Alkaloids from the stem barks of Scutia buxifolia Reissek (Rhamnaceae): Structures and antimicrobial evaluation.

A reinvestigation of the chemical constituents of the stem barks of Scutia buxifolia, a member of the Rhamnaceae, resulted, along with the known alkaloids scutianine C and scutianene L, in the isolation of three undescribed diastereoisomeric alkaloids - scutianine N, 27-epi-scutianine N and 3, 4, 7-tri-epi-scutianine N -, one undescribed non macrocyclic alkaloid - scutianine Q - and a neutral compound -scutianene M. Their structures were determined using extensive NMR techniques and HRMS. The absolute configurations of the stereogenic centers of the three diastereoisomeric alkaloids have been assigned by gas chromatography employing modified cyclodextrins as chiral stationary phases. Scutianine Q had its structure and stereochemistry defined by single crystal X-ray crystallographic analysis. All tested compounds showed good to moderate antibacterial activity (MICs between 1.56 and 100 µg mL-1) when evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria. Some stereochemistry-activity relationships have been identified for the antibacterial activity of diastereoisomeric alkaloids against the Gram-negative bacteria Enterobacter aerogenes. The alkaloid 27-epi-scutianine N was as active as the standard antibiotic chloramphenicol (MIC = 1.56 µg mL-1), while scutianine N and 3,4,27-tris-epi-Scutianine N were inactive (>100 µg mL-1).

Topical antiedematogenic and anti-inflammatory effect of Scutia buxifolia Reissek gel and stability study.

Scutia buxifolia Reissek (Rhamnaceae), popularly known in Brazil as "coronilha", is a plant species used in folk medicine for several disorders, including inflammation. However, no studies have been done with this species to confirm its topical anti-inflammatory action. In this study we evaluate the topical antiedematogenic and anti-inflammatory effects of the gel containing crude extract (CE) and the gel containing ethyl acetate (EtOAc) fraction of S. buxifolia on croton oil or UVB radiation-induced ear edema in mice, and perform gel stability study. Antiedematogenic and anti-inflammatory effects were evaluated through ear edema induced by irritant agent croton oil, UVB irradiation-induced skin injury model and neutrophil infiltration. The gel stability study was performed by analyzing organoleptical aspects, pH, viscosity, and quantification of quercetin and rutin by HPLC. The topical treatment with S. buxifolia gel reduced the ear edema and myeloperoxidase activity. Antiedematogenic and anti-inflammatory effects of S. buxifolia were obtained with concentrations of 0.3, 1 and 3%, with maximal inhibition in the concentration of 1% for gel containing CE (inhibitions of 100, 73±0.05 and 97±0.08% for croton oil- or UVB irradiation-induced ear edema and myeloperoxidase activity, respectively) and EtOAc fraction (inhibitions of 79±0.05, 73±0.05 and 89±0.04% for croton oil- or UVB irradiation-induced ear edema and myeloperoxidase activity, respectively). Such effects may be attributed, at least in part, to rutin and quercetin, as well as other compounds found in this species. No important changes were detected in the stability study, in all aspects analyzed in temperature below 25°C. Our results demonstrate that topically applied S. buxifolia gel presented anti-inflammatory effects, provided that it was maintained at a temperature below 25°C.

Antinociceptive and anti-inflammatory effect of the Scutia buxifolia Reissek stem barks extract.

BACKGROUND: Scutia buxifolia (Rhamnaceae) has been extensively studied for its phenolics groups, which are able to capture free radicals; being therefore, considered promising as an antioxidant in preventing diseases resulting from oxidative stress. HYPOTHESIS: Scutia buxifolia extract (SBE) presents antinociceptive and anti-inflammatory effect in mice. STUDY DESIGN: SBE (400-800mg/kg) was tested in different pain models to investigate its antinociceptive and anti-inflammatory action. METHODS: It was carried out the abdominal writhing test, capsaicin test, thermal hyperalgesia and incisional pain. The inflamed tissue by carrageenan was used for the analysis of interleukins (IL), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), c-reactive protein (CRP), nitrite and nitrate (NOx) determination and myeloperoxidase (MPO) activity. Furthermore, we evaluate the possible action mechanism of SBE using naloxone in capsaicin test. RESULTS: SBE prevented the nociception caused by acetic acid, formalin and capsaicin test. However, neither the SBE prevented the thermal hyperalgesia in hot-plate test, nor the naloxone reversed the SBE antinociceptive effect in capsaicin test. Furthermore, the administration of SBE prevented significantly the increase of MPO activity, the NOx content, and the levels of IL-1, IL-6, TNF-α, INF-γ and CRP and was able to increase the IL-10 levels after the inflammation induced by carrageenan in mice. In addition, SBE prevented mechanical hyperalgesia in a postoperative pain model. CONCLUSION: The SBE presents great antinociceptive and anti-inflammatory activity in mice but this effect not seem to have its action mechanism like opioids. It is possible that its antinociceptive effects are associated with levels decrease of inflammatory mediators.

Chemical constituents, biological activity and therapeutic uses, of Scutia buxifolia Reissek

Scutia buxifolia has been used in the treatment of a number of diseases, which includes bacterial and fungal infections, hypertension, Alzheimer's Disease and cancer. S. buxifolia contains biologically active compounds such as flavonoids, steroids, tanins, lipids, terpens and alkaloids. A range of biological activities has been found from plant extract and fractions, including antioxidant, acetylcholinesterase inhibitor, antiviral and antibiotic. Some studies about the potential toxicity were performed; however the results are not conclusive, suggesting that a single administration of the extract is safe, whereas prolonged use has deleterious effects for the body. The revised databases were SciELO, PubMed, ScienceDirect and Portal da Capes considering studies between 1964 and 2014 and by searching for terms like Scutia buxifolia, Rhamnaceae family, Scutia buxifolia Constituents, Scutia buxifolia use and OECD(AU)

Scutia buxifolia se utiliza en el tratamiento de una serie de enfermedades que incluye infecciones bacterianas y fúngicas, hipertensión, enfermedad de Alzheimer y cáncer. S. buxifolia contiene compuestos biológicamente activos tales como flavonoides, taninos, esteroides, lípidos, terpenos y alcaloides. A partir del extracto y las fracciones de la planta surgen una gama de actividades biológicas, que incluyen antioxidante, inhibidor de la acetilcolinesterasa, antiviral y antibiótico. Se realizaron algunos estudios sobre el potencial tóxico, sin embargo los resultados no son concluyentes, lo que sugiere que una sola administración del extracto es segura, mientras que el uso prolongado tiene efectos perjudiciales para el organismo. Las bases de datos revisadas fueron SciELO, PubMed, ScienceDirect y Portal de Capes, teniendo en cuenta los estudios entre 1964 y 2014 y mediante la búsqueda de términos como Scutia buxifolia, Rhamnaceae family, Scutia buxifolia constituents, Scutia buxifolia uses and OECD(AU)

Hypotensive and diuretic effect of the butanolic soluble fraction of the hydroethanolic extract of bark of Scutia buxifolia Reissek in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia, a native tree popularly known as "coronilha", is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. AIM OF THE STUDY: We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. MATERIAL AND METHODS: We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 µl/min), or phenylephrine (4 µg/kg/min), or l-NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensive rats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. RESULTS: The BuOH soluble fraction of HESB (10mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6 ± 6.0 and 41.8 ± 8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l-NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6-8h after a single oral administration of the BuOH soluble fraction of HESB (10mg/kg), without change in urinary density, pH, or Na(+) and K(+) concentrations. In addition, MAP was lower 3h after the acute oral treatment with the BuOH soluble fraction (82.1 ± 3.8 mm Hg), compared with MAP of animals from the control group (97 ± 3.2 mm Hg). CONCLUSION: This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia, which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway.

Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. MATERIALS AND METHODS: The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. RESULTS: The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. CONCLUSION: Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.

Antiulcerogenic activity of Scutia buxifolia on gastric ulcers induced by ethanol in rats.

Gastric ulcers affect many people around the world and their development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. Scutia buxifolia, commonly known as coronilha, has attracted the interest of the scientific community due to its pharmacological properties and its potential therapeutic applications. In this study, the preventive effects of the crude extract of Scutia buxifolia (ceSb) against gastric ulcer induced by 70% ethanol were evaluated in male Wistar rats. In addition, the composition of ceSb was clarified by high-performance liquid chromatography (HPLC). S. buxifolia extract (100, 200 and 400 mg/kg body weight) attenuated oxidative and histopathological features induced by ethanol. Moreover, all evaluated doses of ceSb caused significant (P<0.001 and P<0.0001) and dose-dependent increase in sulfhydryl groups (NPSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Furthermore, the administration of ceSb reversed the increase in lipid peroxidation produced by ethanol. The protective effect of the extract could be attributed to antioxidant compounds present in the ceSb, such as flavonoids and phenolic acids, which were quantified by HPLC. Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. These results indicate that S. buxifolia could have a beneficial role against ethanol toxicity by preventing oxidative stress and gastric tissue injury.

Antiulcerogenic activity of Scutia buxifolia on gastric ulcers induced by ethanol in rats

Gastric ulcers affect many people around the world and their development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. Scutia buxifolia, commonly known as coronilha, has attracted the interest of the scientific community due to its pharmacological properties and its potential therapeutic applications. In this study, the preventive effects of the crude extract of Scutia buxifolia (ceSb) against gastric ulcer induced by 70% ethanol were evaluated in male Wistar rats. In addition, the composition of ceSb was clarified by high-performance liquid chromatography (HPLC). S. buxifolia extract (100, 200 and 400 mg/kg body weight) attenuated oxidative and histopathological features induced by ethanol. Moreover, all evaluated doses of ceSb caused significant (P<0.001 and P<0.0001) and dose-dependent increase in sulfhydryl groups (NPSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Furthermore, the administration of ceSb reversed the increase in lipid peroxidation produced by ethanol. The protective effect of the extract could be attributed to antioxidant compounds present in the ceSb, such as flavonoids and phenolic acids, which were quantified by HPLC. Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. These results indicate that S. buxifolia could have a beneficial role against ethanol toxicity by preventing oxidative stress and gastric tissue injury.

Antimycobacterial activity of the fractions and compounds from Scutia buxifolia

The antimycobacterial activity of Scutia buxifolia Reissek, Rhamnaceae, leaves extracts and fractions were evaluated for the first time. Four compounds were identified, flavonoids (quercetin and quercitrin) and phenolic acids (gallic and caffeic acids) and quantified by HPLC-DAD. Promising anti-Mycobacterium smegmatis activity was observed with ethyl acetate extract (MIC 312.50 µg/mL) and their fractions (MIC values ranging from 78.12 to above 312.50 µg/mL). The fractions III and VI of S. buxifolia leaves showed a high level of activity against M. smegmatis (MIC 78.12 and 156.25 µg/mL, respectively), M. tuberculosis (MIC 156.25 µg/mL) and M. avium (MIC 312.50 µg/mL), whereas to the other fractions the values varied from 312.50 to 1250.00 µg/mL against these strains. The better MIC result was associated with two fractions that contain bigger amounts of quercetin, quercitrin, gallic and caffeic acids. The results provided evidence that the studied plants fractions might be potential sources of new antimicrobial drug.