DOI: https://doi.org/10.53350/pjmhs2115102512 ORIGINAL ARTICLE 2512 P J M H S Vol. 15, No.10, OCT 2021 Carica papaya Leaf Extract modulates mRNA expression of Aquaporins in Mouse Model of Allergic Airway Inflammation ASMA INAM 1 , MUHAMMAD SAIR 2 , SADIA IKRAM 3 , SADIA MAJEED 4 , GUL-E-NAZISH 5 , MUHAMMAD IMRAN ASHRAF 6 , MUHAMMAD ZAHID 7 1 Associate Professor Pharmacology, Azra Naheed Medical College, Superior University Lahore. 2 Associate Professor Pharmacology, Islam Medical College Sialkot 3 Associate Professor Pathology, Azra Naheed Medical College, Superior University Lahore. 4 Assistant Professor Pharmacology, Continental Medical College, Lahore 5 Assistant Professor Pharmacology, Shalamar Medical and Dental College, Lahore 6 Associate Professor Pharmacology, Allama Iqbal Medical College, Lahore 7 Professor Pharmacology, Azra Naheed Medical College, Superior University Lahore. Correspondence to Dr. Asma Inam, Email ID: asma.inam@superior.edu.pk, Cell Number: +923344554664 ABSTRACT Background: Asthma is a chronic inflammatory disease affecting smaller airways. Airflow obstruction leading to airway hyper-responsiveness and increased mucus production are salient features of asthma pathophysiology. Generally, Th2 cytokines are increased in allergic asthma. Aim: To propose the molecular mechanisms by which Carica Papaya Leaves Extract (CPLE) alleviates pulmonary edema in animal model of allergic airway inflammation comparable to methylprednisolone. Place and duration of study: Pharmacology Department, University of Health Sciences Lahore for 1 year. Methods: We took twenty four male BALB/c mice and divided them equally into four groups. The control group was given PBS only, while Group II served as diseased group and induced airway inflammation by ovalbumin. Group III and IV were first induced with airway inflammation and side by side treated with Carica papaya leaf extract (CPLE) 100mg/kg body weight orally and methylprednisolone 15 mg/kg body weight intraperitoneally for seven consecutive days respectively. At the end of the experimental protocol, mice were euthanized and lung wet/dry ratio was measured. mRNA expression of AQP1 and AQP5 in lung tissue were also determined using RT-PCR. Results: Ethanolic extract of Carica Papaya leaves decreased all markers of pulmonary edema in mouse model of allergic airway inflammation comparable to methylprednisolone by decreasing lung wet/dry ratio and enhancing AQP1 and AQP5 mRNA expression. Conclusion: Carica Papaya leaves extract may diminish pulmonary edema in mice associated with allergic asthma. Keywords: AQP1, AQP5 (Aquaporins), Carica Papaya Leaves Extract (CPLE), Pulmonary Edema, Th2 cytokines. INTRODUCTION Allergic asthma is initiated by a complex interplay of proinflammatory cytokines and inflammatory mediators in lung tissue causing airway narrowing, mucosal edema and airway hyperresponsiveness 1 . Leukotrienes, histamine and major basic protein are the main reasons for underlying bronchoconstriction. According to many studies, Aquaporins (AQP) are found to be responsible for pulmonary edema associated with bronchial asthma. These water channel proteins facilitate fluid transport in alveolar space and affect airway humidification, pleural fluid absorption, and submucosal gland secretion 2 . Out of 20 aquaporins, only AQP1, AQP3, AQP4 and AQP5 are expressed in lung tissue. AQP1 and AQP5 which are main water transport channels are located at apical membranes of capillary endothelial cells & type I alveolar epithelial cells. Some of the aquaporins belong to another subfamily which is mainly involved in glycerol transport across cell membranes 3 . Besides water transport, these protein channels are also found to be involved in cell migration, cell adhesion and inflammatory cascade. Aquaporins also play significant functions in various physiological and pathological manifestations of different lung diseases such as pleural effusion, bronchial asthma ------------------------------------------------------------------------------ Received on 13-05-2021 Accepted on 17-09-2021 and lung cancer. Selective targeting of aquaporins can serve as new treatment modalities for these illnesses 4 . Pharmacological treatment of bronchial asthma includes the use of bronchodilators and anti-inflammatory drugs according to severity and frequency of asthmatic symptoms. Unfortunately, these groups of drugs neither provide long term relief, nor they are devoid of any adverse effects 5 . Keeping in mind these observations, scientists are now exploring to find more specific, potent, and safer drugs to decrease the burden of this prevailing disease 6 . To date, medicinal plants have also gained attention in the field of pharmacology. Their potential against different diseases led us to investigate their active compounds and explore their proposed mechanism of action 7 . Carica Papaya belonging to the family Caricacae has been found to have anti-inflammatory, antioxidant, anticancer, antiviral and antibacterial properties. Alkaloids and flavonoids isolated from its fruit, pulp and leaves have been attributed towards these scientific findings 8 . Kovendin et al., 2012 described that Carica papaya leaves have been traditionally used in the past for relief of asthmatic symptoms but very few studies have been carried out to confirm its anti-inflammatory or bronchodilator potential 9 . n our previous scientific research, Carica papaya leaves extract has been shown to reduce airway inflammation, goblet cell hyperplasia and mRNA