R. de la Puerta

Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet.

Abstract:Objective and Design: The aim of the present study was to examine the effect of a virgin olive oil enriched diet in acute and chronic inflammation models in rats and to determine the effect of supplementing this oil with a higher content of its polyphenolic fraction. The response was compared to oils rich in monounsaturated fatty acids (high oleic sunflower oil and palm olein) and rich in polyunsaturated fatty acids (fish oil).¶Diets: Groups of 6-8 male Wistar rats were fed from weaning on six purified diets differing in type of oil: 2 % corn oil (basal diet, BD), 15 % high oleic sunflower oil (HOSO), 15 % virgin olive oil (VOO), 15 % virgin olive oil supplemented with 600 p.p.m. polyphenols from this oil (PSVOO), 15 % palm olein (POL), and 15 % fish oil (FO).¶Materials and methods: Rats were fed for 8 weeks with BD, HOSO, VOO, PSVOO, POL and FO diets before injecting carrageenan. Rats were fed for 3 weeks with BD, PSVOO and FO diets before induction of adjuvant arthritis. Dietary treatment with or without indomethacin continued during 3 weeks. The data were evaluated using an analysis of variance (ANOVA) followed by the least-significant differences.¶Results: In carrageenan oedema test, the inflammation indices of animals fed on a diet rich in olive oil (VOO) were lower compared to animals fed with oils high in oleic acid (HOSO, POL) and polyunsaturated fatty acids (FO), and markedly diminished in the group fed on PSVOO. In established adjuvant arthritis, the PSVOO diet was even more effective than FO diet in the prevention of inflammation. Both groups of animals showed an increase in weight during the latter days of the experiment compared to the BD. Indomethacin administered to every diet group, exerted a strong inhibitory effect on the inflammatory process throughout which was augmented by the PSVOO and FO diets.¶Conclusions: This study demonstrates that virgin olive oil with a higher content of polyphenolic compounds, similar to that of extra virgin olive oil, shows protective effects in both models of inflammation and improves the disease associated loss of weight. This supplementation also augmented the effects of drug therapy.¶

Anti-inflammatory activity of Agave intermixta Trel. and Cissus sicyoides L., species used in the Caribbean traditional medicine.

Agave intermixta Trel. and Cissus sicyoides L. are two tropical plants originating from the Dominican Republic. Aqueous extracts from these species are used in traditional medicine. In contrast, biological activity and toxicity of these plants are not yet evaluated systematically. The aim of the present work is to investigate a potential anti-inflammatory activity, and to elucidate the toxicity of the extracts. No lethal effects were produced after oral administration of the extracts. The values of the medium lethal doses after intraperitoneal administration were quite high for both species, although A. intermixta seems to be rather more toxic than C. sicyoides. The anti-inflammatory effects have been investigated in two experimental in vivo models. The carrageenan-induced rat paw oedema was chosen as a model for general inflammation, and the mice ear oedema test using tetradecanoylphorbol acetate as inflammatory agent as a model of topical inflammation. Dry extracts from decoctions of A. intermixta leaves and C. sicyoides stems were administered in doses of 300 and 500 mg/kg (p.o.) in the general model, and in doses of 3 and 5 mg/mouse ear for both plants in the topical model. In the general anti-inflammation assay, the oral administration of both extracts produced a significant anti-inflammatory effect, most pronounced for A. intermixta than for C. sicyoides. In the topical model, the administration of both extracts produced similar inhibitions of the oedema, with a reduction of approximately 50% in comparison with the control group. In homogenated tissue samples from the inflamed areas, a distinct decrease in the level of myeloperoxidase enzyme was noted.

Antibacterial Activity and Composition of the Volatile Oil from Achillea Ageratum L.

Artemisia ketone, artemisia alcohol, β‐caryophyllene oxide and 1,8‐cineole were confirmed as the major components of the volatile oil from Achillea ageratum L. In an antibacterial diffusion assay, the volatile oil showed activity mainly against Gram‐positive bacteria Bacillus sp. and Staphylococcus aureus. The oil also showed some activity against the Gram‐negative bacteria, Escherichia coli.

Topical anti-inflammatory effect of tirucallol, a triterpene isolated from Euphorbia lactea latex

Latex from Euphorbia lactea (Euphorbiaceae), a native Dominican medicinal plant, is claimed to be useful in the treatment of inflammation. Topical application of tirucallol, a tetracyclic triterpene isolated from Euphorbia lacteal latex, suppressed ear edema in the mouse model in a dose-dependent manner, as well as affecting the influx of polymorphonuclear cells in response to topical application of 12-O-tetradecanoylphorbol-acetate (TPA) in the mouse ear. In addition, the effect of tirucallol, on some macrophage functions was analyzed in vitro. Non-toxic concentrations of tirucallol potently inhibited nitrite production in lipopolysaccharide-stimulated macrophages. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression although tirucallol slightly affected to prostaglandin E(2) (PGE(2)) generation. The results of the study revealed that tirucallol (0.3%), present in Euphorbia lactea latex, exerts a topical anti-inflammatory effect in vivo, via a mechanism of action related to the neutrophil migration. On the other hand, it can be deduced that the mechanism of the anti-inflammatory activity of this triterpene is related to the control of the production of NO and its effect on the expression of iNOS.

Phytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.

Agave intermixta Trel. (Maguey) and Cissus sicyoides L. (Bejuco caro) are Caribbean plant species from the Dominican Republic used locally in traditional popular medicine that have shown an anti‐inflammatory effect in experimental animal models. A phytochemical analysis on these species allowed us the isolation and identification of the steroidal sapogenins hecogenin and diosgenin from Maguey and the hydroxystilbene resveratrol from Bejuco caro. The effects of these plant extracts and their isolated constituents on compound‐48/80‐induced histamine release from peritoneal mast cells were investigated. Significant inhibition was produced by 0.5 mg mL−1 of a methanolic extract of Bejuco (41.1%) and by its constituent resveratrol (82.4%) at a dose of 250 μM. However, none of the steroidal sapogenins from A. intermixta showed a significant inhibitory effect on histamine release from mast cells. From these results, it can be deduced that the in‐vitro anti‐allergic activity towards the release of histamine from mast cells shown by the methanolic extract of C. sicyoides may be mediated by its constituent resveratrol and might contribute to the anti‐inflammatory activity shown by this species.

Cytostatic activity against HEp‐2 cells of methanol extracts from Viscum cruciatum Sieber parasitic on Crataegus monogyna Jacq. and two isolated principles

We have determined the cytostatic activity in vitro against HEp‐2 cells of methanol extracts from V. cruciatum Sieber (Viscaceae) parasitic on C. monogyna Jacq. (Rosaceae), C. monogyna parasitized and C. monogyna. non‐parasitized. The methanol extracts assayed exhibited a moderate degree of growth inhibition compared with the values obtained with the 6‐mercaptopurine (solution used as a positive control). Hyperoside from C. monogyna showed only a low degree of growth inhibition. However, β‐amyrin acetate, from V. cruciatum, exhibited a high degree of growth inhibition compared with the values obtained with the solution used as a positive control.

Hypocholesterolemic and Hepatoprotective Effects of “Triguero” Asparagus from Andalusia in Rats Fed a High Cholesterol Diet

The cultivated species of the wild autochthonous Asparagus officinalis in Andalusia in Spain is commonly called “triguero” asparagus. This vegetable has traditionally been very much appreciated for its organoleptic and nutritional characteristics. This study has been designed to evaluate the potential effect of different concentrations of freeze-dried asparagus (500, 250, and 125 mg/Kg of body weight/day) on oxidative status and lipid profile in rats fed a cholesterol-rich diet. After five weeks of treatment, doses of 250 and 500 mg/Kg of asparagus were able to significantly reduce total cholesterol and LDL cholesterol levels. Atherogenic index was also significantly reduced in a dose-dependent manner by administrating freeze-dried asparagus. A beneficial effect was observed in the HDL cholesterol levels in asparagus-fed groups although the increase was not significant. Consumption of asparagus also improved antioxidant status, assayed superoxide dismutase (SOD) and catalase (CAT) enzymes, and protected against lipid peroxidation. These results show that the intake of green asparagus from Andalusia (Spain) helps to regulate plasma lipid levels and prevents oxidative damage in hypercholesterolemic conditions.

Gastroprotective Effects of Piper carpunya Against Diclofenac-Induced Gastric Lesions in Rats

Piper carpunya Ruiz & Pav. (Piper lenticellosum C. DC.), a member of the Piperaceae family, is a remedy with anti-inflammatory and antiulcer properties that is used in folk medicine in Ecuador. The present work determined the gastroprotective effects of this plant in a model of diclofenac-induced ulcers in rats and studied the mechanism involved. The aqueous suspension of the ethanol extract of the leaves of P. carpunya was administered twice orally to three groups of Wistar rats at doses of 62.5, 125, and 250 mg/kg, with a 24-h interval between doses. Diclofenac (100 mg/kg) was given 1 h after the last administration of the extract. Pretreatment with P. carpunya decreased the ulcerated area, prevented neutrophil infiltration induced by NSAID administration in vivo, and inhibited the release of the proteolytic enzyme myeloperoxidase by neutrophils stimulated with the calcium ionophore A23187. Superoxide dismutase activity demonstrated a marked increase at the two lowest doses of the extract versus diclofenac group and glutathione peroxidase activity was reverted near to sham levels. On the other hand, P. carpunya treatment did not prevent the increased levels of lipoperoxides in gastric mucosa caused by diclofenac. Furthermore, P. carpunya did not affect PGE2 levels, which were depleted by diclofenac treatment. These results suggest that the gastroprotective effect of P. carpunya in this experimental model appears through anti-inflammatory and antiradical mechanisms.

Potential therapeutic applications of the genus Annona: Local and traditional uses and pharmacology

ETHNO-PHARMACOLOGICAL RELEVANCE Annona species (Annonaceae) have long been used as traditional herbal medicines by native peoples in tropical areas. In different countries they are used against a large variety of illnesses, such as parasitic and infectious diseases, cancer, diabetes, peptic ulcers, and mental disorders. AIM OF THE STUDY This review aims to achieve a comprehensive understanding of the research conducted so far on the local and traditional uses, pharmacological activities, mechanism of actions of active compounds, toxicity, and possible interactions with other drugs of the Annona species. Through analysis of these findings, evidences supporting their applications in ethno-medicines are described. We discuss the possible research opportunities and stand out the weak points in our knowledge that deserves further investigation. MATERIAL AND METHODS Information on ethno-medicinal uses and pharmacological activities of the Annona genus was collected. The main scientific biomedical literature databases (Cochrane, PubMed, Scopus, Lilacs, SeCiMed, Elsevier, SpringerLink, Google Scholar, SciFinder) were consulted. The search covered all the literature available until September 2017. National and regional databases of Herbal Medicine and Complementary and Alternative Medicine were also revised in order to explore further data. For a better understanding of the therapeutic importance of these species, we have classified the pharmacological activities within each group of disorders. The International Classification of Diseases (ICD), used from WHO Member States, was chosen as the reference classification. RESULTS From among the 27 species revised, four species are highlighted for their important pharmacological activities in most of the groups of illnesses: A. muricata, A. squamosa, A. senegalensis, and A. cherimola. Many investigations have been performed with extracts from the leaves, bark, fruit and seeds and have shown a wide range of pharmacological activities, such as antiprotozoal, antitumoural, antidiabetic, hepato-protective, anti-inflammatory and anxiolytic activities. The chemistry on the annonaceous acetogenins (ACGs) has been extensively investigated due to their potent antitumoural activity. Many of the assays were carried out with the isolated acetogenins in different lines of tumour culture cells and were found effective at very low doses even in multidrug-resistant tumours, and hence constitute promising compounds in the treatment of different types of cancers. No studies were found with extracts rich in acetogenins in the clinical field. CONCLUSIONS The experimental results from the pharmacological research enable the validation of their traditional uses in several of the groups of diseases in the countries of origin and reveal these plants to be a valuable source for therapeutic molecules. However, more toxicity assays and clinical trials would be necessary to establish optimal and safe doses of consumption on the application of these medicinal plants.

Antioxidant and cytotoxic activities of Sideritis perezlarae (Borja) Roselló, Stübing and Peris

Sideritis perezlarae is a plant widely used in folk medicine in the South of Andalusia (Cádiz, Spain). In this work, a phytochemical analysis has led to the isolation and identification of the flavonoid 7-O-β-glucosyl-luteolin from a methanol extract. The total phenol content estimated by Folin-Ciocalteau assay and expressed as gallic acid equivalent per gram of dried fraction, was 102.54 ± 2.10 mg phenols per gram dry residue. The flavonoid content, investigated by AlCl3 reagent, was 23.49 ± 0.90 mg flavonoids gram dry residue. The methanol extract has been evaluated for antioxidant (DPPH and TEAC assays) and cytotoxic (SRB assay) properties. In the DPPH radical scavenging assay, the IC50 was 360 µg mL−1. In the total antioxidant activity, calculated by the Trolox equivalent antioxidant activity (TEAC, mg g−1 of dried fraction), the extract showed a high antioxidant capacity (TEAC value of 0.59 ± 0.02 mg g−1). The cytotoxic activity of the extract against a human adenocarcinoma cell line HT-29 presented an IC50 = 69.47 ± 4.64 µg mL−1.