kaempferol-3-o-rhamnoside and Asthma

The modification of natural flavonoid by glycosylation alters their physicochemical and pharmacokinetic properties, such as increased water solubility and stability, reduced toxicity, and sometimes enhanced or even new pharmacological activities. Kaempferol (KF), a plant flavonoid, and its glycosylated derivative, kaempferol-3-O-rhamnoside (K-3-rh), were evaluated and compared for their anti-inflammatory, anti-oxidant, and anti-asthmatic effects in an asthma model mouse. The results showed that K-3-rh fully maintained its anti-inflammatory and anti-asthmatic effects compared with KF in an asthma model mouse. Both KF and K-3-rh significantly reduced the elevated inflammatory cell numbers in the bronchoalveolar lavage fluid (BALF). KF and K-3-rh also significantly inhibited the increase in Th2 cytokines (IL-4, IL-5, and IL-13) and TNF-α protein levels through inhibition of the phosphorylation Akt and effectively suppressed eosinophilia in a mouse model of allergic asthma. The total immunoglobulin (Ig) E levels in the serum and BALF were also blocked by KF and K-3-rh to similar extents. K-3-rh exerts similar or even slightly higher inhibitory effects on Th2 cytokines and IgE production compared with KF, whereas K-3-rh was less effective at DPPH radical scavenging and the inhibition of ROS generation in inflammatory cells compared with KF. These results suggested that the K-3-rh, as well as KF, may also be a promising candidate for the development of health beneficial foods or therapeutic agents that can prevent or treat allergic asthma.

Topics: Alanine Transaminase; Allergens; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Aspartate Aminotransferases; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Glycosides; Immunoglobulin E; Kaempferols; Lung; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species

Asthma is a serious health problem causing significant mortality and morbidity globally. Persistent airway inflammation, airway hyperresponsiveness, increased immunoglobulin E (IgE) levels and mucus hypersecretion are key characteristics of the condition. Asthma is mediated via a dominant T-helper 2 (Th2) immune response, causing enhanced expression of Th2 cytokines. These cytokines are responsible for the various pathological changes associated with allergic asthma. To investigate the anti-asthmatic potential of afzelin, as well as the underlying mechanisms involved, its anti-asthmatic potential were investigated in a murine model of asthma. In the present study, BALB/c mice were systemically sensitized using ovalbumin (OVA) followed by aerosol allergen challenges. The effect of afzelin on airway hyperresponsiveness, eosinophilic infiltration, Th2 cytokine and OVA‑specific IgE production in a mouse model of asthma were investigated. It was found that afzelin‑treated groups suppressed eosinophil infiltration, allergic airway inflammation, airway hyperresponsiveness, OVA-specific IgE and Th2 cytokine secretion. The results of the present study suggested that the therapeutic mechanism by which afzelin effectively treats asthma is based on reduction of Th2 cytokine via inhibition of GATA-binding protein 3 transcription factor, which is the master regulator of Th2 cytokine differentiation and production.

Topics: Allergens; Animals; Asthma; Bronchial Hyperreactivity; Cytokines; Disease Models, Animal; Eosinophils; GATA3 Transcription Factor; Gene Expression Regulation; Humans; Immunoglobulin E; Mannosides; Mice; Ovalbumin; Proanthocyanidins; Th2 Cells