Thymoquinone ameliorates airway scaring in animal models for bronchiolitis obliterans syndrome following human lung transplantation

Background:

Bronchiolitis obliterans (BOS) or chronic rejection is the most serious complication after lung transplantation. Mesenchymal stem cells (MSCs) contribute to fibrous tissue formation in BOS patients. Thymoquinone, the main extract of Nigella sativa oil exhibited cellular anti-proliferative effects of many cancer cell lines. Whether Thymoquinone could inhibit the recruitment of MSCs and relieve fibrosis in BOS patients is unknown.

Material and method:

Heterotopic tracheal transplantation was performed in mouse model simulating bronchiolitis obliterans syndrome following human lung transplantation. Treated group received intraperitoneal Thymoquinone (8 mg/kg bodyweight) daily for 3 weeks. Animals were then sacrificed and tissues were examined histologically. MSCs were also isolated from bronchoalveolar lavage from the lungs of animal recipients. The in-vitro effect of thymoquinone on MSCs was analyzed using proliferation, migration and wound healing assays.

Result:

Histologically, thymoquinone treated mice showed significantly reduced fibrosis in their tracheal allografts as compared to controls. Moreover, Thymoquinone treatment inhibited the proliferation and migration of MSCs in-vitro at 24 hours (p < 0.0001) and 48 hours (p < 0.009) post-treatment. Furthermore, Thymoquinone treatment ameliorates wound healing in cultures of MSCs.

Conclusion:

These results indicate that Thymoquinone eliminates airway scaring after heterotopic tracheal transplantation and inhibits the proliferation, migration of lung MSCs as well as the MSC-mediated wound healing and thus could interfere with the mechanism of BOS. Targeting MSCs by Thymoquinone might be useful complementary treatment for BOS patients after Lung transplantation.