New compounds of Siolmatra brasiliensis and inhibition of in vitro protein glycation damage.

Twenty compounds were isolated from the hydroethanolic extract of the stems of Siolmatra brasiliensis, five flavonoids, two lignans, one glucosyl phytosterol, seven nor-cucurbitacins, one new phenolic derivative named siolmatrin (1) and four new dammarane-type saponins named siolmatrosides II-V (2-5), the structures of the compounds were assigned by means of 1D and 2D NMR experiments and HRESIMS of the natural compounds and some acetyl derivatives. The effects of the crude hydroethanolic extract (SbExt) and the ethyl acetate fraction (SbEtAc) of Siolmatra brasiliensis stems on the formation of advanced glycation end-products (AGEs) were also investigated. In the in vitro model system of protein glycation using bovine serum albumin (BSA) and glucose, addition of SbExt or SbEtAc inhibited the formation of fluorescent AGEs, in parallel to minor levels of fructosamine (SbEtAc) and markers of tyrosine and tryptophan oxidation (SbExt and SbEtAc). Protein crosslinking, which represents changes of late stages of protein glycation, was reduced in the presence of SbExt and SbEtAc. Siolmatra brasiliensis stems seem to be a promising source of compounds having ability to prevent glycoxidation changes, arising as an interesting option to be studied as a complementary therapy for complications of diabetes.

Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: an in vivo mechanism study.

Context Ethnopharmacological studies have demonstrated that plants of the Combretum genus presented antidiabetic activity, including Combretum lanceolatum Pohl ex Eichler (Combretaceae). Objective This study investigated the hepatic mechanisms of action of C. lanceolatum flowers ethanol extract (ClEtOH) related to its antihyperglycaemic effect in streptozotocin-diabetic rats. Materials and methods Male Wistar rats were divided into normal (N) and diabetic control (DC) rats treated with vehicle (water); diabetic rats treated with 500 mg/kg metformin (DMet) or 500 mg/kg ClEtOH (DT500). After 21 d of treatment, hepatic glucose and urea production were investigated through in situ perfused liver with l-glutamine. Changes in the phosphoenolpyruvate carboxykinase (PEPCK) levels and in the activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-signalling intermediates were also investigated. Results Similar to DMet, DT500 rats showed a reduction in the rates of hepatic production of glucose (46%) and urea (22%) in comparison with DC. This reduction was accompanied by a reduction in the PEPCK levels in liver of DT500 (28%) and DMet (43%) when compared with DC. AMPK phosphorylation levels were higher in the liver of DT500 (17%) and DMet (16%) rats. The basal AKT phosphorylation levels were increased in liver of DT500 rats, without differences in the insulin-stimulated AKT phosphorylation and in the insulin receptor levels between DC and DT500 rats. Discussion and conclusion The antidiabetic activity of ClEtOH can be attributed, at least in part, to inhibition of hepatic gluconeogenesis, probably due to the activation of both AMPK and AKT effectors and reduction in the PEPCK levels.

A new dammarane saponin and other triterpenoids from Siolmatra brasiliensis and evaluation of the antidiabetic activity of its extract.

Context Siolmatra brasiliensis (Cogn.) Baill (Cucurbitaceae) is a climbing plant widely used for the treatment of diabetes mellitus symptoms. Objective This work evaluates the antidiabetic activity of an extract of S. brasiliensis in streptozotocin-diabetic rats and promotes the phytochemical investigation to isolate the major compounds of the same extract. Materials and methods Male Wistar rats were divided into normal (N) and diabetic rats (DC) treated with water; diabetic rats treated with 3U insulin (DI) or with 250 (DSb250) or 500 mg/kg (DSb500) of hydroalcoholic extract of the stalks of S. brasiliensis, via oral gavage, for 21 days. Physiological and biochemical parameters classically altered in diabetes were monitored. The triterpenoids were isolated from the ethyl acetate fraction under silica gel column chromatography and Sephadex-LH20 methods and their structures were determined by NMR, HR-ESI-MS and DC analysis. Results When compared with DC, DSb250 rats showed a reduction in the hyperglycemia (DC: 26.46 ± 0.69 versus DSb250: 19.67 ± 1.06 mmol/L) and glycosuria (DC: 43.02 ± 3.19 versus DSb250: 28.46 ± 2.14 mmol/24 h) and increase in hepatic glycogen (DC: 14.44 ± 1.26 versus DSb250: 22.08 ± 4.26 mg/g). Three known cucurbitacins were isolated from a hydroalcoholic extract of S. brasiliensis, i.e., cayaponosides A1, B4, D, and a new dammarane saponin 3-O-ß-d-gentiobiosyl-26-O-ß-d-glucopyranosyl-20-hydroxydammar-24-ene. The structures of these compounds were elucidated by spectral data analysis of the natural products and their acetyl derivatives. Discussion and conclusion The known cucurbitacins and/or the new identified saponin may be related with the antidiabetic activity of S. brasiliensis.

Acute and subchronic antihyperglycemic activities of Bowdichia virgilioides roots in non-diabetic and diabetic rats.

AIM: The present study was undertaken to evaluate the acute and subchronic antihyperglycemic effects of methanolic extract of Bowdichia virgilioides root bark of B. virgilioides in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The extract (100, 250 or 500 mg/kg) was orally administered to male Wistar diabetic (STZ, 42 mg/kg i.v.) and non-diabetic rats into two main protocols: (i) subchronic experiments, where animals were treated for 21 days with B. virgilioides extract and the following parameters were evaluated: Body weight, fluid and food intake (determined daily), urinary glucose and urea (every 3 days) and glycemia (every 5 days). At the end of the experimental period, skeletal muscles (extensor digitorum longus [EDL] and soleus), retroperitoneal and epididymal white adipose tissues were collected and weighed; liver samples were used for the determination of the lipid and glycogen contents; (ii) acute experiments, which evaluated the alterations on fasting and post-prandial glycemia and on glucose tolerance using the oral glucose tolerance test (OGTT). RESULTS: In subchronic experiments, the treatment with B. virgilioides extract did not change any parameter evaluated in diabetic and non-diabetic animals. On fasting and post-prandial glycemia, the extract treatment did not promote changes in the glycemia values in diabetic or non-diabetic animals. In OGTT, the treatment with 500 mg/kg B. virgilioides extract reduced the hyperglycemia peak after a glucose overload, when compared with non-treated diabetic animals, resulting in a lower area under curve. CONCLUSION: The results of our work indicate that B. virgilioides root extract promotes an acute antihyperglycemic effect in STZ-diabetic rats; this effect probably occurs through an inhibition of the intestinal glucose absorption. The continuity of the research is necessary to elucidate these possibilities.

Mechanism of anti-hyperglycemic action of Vatairea macrocarpa (Leguminosae): investigation in peripheral tissues.

AIM OF THE STUDY: Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglycemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle). MATERIAL AND METHODS: Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals. RESULTS: The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. CONCLUSIONS: Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction.

Chemical constituents from leaves of Palicourea coriacea (Rubiaceae).

(E)-methyl-4-hydroxy-3,5-dimethoxycinnamate, (E)-methyl-4-hydroxy-3-methoxycinnamate, (E)-methyl-4-hydroxycinnamate, (Z)-methyl-4-hydroxycinnamate, calycanthine, ursolic acid, 2-hydroxy-3-methylanthraquinone, 4-methoxybenzoic acid, 3,4,5-trimethoxybenzoic acid, methyl 4-hydroxybenzoate and allantoin were isolated from the leaves of Palicourea coriacea (Cham.) K. Schum. The structures were deduced by spectral data analysis and comparison with literature values.

Triterpenos e flavonóides isolados de flores de Laseguea erecta (Apocynaceae) / Triterpenes and flavonoids isolate from the flowers of Laseguea erecta (Apocynaceae)

Das flores de Laseguea erecta isolaram-se o lupeol, ácido ursólico e os flavonóides quercetina (3,5,7,3',4'-pentaidroxiflavona) e 3-O-ß-L-arabinopiranosil quercetina. Esta é o primeiro estudo sobre metabólitos especiais em flores desse gênero. As estruturas foram determinadas através da análise dos dados espectrais de IV, RMN de 1H e 13C (1D e 2D) e comparação com valores registrados na literatura.

From the flowers of Laseguea erecta were isolated the lupeol, ursolic acid, quercetin (3,5,7,3',4'-pentahydroxyflavone) and 3-O-ß-L-arabinopyranosylquercetin. This is the first phytochemical study of this genera flowers'. The structures were established by the IR, 1H and 13C NMR (1D, 2D) spectral data analysis and by comparison with literature data.