Korean J Physiol Pharmacol.  2019 Jul;23(4):251-261. 10.4196/kjpp.2019.23.4.251.

Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice

• Huang Q
• Han L
• Lv R
• Ling L

• KMID: 2450492
• DOI: http://doi.org/10.4196/kjpp.2019.23.4.251

Abstract

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

Keyword

Asthma; Cytokines; JAK-STAT pathway; Magnolol

MeSH Terms

Airway Remodeling
Animals
Asthma
Bronchoalveolar Lavage Fluid
Cytokines*
Dexamethasone
Immunoglobulin E
Immunoglobulins
Interferons
Lung
Mice*
Ovalbumin
Ovum
Th17 Cells
Cytokines
Dexamethasone
Immunoglobulin E
Immunoglobulins
Interferons
Ovalbumin

Figure

• 

  Fig. 1 Effect of magnolol on lung function. (A) Airway resistance and (B) lung compliance of mice exposed to ovalbumin (OVA). Values are represented as mean ± standard deviation; n = 6. *p < 0.05 v.s. control as determined by one way-ANOVA followed by Duncan's multiple range test analysis. Dex, dexamethasone.

• 

  Fig. 2 Effect of magnolol on cell accumulation in bronchoalveolar lavage fluid (BALF). Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against ovalbumin (OVA) alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. Dex, dexamethasone.

• 

  Fig. 3 Magnolol reduced levels of ovalbumin (OVA)-specific immunoglobulin E (IgE). Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against OVA alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. BALF, bronchoalveolar lavage fluid; Dex, dexamethasone.

• 

  Fig. 4 Effect of magnolol on cytokines. Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against ovalbumin (OVA) alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. IL, interleukin; Dex, dexamethasone.

• 

  Fig. 5 Magnolol regulates T helper 17 (Th17) cell populations in bronchoalveolar lavage fluid (BALF). Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against ovalbumin (OVA) alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. Dex, dexamethasone.

• 

  Fig. 6 Magnolol reduced inflammation score following ovalbumin (OVA) induction. Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against OVA alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. Dex, dexamethasone.

• 

  Fig. 7 Magnolol activated the Janus kinase (JAK)/signal transduction and activation of transcription (STAT) pathway following ovalbumin (OVA) challenge. L1, control; L2, OVA; L3, OVA + magnolol (12.5 mg/kg); L4, OVA + magnolol (25 mg/kg); L5, OVA + magnolol (50 mg/kg); L6, OVA + dexamethasone (2 mg/kg).

• 

  Fig. 8 Effect of magnolol on Notch signaling. (A) Representative immunoblot. (B) Relative expressions of proteins. Values are represented as mean ± standard deviation; n = 6. *p < 0.05 compared against control; #p < 0.05 compared against ovalbumin (OVA) alone group; a–eSignificant difference (p < 0.05) between mean values within the groups as determined by one-way ANOVA followed by Duncan's multiple range test analysis. L1, control; L2, OVA; L3, OVA + magnolol (12.5 mg/kg); L4, OVA + magnolol (25 mg/kg); L5, OVA + magnolol (50 mg/kg); L6, OVA + dexamethasone (2 mg/kg).

• 

  Fig. 9 Graphical representation of the protective effects exerted by magnolol. OVA, ovalbumin; Th, T helper; IL, interleukin; IFN, interferon; BALF, bronchoalveolar lavage fluid; IgE, immunoglobulin E; JAK, Janus kinase; STAT, signal transduction and activation of transcription.

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