Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient

Ethnopharmacological relevance

In the traditional medicine, Cynodon dactylon (Linn.) is used in asthma, but scientific studies to provide evidence for medicinal uses are sparse. Thus this study was undertaken to provide evidence for medicinal use in asthma as a bronchodilator, and to identify active ingredient(s).

Materials and methods

In vivo, acetylcholine (Ach)-induced bronchospasm was conducted in guinea pig while isolated rat tracheal strip was suspended in organ bath to measure the concentration response curve using multichannel data acquisition system.

Results

The chloroform extract of Cynodon dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs, similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and high K⁺-induced contraction of rat tracheal strip, similar to atropine and verapamil respectively, suggesting antimuscarinic and calcium channel blocking (CCB) activities, which were confirmed by right ward shifting of CCh and Ca⁺² concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory activity was confirmed by potentiation of isoprenaline-induced inhibitory response, similar to papaverine. Densitometry analyses led to the identification of scopoletin as an active ingredient. Effectively, it significantly inhibited high K⁺, and Ca⁺² induced contractile response, similar to verapamil. The phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of potentiation of isoprenaline-induced inhibitory response, similar to papaverine.

Conclusions

These results suggest that the bronchodilator activity of CECD is partly due to presence of scopoletin, and mediated possibly through CCB and PDE inhibition.     

Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans

Introduction  

Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.     

Tigecycline prevents LPS-induced release of pro-inflammatory and apoptotic mediators in neuronal cells

Pro-inflammatory and pro-apoptotic mediators have been involved in the pathogenesis of neurodegenerative diseases. Tigecycline (Tig), a glycylcycline antibiotic and an analog of Minocycline, is shown to exert anti-inflammatory effects that are distinct from its anti-microbial activity. Its neuroprotective mechanism is unknown. In this study, we investigated the direct protective mechanisms of tigecycline against lipopolysaccharide (LPS)-induced Rat pheochromocytoma (PC12) cells. The results showed that tigecycline significantly attenuated the expression and the release of nuclear factor-kappa beta (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), as well as nitric oxide (NO) levels in LPS-induced PC12 cells. In addition, tigecycline dose-dependently decreased cytochrome c release and caspase-3 activity. This later finding corroborated the results of decreased pro-apoptotic Bad, and increased anti-apoptotic Bcl-2 protein expression thus, confirming a neuroprotective effect of the drug in differentiated PC12 cells induced with LPS. The findings of our study suggest new targets for tigecycline and support the potential for tigecycline to be investigated as a therapeutic agent for neurodegenerative disorders.