Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-α, and IL's

Immunopharmacol Immunotoxicol. 2019 Feb;41(1):55-67. doi: 10.1080/08923973.2018.1545788. Epub 2018 Dec 12.

Abstract

Background: Asthma is a chronic airway immunoinflammatory disorder characterized by airway remodeling. Phyllanthus amarus has been reported to possess antioxidant and anti-inflammatory potential. Aim: To evaluate the possible mechanism of action of isolated phytoconstituents from P. amarus (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR). Material and method: 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. Results: 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 (p < .05) by PA (100 and 200 mg/kg). It also significantly decreased (p < .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 (p < .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 (p < .05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA. Conclusion: Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in P. amarus 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.

Keywords: Airway hyperresponsiveness; asthma; hypophyllanthin; immunoglobulin E; nuclear factor-erythroid 2 related factor 2; phyllanthin.

MeSH terms

  • Airway Remodeling / drug effects
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / immunology*
  • Asthma / pathology
  • Asthma / prevention & control*
  • Biomarkers / blood
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Immunoglobulin E / blood
  • Lignans / isolation & purification
  • Lignans / therapeutic use*
  • Lung / drug effects
  • Lung / immunology
  • Lung / ultrastructure
  • Male
  • Ovalbumin
  • Phyllanthus / chemistry*
  • Rats, Sprague-Dawley
  • Respiratory Function Tests

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cytokines
  • Lignans
  • hypophyllanthin
  • Immunoglobulin E
  • phyllanthin
  • Ovalbumin