Suppression of interleukin (IL)-8 and human beta defensin-2 secretion in LPS-and/or IL-1ß-stimulated airway epithelial A549 cells by a herbal formulation against respiratory infections (BNO 1030).

AIM OF THE STUDY: A special ethanolic-aqueous extract from seven traditional medicinal plants (BNO 1030) has been used for several decades to treat recurrent infections of the respiratory tract. Considering the potential role of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) in inflammation, we investigated the effect of BNO 1030 on lipopolysaccharide (LPS) from Pseudomonas aeruginosa or IL-1ß-induced inflammatory mediators in A549 human type II alveolar epithelial cells. MATERIALS AND METHODS: A549 cells were stimulated with LPS (100 µg/ml) or IL-1ß (50 ng/ml) in the presence of the preparation and the secretion of IL-8 and hBD-2 were measured after 18 h and 24h in cell free supernatants using enzyme-linked immunosorbent assays (ELISA). Cell viability and cell growth was investigated by propidium iodide uptake and WST-1 assay, respectively. RESULTS: BNO 1030 inhibited the secretion of IL-8 and hBD-2 at non-cytotoxic concentrations (0.1-100 µg/ml; cell growth inhibitory concentration, 50% (IC(50))=678 ± 87.6 µg/ml). Stimulation by IL-1ß led to a 7-fold activation of IL-8 secretion, which was reduced by 37.7 ± 4.1% (p<0.05) after incubation with 100 µg/ml BNO 1030. Inducible hBD-2 was suppressed by 91.8 ± 15.6% (p<0.01) at the same concentration of BNO 1030 (IC(50)=0.7 ± 0.1 µg/ml). The 2-fold increase of IL-8 secretion by LPS-stimulated cells was completely abolished at concentration of 50 µg/ml BNO 1030 (IC(50)=5.7±3.6 µg/ml). CONCLUSION: BNO 1030 suppressed the secretion of IL-8 and hBD-2 in cultured epithelial A549 cells. These results support its use as a phytotherapeutic product prepared from traditional remedies in inflammatory diseases, especially those affecting the respiratory tract.

Ethanolic extracts of black cohosh (Actaea racemosa) inhibit growth and oestradiol synthesis from oestrone sulphate in breast cancer cells.

Extracts of black cohosh (Actaea racemosa) and soy are used as 'natural' alternatives to conventional hormone replacement therapy (HRT) and there is some evidence that soy may protect against breast cancer by inhibiting the production of active oestrogens. This study compares the action of ethanolic extracts of black cohosh (BCE) and genistein on growth and enzyme activity in MCF-7 and MDA-MB-123 breast cancer cells. BCE inhibited growth at the two highest doses tested, i.e. 50 and 100 microg/ml, whilst genistein stimulated growth in the oestrogen receptor positive (ER(+)) MCF-7 cells, but at high doses it inhibited growth in both cell lines. BCE did not affect the conversion of androstenedione to oestradiol and only the highest doses (50 and 100 microg/ml) significantly inhibited the conversion of oestrone to oestradiol in MDA cells. In contrast, BCE induced a dose-dependent inhibition of the conversion of oestrone sulphate to oestradiol in both cell lines, whilst in human granulosa lutein (GL) cells enzyme activity was only inhibited at the highest dose of BCE. Genistein had no significant effect on enzyme activity in breast cancer cells and like BCE only the highest doses (10 and 50 microM) inhibited enzyme activity in human GL cells. In vivo genistein may have growth stimulatory effects on breast tissue but BCE not only inhibits growth but inhibits the conversion of oestrone sulphate to active oestradiol, considered by some, to be the preferred pathway of oestradiol synthesis in breast tissue.

Are there any realistic chances to develop new drugs for asthma?

Asthma bronchiale, an inflammatory airway disease, imposes a significant health care problem worldwide. It is characterized by three critical phenotypic traits: intermittent and reversible bronchoconstriction, bronchial hyperresponsiveness and airway inflammation. Conventional therapy basically consists of beta(2)-adrenoceptor agonists in combination with glucocorticoids. Nevertheless, there is an urgent need for novel therapies, both for patients with uncontrollable disease symptoms and for those suffering from glucocorticoid-insensitive asthma. Monotherapy seems to be relatively ineffective against this complex and multifaceted disease, which is evident by the variety of disappointing treatment strategies. Thus, we should instead concentrate on multiple target strategies, such as novel and more potent glucocorticoids or phosphodiesterase type 4 (PDE4) inhibitors with isozyme selectivity. In addition, an examination of the application method should not be neglected, with emphasis on inhalative approaches. To summarize, research into asthma's pathophysiology is of critical importance, concentrating on human-relevant targets and conducting preliminary studies. With these imperatives in mind, we can hope to better manage this multifactor disease in the near future.

Is asthma research in dead end?

Despite enormous therapeutic advances, bronchial asthma remains a highly prevalent and serious health problem. Although we have learnt much about the pathogenesis of asthma and developed some new drugs within the last few years, there is still an urgent need for new treatments. The so-called single mediator approach appears to be ineffective in the treatment of asthma. Drugs with multiple sites of mode of action would have greater chances to be successfully introduced into therapy. The present drug screening strategy should be reconsidered and probably be replaced by new and more serendipity-based research.