Grape seed proanthocyanidin extract attenuates airway inflammation and hyperresponsiveness in a murine model of asthma by downregulating inducible nitric oxide synthase.
Allergic asthma is characterized by hyperresponsiveness and inflammation of the airway with increased expression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). Grape seed proanthocyanidin extract (GSPE) has been proved to have antioxidant, antitumor, anti-inflammatory, and other pharmacological effects. The purpose of this study was to examine the role of GSPE on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice, sensitized and challenged with ovalbumin (OVA), were intraperitoneally injected with GSPE. Administration of GSPE remarkably suppressed airway resistance and reduced the total inflammatory cell and eosinophil counts in BALF. Treatment with GSPE significantly enhanced the interferon (IFN)- γ level and decreased interleukin (IL)-4 and IL-13 levels in BALF and total IgE levels in serum. GSPE also attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. The elevated iNOS expression observed in the OVA mice was significantly inhibited by GSPE. In conclusion, GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to have a potential in the treatment of allergic asthma.
Zhou DY
,Du Q
,Li RR
,Huang M
,Zhang Q
,Wei GZ
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Myxopyrum serratulum ameliorates airway inflammation in LPS-stimulated RAW 264.7 macrophages and OVA-induced murine model of allergic asthma.
Myxopyrum serratulum A. W. Hill. (Oleaceae) is a traditionally used Indian medicinal plant for the treatment of cough, asthma and many other inflammatory diseases.
In this study, the protective effects of M. serratulum on airway inflammation was investigated in ovalbumin (OVA)-induced murine model of allergic asthma and lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 murine macrophages, and the possible mechanisms were elucidated.
The phytochemicals present in the methanolic leaf extract of M. serratulum (MEMS) were identified by reverse phase high performance liquid chromatography (RP-HPLC) analysis. In vitro anti-inflammatory activity of MEMS were evaluated by estimating the levels of nitric oxide (NO), reactive oxygen species (ROS) and cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, G-CSF and GM-CSF) in LPS-stimulated RAW 264.7 macrophages. In vivo anti-asthmatic activity of MEMS was studied using OVA-induced murine model. Airway hyperresponsiveness (AHR), was measured; total and differential cell counts, eosinophil peroxidase (EPO), prostaglandin E2 (PGE2), NO, ROS, and cytokines (IL-4, IL-5 and IL-13), were estimated in bronchoalveolar lavage fluid (BALF). Serum total IgE level was measured; and the histopathological changes of lung tissues were observed. The expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissue homogenates were detected by Western blot.
The chromatographic analysis of MEMS identified the presence of gallic acid, protocatechuic acid, catechin, ellagic acid, rutin, p-coumaric acid, quercetin, naringenin and apigenin. MEMS (125 and 250 μg/mL) dose-dependently reduced the levels of NO, ROS and pro-inflammatory cytokines in LPS-stimulated RAW 264.7 macrophages. MEMS (200 and 400 mg/kg, p.o.) significantly (p < 0.05) alleviated AHR; number of inflammatory cells, EPO, PGE2, NO, ROS, and cytokines (IL-4, IL-5 and IL-13) in BALF; serum total IgE and the histopathological changes associated with lung inflammation. Western blot studies showed that MEMS substantially suppressed COX-2 and iNOS protein expressions in the lung tissues of OVA-sensitized/challenged mice.
The present study corroborates for the first time the ameliorative effects of MEMS on airway inflammation by reducing the levels of oxidative stress, pro-inflammatory cytokines and inhibiting COX-2, iNOS protein expressions, thereby validating the ethnopharmacological uses of M. serratulum.
Maruthamuthu V
,Henry LJK
,Ramar MK
,Kandasamy R
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