Cândida Aparecida Leite Kassuya

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.

Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model

Abstract Objectives Previous studies have shown that essential oil containing (R)-(+)-limonene and α-phellandrene, extracted from fruits of Schinus terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve injury (SNI) model of neuropathic pain in rats. Methods In the present work, essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)-limonene and α-phellandrene compounds, were assayed for their effects on SNI-induced mechanical and cold hyperalgesia, and depressive-like behavior (immobility in forced swim test) in rats. The locomotor activity was evaluated in open-field test. Results Oral administration for up to 15 days of essential oil of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), α-phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. On the 15th day of oral treatment, α-phellandrene, but neither the essential oil from S. terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg) or with compounds (10 mg/kg) did not interfere on locomotor activity. Discussion Together, the results of the present work show that essential oil of S. terebinthifolius and compounds present in this oil, including (R)-(+)-limonene and α-phellandrene, exhibit antihyperalgesic effects against mechanical hyperalgesia, and are antidepressive, while only α-phellandrene inhibited cold hyperalgesia in SNI rats.

Chemical composition and free radical-scavenging, anticancer and anti-inflammatory activities of the essential oil from Ocimum kilimandscharicum.

OBJECTIVE The essential oil from the leaves of Ocimum kilimandscharicum (EOOK), collected in Dourados-MS, was investigated for anticancer, anti-inflammatory and antioxidant activity and chemical composition. MATERIALS AND METHODS The essential oil was extracted by hydrodistillation, and the chemical composition was performed by gas chromatography-mass spectrometry. The essential oil was evaluated for free radical-scavenging activity using the DPPH assay and was tested in an anticancer assay against ten human cancer cell lines. The response parameter (GI50) was calculated for the cell lines tested. The anti-inflammatory activity was evaluated using carrageenan-induced pleurisy in mice. RESULTS The chemical composition showed 45 components with a predominance of monoterpenes, such as camphor (51.81%), 1,8 cineole (20.13%) and limonene (11.23%). The EOOK exhibited potent free radical-scavenging activity by the DPPH assay with a GI50 of 8.31 μg/ml. The major constituents, pure camphor (IC50=12.56 μg/ml) and mixture of the limonene: 1, 8 cineole (IC50=23.25 μg/ml) displayed a potent activity. The oral administration of EOOK (at 30 and 100 mg kg(-1)), as well as the pure camphor or a mixture of 1,8 cineole with limonene, significantly inhibited the carrageenan (Cg) induced pleurisy, reducing the migration of total leukocytes in mice by 82 ± 4% (30 mg kg(-1) of EOOK), 95 ± 4% (100 mg kg(-1) of EOOK), 83 ± 9% (camphor) and 80 ± 5% (mixture of 1,8 cineole:limonene 1:1). In vitro cytotoxicity screening against a human ovarian cancer cell line displayed high selectivity and potent anticancer activity with GI50=31.90 mg ml(-1). This work describes the anti-inflammatory, anticancer and antioxidant effects of EOOK for the first time. CONCLUSIONS The essential oil exhibited marked anti-inflammatory, antioxidant and anticancer effects, an effect that can be attributed the presence of majorital compounds, and the response profiles from chemical composition differed from other oils collected in different locales.

Composition and evaluation of the anti-inflammatory and anticancer activities of the essential oil from Annona sylvatica A. St.-Hil.

The essential oil from the leaves of Annona sylvatica (EOAS) was extracted by hydrodistillation, and the analysis was performed by gas chromatography-mass spectrometry. The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z-caryophyllene, β-maaliene, γ-gurjunene, silphiperfol-5-en-3-ol, ledol, cubecol-1-epi, and muurola-3,5-diene. Oral administration of the EOAS (20 and 200 mg/kg) and subcutaneous injection of dexamethasone (0.5 mg/kg, reference drug) significantly inhibited carrageenan- and complete Freunds adjuvant-induced mouse paw edema. The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration. The EOAS inhibited the growth of human cancer cell lines with GI(50) values in the range of 36.04-45.37 μg/mL on all of the cell lines tested. This work describes for the first time the anti-inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side-effects, the present results may have clinical relevance and open new possibilities for the development of novel anti-inflammatory and anticancer drugs.

Anti-Inflammatory and Antihyperalgesic Activities of Ethanolic Extract and Fruticulin A from Salvia lachnostachys Leaves in Mice.

The anti-inflammatory and analgesic effects of the ethanolic extract (SLEE) and fruticulin A from the leaves of Salvia lachnostachys were evaluated in mice, using experimental models of inflammation (paw oedema and pleurisy induced by carrageenan injection) and hyperalgesia (electronic Von Frey). Oral administration of SLEE (30, 100, and 300 mg/kg) and fruticulin A (0.3 and 3.0 mg/kg) decreased the total leucocytes number in pleural lavage, protein extravasation, and paw oedema. SLEE (100 mg/kg) and fruticulin A (3 mg/kg) also exhibited antihyperalgesic activity in carrageenan induced mechanical hyperalgesia. In addition, fruticulin A (3 mg/kg) prevented mechanical hyperalgesia, inhibiting TNF but not L-DOPA-induced mechanical hyperalgesia. In conclusion, SLEE and fruticulin A display anti-inflammatory and analgesic properties. Therefore, fruticulin A is at least partially responsible for the activity observed in the ethanolic extract of Salvia lachnostachys.

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Aims: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Main methods: Male Swiss mice received gp120, IL‐1&bgr; or TNF‐&agr; intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3 h after the injection. Spinal cord and blood samples were isolated for protein quantification. Key findings: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3 h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3 h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL‐1&bgr; and IL‐10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF‐&agr; and IL‐1&bgr;‐induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4 h after intrathecal IL‐1&bgr; injection. Significance: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL‐1&bgr; and IL‐10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL‐1&bgr; application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF‐&agr; and IL‐1&bgr; emphasizes the anti‐inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.

Antiulcerogenic effect of Croton urucurana Baillon bark.

ETHNOPHARMACOLOGICAL RELEVANCE Croton urucurana (Euphorbiaceae) bark is used to treat gastric ulcers. However, to our knowledge, no study has been conducted to confirm this therapeutic property. AIM OF THE STUDY To evaluate the antiulcerogenic effect and any possible toxic effects of Croton urucurana bark in an induced gastric ulcer model in rats. MATERIALS AND METHODS The preventive and healing properties of Croton urucurana bark methanol extract (CUE) were evaluated in experimental models of acute (ethanol and indomethacin) and chronic (acetic acid) gastric ulcers. The gastric juice and mucous were evaluated using the pylorus ligation model, while the gastroprotective action of sulphydryl compounds and nitric oxide were analysed using the ethanol model. The toxicity was evaluated with acute and subacute toxicity tests. RESULTS No signs of toxicity were observed in the parameters analysed. All of the CUE doses tested (50, 100 and 250mg/kg) significantly reduced the gastric lesions by 70.25, 95.40 and 98.71%, respectively. Treatment with 30mg/kg lansoprazole (positive control) inhibited 82.58% of the gastric lesions. In the indomethacin model, the 50, 100 and 250mg/kg doses of CUE significantly reduced gastric damage by 67.85, 82.50 and 71.01%, respectively, and the positive control, cimetidine (200mg/kg), reduced gastric damage by 91.02%. The CUE (100mg/kg) and cimetidine (200mg/kg) treatments significantly reduced the ulcerative pathology induced by acetic acid, promoting 81.55 and 72.62% healing, respectively. Nitric oxide did not change the cytoprotection generated by CUE. However, the antiulcerogenic activity of CUE appears to involve sulphydryl compounds because CUE activity was inhibited in animals receiving a sulphydryl compound blocker. In addition, CUE exhibited systemic effects, increasing mucous production and decreasing gastric acidity. CONCLUSIONS The present study shows that Croton urucurana bark exerts gastroprotective activity in rats without causing toxicity. This effect appears to involve sulphydryl compounds, increasing mucus production and reducing gastric acidity.

Antinociceptive activity of the ethanolic extract, fractions, and aggregatin D isolated from Sinningia aggregata tubers.

The present study investigated the effects of the ethanolic extract (ESa), fractions, and compounds isolated from Sinningia aggregata in male Swiss mice on carrageenan-induced paw edema, neutrophil migration, mechanical hyperalgesia, formalin-induced nociception, and lipopolysaccharide-induced fever. The ESa did not alter edema, neutrophil migration, or fever at any of the doses tested. However, the ESa reduced phase II of formalin-induced nociception and carrageenan-induced mechanical hyperalgesia. The petroleum ether (PE) and ethyl acetate (EA) fractions and aggregatin D (AgD; isolated from the EA fraction) reduced formalin-induced nociception. Anthraquinones from the PE fraction were ineffective. AgD also inhibited carrageenan-induced mechanical hyperalgesia. Neither the ESa nor AgD altered thermal nociception or motor performance. Local administration of AgD also reduced hyperalgesia induced by carrageenan, bradykinin, tumor necrosis factor-α, interleukin-1β, cytokine-induced neutrophil chemoattractant, prostaglandin E2, and dopamine but not hyperalgesia induced by forskolin or dibutyryl cyclic adenosine monophosphate. The positive control dipyrone reduced the response induced by all of the stimuli. Additionally, glibenclamide abolished the analgesic effect of dipyrone but not the one induced by AgD. AgD did not change lipopolysaccharide-induced nitric oxide production by macrophages or the nociception induced by capsaicin, cinnamaldehyde, acidified saline, or menthol. These results suggest that the ESa has important antinociceptive activity, and this activity results at least partially from the presence of AgD. AgD reduced mechanical hyperalgesia induced by several inflammatory mediators through mechanisms that are different from classic analgesic drugs.

Analgesic effects of the ethanolic extract from Magnolia ovata (Magnoliaceae) trunk bark and of N-acetylxylopine, a semi-synthetic analogue of xylopine

This study investigated the antinociceptive effects of the ethanolic extract (EEMO) obtained from Magnolia ovata (A.St.-Hil.) Spreng and N-acetylxylopine (AXyl), a stable derivative of xylopine in different models of nociception. The EEMO and AXyl inhibited the nociception induced by acetic acid in mice, in a dose-dependent manner with a maximal inhibition of 91 ± 9% and 50 ± 11%, respectively. Oral administration of EEMO or AXyl also significantly inhibited the inflammatory phase of formalin-induced nociception with maximal reduction of 87 ± 3.9% and 71 ± 10%, respectively. Confirming the effectiveness of the extract and the isolated compound in inflammatory responses, EEMO or AXyl inhibited carrageenan-induced mechanical allodynia with percentage of inhibition of 40 ± 6% for EEMO and 82 ± 8% for AXyl. Intraplantar injection of AXyl in the ipsilateral paw, but not in the contralateral paw, also reduced carrageenan-induced mechanical allodynia in mice. The response of the animals for maximal doses tested of EEMO and AXyl in the hot-plate or rota-rod models were not altered. These results show that the extract from M. ovata and the stable derivative AXyl possess analgesic properties towards inflammatory pain acting on peripheral sites.

Antidiabetic, cytotoxic and antioxidant activities of oil extracted from Acrocomia aculeata pulp

Abstract This study evaluated the hypoglycemic effect of the oil extracted from the Acrocomia aculeata pulp (OPAC) in normoglycemic rats and streptozotocin (STZ), fructose-induced diabetic rat models and its in vitro antioxidant and cytotoxic potential. OPAC (3, 30 or 300 mg/kg, v.o.) significantly decreased (p < 0.05) the high glucose levels induced by a high fructose-diet in rats. Persistent treatment with OPAC for 24 days also reduced the high plasmatic glucose induced by STZ. In normoglycemic animals, OPAC significantly decreased glucose levels. While A. aculeata oil exhibited good in vitro antioxidant activity, no sign of cytotoxicity was observed in LLC-PK1 cells (5–500 μg/mL). OPAC has antidiabetic and antioxidant activities without causing in vitro cytotoxicity.