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Asthma is a chronic airway immunoinflammatory disorder characterized by airway remodeling. has been reported to possess antioxidant and anti-inflammatory potential. To evaluate the possible mechanism of action of isolated phytoconstituents from (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR). Phyllanthin and hypophyllanthin were isolated and characterized (HPLC) from the methanolic extract of PA. AHR was induced in Sprague-Dawley rats by OVA-challenged, and animals were treated with PA (50, 100, and 200 mg/kg, p.o.) for 28 days. The HPLC analysis showed the presence of phyllanthin and hypophyllanthin in methanolic extract of PA at RT of 25.243 and 26.832 min, respectively. OVA-induced alterations in hemodynamic parameters, lung functions test, peripheral blood oxygen level, total, and differential cell count in Bronchoalveolar Lavage Fluid was significantly attenuated ( < .05) by PA (100 and 200 mg/kg). It also significantly decreased ( < .05) the levels of total protein and albumin in serum, BALF, and lungs. OVA-induced increase in IgE (total and OVA-specific), and oxido-nitrosative stress (SOD, GSH, MDA, and NO) levels were significantly ( < .05) decreased by PA. RT-PCR analysis revealed that elevated oxido-nitrosative stress (Nrf2 and iNOs), immune-inflammatory makers (HO-1, TNF-α, IL-1β, and TGF-β1), Th2 cytokines (IL-4 and IL-6) levels were significantly attenuated ( < .05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA. Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in alleviated Th2 response in OVA-induced AHR via modulation of endogenous markers in a murine model of asthma. Thus, phyllanthin and hypophyllanthin may be a new therapeutic approach for the management of asthma.

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http://dx.doi.org/10.1080/08923973.2018.1545788DOI Listing

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