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.
BACKGROUND
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.


OBJECTIVE
Current study investigates the immunomodulatory and anti-inflammatory activities of P. integerrima in mouse model of ovalbumin-induced allergic asthma.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmacology, University of Health Sciences, Lahore, Pakistan.
Shazana
S
Rana
Department of Pharmacology, University of Health Sciences, Lahore, Pakistan. Electronic address: shahzad912@hotmail.com.
Muhammad
M
Shahzad
Department of Pharmacology, University of Health Sciences, Lahore, Pakistan.
Arham
A
Shabbir
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051398:Aquaporin 1 / Q000819:agonists* / Q000096:biosynthesis; D051402:Aquaporin 5 / Q000819:agonists* / Q000096:biosynthesis; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D027927:Pistacia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; C496021:Aqp1 protein, mouse; C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D015848:Interleukin-5; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D051398:Aquaporin 1; D015847:Interleukin-4; D010047:Ovalbumin; D008775:Methylprednisolone
Allergic asthma; Aquaporins; Immunomodulation; Inflammation; Interleukin-4