shikonin and Asthma

Shikonin is a naphthoquinone extracted from the root of Lithospermum erythrorhizon, and has been reported to suppress allergic airway inflammation in mice. However, the underlying mechanisms are unclear and need to be further elucidated. In this study, shikonin (0.5, 2 or 4mg/kg) was given intraperitoneally to ovalbumin (OVA)-challenged BALB/c mice. We found that the pathological airway remodeling of asthmatic mice was alleviated by shikonin, and the infiltrated inflammatory cells and collagen deposition in their lungs were reduced. Furthermore, the abnormal activation of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) pathway and the elevation of matrix metalloproteinase 9 (MMP9) in the lung of asthmatic mice were suppressed by shikonin. The inactivation of NF-κB by shikonin was at least in part via inhibiting IκBα activation. In vitro, the treatment of shikonin inhibited the platelet-derived growth factor (PDGF)-induced proliferation of primary airway smooth muscle cells (ASMCs), and induced a G0/G1 arrest in these cells. In addition, ASMCs exposed to PDGF acquired an enhanced migratory ability, and the activities of MMP9 and matrix metalloproteinase 2 (MMP2) and expression of MMP9 of these cells were significantly up-regulated. These PDGF-induced alterations were also inhibited by shikonin. The inhibitory effects of shikonin on the proliferation and migration of ASMCs were comparable to pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF-κB pathway. In conclusion, the present study sheds lights on how shikonin alleviates allergic airway remodeling.

Topics: Airway Remodeling; Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Cell Movement; Cells, Cultured; Lung; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice, Inbred BALB C; Myocytes, Smooth Muscle; Naphthoquinones; NF-kappa B; Platelet-Derived Growth Factor; Rats, Sprague-Dawley; Signal Transduction

Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.. Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.. Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100µg·mL(-1) ) and thymic stromal lymphopoietin (TSLP; 20ng·mL(-1) ). Shikonin-treated BM-DCs were poor stimulators of CD4(+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.. Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bone Marrow Cells; Bronchoalveolar Lavage Fluid; Cytokines; Dendritic Cells; Drugs, Chinese Herbal; Female; Inflammation; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Naphthoquinones; Ovalbumin; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha