Juglans regia <i>L</i> . (Walnut) Leaf Extract Ameliorates Pulmonary Edema Against Airway Inflammation via Upregulation of Tight Junction Proteins and Heme Oxygenase‐1 in the Lungs of Asthmatic Mice

<b>Background:</b> <i>Juglans regia</i> L. is renowned for its traditional use as a cure for respiratory diseases such as asthma and sinusitis. <b>Objectives:</b> This study was intended to assess the protective mechanism of the effects of hydroalcoholic extract of the leaf of <i>Juglans regia</i> L. against airway inflammation and pulmonary edema by measuring the expression levels of heme oxygenase-1 (HO-1), occludin, and Zonula occludens-1 (ZO-1) in the lung tissues. <b>Methods:</b> Ovalbumin (OVA) was used intraperitoneally to sensitize mice on Days 0 and 14 to induce allergic asthma by the intraperitoneal route. Animals were divided into 5 groups, consisting of normal control (NC), disease group (OVA, i.p), low-dose <i>J. regia</i> (LDJR) and high-dose <i>J. regia</i> (HDJR), methylprednisolone (MP), and reference control (RC) drug. On the 28^th day, blood and bronchial alveolar lavage fluid (BALF) were collected for total leukocyte (TLC) and differential leukocyte (DLC) analysis. Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining of the lungs were performed for the architectural changes caused by OVA-induced bronchial asthma. Tight junction proteins were assessed by measuring the expression levels of HO-1, occludin, and ZO-1 in the lung tissues by using real-time polymerase chain reaction. <b>Results:</b> Scores of inflammations, edema, and goblet cell hyperplasia were significantly increased (all <i>p</i> ≤ 0.05) in the DC group compared to the NC group, while treatment with LDJR and HDJR significantly reduced (all <i>p</i> ≤ 0.05) the scores of inflammations, edema, and goblet cell hyperplasia compared to the DC group. Real-time polymerase chain reaction data showed that expression levels of HO-1, occludin, and ZO-1 in lung tissues of the DC group were significantly reduced (all <i>p</i> ≤ 0.05), when the same was compared to the NC group, while treatment with LDJR and HDJR significantly increased (<i>p</i> ≤ 0.05) their expression level when compared to the DC group. <b>Conclusion:</b> <i>Juglans regia</i> L.'s hydroalcoholic extract possesses antiasthmatic activity by normalizing the TLC cells and DLC cells. <i>Juglans regia</i> L.'s hydroalcoholic extract resulted in the amelioration of pulmonary edema which is attributed to the upregulation of HO-1, occludin, and ZO-1 in the lung tissues of the <i>Juglans regia L. treated</i> groups when compared to the diseased control group. Administration of <i>Juglans regia</i> L.'s extract also reduces the scores of inflammation and vascular congestion by evaluation of the lungs' histopathology in the disease control group when compared to the NC group.