Solomon Habtemariam

Andrographolide inhibits the tumour necrosis factor-α-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion

Andrographolide, a diterpene isolated from Andrographis paniculata, has been shown to have several biological activities including analgesic, antipyretic and antiinflammatory effects. Since the upregulation of adhesion molecules expression and endothelial‐leucocytes adhesion are key steps in the development of inflammation, the present study examines whether andrographolide modulates these biological processes in vitro. Incubation of endothelial cells with non‐toxic concentrations (0.16–16.7 υg/mL) of andrographolide attenuated the tumour necrosis factor‐α (TNF)‐induced intercellular adhesion molecule‐1 (ICAM‐1) expression. Similar concentration ranges of andrographolide also inhibited the TNF‐induced endothelial‐monocyte adhesion in a concentration‐dependent manner. These effects of andrographolide may account for its reported in vivoantiinflammatory activity.

The muscle relaxant properties of Portulaca oleracea are associated with high concentrations of potassium ions

The juice and aqueous extracts from the plant Portulaca oleracea have been used in West Africa for a variety of medical purposes, and extracts were previously shown to have muscle relaxant properties on isolated nerve-muscle preparations. We have attempted to characterise the components responsible for this activity. Ethanolic extracts caused an initial augmentation of twitch height in chick biventer cervicis preparations and then blockade which appeared to be mediated by an action directly on muscle fibres rather than on neuromuscular transmission. Solvent fractionation of the crude ethanolic extract followed by bioassay on the chick biventer cervicis preparation showed that muscle paralysis increased with increasing polarity: i.e. water fraction > butanol > ethyl acetate approximately equal to crude extracts. These fractions contained 28%, 18%, 12.2% and 9%, respectively, of potassium by weight of dried extract. Similar concentrations of KCl reproduced the same effect as the extracts on muscle activity, and when the most active fraction (water fraction) was desalted, it had no neuromuscular activity even at 10 times higher concentration than used previously. We conclude that the neuromuscular activity of extracts of Portulaca oleracea is caused by high concentrations of potassium ions.

Modulation of tumour necrosis factor-α-induced cytotoxicity by polyphenols

The effects of several aromatic compounds on tumour necrosis factor‐α (TNF)‐induced cytotoxicity in murine fibroblast L929 cells were studied. Those phenolics which bear the O ‐dihydroxy aromatic structure (catechols), i.e. caffeic acid, catechol, 3,4‐dihydroxybenzoic acid, dopamine and noradrenaline effectively inhibited TNF‐induced cytotoxicity in a concentration dependent manner. Related compounds (cinnamic acid, 3,4‐dimethoxycinnamic acid, 2,4‐dihydroxybenzoic acid, ferulic acid, 3‐hydroxy‐4‐methoxybenzoic acid and p ‐hydroxybenzoic acid) which lack the catecholic functional group failed to protect cells from TNF cytotoxicity. All concentrations of catechols which effectively inhibited the TNF‐induced cytotoxicity were also protective as a post treatment, suggesting an effect at some step(s) in the TNF‐signal transduction pathway following receptor activation.

Cytotoxicity of extracts from the mushroom Paxillus involutus

The cytotoxicity of extracts of freshly collected Paxillus involutus against murine (L929 and RAW 264.7) and human (HeLa and EAhy926) derived cell lines was investigated. The water extract (15.6-1000 micrograms/ml) did not affect the viability of cells, while the butanol extract reduced cell viability by 30-45% at the highest concentration tested (1 mg/ml). The ethyl acetate extract was cytotoxic in a concentration-dependent manner, with IC50 values between 125 and 250 micrograms/ml. The cytotoxic principle appears to be heat and acid stable, as neither incubation at 37 degrees C for 4 hr nor overnight treatment at pH 0.5 altered the cytotoxicity of the ethyl acetate extract. This non-polar, acid- and thermo-stable cytotoxic principle may play a role in the haemolysis and other clinical manifestations that occur during poisoning by P. involutus.

16-Oxygenated withanolides from the leaves of Discopodium penninervium

Abstract Three new 16-oxygenated withanolides have been isolated from the leaves of Discopodium penninervium together with the known withanolide, jaborosala

Extract of gravel root (rhizome of Eupatorium purpureum) inhibits integrin-dependent U937 cell adhesion

The effect of the antirheumatic herbal drug, gravel root (rhizome of Eupatorium purpureum), was investigated on integrin‐dependent U937 cell adhesion to endothelial cells and extracellular matrix protein, fibronectin. In the presence of gravel root extract (6.3–200 μg/mL), U937 cells lowered their capacity for phorbol myristate acetate (PMA)‐mediated adhesion to tumour necrosis factor‐α (TNF)‐activated endothelial cells or ICAM‐1 coated plates. Similarly, the PMA mediated, LFA‐1‐dependent, homotypic cell aggregation in U937 cells was potently inhibited by gravel root extract. The α4β1 and α5β1‐mediated adhesion of unstimulated U937 cells to fibronectin coated plates was also inhibited by gravel root extract. Neither the TNF‐induced enhancement of expression of ICAM‐1 on endothelial cell surface nor the TNF‐induced endothelial adhesiveness to U937 cells was, however, inhibited by gravel root extract. Since all concentrations of gravel root extract tested failed to alter the proliferation of U937 cells, the observed activity was unlikely to be due to nonspecific suppression of cells.

Fareanine and fareanol from leaves of Medicosma fareana

Abstract Two new compounds, named fareanine (1-methyl-3ξ-hydroxy-2,2-dimethoxy-3ξ-methoxycarbonyl-1,4H-quinoline-[2,3: b ]-cyclopentan-4,5-dione) and fareanol (1ξ,2-dihydroxy-1ξ-(4-hydroxy-3,5-dimethoxy-phenyl)-ethane, together with the known compounds 1,3,4-trimethoxy-10-methyl acridone, normelicopicine, melicopidine, and p -hydroxybenzaldehyde, have been isolated from leaves of Medicosma fareana . The identity of the new compounds was established from their spectroscopic data. Fareanine appears to be the product of fission of the C-ring of a normal acridone precursor.