Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice.

Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.

Tanshinone IIA sulfonate protects against cigarette smoke-induced COPD and down-regulation of CFTR in mice.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline. The anti-inflammatory actions of tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied. However, it remains unknown whether sodium tanshinone IIA sulfonate (STS) protects against the development of COPD. Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10 µg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations. Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS.

Manganese in blood cells as an exposure biomarker in manganese-exposed workers healthy cohort.

Elevated exposure to manganese (Mn) has long been a public health concern. However, there is currently no consensus on the best exposure biomarker. Here we aimed to investigate the exposomic characteristics of plasma metals among Mn-exposed workers and explore the potential biomarkers of Mn exposure in the blood pool. First, total sixteen plasma metals (Calcium, Magnesium, Iron, Zinc, Copper, Selenium, Lead, Chromium, Arsenic, Manganese, Nickel, Molybdenum, Cadmium, Mercury, Thallium, and Cobalt) were determined among 40 occupationally Mn-exposed subjects. Second, Mn levels in both plasma and blood cells were detected among 234 workers from the manganese-exposed workers healthy cohort (MEWHC), respectively. Analysis of plasma metal exposome showed that the plasma Mn concentrations were positively correlated to plasma Fe (r=0.361), Ni (r=0.363), Cr (r=0.486), and Hg (r=0.313) (all p<0.05). Mn concentrations in plasma were not significantly correlated to external exposure levels (ptrend=0.200), and it was further confirmed among the 234 subjects (ptrend=0.452). However, Mn concentrations in blood cells progressively increased as the external exposure dose increased (low-exposure group vs high-exposure group, median 11.53µg/L vs 20.41µg/L, ptrend=0.001). Our results suggest that Mn in blood cells, but not plasma, could serve as a potential internal exposure biomarker. Larger validation studies are needed to establish the utility of this biomarker.