Fine needle aspiration cytology: a tool to diagnose cervical and vaginal endometriosis in low-income places.

Regarded as infrequent, vaginal and cervical endometriosis is probably more common than is generally realized. The apparent rarity of the lesion may be ascribed to the limited awareness of its clinical appearance, combined with technical difficulty in obtaining suitable biopsy material for confirmation. Thus, clinical recognition and tissue confirmation become essential. This paper focuses on vaginal and cervical endometriosis, documenting the clinical, macroscopic, cytological and colposcopic findings in 4 cases seen at a single physical vaginal examination. Diagnosis in these patients was facilitated and improved by fine needle aspiration cytology and confirmed by histology. This technique, which is not used for the diagnosis of endometriosis, could be an option in low-income areas.

Gastroprotective effect of Byrsonima sericea DC leaf extract against ethanol-induced gastric injury and its possible mechanisms of action.

Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE) and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg) prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p.), L-NAME (i.p.) or glibenclamide (i.p.), the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.

Anti-inflammatory effect of α,ß-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice.

OBJECTIVE: To evaluate the anti-inflammatory effect of α,ß-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 µg/kg), at 1 h intervals. Mice received α,ß-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. RESULTS: α,ß-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,ß-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. CONCLUSIONS: α,ß-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.

Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models.

Cariniana rubra Miers (Lecythidaceae), popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr) using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (ß-sitosterol, stigmasterol), pentacyclic triterpenes (α- and ß-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-ß-D-glucopyranoside), and triterpenoid saponins (28-ß-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-ß-glucopyranosyl arjunolic acid and 28-O-[α-L-Rhamnopyranosyl-(1→2)-ß-glucopyranosyl]-23- O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.

Anti-inflammatory effect of the ethanolic extract from Bowdichia virgilioides H.B.K stem bark.

Bowdichia virgilioides H.B.K stem bark (Fabaceae), locally known as "sucupira-preta", is a reputed folk-remedy to treat some inflammatory disorders. To validate its traditional claim, the ethanolic extract from B. virgilioides was evaluated in several animal models of inflammation and nociception. The extract at oral doses of 100 to 1000 mg/kg body weight caused a significant inhibition of carrageenan-induced hind paw oedema, suppression of exudate volume and leukocyte immigration in rat pleurisy induced by carrageenan, and reduction of granuloma weights in the model of subcutaneous granulomas promoted by cotton pellets. In addition, the plant extract significantly inhibited the vascular permeability increase induced by intraperitoneal acetic acid. It also showed marked antinociceptive effect in acetic acid-induced writhing test and in the second phase of formalin test in mice. These findings evidence the anti-inflammatory potential of Bowdichia virgilioides bark and supports its traditional use in inflammatory conditions.

Kauren-19-oic acid induces DNA damage followed by apoptosis in human leukemia cells.

This study evaluated the potential cytotoxicity of the natural diterpenoids kauren-19-oic acid (KA), 14-hydroxy-kaurane (1) and xylopic acid (2), and semi-synthetic derivatives of KA (3-5) towards human cancer cell lines (K562, HL60, MDA-MB435 and SF295) and lymphocytes. Mouse erythrocytes were used to verify a possible hemolytic activity Cytotoxicity mechanisms were investigated in HL60 cells. KA showed a moderate antiproliferative effect in MTT assay towards all cancer cells (IC(50), 9.1-14.3 microg ml(-1)). However, KA appeared not selective to cancer cells, since it also inhibited the lymphocytes proliferation (IC(50), 12.6 microg ml(-1)). Unlike KA, compounds 1-5 displayed no cytotoxicity and were also free from antiproliferative and hemolytic effects, suggesting that the exocyclic double bond (C16) unit may be the active pharmacophore of KA cytotoxicity. KA-treated HL60 cells displayed decreased proliferation (5-bromo-2';-deoxyuridine incorporation assay) and topoisomerase I activity (DNA relaxation assay). These assays revealed that KA primarily intercalates with DNA and not with topoisomerase I. Fluorescence microscopy using AO/EB (acridine orange/ethidium bromide) staining indicated that KA can induce both apoptosis and necrosis in HL-60 cell cultures, which corroborate the findings with MTT. From these findings, we conclude that KA, although demonstrating cytotoxic potential, may have a limited or poor therapeutic potential due to lack of selectivity to tumor cells. Further studies on the structure modification of KA and the mechanism of the new derivatives are currently in progress.

(-)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells.

The gastroprotective property of (-)-myrtenol, a monoterpenoid, has been demonstrated previously against acute gastric ulceration induced by ethanol. However, the healing property of (-)-myrtenol in a chronic gastric ulcer model remains to be verified. This study evaluated its healing efficacy and the mechanism involved using the rat model of chronic gastric ulcer induced by serosal injection of 80% acetic acid in vivo, and human gastric adenocarcinoma cells (AGS) in vitro. The results showed that compared to vehicle-treated ulcer controls, oral administration of (-)-myrtenol (50 and 100 mg/kg/day) for 7 days promoted ulcer healing, as indicated by significant decreases in ulcer area and volume. The macroscopic and microscopic findings confirmed the healing potential of (-)-myrtenol. The ulcer healing activity was also associated with significant increases in gastric mucin content, collagen deposition, number of cells with positive marking for proliferating cell nuclear antigen (PCNA), and by changes in the expression of the inflammatory parameters tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and cyclooxygenase (COX)-2, as well as a decrease of metalloproteinases (MMP-9 and MMP-2) activity. Furthermore, in vitro assays using the AGS cultures revealed that (-)-myrtenol favors wound healing activity via stimulation of cell proliferation and migration without altering the cell viability. Taken together, these findings indicate that (-)-myrtenol has gastro-cytoprotective and ulcer healing properties that can be further explored to develop a new therapeutic agent from a natural source for the treatment of gastric ulcer.

Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism.

The gastroprotective effect of DDF (3,6-dimethoxy-6'', 6''-dimethyl-[2'', 3'' : 7,8]-chromeneflavone) from Lonchocarpus araripensis Benth. (Leguminosae) on gastric damage induced by absolute ethanol (96%, 0.2 mL/mouse) and indometacin (30 mg kg(-1), p.o.) in mice was investigated. Intraperitoneally administered DDF at dose levels of 50, 100 and 200 mg kg(-1) markedly reduced the gastric lesions in the ethanol model by 62, 72 and 96%, and in the indometacin model by 34, 70 and 75%, respectively, as compared with misoprostol (50 microg kg(-1), p.o.), the reference compound that caused lesion suppression by 67% in ethanol model and by 72% against indometacin-induced ulceration. The ED50 of DDF in reducing gastric lesions induced by ethanol and indometacin (dose of the DDF that reduced the gastric lesion area by 50% in relation to the control value) was 50.87 and 61.56 mg kg(-1), respectively. Mechanistic studies were carried out at 100 mg kg(-1) DDF using the ethanol model. Compared with N-acetylcysteine (750 mg kg(-1), p.o.), a donor of sulfhydryls, DDF only partially replenished the ethanol-induced depletion of gastric mucosal NP-SH. Pretreatment with TRPV1 antagonist capsazepine (5 mg kg(-1), i.p.) or the non-selective cyclooxygenase inhibitor indometacin (10 mg kg(-1), p.o.) effectively blocked the gastroprotective effect of DDF (100 mg kg(-1)) against ethanol damage. Furthermore, the effect of DDF was significantly reduced in mice pretreated with L-NAME, or glibenclamide, the respective inhibitors of nitric oxide synthase and K+ ATP channel activation. These data provide evidence to show that DDF affords gastroprotection against gastric damage induced by ethanol and indometacin by different and complementary mechanisms, which include involvement of endogenous prostaglandins, nitric oxide release, the activation of TRPV1 receptor or K+ ATP channels, besides a sparing effect on NP-SH reserve.

Dragon's blood from Croton urucurana (Baill.) attenuates visceral nociception in mice.

Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.

Pro-erectile effects of an alkaloidal rich fraction from Aspidosperma ulei root bark in mice.

In recent years, there has been a renewed interest in the search for novel natural substances active against erectile dysfunction. Plants that belong to the genus Aspidosperma (Apocyanaceae) are known to be very rich in indole alkaloids and have an ethnomedical history of use as traditional remedies for erectile dysfunction. This study examined whether the indole alkaloidal rich fraction (F(3-5)) from Aspidosperma ulei Markgr. root bark could manifest penile erection-related behavioral responses (penile erection, erection-like and genital grooming) in mice. Intraperitoneal injection of F(3-5) (25 and 50mg/kg) elicited all the three different behavioral responses in a manner similar to yohimbine (2mg/kg, i.p.), a known indole alkaloid. Seventy-five percent of mice treated with yohimbine or F(3-5) showed penile erections, which were completely blocked by clonidine, an alpha-2-adrenoceptor agonist and haloperidol, a dopaminergic antagonist and as well as by l-NAME, a nitric oxide synthase inhibitor. These results point out that F(3-5) facilitates penile erection in mice possibly through the activation of central dopamine and blockade of presynaptic alpha-2 adrenoceptors with a subsequent enhancement in nitric oxide release from the penile nerves and arteries. This study further supports the traditional use of extracts from Aspidosperma species in erectile dysfunction.

Attenuation of capsaicin-induced acute and visceral nociceptive pain by alpha- and beta-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice.

The triterpene mixture, alpha- and beta-amyrin, isolated from Protium heptaphyllum resin was evaluated on capsaicin-evoked nociception in mice. Orally administered alpha- and beta-amyrin (3 to 100 mg/kg) significantly suppressed the nociceptive behaviors--evoked by either subplantar (1.6 microg) or intracolonic (149 microg) application of capsaicin. The antinociception produced by alpha- and beta-amyrin against subplantar capsaicin-induced paw-licking behavior was neither potentiated nor attenuated by ruthenium red (1.5 mg/kg, s.c.), a non-specific antagonist of vanilloid receptor (TRPV1), but was greatly abolished in animals pretreated with naloxone (2 mg/kg, s.c.), suggesting an opioid mechanism. However, participation of alpha2-adrenoceptor involvement was unlikely since yohimbine (2 mg/kg, i.p.) pretreatment failed to block the antinociceptive effect of alpha- and beta-amyrin in the experimental model of visceral nociception evoked by intracolonic capsaicin. The triterpene mixture (3 to 30 mg/kg, p.o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rota-rod tests, respectively, indicating the absence of sedative or motor abnormality that could account for its antinociception. Nevertheless, alpha- and beta-amyrin could significantly block the capsaicin (10 mg/kg, s.c.)-induced hyperthermic response but not the initial hypothermia. These results suggest that the triterpene mixture, alpha- and beta-amyrin has an analgesia inducing effect, possibly involving vanilloid receptor (TRPV1) and an opioid mechanism.

Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara in rats.

Previous studies have established the gastroprotective, hypoglycemic, and hypolipidemic effects of trans-dehydrocrotonin (t-DCTN), a major diterpene isolated from the Amazon medicinal plant Croton cajucara. This study aims to examine the potential effects of t-DCTN on hemodynamic parameters that include resting arterial blood pressure and heart rate in vivo, and on left atrial force, spontaneous beating atria, and aortic rings of rats in vitro. Intravenous bolus injections of t-DCTN (5, 10, or 15 mg/kg) to urethane anesthetized normotensive rats reduced the mean arterial pressure and heart rate in a dose-dependent manner. The hypotensive effect of t-DCTN (10 mg/kg) appears not mediated through effects on the muscarinic cholinergic receptor, beta-adrenoceptor, or ganglionic blockade, for it was not affected by atropine, propranolol, or hexamethonium but was abolished by N(w)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. The diterpene t-DCTN showed no significant influence on inotropism. In isolated rat aortic rings with intact or denuded endothelium, t-DCTN relaxed the tonic contraction induced by phenylephrine (1 microM). Its vasorelaxant effect seen at smaller concentrations in endothelium intact preparations was, however, abolished in endothelium denuded or in l-NAME treated tissues. These data indicate the hypotensive and bradycardia effects of t-DCTN, possibly related in part to the release of nitric oxide and in part to direct effects on vascular smooth muscle, and cardiac pacemaker activity.

In vitro antifungal activity of dragon's blood from Croton urucurana against dermatophytes.

Based on ethnobotanical approach, the dragon's blood collected from Croton urucurana Baill. bark (Euphorbiaceae) was tested for antifungal activity against five dermatophytes by paper disk diffusion method. The minimal inhibitory concentration (MIC) showing no visible fungal growth was also determined, using tube dilution technique. The test dermatophytes were Tricophyton tonsurans, Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Epidermophyton floccossum. The dragon's blood (0.175-3.0 mg/ml) exhibited an inhibition zone range of 7.6-26.9 mm against all the tested fungi with minimal inhibitory concentrations of 1.25-2.5 mg/ml.

Pentacyclic triterpenoids, alpha,beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.

In the search for natural compounds useful against pruritus, alpha,beta-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant Protium heptaphyllum were examined on scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with alpha,beta-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with alpha,beta-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with alpha,beta-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, alpha,beta-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of alpha,beta-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.

Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: role of endogenous opioids, K(ATP)-channels and adenosine.

This study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100 mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30 mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with L-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of K(ATP) channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10-100 mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, K(ATP)-channels and adenosine receptors.

Mangiferin ameliorates 6-hydroxydopamine-induced cytotoxicity and oxidative stress in ketamine model of schizophrenia.

BACKGROUND: Accumulating evidence indicates that mangiferin (MGF), a natural xanthone, by virtue of its antioxidant and antiinflammatory properties is neuroprotective. Here we sought to verify the cytoprotective role of MGF on cultured rat primary mesencephalic cells exposed to 6-hydroxydopamine (6-OHDA) in vitro, and the MGFs anti-inflammatory potential in mouse model of ketamine-induced schizophrenia in vivo. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay was performed tomeasure cell viability inmesencephalic cell cultures exposed to neurotoxin (6-OHDA, 40 µM). Schizophrenia was induced in mice by ketamine (50 mg/kg, ip, twice a day, for 7 days). The treatment effects of MGF (50 mg/kg, po, for 7 days) were verified on locomotor behavioral changes in open-field test, and on the oxidant stress-related increase in lipid-peroxidation (malondialdehyde) and interleukin-6 (IL-6) levels in brain tissues. RESULTS: MGF (10-100 µM) produced no per se effect on cell viability as measured by MTT assay, but significantly prevented the 6-OHDA-induced cell death in a concentration-dependent manner. Acridine orange/ethidium bromide (AO/EtBr) staining confirmed the absence of 6-OHDA-induced morphological changes characteristic of apoptosis/necrosis. In open-field test, ketamine-induced impaired locomotor activity and behavioral changes such as grooming and stereotyped but not rearing were effectively ameliorated by MGF pretreatment. Also, ketamine-associated increase in brain tissue levels of IL-6 and MDA were significantly lowered in MGF-pretreated mice. CONCLUSION: Mangiferin has a neurocytoprotective role related, at least in part, to an antioxidant and anti-inflammatory mechanism, which could be explored for more effective therapies of schizophrenia and other neurodegenerative diseases.

Ursolic acid, a pentacyclic triterpene from Sambucus australis, prevents abdominal adiposity in mice fed a high-fat diet.

Currently, there is renewed interest in plant-based medicines and functional foods for the prevention and cure of obesity and its associated risk of cardiovascular disease and metabolic syndrome. In the search for potential anti-obesity compounds from natural sources, the effects of ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, was evaluated for its effects on blood glucose, lipids, and abdominal fat deposition in mice fed a high-fat diet (HFD). Adult male Swiss mice treated or not with UA (0.05%, 50 mg/L, in drinking water) were fed HFD for 15 weeks. A sibutramine (SIB)-treated group (0.05% in drinking water) was included as the positive control. Weekly body weights and food and water consumption were measured, and at the end of the study period, the levels of blood glucose and lipids, the plasma hormones insulin, ghrelin, and leptin, and the abdominal fat accumulation were analyzed. Mice treated with UA and fed HFD showed significantly (P<.05) decreased body weights, visceral adiposity, and levels of blood glucose and plasma lipids relative to their respective controls not fed UA. Also, a significant increase was observed in plasma leptin with a decrease in ghrelin, as well as of amylase and lipase activities. The SIB-treated group also manifested effects similar to those of UA except for the blood glucose level, which was not different from the HFD control. These findings suggest that UA ameliorates abdominal adiposity and decreases the levels of blood glucose and plasma lipids in mice and thus manifests an anti-obesity potential through absorptive and metabolic targets.

Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa.

Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2-200 µmol l⁻¹), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 µmol l⁻¹) or a high concentration of K(+) (60 mmol l⁻¹) in vitro. In addition to SEC's effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1-100 mmol l⁻¹) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-ω-nitro-l-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-(1, 2, 4)oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias.

Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet.

Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p<0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.

Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice.

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.