kg of distilled water
Groups 3–6: Diabetic rats administered with the AE at different doses (38, 75, 150, and 300 mg/kg, respectively)
Groups 7–10: Diabetic rats administered with the dichloromethane/methanol extract (OE) at different doses (38, 75, 150, and 300 mg/kg, respectively)
Group 11: Diabetic positive control rats administered with GB (10 mg/kg).

Blood glucose level was measured in 12 h fasted rats before the first treatment administration (day 0) and weekly (day 8 and day 15, respectively, weeks W1 and W2). Body weight (BW) and food and water intakes were recorded daily. At the end of the experimental period, on day 15 (18 days post-STZ), after fasting blood glucose determination, the rats were anesthetized (ketamine 50 mg/kg and xylazine 10 mg/kg, i.p.)[24] and blood samples were collected from the abdominal aorta accessed via laparotomy.[21] The anesthetized animals were then euthanized by decapitation. The serum obtained after blood centrifugation (3000 g, 10 min) was stored at −20°C until analysis.

Biochemical analysis of serum

The serum was analyzed using commercially available diagnostic kits (Fortress Diagnostics, Antrim, UK) for total proteins (Biuret), creatinine (enzymatic UV), total cholesterol (CHOD-PAP method), triglycerides (GPO-PAP method), ALT (colorimetric), AST (colorimetric).

Statistical analysis

Data are presented as mean ± standard error of mean. One-way analysis of variance with Dunnett's multiple comparison posttest was performed to assess differences between groups (GraphPad Software, San Diego, California, USA). P <0.05 was considered statistically significant.

RESULTS

Phytochemical screening of aqueous and CH₂Cl₂/CH₃ OH extracts of Pterocarpus soyauxii

According to the previous experiments with the experimental methods used,[19] the screening evidenced alkaloids, saponins, flavonoids, tannins, terpenoids, phenols, polyphenols, and glucids classes; no lipid component was revealed.

Effect of single doses of Pterocarpus soyauxii extracts on blood glucose of normal rats

Single administration of aqueous (AE) and organic CH₂Cl₂/CH₃ OH (OE) stem bark extracts of P. soyauxii and antidiabetic treatment GB (10 mg/kg) produced hypoglycemic effects in nondiabetic rats with time-dependent reduction of glycemia [Figure 1a and b]. GB was the most efficient with a maximum fall in glycemia to 38.8 ± 4.4 mg/dL at 5 h (P < 0.001 compared with NC group or to time 0). The AE induced a fall to 68.2 ± 3.3–72 ± 2.2 mg/dL with the 150–300 mg/kg doses, respectively, (P < 0.001) [Figure 1a] and the OE induced a maximum fall to 78.4 ± 5.1 mg/dL at 150 mg/kg (P < 0.001) [Figure 1b].

Figure 1

Effects of single doses of aqueous (A) and CH₂Cl₂/CH₃OH (B) P. soyauxii extracts on blood glucose level of non diabetic rats. Results are expressed as mean ± SEM, n = 5; *P < 0.05; **P < 0.01; ***P < 0.001 compared to NC; ^aP < 0.05; ^aaP < 0.01 compared to initial value (0 h). AE: Aqueous extract at the doses indicated in mg/kg; OE: CH₂Cl₂/CH₃OH extract at the doses indicated in mg/kg; GB: Glibenclamide at 10 mg/kg; NC: Non diabetic control

Effect of single doses of Pterocarpus soyauxii extracts on blood glucose of streptozotocin-diabetic rats

Blood glucose level was increased over 350 mg/dl in diabetic rats, 3 days after induction. Single administration of AE (38–300 mg/kg) did not significantly alter hyperglycemia [Figure 2a]. Administration of OE tended to reduce glycemia similarly to GB [Figure 2b].

Figure 2

Effects of single doses of aqueous (A) and CH₂Cl₂/CH₃OH (B) P. soyauxii extracts on blood glucose level of STZ--diabetic rats. Results are expressed as mean ± SEM, n = 5; *P < 0.05 compared to diabetic control DC; ^aP < 0.05 compared to initial value (0h). AE: Aqueous extract at the doses indicated; OE: CH₂Cl₂/CH₃OH extract at the doses indicated; GB: Glibenclamide at 10 mg/kg; DC: Diabetic control

Subacute effects of Pterocarpus soyauxii extracts on blood glucose level of streptozotocin-diabetic rats

Persistent hyperglycemia was observed in DC rats (glycemia up to 373 mg/dL at day 14). Hyperglycemia was significantly reduced by AE and OE treatments from day 7 [Figure 3a and b, respectively]. The AE dose-dependently reduced glycemia up to complete correction to normal blood glucose value (with the AE 150 and 300 mg/kg doses from day 7, P < 0.001 compared to DC) [Figure 3a]. The OE time-dependently reduced hyperglycemia. Maximum lowering to 142.6 ± 8.4 and 127.4 ± 9.6 mg/dL of blood glucose was observed at day 14 with the OE 38 and 75 mg/kg doses, respectively (P < 0.001 compared to DC) [Figure 3b]. Similarly to OE, GB time-dependently reduced hyperglycemia up to 172.4 ± 46.5 mg/dL (P < 0.001).

Figure 3

Effects of sub-acute treatment with aqueous (A) and CH₂Cl₂/CH₃OH (B) P. soyauxii extracts on blood glucose level of STZ-diabetic rats. Results expressed as mean ± SEM, n = 5; *P < 0.05, **P < 0.01, ***P < 0.001 compared to DC; ^aP < 0.05; ^aaP < 0.01 compared to initial value (day 0). AE: Aqueous extract at the doses indicated; OE: CH₂Cl₂/CH₃OH extract at the doses indicated; GB: Glibenclamide at 10 mg/kg; DC: Diabetic control; NC: Non diabetic control

Subacute effects of Pterocarpus soyauxii extracts on body weight and food and water intake of streptozotocin-diabetic rats

In the NC group, BW increased (positive percent change) during weeks 1 and 2 (W1 and W2) [Table 1]. In untreated diabetic (DC) rats, BW decreased (P < 0.01 compared to NC) whereas food and water consumptions markedly increased. AE treatment reduced BW loss (AE 150 and 300 mg/kg doses; P < 0.05–0.01 compared to DC). These high AE doses also lowered excess intakes (P < 0.01 compared to DC). OE did not reduce BW loss and intakes of food and water. GB failed to reduce BW loss and partly diminished consumptions.

Table 1

Effects of sub-acute treatment with aqueous and CH₂Cl_l2/CH₃OH extracts of P. soyauxii on body weight, food and water consumptions of diabetic rats

Subacute effects of Pterocarpus soyauxii extracts on serum biochemical parameters of streptozotocin-diabetic rats

At the end of the experiment, DC rats had significant increases in serum total cholesterol, triglycerides, creatinine, and ALT activity (P < 0.01 compared to NC rats) [Table 2]. Trends to decrease in serum total protein and increase in AST were not significant. AE normalized total cholesterol, triglycerides, creatinine (AE 38–300 mg/kg; P < 0.05–0.01 compared to DC), and ALT (AE 150–300 mg/kg; P < 0.01), lowered AST (AE 38–150 mg/kg; P < 0.01), and increased total serum protein (AE 38–75 mg/kg; P < 0.01). OE reduced total cholesterol and triglycerides (OE 38–300 and OE 75–150, respectively; P < 0.05–0.01), normalized creatinine (OE 38–150 mg/kg; P < 0.01), and lowered ALT and AST (OE 38–300; P < 0.05–0.01). The high OE 300 dose did not improve creatinine, triglycerides, and total protein. By contrast, GB restored ALT only (P < 0.01 compared to DC) but did not significantly change other (total protein, creatinine, total cholesterol, triglycerides) serum parameters.

Table 2

Effects of sub-acute treatment with aqueous and CH₂Cl₂/CH₃OH P. soyauxii extracts on serum biochemical parameters of diabetic rats

DISCUSSION

Plants of the Pterocarpus genus (P. marsupium[4] and P. santalinus[18]) have established antidiabetic properties. In the present study, hypoglycemic and antidiabetic effects of aqueous (AE) and CH₂ Cl₂/CH₃ OH (OE) P. soyauxii Taub stem bark extracts were studied against STZ-induced type 1 diabetes mellitus in rats, GB being used as antidiabetic positive control.[8] The STZ model is widely used to test potential antidiabetic properties of natural products derived from medicinal plants.[25] Diabetes in the STZ-induced hyperglycemic rats was confirmed here by BW loss, increased food and water intakes and at the 18th day post STZ injection, by altered serum parameters such as hyperlipidemia (elevated serum triglycerides and total cholesterol), elevated creatinine and ALT activity's, and trends to hypoprotidemia and elevated AST activity's. Herein, the results indicate for the first time that P. soyauxii bark extracts induce potent antidiabetic activities. The data enlarge the panel of antidiabetic plants in the Pterocarpus genus, with P. soyauxii (bark).

In acute administration, both the aqueous (AE) and CH₂ Cl₂/CH₃ OH (OE) stem bark extracts of P. soyauxii decreased blood glucose level, moderately compared to GB, and significantly in normal rats but nonsignificantly in diabetic rats. Interestingly, in the Pterocarpus genus, P. marsupium[26] demonstrated hypoglycemic activity in normal rats whereas P. santalinus did not but reduce glycemia in diabetic rats.[17] GB is known to stimulate insulin from remnant β-cells and to inhibit glucagon secretion.[8] Since severe hypoglycemia due to excess insulin secretion is a major life-threatening limitation to pharmacological diabetes treatment, the low hypoglycemiant effect of P. soyauxii may be a desirable feature.

The most important result of the present study was the observation that a 14-day treatment with P. soyauxii extracts reduced hyperglycemia in diabetic rats at a magnitude superior to GB. OE at low doses (38–75 mg/kg) was slightly more efficient than GB and showed similar kinetics. Besides, AE (150–300 mg/kg) completely normalized glycemia from the treatment day 7. For the Pterocarpus genus, the ethylacetate: Methanol (9:1) fraction of P. santalinus bark ethanolic (150 mg/kg/day) extract[20] and aqueous or methanolic P. marsupium extracts (at 0.5–1 g/kg/day[26] or 150 mg/kg/day[16]) showed antihyperglycemic activity, but without recovery of normal glycemia. Therefore, P. soyauxii evidenced marked antihyperglycemic effects, in which potency could be further compared to other Pterocarpus species and plants.[4 11]

Type 1 diabetes is associated to alterations of general body parameters, weight loss, polydipsia, and polyphagia. BW loss, despite increased food intake, is known to be due to insulin deficiency induced catabolism of proteins and muscle wasting. Consistent with its potent antihyperglycemic effect, the aqueous P. soyauxii extract (150 and 300 mg/kg) reduced these general alterations and much better than OE extracts and GB. Reduction in BW loss with P. soyauxii AE extracts argues for improved insulin secretion as observed for P. santalinus.[20]

Inadequate protein catabolism with increased serum creatinine may cause glomerular dysfunction in kidney. Diabetic nephropathy is an increasing comorbidity of diabetes. Here, elevation of serum creatinine in diabetic rats was blunted by P. soyauxii treatment but not by GB. Consistently, AE of P. soyauxii-treated but not GB-treated rats had reduced BW loss (muscle atrophy). The observation highlights a possible nephroprotective potential of the plant.

Elevation of liver transaminases is a common feature of diabetes directly related to increased amino acids availability.[16] Here, STZ-diabetic rats had increased ALT activity in serum while AST elevation was not significant. Both AE and OE of P. soyauxii significantly decreased the ALT/AST transaminases. This indicates liver protection, by possibly restored insulin secretion, as described with P. marsupium bark extracts.[16]

Elevation of total cholesterol and triglycerides is a hallmark of metabolic disorders often linked to diabetes, as a consequence of impaired insulin secretion or insulinoresistance and subsequent increased mobilization of free fatty acids.[20] The AE and OE of P. soyauxii normalized serum triglycerides and total cholesterol after 2 weeks treatment in STZ-diabetic rats. This P. soyauxii impact contrasted with the lack of protective effect of GB and is consistent with the better antihyperglycemic effect of the plant. Similar antihyperlipidemic effects have been reported with ethanol bark extracts of P. santalinus[20] and methanol and aqueous bark extracts of P. marsupium Roxb,[16] the effect being attributed to a flavonoid (pterosupin).[4] Antihyperlipidemic activity of P. soyauxii extracts may have cardiovascular protective impact in diabetes.

Both aqueous and CH₂ Cl₂/CH₃ OH extracts of P. soyauxii demonstrated blood glucose lowering efficacy. This was achieved in acute administration with high doses (AE 300 mg/kg and OE 150 mg/kg) while in prolonged administration lower doses (AE 150 and OE 75 mg/kg) were efficient. The better efficiency of the OE compared to AE low doses suggests that the active compounds should be more liposoluble than hydrosoluble. The bad OE dose-response, with reduced efficiency of the high doses, could be due to glycosides or antagonist compounds in OE extracts. Conversely, the clear AE dose response, with performing antihyperglycemic high doses, suggests that adverse compounds were not or slowly water extracted.

The present preliminary phytochemical analyses of aqueous AE and organic OE P. soyauxii stem barks extracts is consistent with previous reports.[19] Recently, three new benzofurans (1–3) and one new isoflavan (4), pteroyanin G, H, I, and J, together with 21 known compounds, were isolated from the heartwood of P. soyauxii.[27] Other species of the Pterocarpus genus (P. marsupium[4] and P. santalinus[18]) present similarities in phytochemical composition with P. soyauxii and also contain other phenolic constituents.[28] Most compounds evidenced in the present P. soyauxii Taub bark extracts could be involved in antidiabetic activity, in particular flavonoids, tannins,[4] terpenes,[11] saponins,[7] and phenolic compounds.[9]

Phytocompounds exert antidiabetic action by stimulating insulin secretion (pterostilbene, Roxb-(-)-epicatechin)[28] and β cells regeneration (flavonoid),[4] improving insulin sensitivity or insulin-like effect (vestitol, claussequinone),[29] activating liver peroxisome proliferator-activated receptor (pterostilbene), modifying glucose intestinal or hepatic metabolism.[20] In addition, P. marsupium extracts may have potent dipeptidyl-peptidase-4 inhibitory action and hypoglycemic action by increased plasma active glucagon-like peptide-1 levels.[30] Further pharmacological, biological, and biochemical investigations will be required to clarify the mechanism of action and the main active principles of P. soyauxii Taub stem bark responsible for the antidiabetic effects. In particular, measurement of blood insulin, glucose tolerance tests, evaluation of pancreatic β cells destruction/regeneration, and investigation of skeletal muscle glucose metabolism will bring information. In addition, translation to other animal models will be necessary to test extension of the antihyperglycemic effect to other Type 1 and Type 2 diabetic models. Safety of oral P. soyauxii utilization in rodents has been previously shown.[19] The present demonstration of an antidiabetic effect of P. soyauxii in STZ-diabetic rats is a further valuable step toward P. soyauxii Taub as antidiabetic therapy which could be relevant to human pathology.

CONCLUSION

The study shows that aqueous and CH₂ Cl₂/CH₃ OH stem bark extracts of P. soyauxii Taub have only moderate hypoglycemic impact and potent antihyperglycemic effects with improved metabolic parameters in experimental STZ-diabetic rats, compared to GB. Therefore, P. soyauxii extracts may be useful for alternative oral treatment of diabetes and related metabolic disorders. Further studies are needed to address the mechanism of action for P. soyauxii in treating diabetes.

Financial support and sponsorship

This work was funded by the Third World Academy of Sciences (Grant 06-020RG/BIO/AF/AC-UNESCOFR 3240144852), the French-Cameroon Cooperation (French Embassy in Cameroon) and INSERM, U1048,-I2MC, Toulouse, France.

Conflicts of interest

There are no conflicts of interest.

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