Antitussive Effect of Naringin on Experimentally Induced Cough in Guinea Pigs

Abstract

The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels.

Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke

“…Smoke-exposed guinea pigs with enhanced cough are suitable for assessing the antitussive effect of candidates on pathological cough [26]. The peripheral antitussive effect of naringin on non-pathological cough had been confirmed in healthy guinea pig models [14]. Here we further demonstrated the antitussive effect of naringin on enhanced cough and inhibiting effect on AHR in this guinea pig model of smokeinduced chronic bronchitis.…”

“…Naringin can exert expectorant effect via promoting tracheal cilia movement, inhibiting the over expression and secretion of MUC5AC and MUC5B mucin, and preventing the hyperplasia of airway goblet cells [13]. Naringin also exhibits peripheral antitussive effect in experimental cough models in guinea pigs [14]. Besides, it has been reported that naringin could suppress the AHR and eosinophilic airway inflammation in OVA-induced asthma and attenuate acute neutrophilic airway inflammation in LPS-induced acute lung injury in mice through blocking the NF-κB pathway [15,16].…”

Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma

“…Pretreatment with naringin (18.4 mg/kg) substantially inhibited both enhanced cough and airway neurogenic inflammation in cigarette smoke-exposed guinea pigs [16,18]. Gao et al [22] observed an antitussive effect of naringin at 30 mg/kg in guinea pigs and pointed out that naringin was not a central antitussive drug. Moreover, naringin did not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K(þ) channels.…”

Tissue Distribution Study of Naringin in Rats by Liquid Chromatography-Tandem Mass Spectrometry

“…Extensive studies have shown that naringin has multiple bioactivities, including anti-infl ammatory [ 1 ] , anti-oxidation [ 2 ] , anti-ulcer [ 3 ] , anti-atherogenic [ 4 ] and anticancer [ 5 ] activities. Recently, we demonstrated that naringin, purifi ed from the aqueous extract of Huajuhong with purity over 98 %, was an eff ective peripheral antitussive [ 6 ] by signifi cantly inhibiting the responses of rapidly adapting receptors (RARs) [data to be published], which evoke cough refl ex and are distributed to the organs of trachea and lung [ 7 ] . Thus it could avoid side eff ects such as sedation, nausea, addictive potential, and constipation, often caused by centrally-acting antitussives [ 8 ] .…”