Studies on Bronchodilator Activity of Salvia officinalis (Sage): Possible Involvement of K⁺ Channel Activation and Phosphodiesterase Inhibition

Abstract

The aqueous methanolic extract of the aerial parts of Salvia officinalis (So.Cr) was studied to provide possible underlying mechanism(s) for its medicinal use in asthma using the in vivo bronchodilatory assay and isolated tracheal preparations. S. officinalis (1-10 mg/kg) dose-dependently inhibited carbachol (CCh)-induced bronchospasm in anesthetized rats with three-fold greater potency than the positive control, aminophylline. In tracheal preparations, So.Cr inhibited the low K (25 mM)-induced contractions. Pretreatment of the tissues with 4-aminopyridine reversed the inhibitory effect of the plant extract against low K , whereas glibenclamide did not show any effect, thus showing the involvement of voltage-sensitive K channels. When tested against the CCh-induced pre-contractions for the involvement of any additional mechanism, interestingly, the extract showed a dose-dependent (0.03-0.1 mg/mL) inhibitory effect and shifted the inhibitory concentration response curves of isoprenaline to the left, thus showing phosphodiesterase enzyme inhibitory-like action, similar to that of papaverine. These results indicate that the crude extract of S. officinalis possesses bronchodilatory activity mediated predominantly via activation of voltage-dependent K channels and inhibition of phosphodiesterase enzyme; thus, this study provides sound pharmacological basis for its medicinal use in hyperactive airways disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.

Dose-dependent Spasmolytic, Bronchodilator, and Hypotensive Activities of Panicum miliaceum L.

“…Potassium channel opener drugs have widespread therapeutic use in gastrointestinal disorders like diarrhea, 32 in CVS as antihypertensive, 33 and as bronchodilator in hyperactive airways diseases like asthma and cough. 34 …”

“…Potassium channel opener drugs have widespread therapeutic use in gastrointestinal disorders like diarrhea, 32 in CVS as antihypertensive, 33 and as bronchodilator in hyperactive airways diseases like asthma and cough. 34 Cromakalim (ATP dependent K + channel opener) inhibited low K + induced contractions. To confirm the K + channel activation mechanism, low-K + triggered contractions pretreated with glibenclamide was tested with extract doses which inhibited its relaxing effect having similar pattern as cromakalim confirmed opening of K + -ATP channel.…”

Natural Products Useful in Respiratory Disorders: Focus on Side-Effect Neutralizing Combinations

“…Interestingly, one of its known constituents, chrysoeriol, was found to exhibit high selectivity for its inhibitory effect on airways compared with other smooth muscles (Khan and Gilani, ), thus showing potential to be developed for airways disorders. Interestingly, few recent studies on Morus alba , Salvia officinalis (Sage) and Vitex negun showed that their bronchodilator action is mediated through a combination of predominant K + channel activation, PDE inhibition and reasonable Ca ++ channel blockade (Khan et al , ; Gilani et al , ; Khan et al , ).…”

Vasodilator effect of 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea is predominantly mediated through activation of voltage-dependent K+ channels

“…The tissues were initially incubated for 30 min and finally equilibrated for 1 h prior to addition of any chemical agent. K + at low (25 mM) and high (80 mM) concentration was used to stabilize the respective tissue preparations until achievement of constant responses usually after 2 -3 times application followed by washing of the tissue with fresh Kreb's solution [14]. After stabilization state, low and high K + was administered to the tissue to induce sustained contractions, respectively.…”

“…To characterize and confirm the type of K + -channels involved in the vasodilating effect, the inhibitory effect of TPPU was reproduced in the aortic preparation pretreated with glibenclamide (Gb, 10 µM), an ATP-dependent K + channel antagonist [16], tetraethyl ammonium (TEA, 10 mM), a nonselective antagonist of the K + channels [17] and 4 -aminopyridine (4-AP, 1 mM), a voltage-dependent K + channel blocker add [14].…”