Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell proliferation in gastric mucosa during the healing process.

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.

Anticholinesterasic activity of endosulfan in Wistar rats.

The in vivo and in vitro effects of the pesticide endosulfan on the cholinesterase (ChE) activity were investigated in rats. ChE activity decreased in dams and in male pups within 65 days corresponding to 35% and 32% of inhibition respectively in the higher endosulfan dose (1.5 mg/kg). In vitro, the enzyme activity was found to be inhibited in a concentration dependent manner. The results suggest that endosulfan is able to inhibit the ChE activity and to cross the placental barrier and/or to be eliminated through milk affecting the enzyme activity in male rat pups.

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb.

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30-1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H+, K+-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H+, K+, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.

Mikania laevigata syrup does not induce side effects on reproductive system of male Wistar rats.

Mikania laevigata (Asteraceae) is a native plant from South America and popularly used as antispasmodic and to treat respiratory diseases. Coumarin is the major chemical substance found in this plant, which have been shown to have antifertility activity in female rats. This study evaluates the toxicity of the exposure to the Mikania laevigata syrup using coumarin as chemical marker on reproductive endpoints in male Wistar rats. Endpoints including reproductive organs weight, sperm and spermatids numbers and sperm morphology were evaluated. Animals were treated daily with Mikania laevigata syrup (3.5; 7.0 and 14.0mg/kg of coumarin) during 90 days by oral gavage. No alterations were observed in body and organ weights, sperm and spermatids numbers as well as sperm morphology of the male rats after the exposure to the Mikania laevigata syrup. Results therefore suggest absence of male reproductive toxicity of the Mikania laevigata syrup at tested doses.

Flavonoid-rich fraction of Maytenus ilicifolia Mart. ex. Reiss protects the gastric mucosa of rodents through inhibition of both H+,K+ -ATPase activity and formation of nitric oxide.

Maytenus ilicifolia Mart. ex. Reissek (Celastraceae), a medicinal plant known in Brazil as "espinheira-santa" is commonly used to treat gastric disorders. The effect of the flavonoid-rich fraction separated from the leaves was evaluated for its gastroprotective properties and the mechanism(s) involved in this activity. Intraperitoneal administration of the flavonoid-rich fraction potently protected rats from experimentally induced chronic (ED(50)=79 mg/kg) and acute gastric lesions by ethanol (ED(50)=25mg/kg) and indomethacin (ED(50)=4 mg/kg) without altering the decreased amount of cytoprotective glutathione and mucus amount in the injured gastric mucosa. A potent reduction of gastric acid hypersecretion (ED(50)=7 mg/kg, i.p.) was accompanied by a reduction of nitric oxide release (ED(50)=1.6 mg/kg, i.p.) in the gastric secretion of 2h pylorus ligated rats which suggests an important role for nitric oxide-dependent mechanisms. Inhibition of gastric acid secretion in vivo was correlated with the in vitro inhibition of rabbit gastric H(+),K(+)-ATPase activity (IC(50)=41 microg/mL). Chemical investigation of the fraction showed galactitol (25%), epicatechin (3.1%) and catechin (2%) as the majoritary components. Collectively, the results show that the flavonoid-rich fraction of Maytenus ilicifolia potently protects animals from gastric lesions with high potency through inhibition of gastric acid secretion.

In vivo assessment of safety and mechanisms underlying in vitro relaxation induced by Mikania laevigata Schultz Bip. ex Baker in the rat trachea.

Mikania laevigata, popularly known in Brazil as "guaco", is largely used in folk medicine against respiratory diseases. However, neither the assessment of the toxicity of "guaco" syrup (GS, used by humans) nor its efficacy or mechanisms of action has been properly investigated. Using in vitro procedures, we showed that the hydroalcoholic extract (HE) from Mikania laevigata induces a concentration-dependent relaxation of rat trachea which does not depend on epithelium-derived substances but involves changes in the cellular mobilization of calcium, perhaps due to a direct effect on membrane potassium channels. In addition, we assessed both oral and intraperitoneal acute toxicity, as well as the oral subchronic and chronic toxicity of GS containing controlled amounts of coumarin, the main biological marker of Mikania laevigata preparations used in humans. The calculated LD(50) of GS after intraperitoneal administration was 0.904 g/kg in mice (both sexes) and 0.967 and 0.548 g/kg in male and female rats, respectively. However, the LD(50) values of GS by the oral route were calculated to be up to 10 g/kg, in both male and female mice and rats. Repeated dose 28- or 90-day oral treatment with GS (75, 150 and 300 mg/kg) did not produce any disturbances in the hematological or biochemical parameters of either male or female rats, nor did it provide evidence of toxicity in the hepatic, renal or pancreatic systems. Besides the mechanistic findings, our results provide evidence of the safety of Mikania laevigata in rodents, even after subchronic and chronic administration, at least in relation to the evaluated parameters.

Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats.

Achillea millefolium L. (Asteraceae), popularly known as yarrow, has been used in folk medicine to treat complaints such as inflammation, pain, wounds, hemorrhages and gastrointestinal disturbances. The aim of the present study was to assess the safety and efficacy of the aqueous extract (AE) of the plant after chronic exposure. Indeed, the AE was effective in protecting the gastric mucosa against acute gastric lesions induced by ethanol and indomethacin and in healing chronic gastric lesions induced by acetic acid with (ED(50)=32 mg/kg, p.o.). Safety studies were performed in female and male Wistar rats treated daily with AE (0.3-1.2 g/kg, p.o./day) or vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive days. Satellite groups consisted of animals sacrificed 30 days after the end of these treatments. Clinical observations, body and organ weight measurements, gross autopsy, hematology, clinical biochemical and histopathological examinations were performed. Slight changes in liver weight, cholesterol, HDL-cholesterol and glucose were observed in male and female animals. These changes were not correlated with dose or time of exposure of the animals to the AE. Overall, the results show the antiulcer potential of the aerial parts of the Achillea millefolium which is accompanied by no signs of relevant toxicity even at very long chronic exposure.

Modulation of antioxidant systems by subchronic exposure to the aqueous extract of leaves from Achillea millefolium L. in rats.

We determined the effects of subchronic exposure to aqueous extract of leaves from Achillea millefolium (AE) on enzyme- and non-enzyme-dependent antioxidant systems in rats. Seven days treatment with AE (1 g/kg/twice a day, p.o.) altered the reduced glutathione (GSH) levels and antioxidant enzyme activities in several organs of the animals. Amount of GSH in uterus was increased (73%) while in kidneys it was decreased (23%). Besides, NAD(P)H quinone oxidoreductase 1 (NQO1) activity was increased in forestomach (26%) and in liver (64%), while glutathione S-transferase activity was decreased in the forestomach (32%) and increased in the liver (41%), kidney (35%) and uterus (37%). In preliminary experiments targeting the interaction of AE with acetaminophen (600 mg/kg, p.o.), we observed augmentation of acetaminophen-induced increase of the plasmatic alanine aminotransaminase, aspartate aminotransaminase and lactate dehydrogenase. Overall, the results indicate a potential toxic interaction of AE compounds with xenobiotics that use the glutathione pathway.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats.

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NOx levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach.

Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats. MATERIALS AND METHODS: Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H(+),K(+)-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats. RESULTS: In the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684g/kg, respectively. The DFPT (ED50=29mg/kg, p.o.) and piplartine (4.5mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro, the DFPT and piplartine inhibited the H(+),K(+)-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin. CONCLUSIONS: These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.

Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.

Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro. RESULTS: HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ. CONCLUSION: Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.

Endothelium-dependent and independent vasorelaxation induced by an n-butanolic fraction of bark of Scutia buxifolia Reiss (Rhamanaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia has been widely used in Brazilian folk medicine as an anti-hypertensive agent. We evaluated the vascular effects and mechanism involved in the relaxation of aorta induced by an n-butanolic fraction (BuOH) from Scutia buxifolia. MATERIALS AND METHODS: Rat aortic rings precontracted by phenylephrine (1 µM) were exposed to cumulative concentrations (3­3000 µg/ml) of crude extracts or fractions obtained from bark or leaves of Scutia buxifolia. Classical receptor antagonists, channel and enzymatic inhibitors were used to check the mechanisms involved. RESULTS: The crude extracts of both leaves and bark of Scutia buxifolia, as well as several fractions, were able to induce partial or total relaxation of rat aortic rings. The BuOH fraction of bark of Scutia buxifolia was the most potent in endothelium-intact (E+) preparations, and also induced a partial, but very significant relaxation in endothelium-denuded (E−) vessels. The non-selective nitric oxide synthase inhibitor L-NAME, as well as the soluble guanylate cyclase inhibitor ODQ, vanished the relaxation in E+. In E− preparations, K+ channel blockers, such as tetraethylammonium, glibenclamide, 4-aminopyridine, and the large-conductance calcium-activated K+ channel blocker iberiotoxin, were able to significantly reduce the maximum relaxation elicited by BuOH fraction. CONCLUSION: Our results demonstrated that BuOH fraction obtained from barks of Scutia buxifolia induced both endothelium-dependent and -independent relaxation in rat aortic rings. The endothelium-dependent relaxation is fully dependent on NO/cGMP system, while direct activation of K+ channels may explain, at least in part, the endothelium-independent relaxation induced by BuOH fraction of Scutia buxifolia.

Antinociception of ß-D-glucan from Pleurotus pulmonarius is possibly related to protein kinase C inhibition.

ß-D-Glucan, a polysaccharide isolated from an edible mushroom Pleurotus pulmonarius (Fr.) Quel., presented antinociceptive activity in mice. This study evaluated the involvement of transient receptor potential (TRP) channels and protein kinase C (PKC) on antinociceptive effect of a (1→3),(1→6)-linked ß-D-glucan (GL) in mice. Intraperitoneal administration of GL potently inhibited nociceptive responses induced by intraplantar injections of capsaicin, cinnamaldehyde, menthol, acidified saline and phorbol myristate acetate (PMA). Moreover, Western blot analysis revealed that GL treatment also prevented PMA-induced PKCɛ activation. Collectively, present results demonstrate that GL could constitute an attractive molecule of interest for the development of new analgesic drugs.

Hypotensive mechanism of the extracts and artemetin isolated from Achillea millefolium L. (Asteraceae) in rats.

Traditional uses of Achillea millefolium L. (Asteraceae) include the treatment of cardiovascular diseases. In the present study, we used anesthetized rats to assess the hypotensive effect of a hydroethanolic extract (HEAM), and its dichloromethane (DCM), ethyl acetate (EA), butanolic (BT), and dichloromethane-2 (DCM-2) fractions, besides the flavonoid artemetin, isolated from A. millefolium. The oral administration of HEAM (100-300 mg/kg), DCM (20mg/kg), DCM-2 (10-30 mg/kg), but not EA (10 mg/kg) and BT (50 mg/kg) fractions significantly reduced the mean arterial pressure (MAP) of normotensive rats. The phytochemical analysis by NMR (1)H of DCM and DCM-2 fractions revealed high amounts of artemetin, that was isolated and administered by either oral (1.5 mg/kg) or intravenous (0.15-1.5 mg/kg) routes in rats. This flavonoid was able to dose-dependently reduce the MAP, up to 11.47 ± 1.5 mmHg (1.5 mg/kg, i.v.). To investigate if artemetin-induced hypotension was related to angiotensin-converting enzyme inhibition, we evaluated the influence of this flavonoid on the vascular effects of both angiotensin I and bradykinin. Intravenous injection of artemetin (0.75 mg/kg) significantly reduced the hypertensive response to angiotensin I while increased the average length of bradykinin-induced hypotension. Artemetin (1.5 mg/kg, p.o.) was also able to reduce plasma (about 37%) and vascular (up to 63%) ACE activity in vitro, compared to control group. On the other hand, artemetin did not change angiotensin II-induced hypertension. Our study is the first showing the hypotensive effects induced by the extract and fractions obtained from A. millefollium. In addition, our results disclosed that this effect may be, at least in part, associated with high levels of artemetin and its ability to decrease angiotensin II generation in vivo, by ACE inhibition.

Inhibition of gastric H+, K(+)-ATPase activity by compounds from medicinal plants.

H+, K(+)-ATPase enzyme is a therapeutic target for the treatment of gastric disturbances. Several medicinal plants and isolated compounds inhibit the acid gastric secretion through interaction with the proton pump. In order to add new properties to some natural constituents, five compounds, a benzylated derivative of vincoside, a diterpene (abietic acid) and three alkaloids (cephaeline, vinblastine and vindoline), were tested for their activities on gastric H+, K(+)-ATPase isolated from rabbit stomach. All the compounds inhibited H+, K(+)-ATPase activity with varied potency. The IC50 value for benzylvincoside was 121 (50-293) microM, and for abietic acid 177 (148-211) microM. The alkaloids cephaeline, vinblastine and vindoline inhibited the H+, K(+)-ATPase activity with IC50 values of 194, 761 and 846 microM, respectively. The results suggest that benzylvincoside, abietic acid and cephaeline can be important sources for the development of anti-secretor agents.

Diuretic and potassium-sparing effect of isoquercitrin-an active flavonoid of Tropaeolum majus L.

AIM OF THE STUDY: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. MATERIAL AND METHODS: Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100mg/kg) and isoquercitrin (5-10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals. RESULTS: The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+). Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. CONCLUSION: This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.

Vasorelaxant and hypotensive effects of the extract and the isolated flavonoid rutin obtained from Polygala paniculata L.

OBJECTIVES: This study aimed to investigate the in-vitro and in-vivo cardiovascular effects of the crude hydroalcoholic extract from Polygala paniculata (HEPP) in rats. METHODS: The procedures were performed on aortic rings and on normotensive anaesthetized rats. KEY FINDINGS: When tested in endothelium-intact aorta rings, HEPP (30-1000 µg/ml) produced a significant non-concentration-dependent relaxing effect (∼40%), which was completely prevented by incubation with L-NAME (nitric oxide synthase inhibitor), ODQ (soluble guanylate cyclase inhibitor) and partially inhibited by tetraethylammonium (TEA; a non-selective potassium channel blocker) and charybdotoxin (a large- and intermediate-conductance calcium-activated potassium channel blocker). In contrast, atropine (a muscarinic receptor antagonist) or pyrilamine(a histamine H1 receptor antagonist) had no effect. Furthermore, oral administration of HEPP (30-300 mg/kg) in anaesthetized rats caused a dose-dependent and sustained hypotensive action. This effect was unchanged by atropine or TEA, but was strongly reduced in rats continuously infused with L-NAME or methylene blue. Moreover, rutin (1-3 mg/kg) administered by an intravenous route also caused a dose-dependent hypotensive effect in rats. CONCLUSIONS: Our results demonstrated that the extract obtained from P. paniculata induces potent hypotensive and vasorelaxant effects that are dependent on the nitric oxide/guanylate cyclase pathway. These effects could be related, at least in part, to the rutin contents in this extract.

Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: evidence for the inhibition of angiotensin converting enzyme.

AIM OF THE STUDY: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE). METHODS AND METHODS: Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5-4 mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF. RESULTS: The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90 min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats. CONCLUSION: Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE.

Antinociceptive effects of (1→3),(1→6)-linked ß-glucan isolated from Pleurotus pulmonarius in models of acute and neuropathic pain in mice: evidence for a role for glutamatergic receptors and cytokine pathways.

UNLABELLED: The present study evaluated the antinociceptive effect of (1→3),(1→6)-linked ß-glucan (GL) isolated from Pleurotus pulmonarius (Fr.) Quel. in mice and its possible mechanism of action. Intraperitoneal administration of GL inhibited glutamate-induced licking with an ID(50) of 0.34 mg/kg and inhibition of 96% ± 3%. The treatment of animals with GL (1 mg/kg i.p.) inhibited nociception induced by intrathecal injection of N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate and interleukin -1ß in 67% ± 13%, 89% ± 11%, 74% ± 9%, and 75% ± 7%, respectively, but not the nociceptive response induced by (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P, and tumor necrosis factor-α. Moreover, GL (30 mg/kg i.p.) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 2 hours, with inhibition of 47% ± 10% observed 0.5 hours after treatment. When given chronically (twice a day) over 7 days, GL reversed the mechanical allodynia caused by partial sciatic nerve ligation (inhibition of 45% ± 13% to 60% ± 8%). Interestingly, GL did not affect the locomotor activity of mice in an open field test with doses that produce antinociceptive effects. Our findings show that GL inhibits acute and neuropathic pain in mice through mechanisms that involve the inhibition of ionotropic glutamate receptors and the interleukin -1ß pathway. PERSPECTIVE: This article presents the antinociceptive activity of GL in acute and neuropathic pain with participation of ionotropic glutamate receptors and pro-inflammatory cytokines (interleukin-1ß). After further experiments, this compound may represent a new pharmacological agent for the treatment of clinical pain.