<p>The Protective Role of Tanshinone IIA in Silicosis Rat Model via TGF-β1/Smad Signaling Suppression, NOX4 Inhibition and Nrf2/ARE Signaling Activation</p>

Abstract

Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/kPjjBxXCkyc Purpose: Silicosis is an occupational disease caused by inhalation of silica and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a traditional natural component, has been reported to possess anti-inflammatory, antioxidant, and anti-fibrotic properties. The current study's purpose was to examine Tan IIA's protective effects against silicainduced pulmonary fibrosis and to explore the underlying mechanisms. Methods: 48 male SD rats were randomly divided into four groups (n=12): i) Control group; ii) Silicosis group; iii) Tan IIA group; iv) Silicosis +Tan IIA group. Two days after modeling, the rats of Tan IIA group and Silicosis +Tan IIA group were given intraperitoneal administration 25 mg/kg/d Tan IIA for 40 days. Then, the four groups of rats were sacrificed and the lung inflammatory responses were measured by ELISA, lung damage and fibrosis were analyzed by hematoxylin and eosin (H&E) staining and Masson staining, the expression levels of collagen I, fibronectin and α-smooth muscle actin (α-SMA) were measured by immunohistochemistry. The markers of oxidative stress were measured by commercial kits, and the activity of the TGF-β1/Smad and NOX4, Nrf2/ARE signaling pathways were measured by RT-PCR and Western blotting. Results: The silica-induced pulmonary inflammtory responses, structural damage and fibrosis were significantly attenuated by Tan IIA treatment. In addition, treatment with Tan IIA decreased collagen I, fibronectin and α-SMA expression, and inhibited TGF-β1/Smad signaling in the lung tissue. The upregulated levels of oxidative stress markers in silicosis rats were also markedly restored following Tan IIA treatment. Furthermore, treatment with Tan IIA reduced NOX4 expression and enhanced activation of the Nrf2/ARE pathway in the lung tissue of silicosis rats. Conclusion: These findings suggest that Tan IIA may protect lung from silica damage via the suppression of TGF-β1/Smad signaling, inhibition of NOX4 expression and activation of the Nrf2/ARE pathway.

The role of NOX4 in pulmonary diseases

“…increases (Feng et al, 2019;Gogoi et al, 2019;Peng et al, 2019). In contrast, protective substances such as ethyl acetate extract of salvia miltiorrhiza and the major constituent tanshinone IIA contain many lipophilic diterpenoid quinones with anti-inflammatory and antioxidative effects (Feng et al, 2019;Gogoi et al, 2019;Peng et al, 2019).…”

“…The relationship between Nrf2 and NOX4 has not been explicitly described (Feng et al, 2019;Gogoi et al, 2019;Peng et al, 2019).…”

“…Based on these findings, we can hypothesize that the expressions of NOX4 and Nrf2 are positively correlated, while in some particular experiments, the Nrf2 and NOX4 expressions are negatively correlated (Gogoi et al, 2019). Toxic substances, such as silicon or circulatory heavy metals, inactivate Nrf2, whereas the level of NOX4 increases (Feng et al, 2019; Gogoi et al, 2019; Peng et al, 2019). In contrast, protective substances such as ethyl acetate extract of salvia miltiorrhiza and the major constituent tanshinone IIA contain many lipophilic diterpenoid quinones with anti‐inflammatory and antioxidative effects (Feng et al, 2019; Gogoi et al, 2019; Peng et al, 2019).…”

<p>Emodin Retarded Renal Fibrosis Through Regulating HGF and TGFβ–Smad Signaling Pathway</p>

“…32 Moreover, Notch3 relieves symptom of cardiac fibrosis via downregulation of αSMA. 25 Collagen II has been regarded as being downregulated during the progression of fibrosis. 33 Consistent with these data, emodin in combination with HGF suppressed the development of renal fibrosis via decreasing fibronectin and αSMA and upregulating collagen II in vitro.…”

“…As we know, fibronectin, collagen II, and αSMA are the key markers in fibrosis. 24,25 Emodin 10 μM affected collagen II, fibronectin, and αSMA expression to a limited. Therefore, 20 μM emodin was selected for the following experiments.…”