Liquiritin apioside attenuates laryngeal chemoreflex but not mechanoreflex in rat pups

Abstract

Laryngeal chemoreceptors (TRPV1; acid‐sensitive ion channels, ASIC; and osmotic receptors) and mechanoreceptors play an important role in triggering apnea, especially in infants, which has been related to the pathogenesis of sudden infant death syndrome (SIDS). LA, a main flavonoid component of licorice widely used as an antitussive herbal medicine in China even via taking lozenge, is reportedly able to suppress cough responses to inhalation of aerosolized capsaicin (a selective stimulant of TRPV1) in conscious guinea pigs. These results imply an inhibitory impact of LA on airway TRPV1; however, it remains unknown whether LA affects the apneic responses to selective stimulation of these laryngeal receptors, and if so whether its effect is achieved by directly acting on the superior laryngeal nerve (SLN). In anesthetized and spontaneously breathing rat pups, the following stimulations were applied after intralaryngeally loading 50 μl LA (10 μg/μl) and vehicle for 10 min. Intralaryngeal perfusion of capsaicin (CAP), hydrochloric acid solution (HCl), and distilled water (DW) for 10 s was employed to selectively stimulate local TRPV1, ASIC, and osmotic receptors respectively. Intralaryngeal delivery of air‐puff (AP for 2 s) with peak pressure at ~40 mmHg was utilized to stimulate laryngeal mechanoreceptors. The results showed that CAP, HCl, DW, and AP triggered an immediate apnea with TE prolonged by 24‐, 17‐, 18‐ and 3‐fold respectively. LA per se did not alter baseline ventilation but shortened the CAP‐, HCl‐, and DW‐evoked apneic durations by 75%, 68%, and 54% respectively (P < 0.01) with little effect on the apneic response to AP. To determine the direct effect of LA on the SLN, the latter was bilaterally isolated and pretreated by perilaryngeal LA treatment (10 μg/μl) or vehicle for 20 min. Perilaryngeal LA treatment produced a similar inhibition in CAP‐ and HCl‐induced apneic responses but failed to change DW‐induced apnea. Our results, for the first time, suggest that LA applied on the laryngeal mucosa depresses the stimulatory effects of CAP, HCl, and DW on laryngeal chemoreceptors in which CAP and HCl are capable of directly act on TRPV1 and ASIC of SLN. This finding may extend the therapeutic use of LA to treat a subgroup of SIDS victims with laryngeal disorders and explain, at least partially, the antitussive effect of LA due the critical role of laryngeal sensory afferents in cough initiation. The cellular mechanisms underlying this inhibition are warranted for further investigation. Support or Funding Information NIH HL119683 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Network Pharmacology-Based Strategy for Elucidating the Molecular Basis Forthe Pharmacologic Effects of Licorice (Glycyrrhiza spp.)

“…Liquiritin apioside, which was also present at a high level in licorice, can be used as a marker for the quality assessment of Glycyrrhiza species ( Jiang et al, 2016 ). The phlegm-expulsion and cough-suppressant effects of liquiritin apioside have been reported ( Kuang et al, 2018 ; Wei et al, 2020 ). Also, liquiritin apioside has been linked to TNF, NF-κB, NLR, TLR, and adipocytokine signaling pathways, which have important roles in anti-inflammatory immune activity, energy production, and metabolism ( Guan et al, 2012 ).…”

Apneic response to fentanyl in adult rats: Role of laryngeal afferents

“…Additionally, IVb injection of morphine causes immediate excitation of the recurrent laryngeal nerve and augmentation of laryngeal resistance in anesthetized rats , indicating a stimulatory effect of systemic administration of opioids on laryngeal efferents. While the sensitivity of the SLN to chemicals and its ability to induce immediate apnea, bradycardia, and hypertension have been well-documented in previous studies (Bohm et al, 2007;Carreau et al, 2011;Forsberg et al, 1988;Gao et al, 2017;Liu et al, 2013;Miller, 1976;Mutoh et al, 2000;Wei et al, 2020), it is still unknown whether opioids applied directly onto the larynx could affect cardiorespiratory activities. Our study introduces a novel concept by demonstrating that the application of FNT into the larynx of anesthetized rats can trigger a brief apnea, bradycardia, and hypertension.…”

“…The rats were anesthetized with urethane (1200 mg kg −1 , ip) with supplemental dose (300 mg kg −1 , ip) administered, as needed, to completely suppress eye‐blink and limb‐withdrawal reflex throughout the experiment. The rat was placed in a supine position and the trachea (5 mm below the larynx) was opened with a transverse incision to expose the lumen but leave the posterior tracheal wall intact (Gao et al., 2017 ; Wei et al., 2020 ). Both the rostral and caudal segments of the trachea were cannulated separately.…”

“…First, chemical stimulation of the larynx reflexively triggers central expiratory apnea, laryngeal constriction, cough and swallowing associated with bradycardia and hypertension (Abu‐Shaweesh et al., 2001 ; Lee et al., 1977 ). In the SLN, C‐ and Aδ‐fibers, especially C‐fibers, mediate the chemoreflex in various animals (Gao et al., 2017 ; Liu et al., 2013 ; Mutoh et al., 2000 ; Wei et al., 2020 ). Second, endogenous opioids have been reported to modulate the apneic and vocal closure responses to the activation of laryngeal afferents (Jimenez‐Vargas & Carreira‐Monteiro, 1986 ; Mutolo et al., 1995 ).…”

The Japanese Herbal Medicine Yokukansan Exerted Antioxidant and Analgesic Effects in an Experimental Rat Model of Hunner-Type Interstitial Cystitis

“…Influenza A virus infection increases oxidative stress by upregulating the expression of TLR7 [52]. Liquiritin [53], liquiritin apioside [54], and ferulic acid [55] included in YKS are reported to suppress the activity of NADPH oxidase. It is possible that these ingredients were involved in the YKS antioxidant activity exhibited in this study, and in the future, we will investigate the effect of YKS on TLR7 and NADPH oxidase in this experimental system.…”