Anti-inflammatory and anti-arthritic effects of compounds from Buddleja coriacea.

Buddleja coriacea (B. coriacea) commonly known as 'Kiswara' is used as infusions for stomach and joint pain. This study aims to evaluate the in vitro and in vivo anti-inflammatory and anti-arthritic activity was evaluated by measuring inflammatory parameters (TNF-α, C-reactive protein and Fibrinogen) in murine models of the aqueous extract and isolated compounds of B. coriacea. A bio-guided phytochemical analysis based on NMR/MS was performed identifying three (1-3) compounds of the aqueous extract. All compounds inhibited the production of TNF-α in RAW 264.7 cell line, with IC50 of 13.44 (1), 1.13 (2) and 0.57 µM (3), respectively. In addition, compounds 2 and 3 decreased the levels of TNF-α, C-reactive protein and fibrinogen at a concentration of 5 mg/kg in murine models. Our research shows that the compounds isolated from B. coriacea have anti-inflammatory and anti-arthritic properties, providing scientific evidence for the traditional use of this plant species.

New celecoxib multiparticulate systems to improve glioblastoma treatment.

Treatment of malignant gliomas consists of resection followed by radiotherapy and chemotherapy. Celecoxib (CXB), a selective COX-2 inhibitor, is able to control inflammation and pain, to improve the efficacy of radiotherapy, and to inhibit at high doses the growth of cancer cells. Two new delivery systems for CXB are developed: microspheres (MPs) for implantation in the brain after partial/complete removal of the tumor, and nanoparticles (NPs) for their potential to cross the blood brain barrier and deliver CXB into the CNS. Cell culture assays performed in PC12, SKN-AS and U373-MG cells demonstrate the antiproliferative affects of CXB, with EC50 values of 99.81 µM and 82.4 µM in U373-MG and SKN-AS cells. Encapsulation efficacy of CXB in formulation MP2 (20% CXB) was 74.6 ± 2.2% with a zero-order release rate of 47.8 µg/day/20mg microspheres for 34 days. Uncoated and polysorbate 80-coated CXB-NPs are prepared by nanoprecipitation. Mean sizes of uncoated and coated CXB-NPs were 173.6 ± 44.9 nm and 100.6 ± 62.1 nm. Cerebral cortex images showed a marked increase of fluorescence when the surfactant-coated NPs were administered to rats. These results suggest that both CXB formulations (MPs and NPs) are adequate systems to enhance the effects of chemotherapy in the treatment of malignant brain tumor.

Controlled release of rasagiline mesylate promotes neuroprotection in a rotenone-induced advanced model of Parkinson's disease.

Microencapsulation of rasagiline mesylate (RM) into PLGA microspheres was performed by method A (O/W emulsion) and method B (W/O/W double emulsion). The best formulation regarding process yield, encapsulation efficiency and in vitro drug release was that prepared with method A, which exhibited constant drug release for two weeks (K(0)=62.3 µg/day/20mg microspheres). Exposure of SKN-AS cells to peroxide-induced oxidative stress (1 mM) resulted in cell apoptosis which was significantly reduced by RM (40.7-102.5 µM) as determined by cell viability, ROS production and DNA fragmentation. Daily doses of rotenone (2 mg/kg) given i.p. to rats for 45 days induced neuronal and behavioral changes similar to those occurring in PD. Once an advanced stage of PD was achieved, animals received RM in saline (1 mg/kg/day) or encapsulated within PLGA microspheres (amount of microspheres equivalent to 15 mg/kg RM given on days 15 and 30). After 45 days RM showed a robust effect on all analytical outcomes evaluated with non-statistically significant differences found between its administration in solution or within microparticles however; with this controlled release system administration of RM could be performed every two weeks thereby making this new therapeutic system an interesting approach for the treatment of PD.

Standardized Hypericum perforatum reduces oxidative stress and increases gene expression of antioxidant enzymes on rotenone-exposed rats.

Since oxidative stress is implicated in the pathophysiology of dementia and depression, this study was designed to investigate the pro-oxidant activity of rotenone, the protective role of standardized extract of Hypericum perforatum (SHP), as well as the mRNA levels of antioxidant enzymes, in brain homogenates of rats following exposure to rotenone and SHP extract. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions to serve as a positive control. The animals received pretreatment with SHP (4 mg/kg) or quercetin liposomes (25 and 100 mg/kg) 60 min before of rotenone injection (2 mg/kg). All treatments were given intraperitoneally in a volume of 0.5 ml/kg body weight, for 45 days. Rotenone treatment increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). The content of reduced glutathione (GSH) was decreased due to chronic rotenone treatment. Rotenone significantly induced the gene expression of CuZnSOD, MnSOD; CAT and GPx in brain. In contrast, SHP extract exerted an antioxidant action which was related with a decreased of MnSOD activity and mRNA levels of some antioxidant enzymes evaluated. Liposomal quercetin treatment resulted in a significant preservation of the activities of antioxidant enzymes and a decreased in the mRNA levels of these antioxidant enzymes. One possible mechanism of action of SHP extract may be related to quercetin in protecting neurons from oxidative damage. Therefore standardized extract of H. perforatum could be a better alternative for depressed elderly patients with degenerative disorder exhibiting elevated oxidative stress status.

Antiulcerogenic activity of Lippia alba (Mill.) N. E. Brown (Verbenaceae).

Lippia alba (Mill.) N. E. Brown Verbenaceae, known popularly as 'Juanilama' or 'Salvia Sija', is prized widely in folk medicine in Guatemala. Its leaves are employed as an infusion and decoction as a remedy for stomach problems, dysentery, colds and cough, febrifuge, as well as a sedative and in spasmolitic remedies. The present study reports the effects of the infusion of L. alba on the rat gastric mucosa. The following behavioural parameters were evaluated: (a) gastric irritancy test in Wistar rats; (b) antiulcer activity, short term and long term; (c) acid secretion; (d) measurement of total proteins; (e) estimation of total protein bound and nonprotein sulfhydryl groups. Ranitidine (100 mg/kg, p.o.) was used as the reference antiulcer drug. Oral treatment with the infusion (12.5 g dry plant/kg) did not cause gastric irritancy in the rats treated during five consecutive days. In addition, the oral administration of L. alba was found to be effective at preventing gastric ulceration induced by indomethacin (50 mg/kg, p.o.) in rats in the short term (1 day) and long term (5 days).

Lippia: traditional uses, chemistry and pharmacology: a review.

The chemical composition, pharmacological activity and traditional uses of 52 species attributed to the genus Lippia (Verbenaceae) as used in the South and Central America, and Tropical Africa, were revised and compared. A survey of the available literature shows that these species are used mostly for the treatment of gastrointestinal and respiratory disorders and as seasoning. Additionally, some of these Lippia species showed antimalarial, spasmolitic, sedative, hypotensive and, anti-inflammatory activities. Generally, the essential oil or the phenolic compounds (flavonoids) from these plant extracts are assumed to be the active principles.

Study of garlic extracts and fractions on cholesterol plasma levels and vascular reactivity in cholesterol-fed rats.

Garlic is known for its pharmacologic and nutritional properties. In previous studies, garlic elicited a reduction in plasma levels of lipids by inhibiting hepatic cholesterol synthesis. The aim of this study was to investigate in an in vivo model the effects of garlic extract and some fractions on cholesterol levels and vascular reactivity in cholesterol-fed rats. Rats were fed a cholesterol-enriched diet for 16 wk and were divided into 10 groups as follows: control and hypercholesterolemic diet groups, 4 groups fed frozen garlic fractions and 4 groups fed raw garlic fractions with different doses. Blood samples were obtained to analyze HDL and LDL cholesterol levels. After treatment, rats were killed. The heart, liver and kidneys were weighed; the aorta was isolated, mounted in organ chambers and vascular reactivity was tested. Plasma concentration of cholesterol was 58 mg/dL (100%) at the beginning of the study and increased to 102 mg/dL (153%; hypercholesterolemic group) at the end of the treatment. Plasma total cholesterol decreased in all groups treated with garlic; moreover, this effect was higher in rats fed raw garlic fractions and extracts. LDL decreased significantly with respect to the hypercholesterolemic group in all groups treated with garlic fractions and extracts (P: < 0.01); however, an increase in HDL was found in those treated with frozen fractions and extracts. The liver:body weight ratio decreased in all treated groups. The relaxing effect of acetylcholine (ACh) was enhanced in arteries contracted with noradrenaline (NE). These data suggest that garlic fractions could prevent diet-induced hypercholesterolemia and vascular alterations in the endothelium-dependent relaxation associated with atherosclerosis.

Study of polyphenols in grape berries by reversed-phase high-performance liquid chromatography.

Several polyphenols have been tested in grape berries from Spain. The flavonoid content is important because of the pharmacological properties of these compounds, whereas resveratrol has been proved to be an antifungal, antiinflammatory and an anticarcinogenic compound. A reversed-phase HPLC method has been developed and applied to determine resveratrol, quercetine, quercitrine and rutine content in several grape berries samples in a single analysis. Covering the grapes with a preservative paper yields a healthier product, but one which has a lower polyphenol content than unprotected grapes.

Anti-inflammatory activity of Pothomorphe peltata leaf methanol extract.

The methanol extract of Pothomorphe peltata leaves, orally administered at the dose of 20 mg/kg (equivalent to 2.50 g dry plant/kg) body weight, exhibited a significant anti-inflammatory activity, comparable with phenylbutazone (80 mg/kg, p.o.), against adjuvant-carrageenan-induced edema in rats.

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador.

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.

Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

Flavonoid glycosides from Eugenia jambos.

Two flavonol diglycosides isolated from the leaves of Eugenia jambos were characterized as quercetin and myricetin 3-O-beta-D-xylopyranosyl(1-->2) alpha-L-rhamnopyranosides by means of spectral analyses applying 2D NMR techniques and NOE experiments.

Anti-inflammatory activity of leaf extracts of Eugenia jambos in rats.

The anti-inflammatory activities of four organic extracts from the leaves of Eugenia jambos were investigated in rats using the Mizushima et al. model of acute and chronic inflammation (Mizushima et al. (1972) Journal of Pharmacy and Pharmacology 24, 781-785). Orally administered organic extracts of E. jambos (hexane, dichloromethane, ethyl acetate and methanol), given at daily doses equivalent to 12.5 g/kg of dried leaf material, inhibited both the acute and chronic phases of this experimental model of inflammation. The ethyl acetate and methanol extracts were the most effective and were equal or more effective than 80 mg/kg of phenylbutazone. The methanolic extract was the most active in the chronic phase. A 10% aqueous extract (infusion) of the leaves tested in the same model was more effective than all of the organic extracts.