Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS levels.

Natural products have a prime importance as an essential source for new drug discovery. Carica papaya leaves (CPL) have been used to treat inflammation in traditional system of medicine. Current study evaluates the anti-inflammatory and immunomodulatory effects of CPL extract using mouse model of ovalbumin- (OVA) induced allergic asthma. All the mice were intraperitoneally sensitized and subsequently given intranasal challenge with OVA except the control group. Group-III and -IV were treated for seven consecutive days with CPL extract and methylprednisolone (MP), respectively. At the end of study, histopathological examination of the lungs was performed and inflammatory cell counts were done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS were measured using reverse transcription polymerase chain reaction (RT-PCR). Results showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and goblet cell hyperplasia after treatment with CPL extract. We also found significant suppression of total and differential leukocyte counts in both blood and BALF samples of CPL extract treated group. CPL extract also alleviated the expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS. Similarly, treatment with MP, used as a reference drug, also significantly ameliorated all the pro-inflammatory markers. Current study shows that CPL extract possesses anti-inflammatory effect in mouse model of allergic airway inflammation by down-regulating IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS expression levels.

Inam A ，Shahzad M ，Shabbir A ，Shahid H ，Shahid K ，Javeed A ... -  《-》

Pistacia integerrima ameliorates airway inflammation by attenuation of TNF-α, IL-4, and IL-5 expression levels, and pulmonary edema by elevation of AQP1 and AQP5 expression levels in mouse model of ovalbumin-induced allergic asthma.

Natural products are considered as an essential source for the search of new drugs. Pistacia integerrima galls (PI) have been used for the treatment of asthma and cough in traditional system of medicine. Current study investigates the immunomodulatory and anti-inflammatory activities of P. integerrima in mouse model of ovalbumin-induced allergic asthma. Mice were intraperitoneally sensitized and subsequently challenged intranasally with ovalbumin to induce allergic asthma. Experimental group mice were treated with methanol extract of P. integerrima extract (200mg/kg b. w.) and Methylprednisolone (MP) (15mg/kg b. w.) for 07 consecutive days, alongside intranasal challenge. Lung tissues were stained with Hematoxyline and Eosin (H & E), and Periodic Acid-Schiff (PAS) stains for histopathological evaluation. Lung wet/dry weight ratio was measured as an index of lung tissue edema. Albumin was injected in the right ear 24h before sacrificing the mice and difference of weight was taken as a degree of delayed type hypersensitivity (DTH). mRNA expression levels of TNF-α, IL-4, IL-5, Aquaporin-1 (AQP1), and AQP5 were evaluated using reverse transcription polymerase chain reaction (RT-PCR) followed by gel electrophoresis. The data showed both PI extract and MP significantly alleviated DTH and nearly normalized total leukocyte count and differential leukocyte count in both blood and BALF. We found significantly suppressed goblet cell hyperplasia and inflammatory cell infiltration after treatment with both PI extract and MP. Expression levels of TNF-α, IL-4, and IL-5 were also found significantly reduced after treatment with both PI extract and MP, which might have resulted in the amelioration of airway inflammation. Current study displayed that both PI extract and MP significantly decreased lung wet/dry ratio, suggesting reduction in pulmonary edema. RT-PCR analysis showed significant increase in AQP1 and AQP5 expression levels after treatment with both PI extract and MP, which might have caused the alleviation of pulmonary edema. Our study displays that P. integerrima possesses significant anti-asthmatic activity which may be attributed to reduction in TNF-α, IL-4, and IL-5 expression levels, and increase in AQP1 and AQP5 expression levels.

Rana S ，Shahzad M ，Shabbir A 《-》

Bupleurum chinense extract ameliorates an OVA-induced murine allergic asthma through the reduction of the Th2 and Th17 cytokines production by inactivation of NFκB pathway.

Bupleurum chinense belongs to the Bupleurum spp. family that has been used in traditional herbal medicine for over thousand years. It has been reported to have anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic, anti-fibrotic and immunomodulatory effect. However, the effect of B. Chinense on allergic asthma remains unclear. This study investigated the immunomodulatory effects of B. Chinense extracts (BCE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we evaluated the number of total cells, differential inflammatory cells and the production of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung homogenate as well as histological structure. The levels of NFκB p65, IκBα, p-NFκB p65, p-IκBα and the total immunoglobulin (Ig) E, anti-OVA IgE, anti-OVA IgG were also examined. The oral administration of 200mg/kg BCE inhibited the accumulation of inflammatory cells especially eosinophils in BALF. Also, BCE regulated the imbalance of Th1, Th2 and Th17-related production, with attenuated the expression of GATA3, IL-1β, IL-4, IL-5, IL-6, TNF-α and RORγt, IL-17A in BALF and lung homogenate, meanwhile, up-regulated the secretion of INF-γ in lung homogenate. The levels of IgE, anti-OVA IgE, anti-OVA IgG1 and anti-OVA IgG2a were also suppressed by BCE treatment in serum. Futhermore, BCE inhibited the proinflammatory cytokines via inactivation of NFκB p65 phosphorylation and IκBα degradation in cytoplasm. The histological analysis showed that the infiltration of inflammatory cells, mucus hypersecretion and collagen fiber deposits were ameliorated in BCE treated mice. In addition, BCE induced the functional differentiation of naive CD4+ T cells forward to Th1 and Tr1 through producing INF-γ and IL-10. These results suggest that BCE may have therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 cytokines production by inactivation of NFκB pathway.

Bui TT ，Piao CH ，Song CH ，Shin HS ，Chai OH ... -  《-》

Effects of (±)-praeruptorin A on airway inflammation, airway hyperresponsiveness and NF-κB signaling pathway in a mouse model of allergic airway disease.

The root of Peucedanum praeruptorum Dunn is a traditional Chinese medicine commonly used to treat asthma in China. (±)-praeruptorin A (PA) is the most abundant constituent of P. praeruptorum Dunn, the effects of which on asthma were investigated using a murine model of allergic airway disease. BALB/c mice were sensitized and challenged by ovalbumin to induce airway inflammation. PA was administered intragastrically before every OVA challenge. Airway responsiveness was measured by a lung function analysis system. The number of total leukocytes in bronchoalveolar lavage fluid was counted using a hemocytometer, and differential cell counts were determined using Diff-Quick-stained smears. Histopathology of lung tissue was analyzed by hematoxylin-eosin and Congo red staining. Levels of inflammatory mediators in bronchoalveolar lavage fluid and immunoglobulins in serum were measured by enzyme-linked immunosorbent assay. The expression of pulmonary eotaxin was detected by immunohistochemistry and reverse transcription polymerase chain reaction. The activation of NF-κB was evaluated by electrophoretic mobility shift assay and western blot analysis. Compared with model group, PA significantly reduced airway hyperresponsiveness and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of interleukin (IL)-4, IL-5, IL-13 and LTC₄ in bronchoalveolar lavage fluid and immunoglobulin (Ig) E in serum, and inhibited eotaxin protein and mRNA expression, IκBα degradation, NF-κB nuclear translocation, NF-κB DNA-binding activity and RelA/p65 phosphorylation in lung, which suggested that PA can significantly suppress OVA-induced airway inflammation and airway hyperresponsiveness in mice, showing great therapeutic potential for the treatment of allergic asthma.

Xiong Y ，Wang J ，Wu F ，Li J ，Zhou L ，Kong L ... -  《-》

Herbal decoction Divya-Swasari-Kwath attenuates airway inflammation and remodeling through Nrf-2 mediated antioxidant lung defence in mouse model of allergic asthma.

Asthma is a chronic respiratory disease orchestrated by immune and structural cells. Identification of novel therapeutic strategies are needed for asthma due to the limitations of existing therapies. We have validated the anti-inflammatory, anti-asthmatic and immunomodulatory therapeutic properties of herbal decoction, Divya-Swasari-Kwath (DSK) using mouse model of ovalbumin (OVA) induced allergic asthma. HPLC analysis identified the presence of Rutin, Glycyrrchzin, Gallic acid, Cinnamic acid, Chlorogenic acid, Caffeic acid and Piperine as bioactive herbal metabolites in DSK. Therapeutic treatment with herbal decoction DSK significantly alleviated the pathological features of allergic asthma including inflammatory cell accumulation in Broncho-Alveolar Lavage (BAL) fluids, specifically lymphocytes and eosinophils, lung inflammation, oxidative stress, airway remodelling, and pro-inflammatory cytokine levels. H&E analysis of lung tissue sections identified attenuated inflammatory cell infiltration and thickening of bronchial epithelium by DSK. PAS staining and MT staining identified decrease in OVA-induced mucus hyper secretion and peri-bronchial collagen deposition respectively, upon DSK treatment. Treatment with DSK increased the mRNA expression of antioxidative defence gene Nrf-2 and its downstream target genes HO-1 and NQO-1. In the same line, biochemical analysis for the markers of oxidative/antioxidant system confirmed the restoration of activity of Catalase, GPx, SOD and EPO and the levels of GSH, GSSG, MDA and Nitrite in whole lungs. In line with PAS staining, DSK treatment decreased the OVA-induced expression of Muc5AC and Muc5B genes. DSK treatment reduced the steady state mRNA expression levels of IL-6, IL-1β, TNF-α, IL-4, -5, -33, IFN-γ in whole lung; and IL-6, TNF-α and IL-1β protein levels in BALF. Collectively, our results suggest that herbal decoction DSK is effective in protecting against allergic airway inflammation and remodelling by regulating anti-oxidant mechanisms. We postulate that DSK could be the potential therapeutic option for allergic asthma management.

Balkrishna A ，Solleti SK ，Singh H ，Verma S ，Sharma N ，Nain P ，Varshney A ... -  《-》