Hypolipidemic and reduced nitrergic effects of p-hydroxycinnamic diesters extracted from Copernicia prunifera in mice challenged by a high-fat diet.

Dyslipidemia is a chronic non-transmissible condition that has increased due to an unhealthy lifestyle. Statins have been used as the standard treatment to control hyperlipidemia. However, side effects and high costs may be associated with its prolonged treatment, so plants derivatives have been an attractive therapy to overcome these problems. Among the compounds extracted from plants, the p-hydroxycinnamic diesters (HCE), present in carnauba wax (CW), have been found with good pharmacological properties. Therefore, this study aimed to evaluate the potential anti-hypercholesterolemic and possible toxicological effects of HCE in C57BL/6J mice under a high-fat (HF) diet. Male C57BL/6J mice were fed during 60 days under the HF diet and therefore were either treated with HCE (200 and 400 mg/kg) or simvastatin (20 mg/kg) or received saline (controls) by gavage for 30 days under the same diet. HCE treatment was able to reduce serum total cholesterol and LDL levels. Besides, this compound increased liver X receptor (LXR) and but not significantly affected IL-1ß and TNF-α liver mRNA transcription activity. In conclusion, HCE treatment was found safe and may attenuate the deleterious effects of dyslipidemia due to chronic feeding with western diets.

Toxicological assessment of Opuntia dillenii (Ker Gawl.) Haw. cladode methanol extract, fractions and its alpha pyrones: Opuntiol and opuntioside.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Opuntia dillenii (Ker Gawl.) Haw. commonly known as Nagphana, belongs to the Cactaceae family. It is traditionally used to treat various ailments including inflammation, gastric ulcers, diabetes, hepatitis, asthma, whooping cough and intestinal spasm. AIM OF THE STUDY: Despite its traditional use in various countries, detailed toxicological studies of O. dillenii cladode are few. Thus in the current study, toxicity of O. dillenii cladode derived methanol extract, fractions and its α-pyrones: opuntiol and opuntioside have been addressed. METHODS: The test agents were assessed using both in vitro and in vivo toxicity assays. MTT on human embryonic kidney cell line (HEK-293), tryphan blue exclusion in rat neutrophils, Cytokinesis-B block micronucleus (CBMN) in human lymphocytes and genomic DNA fragmentation using agarose gel electrophoresis were performed. In acute toxicity test, mice orally received extract (5 g/kg) for 7 days followed by measurements of relative organ weight, biochemical (blood profile, liver and kidney function test) and histological studies (liver and kidney) were carried out. Rat bone marrow micronucleus genotoxicity assay was also conducted. RESULTS: O. dillenii derived test agents were non-cytotoxic and had no effect on the integrity of DNA. Methanol extract (5 g/kg) orally administered in mice did not cause any significant change in relative organ weights, biochemical parameters and liver and kidney histology as compared to vehicle control. In parallel, extract did not stimulate micronuclei formation in rat bone marrow polychromatic erythrocytes. CONCLUSION: These results led to conclude that edible O. dillenii extract is non-toxic via the oral route and appears to be non-cyto-, hepato-, nephro- or genotoxic, thereby supporting its safe traditional use against various ailments. Therefore, opuntiol and opuntioside may serve as lead compounds in designing new drug(s) derived from edible plants.

Are Supplements Safe? Effects of Gallic and Ferulic Acids on In Vitro Cell Models.

Polyphenols display health-promoting properties linked to their biological activities. They are initially absorbed in the small intestine, then they are largely metabolized in the colon, whereupon they are able to exert systemic effects. The health-promoting properties of polyphenols have led to the development of food supplements, which are also largely consumed by healthy people, even if data on their safety are still yet lacking. In the present paper, the content of gallic acid and ferulic acid was analyzed in two supplements, and shown to be higher than the relative contents found in fruit and flour. To evaluate the effects of these phenolic compounds on epithelial intestinal tissue, gallic and ferulic acids were added to a new in vitro model of the intestinal wall at different concentrations. The effects on viability, proliferation and migration of these compounds were respectively tested on three different cell lines (Caco2, L929 and U937), as well as on a tridimensional intestinal model, composed of a mucosal layer and a submucosa with fibroblasts and monocytes. Results indicated that gallic and ferulic acids can exert toxic effects on in vitro cell models at high concentrations, suggesting that an excessive and uncontrolled consumption of polyphenols may induce negative effects on the intestinal wall.

Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: o-coumaric acid.

Among hydroxycinnamic acids, caffeic, ferulic and p-coumaric acids have received considerable attention due to their biological activities. However, studies related to the biological activities of o-coumaric acid (OCA) are limited. In this regard, this study was designed to determine the chemopreventive potential of OCA in human breast cancer cells (MCF-7). The EC50 value of OCA was found to be 4.95 mM and was used throughout the study. Caspase-3 protein and mRNA levels increased by 59% and 72%. Similarly, protein and mRNA levels of Bax were increased by 115% and 152%. However, OCA treatment caused 48% and 35% decreases in Bcl-2 protein and mRNA levels. Cyclin D1 and cyclin dependent kinase-2 protein and mRNA levels decreased significantly. Moreover, p53 protein and mRNA levels increased by 178% and 245%, respectively. In addition to p53, PTEN protein and mRNA levels were induced. Although, CYP1A1, CYP1A2 and CY2E1 mRNA levels increased, CYP3A4 and CYP2C9 mRNA levels decreased in response to OCA treatment. These results suggest that OCA demonstrates anticarcinogenic activity on MCF-7 cells by activating multiple pathways. However, it also has high carcinogen activating and drug interaction potential. Therefore, serious precautions must be taken before using OCA.

Administration of caffeic acid worsened bone mechanical properties in female rats.

Natural phenolic acids, commonly present in plants that are normally consumed in the diet, have been reported to exert antiresorptive and/or bone formation increasing activity. The aim of the present study was to investigate the effects of ferulic, caffeic, P-coumaric, and chlorogenic acids on the skeletal system of normal, mature female rats. The phenolic acids (10 mg/kg p. o. daily for 4 weeks) were administered to 3-month-old female Wistar Cmd:(WI)WU rats. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. Phenolic acids had differential effects on the rat skeletal system. Although none of them affected bone macrometric parameters, mass and mineralization, all of them increased the width of femoral trabeculae. Administration of caffeic acid worsened bone mechanical properties (decreasing ultimate load sustained by the femur in three-point bending test). In conclusion, high intake of caffeic acid may unfavorably affect the skeletal system.

[Dynamic change of phenolic acids in soils around rhizosphere of replanted Rehmannia glutinosa].

OBJECTIVE: To determine 5 phenolic acids in the soils around rhizosphere of Rehmannia glutinosa in the field under normal rotation and successive cropping. METHOD: Phenolic acids related to allelopathy effect in the soils around rhizosphere of R. glutinosa were determined by HPLC. RESULT: The growth of R. glutinosa under normal rotation was strong. During harvest, the dry weight of the root tube and the volume of the R. glutinosa under normal rotation were 6.02 and 7.71 times of the ones under successive cropping. CONCLUSION: The seeding stage and elongating stage are the crucial periods for the autotoxic effect of the R. glutinosa under continuous cropping. During these periods, the content of coumaric acid, 4-hydroxybenzoic acid, syringic acid, and ferulic acid of R. glutinosa under successive cropping are notably negative correlation with the growth of the leaf and root tuber of R. glutinosa under successive cropping. Among them, ferulic acid plays a major role in the restriction effect on R. glutinosa under successive cropping.

Enzymatic oxidation products of allelochemicals as a basis for resistance against insects: effects on the corn leafhopper Dalbulus maidis.

Oxidation products of com allelochemicals generated by peroxidases or tyrosinases were tested in 10% sucrose solutions for effects on the corn leafhopper Dalbulus maidis. Some reduction in feeding was noted with hydrogen peroxide (a cofactor for peroxidase). Significant reduction in feeding was noted with chlorogenic acid, ferulic acid, p-coumaric acid, and 6-methoxybenzoxazolinone (MBOA), but not rutin at 400 ppm in solution. Oxidation products of these compounds all caused significantly less feeding by the leafhoppers compared to the original compound. Oxidation products generated by peroxidase from ferulic acid and 6-methoxybenzoxazolinone caused significant mortality to the leafhoppers within 5 days. Thus, provided conditions are such that oxidizing enzymes and allelochemicals can interact due to damage by insects, resistance may be significantly enhanced by the oxidized products as opposed to the effects of the allelochemicals alone.

Insecticidal and fungicidal compounds from Isatis tinctoria.

Tryptanthrin (1), indole-3-acetonitrile (2) and p-coumaric acid methylester (3) were isolated from the aerial parts of Isatis tinctoria L. The compounds show insecticidal and anti-feedant activity against termites (Reticulitermis santonensis), insect preventive and control activity against larvae of the house longhorn beetle (Hylotrupes bajulus) and fungicidal activity against the brown-rot fungus (Coniophora puteana).

[Effects of tetramethylpyrazine and ferulic acid alone or combined on vascular smooth muscle, blood viscosity and toxicity].

The experiments showed that both tetramethylpyrazine and ferulic acid relaxed the norepinephrine-induced spasmodic contraction of rabbit and rat aorta strips, increased the coronary flow of isolated guinea pig hearts and reduced the whole blood viscosity in rats. Evaluated with Burgi's equation, the combined effect of these 2 drugs was obviously potentiated, but the combined acute toxicity in mice was greatly reduced.

Analysis and pharmacotoxicity of feruloyltyramine as a new constituent and p-coumaroyltyramine in Cannabis sativa L.

Feruloyltyramine (FT), a new amide compound, together with p-coumaroyltyramine (p-CT) was isolated and identified in ethanol extract of cannabis seeds. FT and p-CT were also detected in the roots, leaves and resin of Cannabis sativa L. The intracerebroventricular injection of these amides caused hypothermia and motor incoordination in mice, and the maximal effects were caused 160 to 240 min after the injection. Furthermore, p-CT also exhibited cataleptogenic effect in mice, although FT did not show any effect. These results suggest that these amide compounds may be responsible for some pharmacotoxicity of marihuana.

Modifying effects of components of plant essence on the induction of sister-chromatid exchanges in cultured Chinese hamster ovary cells.

The influence of 21 kinds of components of plant essence on sister-chromatid exchanges (SCEs) induced by mitomycin C was investigated in cultured Chinese hamster CHO K-1 cells. Posttreatment with scopoletin, jasmone, caffeic acid and ferulic acid significantly increased the frequency of SCEs. Further investigation of the SCE-enhancing effect of analogues of caffeic acid and ferulic acid revealed that an alpha,beta-unsaturated carbonyl group may be necessary for SCE-enhancing effects. The influence of caffeic acid and ferulic acid on X-ray- or UV-induced SCEs was also studied. The frequencies of SCEs induced by UV were increased by treatment with these compounds. This increasing effect was observed in the S phase of the cell cycle. On the contrary, X-ray-induced SCEs were reduced by the treatment with these compounds. The decreasing effect was observed in the G1 phase but not in the S or G2 phase. To explain these contradictory results, we assumed that caffeic acid and ferulic acid may modify the repair of DNA strand breaks.