The synergistic anti-asthmatic effects of glycyrrhizin and salbutamol.
OBJECTIVE
To investigate the efficacy of glycyrrhizin (GL) combined with salbutamol (SA) as an anti-asthma therapy.


METHODS
Rat lung beta2-adrenergic receptor (beta(2)-AR) mRNA level was measured by real-time RT PCR. Intracellular cAMP accumulation was evaluated with a reporter gene assay. An in vitro acetylcholine-induced guinea pig tracheal strip contraction model was used to test the relaxing effects of GL and SA. The anti-inflammatory effects of GL and SA were tested using tumor necrosis factor-alpha-induced NF-kappaB transcriptional activation reporter assay, I-kappaB Western blotting and interleukin-8 ELISA. An in vivo guinea pig asthma model was used to prove further the synergistic effect of GL and SA.


RESULTS
GL (0.3 micromol/L) increased mRNA levels of beta(2)-AR in vivo and the accumulation of cAMP in vitro. The combination of GL and SA also resulted in significant complementary anti-inflammatory effects via inhibition of NF-kappaB activation, degradation of I-kappaB and production of interleukin-8. A significant synergistic effect of the combination was detected both in vitro and in vivo in a guinea pig mode.


CONCLUSIONS
The results demonstrate that GL and SA have synergistic anti-asthmatic effects and offer the possibility of a therapeutic application of GL in combination with beta(2)-AR agonists in the treatment of asthma.
College of Life Sciences, Nankai University, Tianjin 300071, China.
Yang
Y
Yang
Qian
Q
Shi
Ze
Z
Liu
Ruo-jie
RJ
Li
Peng-wei
PW
Pan
Yuan-yuan
YY
Hou
Wan-ge
WG
Lu
Gang
G
Bai
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D019695:Glycyrrhizic Acid; D000242:Cyclic AMP; D000420:Albuterol