In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity.

Erythrina mulungu Benth. (Fabaceae), Cordia verbenacea A. DC. (Boraginaceae), Solanum paniculatum L. (Solanaceae) and Lippia sidoides Cham. (Verbenaceae) are medicinal plant species native to Brazil shortlisted by the Brazilian National Health System for future clinical use. However, nothing is known about their effects in metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). In this work, we assess non-toxic concentrations (100 μg/mL) of the plant infusions for their in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). Their mechanisms of action were further studied by measuring the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of γ-glutamyl transferase (GGT) in HepG2 cells. Our results show that P-gp activity was not affected in any case and that only Solanum paniculatum was able to significantly change CYP3A4 mRNA gene expression (twofold decrease, p < 0.05), this being correlated with an antagonist effect upon hPXR (EC50 = 0.38 mg/mL). Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p < 0.001), Lippia sidoides (-12%, p < 0.05) and Cordia verbenacea (-47%, p < 0.001). The latter plant extract was able to decrease GGT activity (-48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines may be able to cause disturbances to metabolic mechanisms in vitro. Although Erythrina mulungu appears safe in our tests, active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum

Database Survey of Anti-Inflammatory Plants in South America: A Review

Inflammation is a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. This physiological response is coordinated largely by a variety of chemical mediators that are released from the epithelium, the immunocytes and nerves of the lamina propria. However, if the factor that triggers the inflammation persists, the inflammation can become relentless, leading to an intensification of the lesion. The present work is a literature survey of plant extracts from the South American continent that have been reported to show anti-inflammatory activity. This review refers to 63 bacterial families of which the following stood out: Asteraceae, Fabaceae, Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used, types of extract used, model bioassays, organisms tested and their activity

Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study

Emphysema on CT is common in older smokers. We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers.Participants in a lung cancer screening study age ≥ 60 years were recruited into a prospective cohort study in 2001-02. Two radiologists independently visually assessed the severity of emphysema as absent, mild, moderate or severe. Percent emphysema was defined as the proportion of voxels ≤ -910 Hounsfield Units. Participants completed a median of 5 visits over a median of 6 years of follow-up. The primary outcome was hospitalization, emergency room or urgent office visit for chronic lower respiratory disease. Spirometry was performed following ATS/ERS guidelines. Airflow obstruction was defined as FEV1/FVC ratio <0.70 and FEV1<80% predicted.Of 521 participants, 4% had moderate or severe emphysema, which was associated with acute episodes of care (rate ratio 1.89; 95% CI: 1.01-3.52) adjusting for age, sex and race/ethnicity, as was percent emphysema, with similar associations for hospitalisation. Emphysema on visual assessment also predicted incident airflow obstruction (HR 5.14; 95% CI 2.19-21.1).Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease, with the former predicting incident airflow obstruction among older smokers

Estudo farmacológico da Stachytarpheta cayennensis Schauer (gervão-roxo), planta medicinal utilizada como antisecretora ácida, antiúlcera e analgésica

BV UNIFESP: Teses e dissertaçõe

Mechanism of gastric antisecretory and antiulcer activities of principles isolated from gervão-roxo (Stachytarpheta cayennensisnVahl)

As plantas do gênero Stachytarpheta, conhecidas como gervao sao utilizadas popularmente como analgésicas/antiinflamatórias e antipiréticas, hepatoprotetoras e laxantes, mas principalmente para tratar os distúrbios gastrointestinais (Coimbra, 1958; De Luca, 1980; De Luca, 1983; Corrêa, 1984; Chaves e col., 1988; Caribé e Campos, 1991; Ficha Ceme,1992; Sankana e Ramachandran, 1974). Os experimentos deste estudo foram orientados para a validaçao pré-clínica do uso popular do chá da S. cayennensis para tratar as úlceras e distúrbios gástricos. Em continuaçao à caracterizaçao farmacológica das atividades da S. cayennensis, foi também parte dos objetivos o estudo dos mecanismos de açao responsáveis pelas atividades antiúlcera e anti-secretora de ácido gástrico. 1. A planta foi coletada no Rio de Janeiro, e processada por extraçao com água (2,5 por cento ; 73 OC) por 30 min. O extrato obtido foi concentrado a vácuo e liofilizado. O rendimento do extrato foi de 10,8 por cento do material bruto. O extrato seco foi dissolvido em água previamente à administraçao aos animais. No modelo de ligadura de piloro de ratos, o EA (1 g/kg, i.d.) apresentou atividade anti-secretora de ácido gástrico até a 4a hora da administraçao na luz duodenal no modelo. A atividade anti-secretora de ácido gástrico do EA foi equipotente em ratos e camundongos. O extrato aquoso (EA) mostrou atividade antiúlcera gástrica em modelos de lesao aguda, subaguda e crônico em ratos. O EA (O,5- l g/kg, p.o.) inibiu as tesoes gástricas agudas induzidas por indometacina (lO mg/kg, s.c.), etanol (75 por cento , l mL/2OOg, p.o.), estresse por imobilizaçao em frio (4ºC x 2 horas) e, hidróxido de amônio (2,5 por cento , l mL/2OOg, p.o.). As lesoes subagudas induzidas por serotonina (20 mg/kg, s.c.) e ligadura de piloro por 18 horas (í.d.) também foram inibidas pelo EA. 4. Nas lesoes gástricas crônicas induzidas por injeçao de ácido acético 10 por cento na subserosa gástrica de ratos o tratamento com o EA (l g/kg, p.o./7dias) tanto impediu o desenvolvimento de úlceras (açao preventiva) como acelerou a cura de úlceras já instaladas (açao curativa). S. A atividade anti-secretora ácida foi maior no extrato da inflorescência que no extrato da folha. O EA do Caule nao foi ativo. 6. O fracionamento do EA da partes aéreas da planta, por partiçao líquido-líquido sucessivo com butanol e etanol, forneceu uma fraçao semipudficada (FEt) com atividade anti-secretora do ácido gástrico ...(au).BV UNIFESP: Teses e dissertaçõe

Inhibition of gastric acid secretion by the aqueous extract and purified extracts of Stachytarpheta cayennensis

Stachytarpheta cayennensis Schauer (Verbenaceae) is used in folk medicine to treat gastric and intestinal disturbances. the freeze-dried aqueous extract of the whole plant tested to rodents up to the dose of 2 g kg(-1), p.o., did not produce signs of toxicity. the extract (0.5-2 g kg(-1), p.o.) increased the intestinal motility and protected mice against ulcers induced by restraint-in-cold, ethanol or indomethacin. Injected into the duodenal lumen the extract inhibited the basal acid secretion as well as that induced by histamine and bethanecol in pylorus-ligated mice. Partition of the aqueous extract in organic solvents yielded semipurified fractions whose antiacid activity guided further chemical purification. All the fractions were chromatographically characterized, the main substances in the active extract being flavonoids and amines; some substances were revealed only under UV light. the most purified active fraction obtained presented a specific activity 5-10 times higher than that detected in the original extract. Data from pharmacological studies indicate that the antiulcer activity of S. cayennensis is related to a specific inhibition of gastric acid secretion. Cholinergic and histaminergic stimulation of acid secretion were similarly reduced by the extracts suggesting inhibition of common steps in both pathways, possibly at the level of histamine release/H-2 receptor interaction, or at the proton pump. Whatever the mechanisms involved, the present data confirm the plant effectiveness as antiacid/antiulcer and laxative.Universidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PHARMACOL,NAT PROD SECT,BR-04044020 São Paulo,BRAZILUniversidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PHARMACOL,NAT PROD SECT,BR-04044020 São Paulo,BRAZILWeb of Scienc