19 research outputs found
C-Kit Binding Properties of Hesperidin (a Major Component of KMP6) as a Potential Anti-Allergic Agent
Accumulation of mast cells can be causally related to several allergic inflammations. Stem cell factor (SCF) as a mast cell chemotaxin induces mast cell migration. To clarify a new effect of Pyeongwee-San extract (KMP6, a drug for indigestion) for the treatment of allergy, we investigated the effects of KMP6 on SCF-induced migration of rat peritoneal mast cells (RPMCs). A molecular docking simulation showed that hesperidin, a major component of KMP6, controls the SCF and c-kit binding by interaction with the active site of the c-kit. KMP6 and hesperidin significantly inhibited SCF-induced migration of RPMCs (P<0.05). The ability of the SCF to enhance morphological alteration and F-actin formation was also abolished by treatment with KMP6 or hesperidin. KMP6 and hesperidin inhibited SCF-induced p38 MAPK activation. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with KMP6 or hesperidin (P<0.05). Our results show for the first time that KMP6 potently regulates SCF-induced migration, p38 MAPK activation and inflammatory cytokines production through hindrance of SCF and c-kit binding in RPMCs. Such modulation may have functional consequences during KMP6 treatment, especially mast cell-mediated allergic inflammation disorders
Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA-134a or CFC propellant in a broad range of doses
AbstractThe aim of the present study was to demonstrate an equivalent asthma control and safety of inhaled budesonide 200μg unit-dose via a spacer device (Jet® Spacer, Chiesi Farmaceutici S.p.A.) given with an HFA-134a or CFC propellant in stable patients treated with inhaled corticosteroids. A total number of 270 patients, 134 in the HFA-134a group and 136 in the CFC group, completed a 2-week run-in period and were then randomised to receive a daily dose of inhaled budesonide (low dose: 400μg, medium dose: 800μg, high dose: 1200 or 1600μg), defined on the basis of the dose of previous inhaled steroids given twice daily for 12 weeks. Morning and evening PEFR, intake of rescue salbutamol, number of day-time and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR and MEF50) and vital signs were measured at the clinics at study entry, at the start of treatment and after 2, 4, 8 and 12 weeks thereafter. Morning serum cortisol (8.00–10.00AM) was measured at baseline and in the final visit. Adverse events and vital signs were recorded throughout the total study period.Small increases vs. baseline for lung function (more markedly in the high-dose subsets) and significant decreases of symptoms and use of rescue salbutamol were similarly observed in both groups. Equivalence was demonstrated for the primary endpoint morning PEFR (difference between means=−1.51l/min; 95% CI: −9.40–6.37l/min; pre-defined limits: ±42.16l/min, i.e. ±10% of the reference LSM) as well as for evening PEFR and FEV1, both in the ITT population or on a per-protocol basis. No statistically significant differences between groups were observed in any of the other efficacy variables.A similar proportion of drug-related adverse events was observed in the two groups, without drug-related serious events in either group. No evidence of adrenal depletion was also noted with both propellants.In conclusion, the budesonide HFA-134a formulation given with a spacer device provided an equivalent asthma control with that of a corresponding CFC product, when administered in stable patients treated with inhaled corticosteroids in a broad range of daily doses. The use of the new propellant did not modify the safety profile of inhaled budesonide