Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5.

Current study investigates the immunomodulatory effects of T. stocksianum using mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were treated with methanolic extract, n-hexane, and ethyl acetate fractions for consecutive 7 days along with intranasal challenge. The mRNA expression levels of interleukin-4 (IL-4), IL-5, Aquaporin-1 (AQP1) and Aquaporin-5 (AQP5) were evaluated using reverse transcription polymerase chain reaction. The data showed that T. stocksianum significantly reduced airway inflammation as indicated by reduced inflammatory cell infiltration in lungs, and attenuated total and differential leukocyte counts both in blood and BALF. Expression levels of pro-inflammatory IL-4 and IL-5 in lungs were also found significantly reduced. T. stocksianum significantly reduced pulmonary edema as indicated by reduced lung wet/dry ratio and goblet cell hyperplasia. AQP1 and AQP5 expression levels were also found elevated in treatment groups. In conclusion, T. stocksianum possesses anti-asthmatic activity which may be attributed to reduction in IL-4 and IL-5 expression levels, and elevation in AQP1 and AQP5 expression levels.

Ijaz B ，Shabbir A ，Shahzad M ，Mobashar A ，Sharif M ，Basheer MI ，Tareen RB ，Syed NI ... -  《-》

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.

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

Rana S ，Shahzad M ，Shabbir A 《-》

Amelioration of allergic asthma by Ziziphora clinopodioides via upregulation of aquaporins and downregulation of IL4 and IL5.

Ziziphora clinopodioides has been frequently used as an anti asthmatic plant in traditional medication. Recent work explores the anti-asthmatic activity of Z. clinopodioides in allergen-induced asthmatic mice. Intraperitoneal sensitization followed by intranasal challenge were given with ovalbumin (allergen) to develop allergic asthma. Investigational groups of animals were administered with drug methylprednisolone (MP) (15 mg/kg body weight), n-hexane fraction, ethylacetate fraction, and methanolic extract of Z. clinopodioides extract (500 mg/kg b.w.) for successive 07 days. Hematoxyline and eosin (H&E) and periodic acid-Schiff (PAS) stains were used to evaluate histopathological parameters on lung tissues. As an index of lungs tissues edema, wet/dry weight ratio of lungs was determined. Evaluation of expression levels of AQP1, AQP5, IL4, and IL5 was conducted by using RT-PCR. The data exhibited that both Z. clinopodioides and MP attenuated differential and total leukocyte counts in hematological examination i.e. in BALF and blood. Treatment with Z. clinopodioides also caused suppression of inflammatory cell infiltration and expression levels of IL4 and IL5, the later could have caused attenuation of pulmonary inflammation. The study also found decline in lung wet/dry ratio and goblet cellh hyperplasia in treated groups which indicates amelioration of lung edema. Treatment with Z. clinopodioides significantly increased the expression levels of aquaporin-1 and -5, which could have led to reduction in lung edema. The treatment with MP showed comparable results to Z. clinopodioides. Current investigation revealed that Z. clinopodioides possessed anti-asthmatic property which might be accredited to upregulagted AQP1 and AQP5 levels and downregulated IL4 and IL5 levels.

Ahsan F ，Shabbir A ，Shahzad M ，Mobashar A ，Sharif M ，Basheer MI ，Tareen RB ，Syed NI ... -  《-》

Anti-asthmatic agents alleviate pulmonary edema by upregulating AQP1 and AQP5 expression in the lungs of mice with OVA-induced asthma.

Ovalbumin (OVA)-induced asthma in mouse lungs causes changes in the mRNA and protein levels of aquaporins (AQPs). AQP expression was examined in the presence of various anti-asthmatic agents, including dexamethasone, ambroxol, and terbutaline. The influence of these agents on OVA-induced airway inflammation was also evaluated. The mRNA expression levels of AQP1, 4, and 5 were significantly reduced and that of AQP3 was significantly increased 24h after the last OVA exposure. The protein levels of AQP1, 3, and 5 mirrored the mRNA expression profiles, but AQP4 did not exhibit any changes. Only the mRNA and protein expression levels of AQP1 and AQP5 were significantly increased by these three anti-asthmatic agents. Dexamethasone and ambroxol improved the eosinophil infiltration, mucus secretion, and pulmonary edema caused by OVA, but terbutaline only alleviated pulmonary edema. These results indicate that AQP1 and AQP5 are closely related to pulmonary edema but not to eosinophil infiltration or mucus secretion during asthma. Anti-asthmatic agents could alleviate pulmonary edema through upregulating the expression of AQP1 and AQP5 in mouse lungs that have OVA-induced asthma.

Dong C ，Wang G ，Li B ，Xiao K ，Ma Z ，Huang H ，Wang X ，Bai C ... -  《-》

Immunomodulatory and Anti-Inflammatory Potential of Curcumin for the Treatment of Allergic Asthma: Effects on Expression Levels of Pro-inflammatory Cytokines and Aquaporins.

Shahid H ，Shahzad M ，Shabbir A ，Saghir G ... -  《-》