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Effect of Solanum lycocarpum St. Hill on various haematological parameters in diabetic rats
Journal of Ethnopharmacology 106 (2006) 442–444
Ethnopharmacological communication
Effect of Solanum lycocarpum St. Hill on various haematological parameters in diabetic rats A.C. Perez ∗ , V. Franca, V.M. Daldegan Jr., I.D.G. Duarte Department of Pharmacology, UFMG (Federal University of Minas Gerais), Brazil Received 6 October 2005; received in revised form 30 January 2006; accepted 26 February 2006 Available online 5 April 2006
Abstract Solanum lycocarpum St. Hill (SL) is commonly used in Brazilian folk medicine. The aim of the present study was to evaluate the validity of the traditional therapeutic indication of SL as hypoglycaemic agent. The extract reduced glycemia to 92.4 mg/dl in alloxan induced diabetic rats (230.5 mg/dl). We also investigated the potential of SL as antioxidant (it reduced in 27% nitrate generation in diabetic animals). Our results also demonstrated that SL is not ulcerogenic and restored haemoglobin and haematocrit to normal values in diabetic animals. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Solanum lycocarpum; Nitric oxide; Hypoglycaemic agent
1. Introduction
2. Material and methods
Solanum lycocarpum St. Hill (SL) commonly known as “Lobeira” is a medicinal plant specie growing in the Brazilian savana.1,2,3 The species is widely employed as an hypoglycaemic agent. As non-insulin dependent diabetes is much more common than type I, affecting usually elderly and/or overweight people leading to many other health problems, the objective of the present study was to determine the effects of SL on various haematological parameters after diabetes induction.
2.1. Plant preparation The fruit from the plant was sliced and put in a microwave oven to dry. Then the fruits were grounded in a mill and protected against humidity and luminosity (Maruo et al., 2003a). 2.2. Animals Male wistar rats weighing 200 ± 40 g obtained from UFMG, Brazil were used and were allowed free access to water and food before and during the experiment.
∗
Corresponding author. Tel.: +55 31 3499 2721. E-mail address: [email protected] (A.C. Perez). 1 Plant: Unripe fruits of Solanum lycocarpum St. Hill (SL; Solanaceae) were collected in December from the region of Minas Gerais, Brazil and authenticated by J.R. Stehmann, voucher number BHCB64921, deposited at the herbarium of Universidade Federal de Minas Gerais (Brazil). 2 Uses in traditional medicine: SL is popularly employed in some areas of Brazil for type II diabetes management. It has been reported that it enhances satiety and decreases or even suppresses daily insulin requirement and lowers cholesterol levels (Dall’Agnol and Von Poser, 2000), however no study has confirmed its anti-diabetic activity. 3 Previously isolated classes of constituents: The powder of unripe fruits is commercialised and a phytochemical analysis performed by Dall’Agnol and Von Poser (2000) revealed polysaccharides and two major glycoalkaloids (solamargine and solasonine; Motidome et al., 1970; Schwarz et al., 2005a) among other compounds. 0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2006.02.017
2.3. Experimental protocol The animals were divided into four groups of six animals each. Diabetic animals received alloxan monohydrate (150 mg/kg, i.p.). They were deprived of food for 24 h before induction of diabetes. After 1 week, rats with marked hyperglycemia (fasting blood glucose range of 220–260 mg/100 ml) were used. One group (D) was composed of those diabetic animals (receiving 1 ml saline/day by gastric intubation). Another group of diabetic animals (D + E) received 1 ml of the extract (1000 mg/kg/day) by gastric intubation for 2 weeks. The last group of diabetics animals (D + E + exercise) received the extract
A.C. Perez et al. / Journal of Ethnopharmacology 106 (2006) 442–444
as above and also performed exercise on a rodent treadmill for a 2-week period during which the intensity of the exercise was gradually increased to 27 m/min, 0% grade for 1 h/day (Perez et al., 2002). The control group received 1 ml saline solution per day by gastric intubation. Another group of normal rats received the extract (1000 mg/kg/day by gastric intubation) for 1 week (control + E). 2.4. Experimental analysis (blood and stomach) Blood samples were collected from the tail vein before feeding the plant extracts and 2 and 8 h after. The blood glucose level was determined by using electronic glucometer (Boheringer Mannheim), haemoglobin determination was carried out automatically by means of a Coulter Counter. Nitrate concentrations (NO metabolite) in plasma were measured by an enzymatic method using nitrate reductase from Aspergillus species, as previously described (Perez et al., 2002). The stomach of each animal was examined for lesions developed in the glandular portion. 2.5. Statistical analysis All data are expressed as means ± S.E. One-way analysis of variance was performed on the variables using the Newman–Keuls test. Differences with a p-value of <0.05 were considered as statistically significant. 3. Results and discussion Per os administration of the extract (1000 mg/kg, daily) caused blood glucose lowering effect (Table 1). Blood samples taken 2 and 8 h after treatment showed that the effect is long lasting and not metabolic. To address the effects of the extract on glycemic levels of normal rats (control + E), glycemia was evaluated three times (days 1, 4 and 7) before, and 2 and 8 h after the administration of the extract. At no time were glycemic levels altered: day 1: 100 ± 4.2, 82.8 ± 4.3, 80.8 ± 3.8 mg/dl (before E, 2 and 8 h, respectively); day 4: 87.6 ± 2.6, 92.3 ± 7.2, 86.5 ± 4.1 mg/dl (before E, 2 and 8 h, respectively); day 7: 89.8 ± 5.1, 110.5 ± 4.2, 96.5 ± 5.9 mg/dl (before E, 2 and 8 h, respectively).
443
The extract did not induce body weight gain or loss and food consumption did not differ among groups and no gastric mucosal lesions were observed. It has been demonstrated that some polysaccharides slow gastric emptying, which in turn may slow the absorption of glucose and other nutrients (Spiller, 1994), however Oliveira et al. (2003) demonstrated that the extract of SL at the same or higher dose did not attenuate the elevation of the glycemia induced by per os administration of glucose in fasted mice. Our results differ from those of Oliveira et al. (2003) although they used a different animal model and a different diabetogenic drug. Marked interspecies differences emphasize the relevance of repair/defense mechanism in beta cell destruction and raise the possibility that such differences may also be present among individuals of the same species (Eizirik et al., 1994). The cytotoxic action of alloxan and streptozotocin (both diabetogenic agents) is mediated by reactive oxygen species (such as NO), however the source of their generation is different. It seems unlikely that alloxan, streptozotocin and NO have a common feature in their toxic action. The lack of NO can facilitate maintenance of glycemic levels (Peschke et al., 2000). In fact our results showed lower NO levels in SL treated groups (Table 1). Reduced activities of superoxide dismutase and catalase in liver and kidney have been observed during diabetes and this may result in a number of deleterious effects due to the accumulation of superoxide radicals and hydrogen peroxide (Prince et al., 1998). The fact that the extract reduced NO levels could involve mechanism related to scavenging activity. Aerobic training increases capillary growth, oxygen delivery to the muscle, fatty acid metabolism and muscle antioxidant capacity, resulting in increased O2 delivery while reducing oxidative stress (Perez et al., 2002). The increase in the number of capillaries associated with resistance training may also increase the clearance of NO metabolites (Perez et al., 2002), however there is no clear synergetic effect when comparing the benefits of SL ingestion and exercise although in those groups NO levels are similar to control. It is also known that aerobic exercise produces a reduction in the number of erythrocytes in the first phase of the exercise due to increased destruction of these blood cells (sports anaemia), but exercise at the same time causes greater erythropoietic activity
Table 1 Mean values ± S.E. for glycemia (mg/dl), nitrate concentration in plasma (M), haemoglobin concentration (g/dl) and haematocrit (%) in normal (control) or diabetics (D) animals treated with Solanum lycocarpum extract (E; 1000 mg/kg/day) or saline (S) after 2 weeks Control + S Glycemia before E or S Glycemia 2 h after E or S Glycemia 8 h after E or S Nitrate Haemoglobin Haematocrit
91.1 80.5 89.3 42.1 16.2 44
± ± ± ± ± ±
7.1 12.1 2.1 3.2 1.2 1
D+S 247.2 230.5 249.0 70.2 11.0 41
D+E ± ± ± ± ± ±
4.2a 10.3a 5.4a 3.1a 0.5a 1a
247.8 92.4 89.1 50.4 15.1 44
D + E + exercise ± ± ± ± ± ±
5.1a 7.1b 5.1b 5.1 0.8 2
One group also performed exercise on a rodent treadmill. a Significant differences (p < 0.05) of each group (n = 6) in comparison with control + S. b Significant differences (p < 0.05) of glycemia before E in comparison with glycemia 2 or 8 h after E within the same group.
253.5 87.4 83.8 50.8 18.5 47
± ± ± ± ± ±
3.2a 5.1b 4.4b 4.3 1.2 1a
444
A.C. Perez et al. / Journal of Ethnopharmacology 106 (2006) 442–444
leading to a response of adaptation with continued exercise which would in turn lead to the number of erythrocytes increasing (Ferrando et al., 1999). Also exercise can cause a lowering of the total plasma volume leading implicity to haemoconcentration, which would explain the tendency to an increase in the haematocrit values (Table 1). Exercise causes a gradual increase in the haematological parameters. The haemoglobin concentration also increases due to the exercise (Table 1). The fruits contain steroidal alkaloids accounting for the antiinflammatory effect (Vieira et al., 2003). As an increased steroid production increase the production of erythropoietin (Ferrando et al., 1999) this could explain increased haematocrit in our results (Table 1). The level of total haemoglobin decreased during diabetes when compared with the corresponding control group. This may be due to the formation of glycosylated haemoglobin (Prince et al., 1998). Administration of SL tends to bring the values near to normal, and may be due to the decreased level of blood glucose. We could see that diabetics animals had a substantial improvement in the maintenance of glycemia and blood parameters. Although diabetes is a very debilitating disease the animals were able to perform the exercise session daily. This could imply in a better quality of life with lesser side effects that are associated with the use of most oral hypoglycaemic drugs. Those studies are important so more potent hypoglycaemic herbs can be selected for their use in medicinal preparations in crude forms either singly or in combinations, however as pointed out by several and important studies it is possible that the alkaloids found in this plant may act as phytoestrogen and cause embryo toxicity (Sa et al., 2000; Peters et al., 2001; Chang et al., 2002; Maruo et al., 2003a,b; Schwarz et al., 2005a,b). Therefore its use in pregnancy should be taken with extremely caution. References Chang, C.V., Felicio, A.C., Reis, J.E.P., Guerra, M.O., Peters, V.M., 2002. Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats. Journal of Ethnopharmacology 81, 265–269. Dall’Agnol, R., Von Poser, G.L., 2000. The use of complex polysacchharides in the management of metabolic diseases: the case of Solanum lycocarpum fruits. Journal of Ethnopharmacology 71, 337–341.
Eizirik, D.L., Pipeleers, D.G., Ling, Z., Welsh, N., Hellerstrom, C., Andersson, A., 1994. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proceedings of the National Academy of Sciences 91, 9253–9256. Ferrando, A., Vila, L., Voces, J.A., Cabral, A.C., Alvarez, A.I., Prieto, J.G., 1999. Effect of ginseng extract on various haematological parameters during aerobic exercise in the rat. Planta Medica 65, 288–290. Maruo, V.M., Soares, M.R., Bernardi, M.M., Spinosa, H.S., 2003a. Embryotoxic effects of Solanum lycocarpum St. Hill fruits consumption during preimplantation and organogenesis in rats. Neurotoxicology and Teratology 25, 627–631. Maruo, V.M., Bernardi, M.M., Spinosa, H.S., 2003b. Toxicological evaluations of long-term consumption of Solanum lycocarpum St. Hill fruits in male and female adult rats. Phytomedicine 10, 48–52. Motidome, M., Leekning, M.E., Gottlieb, O.R., 1970. A qu´ımica das solan´aceas brasileiras. Anais da Academia Brasileira de Ciˆencias 42, 375–376. Oliveira, A.C.P., Endringer, D.C., Ara´ujo, R.J.P., Brand˜ao, M.G.L., Coelho, M.M., 2003. The starch from Solanum lycocarpum St. Hill fruit is not a hypoglycemic agent. Brazilian Journal of Medical and Biological Research 36, 525–530. Perez, A.C., Oliveira, C.C., Prieto, J.G., Ferrando, A., Vila, L., Alvarez, A.I., 2002. Quantitative assessment of nitric oxide in rat skeletal muscle and plasma after exercise. European Journal of Applied Physiology 88, 189–191. Peschke, E., Ebelt, H., Bromme, H.J., Peschke, D., 2000. Classical and new diabetogens—comparison of their effects on isolated rat pancreatic islets in vitro. Cellular and Molecular Life Sciences 57, 158–164. Peters, V.M., Pinheiro, N.L., Reis, J.E.P., Guerra, M.O., 2001. Absence of interceptive effect in rats trated with Solanum lycocarpum (St. Hill). Contraception 63, 53–55. Prince, P.S.M., Menon, V.P., Pari, L., 1998. Hypoglycaemic activity of Syzigium cumini seeds: effect on lipid peroxidation in alloxan diabetic rats. Journal of Ethnopharmacology 61, 1–7. Sa, R.C.S., Vireque, A.A., Reis, J.E., Guerra, M.O., 2000. Evaluation of the toxicity of Solanum lycocarpum in the reproductive system of male mice and rats. Journal of Ethnopharmacology 73, 283–287. Schwarz, A., Felippe, E.C.G., Bernardi, M.M., Spinosa, H.S., 2005a. Impaired female sexual behaviour of rat offsprind exposed to Solanum lycocarpum unripe fruits during gestation and lactation: lack of hormonal and fertility alterations. Pharmacology, Biochemistry and Behavior 81, 928–934. Schwarz, A., Soares, M.R., Florio, J.C., Bernardi, M.M., Spinosa, H.S., 2005b. Rats exposed to Solanum lycocarpum fruit in uterus and during lactation: neurochemical, behavioral and histopathological effects. Neurotoxicology and Teratology 27, 861–870. Spiller, R.C., 1994. Pharmacology of dietary fiber. Pharmacology and Therapeutics 62, 407–427. Vieira, G., Ferreira, P.M., Matos, L.G., Ferreira, E.C., Rodovalho, W., Ferri, P.H., Ferreira, H.D., Costa, E.A., 2003. Anti-inflammatory effect of Solanum lycocarpum fruits. Phytotherapy Research 17, 892–896.
Ethnopharmacological communication
Effect of Solanum lycocarpum St. Hill on various haematological parameters in diabetic rats A.C. Perez ∗ , V. Franca, V.M. Daldegan Jr., I.D.G. Duarte Department of Pharmacology, UFMG (Federal University of Minas Gerais), Brazil Received 6 October 2005; received in revised form 30 January 2006; accepted 26 February 2006 Available online 5 April 2006
Abstract Solanum lycocarpum St. Hill (SL) is commonly used in Brazilian folk medicine. The aim of the present study was to evaluate the validity of the traditional therapeutic indication of SL as hypoglycaemic agent. The extract reduced glycemia to 92.4 mg/dl in alloxan induced diabetic rats (230.5 mg/dl). We also investigated the potential of SL as antioxidant (it reduced in 27% nitrate generation in diabetic animals). Our results also demonstrated that SL is not ulcerogenic and restored haemoglobin and haematocrit to normal values in diabetic animals. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Solanum lycocarpum; Nitric oxide; Hypoglycaemic agent
1. Introduction
2. Material and methods
Solanum lycocarpum St. Hill (SL) commonly known as “Lobeira” is a medicinal plant specie growing in the Brazilian savana.1,2,3 The species is widely employed as an hypoglycaemic agent. As non-insulin dependent diabetes is much more common than type I, affecting usually elderly and/or overweight people leading to many other health problems, the objective of the present study was to determine the effects of SL on various haematological parameters after diabetes induction.
2.1. Plant preparation The fruit from the plant was sliced and put in a microwave oven to dry. Then the fruits were grounded in a mill and protected against humidity and luminosity (Maruo et al., 2003a). 2.2. Animals Male wistar rats weighing 200 ± 40 g obtained from UFMG, Brazil were used and were allowed free access to water and food before and during the experiment.
∗
Corresponding author. Tel.: +55 31 3499 2721. E-mail address: [email protected] (A.C. Perez). 1 Plant: Unripe fruits of Solanum lycocarpum St. Hill (SL; Solanaceae) were collected in December from the region of Minas Gerais, Brazil and authenticated by J.R. Stehmann, voucher number BHCB64921, deposited at the herbarium of Universidade Federal de Minas Gerais (Brazil). 2 Uses in traditional medicine: SL is popularly employed in some areas of Brazil for type II diabetes management. It has been reported that it enhances satiety and decreases or even suppresses daily insulin requirement and lowers cholesterol levels (Dall’Agnol and Von Poser, 2000), however no study has confirmed its anti-diabetic activity. 3 Previously isolated classes of constituents: The powder of unripe fruits is commercialised and a phytochemical analysis performed by Dall’Agnol and Von Poser (2000) revealed polysaccharides and two major glycoalkaloids (solamargine and solasonine; Motidome et al., 1970; Schwarz et al., 2005a) among other compounds. 0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2006.02.017
2.3. Experimental protocol The animals were divided into four groups of six animals each. Diabetic animals received alloxan monohydrate (150 mg/kg, i.p.). They were deprived of food for 24 h before induction of diabetes. After 1 week, rats with marked hyperglycemia (fasting blood glucose range of 220–260 mg/100 ml) were used. One group (D) was composed of those diabetic animals (receiving 1 ml saline/day by gastric intubation). Another group of diabetic animals (D + E) received 1 ml of the extract (1000 mg/kg/day) by gastric intubation for 2 weeks. The last group of diabetics animals (D + E + exercise) received the extract
A.C. Perez et al. / Journal of Ethnopharmacology 106 (2006) 442–444
as above and also performed exercise on a rodent treadmill for a 2-week period during which the intensity of the exercise was gradually increased to 27 m/min, 0% grade for 1 h/day (Perez et al., 2002). The control group received 1 ml saline solution per day by gastric intubation. Another group of normal rats received the extract (1000 mg/kg/day by gastric intubation) for 1 week (control + E). 2.4. Experimental analysis (blood and stomach) Blood samples were collected from the tail vein before feeding the plant extracts and 2 and 8 h after. The blood glucose level was determined by using electronic glucometer (Boheringer Mannheim), haemoglobin determination was carried out automatically by means of a Coulter Counter. Nitrate concentrations (NO metabolite) in plasma were measured by an enzymatic method using nitrate reductase from Aspergillus species, as previously described (Perez et al., 2002). The stomach of each animal was examined for lesions developed in the glandular portion. 2.5. Statistical analysis All data are expressed as means ± S.E. One-way analysis of variance was performed on the variables using the Newman–Keuls test. Differences with a p-value of <0.05 were considered as statistically significant. 3. Results and discussion Per os administration of the extract (1000 mg/kg, daily) caused blood glucose lowering effect (Table 1). Blood samples taken 2 and 8 h after treatment showed that the effect is long lasting and not metabolic. To address the effects of the extract on glycemic levels of normal rats (control + E), glycemia was evaluated three times (days 1, 4 and 7) before, and 2 and 8 h after the administration of the extract. At no time were glycemic levels altered: day 1: 100 ± 4.2, 82.8 ± 4.3, 80.8 ± 3.8 mg/dl (before E, 2 and 8 h, respectively); day 4: 87.6 ± 2.6, 92.3 ± 7.2, 86.5 ± 4.1 mg/dl (before E, 2 and 8 h, respectively); day 7: 89.8 ± 5.1, 110.5 ± 4.2, 96.5 ± 5.9 mg/dl (before E, 2 and 8 h, respectively).
443
The extract did not induce body weight gain or loss and food consumption did not differ among groups and no gastric mucosal lesions were observed. It has been demonstrated that some polysaccharides slow gastric emptying, which in turn may slow the absorption of glucose and other nutrients (Spiller, 1994), however Oliveira et al. (2003) demonstrated that the extract of SL at the same or higher dose did not attenuate the elevation of the glycemia induced by per os administration of glucose in fasted mice. Our results differ from those of Oliveira et al. (2003) although they used a different animal model and a different diabetogenic drug. Marked interspecies differences emphasize the relevance of repair/defense mechanism in beta cell destruction and raise the possibility that such differences may also be present among individuals of the same species (Eizirik et al., 1994). The cytotoxic action of alloxan and streptozotocin (both diabetogenic agents) is mediated by reactive oxygen species (such as NO), however the source of their generation is different. It seems unlikely that alloxan, streptozotocin and NO have a common feature in their toxic action. The lack of NO can facilitate maintenance of glycemic levels (Peschke et al., 2000). In fact our results showed lower NO levels in SL treated groups (Table 1). Reduced activities of superoxide dismutase and catalase in liver and kidney have been observed during diabetes and this may result in a number of deleterious effects due to the accumulation of superoxide radicals and hydrogen peroxide (Prince et al., 1998). The fact that the extract reduced NO levels could involve mechanism related to scavenging activity. Aerobic training increases capillary growth, oxygen delivery to the muscle, fatty acid metabolism and muscle antioxidant capacity, resulting in increased O2 delivery while reducing oxidative stress (Perez et al., 2002). The increase in the number of capillaries associated with resistance training may also increase the clearance of NO metabolites (Perez et al., 2002), however there is no clear synergetic effect when comparing the benefits of SL ingestion and exercise although in those groups NO levels are similar to control. It is also known that aerobic exercise produces a reduction in the number of erythrocytes in the first phase of the exercise due to increased destruction of these blood cells (sports anaemia), but exercise at the same time causes greater erythropoietic activity
Table 1 Mean values ± S.E. for glycemia (mg/dl), nitrate concentration in plasma (M), haemoglobin concentration (g/dl) and haematocrit (%) in normal (control) or diabetics (D) animals treated with Solanum lycocarpum extract (E; 1000 mg/kg/day) or saline (S) after 2 weeks Control + S Glycemia before E or S Glycemia 2 h after E or S Glycemia 8 h after E or S Nitrate Haemoglobin Haematocrit
91.1 80.5 89.3 42.1 16.2 44
± ± ± ± ± ±
7.1 12.1 2.1 3.2 1.2 1
D+S 247.2 230.5 249.0 70.2 11.0 41
D+E ± ± ± ± ± ±
4.2a 10.3a 5.4a 3.1a 0.5a 1a
247.8 92.4 89.1 50.4 15.1 44
D + E + exercise ± ± ± ± ± ±
5.1a 7.1b 5.1b 5.1 0.8 2
One group also performed exercise on a rodent treadmill. a Significant differences (p < 0.05) of each group (n = 6) in comparison with control + S. b Significant differences (p < 0.05) of glycemia before E in comparison with glycemia 2 or 8 h after E within the same group.
253.5 87.4 83.8 50.8 18.5 47
± ± ± ± ± ±
3.2a 5.1b 4.4b 4.3 1.2 1a
444
A.C. Perez et al. / Journal of Ethnopharmacology 106 (2006) 442–444
leading to a response of adaptation with continued exercise which would in turn lead to the number of erythrocytes increasing (Ferrando et al., 1999). Also exercise can cause a lowering of the total plasma volume leading implicity to haemoconcentration, which would explain the tendency to an increase in the haematocrit values (Table 1). Exercise causes a gradual increase in the haematological parameters. The haemoglobin concentration also increases due to the exercise (Table 1). The fruits contain steroidal alkaloids accounting for the antiinflammatory effect (Vieira et al., 2003). As an increased steroid production increase the production of erythropoietin (Ferrando et al., 1999) this could explain increased haematocrit in our results (Table 1). The level of total haemoglobin decreased during diabetes when compared with the corresponding control group. This may be due to the formation of glycosylated haemoglobin (Prince et al., 1998). Administration of SL tends to bring the values near to normal, and may be due to the decreased level of blood glucose. We could see that diabetics animals had a substantial improvement in the maintenance of glycemia and blood parameters. Although diabetes is a very debilitating disease the animals were able to perform the exercise session daily. This could imply in a better quality of life with lesser side effects that are associated with the use of most oral hypoglycaemic drugs. Those studies are important so more potent hypoglycaemic herbs can be selected for their use in medicinal preparations in crude forms either singly or in combinations, however as pointed out by several and important studies it is possible that the alkaloids found in this plant may act as phytoestrogen and cause embryo toxicity (Sa et al., 2000; Peters et al., 2001; Chang et al., 2002; Maruo et al., 2003a,b; Schwarz et al., 2005a,b). Therefore its use in pregnancy should be taken with extremely caution. References Chang, C.V., Felicio, A.C., Reis, J.E.P., Guerra, M.O., Peters, V.M., 2002. Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats. Journal of Ethnopharmacology 81, 265–269. Dall’Agnol, R., Von Poser, G.L., 2000. The use of complex polysacchharides in the management of metabolic diseases: the case of Solanum lycocarpum fruits. Journal of Ethnopharmacology 71, 337–341.
Eizirik, D.L., Pipeleers, D.G., Ling, Z., Welsh, N., Hellerstrom, C., Andersson, A., 1994. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proceedings of the National Academy of Sciences 91, 9253–9256. Ferrando, A., Vila, L., Voces, J.A., Cabral, A.C., Alvarez, A.I., Prieto, J.G., 1999. Effect of ginseng extract on various haematological parameters during aerobic exercise in the rat. Planta Medica 65, 288–290. Maruo, V.M., Soares, M.R., Bernardi, M.M., Spinosa, H.S., 2003a. Embryotoxic effects of Solanum lycocarpum St. Hill fruits consumption during preimplantation and organogenesis in rats. Neurotoxicology and Teratology 25, 627–631. Maruo, V.M., Bernardi, M.M., Spinosa, H.S., 2003b. Toxicological evaluations of long-term consumption of Solanum lycocarpum St. Hill fruits in male and female adult rats. Phytomedicine 10, 48–52. Motidome, M., Leekning, M.E., Gottlieb, O.R., 1970. A qu´ımica das solan´aceas brasileiras. Anais da Academia Brasileira de Ciˆencias 42, 375–376. Oliveira, A.C.P., Endringer, D.C., Ara´ujo, R.J.P., Brand˜ao, M.G.L., Coelho, M.M., 2003. The starch from Solanum lycocarpum St. Hill fruit is not a hypoglycemic agent. Brazilian Journal of Medical and Biological Research 36, 525–530. Perez, A.C., Oliveira, C.C., Prieto, J.G., Ferrando, A., Vila, L., Alvarez, A.I., 2002. Quantitative assessment of nitric oxide in rat skeletal muscle and plasma after exercise. European Journal of Applied Physiology 88, 189–191. Peschke, E., Ebelt, H., Bromme, H.J., Peschke, D., 2000. Classical and new diabetogens—comparison of their effects on isolated rat pancreatic islets in vitro. Cellular and Molecular Life Sciences 57, 158–164. Peters, V.M., Pinheiro, N.L., Reis, J.E.P., Guerra, M.O., 2001. Absence of interceptive effect in rats trated with Solanum lycocarpum (St. Hill). Contraception 63, 53–55. Prince, P.S.M., Menon, V.P., Pari, L., 1998. Hypoglycaemic activity of Syzigium cumini seeds: effect on lipid peroxidation in alloxan diabetic rats. Journal of Ethnopharmacology 61, 1–7. Sa, R.C.S., Vireque, A.A., Reis, J.E., Guerra, M.O., 2000. Evaluation of the toxicity of Solanum lycocarpum in the reproductive system of male mice and rats. Journal of Ethnopharmacology 73, 283–287. Schwarz, A., Felippe, E.C.G., Bernardi, M.M., Spinosa, H.S., 2005a. Impaired female sexual behaviour of rat offsprind exposed to Solanum lycocarpum unripe fruits during gestation and lactation: lack of hormonal and fertility alterations. Pharmacology, Biochemistry and Behavior 81, 928–934. Schwarz, A., Soares, M.R., Florio, J.C., Bernardi, M.M., Spinosa, H.S., 2005b. Rats exposed to Solanum lycocarpum fruit in uterus and during lactation: neurochemical, behavioral and histopathological effects. Neurotoxicology and Teratology 27, 861–870. Spiller, R.C., 1994. Pharmacology of dietary fiber. Pharmacology and Therapeutics 62, 407–427. Vieira, G., Ferreira, P.M., Matos, L.G., Ferreira, E.C., Rodovalho, W., Ferri, P.H., Ferreira, H.D., Costa, E.A., 2003. Anti-inflammatory effect of Solanum lycocarpum fruits. Phytotherapy Research 17, 892–896.