Hesperidin-3′-O-Methylether Is More Potent than Hesperidin in Phosphodiesterase Inhibition and Suppression of Ovalbumin-Induced Airway Hyperresponsiveness

Abstract

Hesperidin is present in the traditional Chinese medicine, “Chen Pi,” and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3′-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3′-O-methylether, but not hesperidin, at 30 μmol/kg (p.o.) significantly attenuated the enhanced pause (P enh) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG2a in the serum of sensitized and challenged mice, suggesting that hesperidin-3′-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by β-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3′-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4H/PDE4L) ratio than hesperidin. Thus, hesperidin-3′-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.

In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

“…Few studies demonstrated that HSP protected the organ tissues against various toxic agents, which induced oxidative damage such as TCDD, cadmium, and dimethylbenzanthracene [23,24]. Different mechanisms have been suggested for the beneficial effects of HSP against LPS damage including its antioxidant ability or suppression of AhR receptors in the cells [25].…”

Oral administration of hesperidin, a citrus flavonone, in rats counteracts the oxidative stress, the inflammatory cytokine production, and the hepatotoxicity induced by the ingestion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

“…However, HP prevents the oxidative effects of TCDD and these protective effects are mainly due to its antioxidant properties such as being a scavenger of free radicals or an inhibitor of bio-molecule oxidation. Also, Yang et al [25] have claimed that HP suppressed the AhR receptors, thus the beneficial effects of HP against TCDD toxicity may be partially accounted for by the suppression of these AhR receptors. The present study demonstrated that TCDD treatment caused severe histological damage (eosinophilic-stained and pyknotic nuclei cells, congestion, intracytoplasmic vacuolization and cell infiltration) in liver tissues of rats.…”

“…It was claimed that these effects of HP were due to its suppression of the AhR receptors. It was also determined that [25] Q binds directly AhR as a natural ligand. In this context, the immunoprotective effects of HP in TCDD toxicity may occur because Q and TCDD bind AhR competitively.…”

Dried Yeast Extracts Curtails Pulmonary Oxidative Stress, Inflammation and Tissue Destruction in a Model of Experimental Emphysema

“…Several studies show potential roles of natural plant extracts and compounds for the treatment of asthma and COPD [22,23]. Anti-inflammatory and antioxidant polyphenols including resveratrol, curcumin, quercetin, sulforaphane, lycopene, mangiferin, and dihydroquercetin suppress experimental pulmonary fibrosis and modulate various biochemical features of COPD [24,25].…”