The Starch from Solanum Lycocarpum St. Hill. Fruit Is Not a Hypoglycemic Agent

SolanumBrazilian lycocarpumJournal of Medical starch isand not Biological hypoglycemic Research (2003) 36: 525-530 525 ISSN 0100-879X Short Communication The starch from Solanum lycocarpum St. Hill. fruit is not a hypoglycemic agent A.C.P. Oliveira1, Laboratórios de 1Farmacologia and 2Farmacognosia, D.C. Endringer2, Faculdade de Farmácia, Universidade Federal de Minas Gerais, R.J.P. Araújo1, Belo Horizonte, MG, Brasil M.G.L. Brandão2 and M.M. Coelho1 Abstract Correspondence We have investigated the hypoglycemic effect induced by the starch Key words M.M. Coelho obtained from the unripe fruits of Solanum lycocarpum (Solanaceae). · Solanum lycocarpum St. Hill. Laboratório de Farmacologia Per os administration of the starch (1000 or 2000 mg/kg, twice daily · Glycoalkaloids Faculdade de Farmácia, UFMG for 7 days, N = 6) did not change glycemia levels of nondiabetic female · Starch fraction Av. Olegário Maciel, 2360 Swiss mice weighing 25-30 g. In streptozotocin-induced diabetic · Diabetes mellitus 30180-112 Belo Horizonte, MG mice, similar treatment with the starch did not change the elevated · Hypoglycemic effect Brasil glycemia 3 h after the last dose (diabetic treated with saline = 288 ± 17/ Fax: +55-31-3339-7666 E-mail: [email protected] 309 ± 18; starch 1000 mg/kg = 295 ± 33; starch 2000 mg/kg = 258 ± 37; N = 5). In animals fasted for 15 h, per os administration of glucose Research supported by CNPq (600 mg/kg) significantly increased glycemia 1 h later. Previous (-30 (No. 523281/95-1). min) treatment of the animals with the starch (1000 or 2000 mg/kg; N = 5) did not change the increase of glycemia. Per os administration of the starch (1000 or 2000 mg kg-1 day-1, twice daily for 7 days) did not induce body weight gain or loss. The chemical analysis of the starch Received May 25, 2002 Accepted January 6, 2003 indicated the presence of glycoalkaloids, a finding that represents a reason for concern since many of these substances are generally toxic. In interviews with 56 diabetic patients, 29 medicinal plants were reported as useful in their treatment of diabetes and S. lycocarpum was the sixth most frequently mentioned. All patients interviewed reported that they also used insulin or oral hypoglycemic drugs. The results of the present study do not provide evidence for a hypoglycemic effect associated with the polysaccharide fraction of S. lycocarpum in either normal or hyperglycemic mice. These data demonstrate the need for adequate pharmacological investigation of the natural products widely used in folk medicine. Diabetes mellitus represents an impor- frequently treated with drugs that stimulate tant health problem in the world. Patients insulin release or the sensitivity of the tissues with type 1 diabetes are treated with insulin to this hormone, such as sulfonylureas, bi- since the function of pancreatic ß cells is guanides and thiazolidinediones. Despite the practically null. Type 2 diabetes is frequently existence of different forms of insulin and characterized by a reduced production of many oral hypoglycemic drugs, the develop- insulin and also a low sensitivity of the tis- ment of new drugs for the treatment of diabe- sues to this hormone. This form of diabetes is tes mellitus is needed, since its treatment is Braz J Med Biol Res 36(4) 2003 526 A.C.P. Oliveira et al. chronic and represents a high cost for the powder was obtained. The starch was dried patient. Another important aspect is the high at 105ºC for 5 min and stored under refrig- incidence of side effects associated with the eration. use of some oral hypoglycemic drugs. Phen- The starch of S. lycocarpum (500 mg) formin, one representative of the biguanides, was extracted with 6 ml ethanol for 30 min at although commercialized in Brazil, was with- 95ºC, filtered and the solvent evaporated to drawn in many countries during the 1970s dryness under reduced pressure. The residue because of an association with lactic acido- was dissolved in 40 µl of methanol. This sis (1). Troglitazone, the first thiazolidinedi- material was submitted to silica gel thin- one to be synthesized and used in the treat- layer chromatography using chloroform: ment of diabetes mellitus, has been with- methanol (3:2) as a solvent system, followed drawn from the market in the United States by visual detection using Dragendorffs re- because its use was associated with severe agent and 10% sodium nitrite, the latter used hepatic toxicity (2). to intensify the color of the spots. Solasodine The Brazilian flora is one the world rich- (1%) was used as a reference compound. est sources of bioactive material due to its The observed Rfs and the color of the spots biodiversity. Several plants are currently used were used to identify the steroidal alkaloids. in Brazilian traditional medicine to treat dia- Female Swiss mice weighing 25-30 g betes (3-5). The starch obtained from the were used to evaluate the potential hypogly- unripe fruits of Solanum lycocarpum St. Hill. cemic effect of the starch. The animals were (Solanaceae) has been widely used and com- maintained on a 12:12-h light-dark cycle, mercialized as a hypoglycemic agent in Bra- with food and water available ad libitum. zil. Recently, DallAgnol and von Poser (6) The starch suspension was prepared in sa- carried out a chemical analysis of the starch line immediately before the experiments and tried to correlate its supposed hypogly- and administered per os in a volume of 100 cemic activity with the polysaccharide con- µl/25 g. tent. However, these investigators did not Two daily doses (8:00 and 18:00 h) of the conduct any experimental test to directly starch (1000 or 2000 mg/kg) were adminis- demonstrate the hypoglycemic effect attrib- tered for 7 days and glycemia was deter- uted to the starch. As far as we know, no mined 3 h after the last dose. The first dose of studies have evaluated the potential hypogly- the starch was administered at 18:00 h on cemic effect of the starch of S. lycocarpum day 1 and the last dose at 8:00 h on day 7. in experimental animals or the pattern of its Food was removed immediately after the last use by a group of diabetic patients. In the dose. In parallel, on the last day, one exper- present study, we evaluated both aspects. imental group was treated with one dose of Unripe fruits and branches with leaves glibenclamide (Teuto, Anápolis, GO, Bra- and flowers of S. lycocarpum were collected zil; 3 mg/kg, per os) and glycemia was deter- in the State of Minas Gerais, Brazil. The mined 3 h later. plant was identified by J.R. Stehmann (Belo To evaluate the effect of the starch on the Horizonte Ciências Biológicas - BHCB, glycemia of diabetic mice, 200 mg/kg strep- voucher specimen No. BHCB64921). The tozotocin was dissolved in sodium citrate unripe fruits were peeled, cut into small buffer, pH 4.5, and injected intraperitoneal- pieces and submitted to turbolysis in water. ly. In this protocol, the animals were treated The water extract was filtered and kept in a with two daily doses of the starch (1000 or refrigerator for 24 h for starch precipitation. 2000 mg/kg) for 7 days, administered at 8:00 The starch was submitted to successive and 18:00 h, with the first dose administered washings and filtrations until a clear white 4 h after the treatment with streptozotocin. Braz J Med Biol Res 36(4) 2003 Solanum lycocarpum starch is not hypoglycemic 527 The first dose of the starch was administered starch (1000 or 2000 mg/kg, twice daily). at 18:00 h on day 1 and the last dose at 8:00 However, glycemia was significantly reduced h on day 7. Glycemia was determined 3 h after administration of a single dose of gli- after the last dose of the starch. In parallel, benclamide (3 mg/kg, per os) (Figure 1A). on the last day, an experimental group re- We then investigated the effect of the ceived a subcutaneous (sc) injection of hu- starch on the glycemia of streptozotocin- man NPH insulin (Biobrás S.A., Montes induced diabetic mice. As expected, animals Claros, MG, Brazil; 1 U/kg) and glycemia treated with streptozotocin presented elevated was determined 3 h later. glycemia. One week treatment with the starch To evaluate the effect of the starch on the (1000 or 2000 mg/kg, twice daily) did not elevation of glycemia induced by oral ad- significantly reduce the glycemia of the ani- ministration of glucose, mice were fasted for mals. On the other hand, glycemia was sig- 15 h before being treated with glucose (600 nificantly reduced after administration of a mg/kg, per os). The starch suspension was administered 30 min before glucose and gly- Figure 1. Effect of Solanum cemia was determined 3 h later. 150 A lycocarpum starch on the glyce- 123456 mia of nondiabetic and diabetic 123456 The daily food consumption for each 123456 mice, measured 3 h after the 123456 123456 100 123456 * last dose. A, Effect of the starch experimental group and body weight of each 123456 123456 123456 (1000 or 2000 mg/kg, per os, animal treated with the starch for 7 days 123456 123456 twice daily for 7 days) on the 123456 were determined. 123456 123456 glycemia of nondiabetic mice. 50 123456 123456 Glucose (mg/dl) Data are reported as means ± To determine glycemia, the animals were 123456 123456 123456 SEM. One group was treated decapitated and blood was collected into 123456 123456 0 with a single dose of glibencla- tubes containing Na2EDTA:NaF (2:1). Saline Starch Starch Glib mide (Glib; 3 mg/kg, per os) 3 h 1000 2000 3 mg/kg Plasma glucose concentrations were deter- before.

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