Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice.

Silicosis is an irreversible occupational disease caused by silica particle exposure. Abundant evidences suggest that NLRP3-mediated inflammation acts an essential role in fibrogenesis and the pathogenesis of silicosis. In the current work, we firstly reported that (8R-12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of Chinese traditional medicinal plant Andrographis paniculata (Burm.f.) Nees, could reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, and thereby ameliorate silicosis. ISA administration significantly alleviated lung injury, and attenuated inflammatory response, EMT, as well as collagen deposition in the lung of silica-induced mice. Further studies verified that ISA inhibited the expressions of NLRP3 inflammasome-related proteins NLRP3, ASC and caspase-1 in vivo and in vitro, leading to the attenuation of inflammation and EMT. Additionally, the molecular docking assay indicated that ISA possibly interacted with the residues of LYS26 and GLU47 of NLRP3, implying that ISA might directly bond to protein NLRP3. Of note, ISA revealed a lower cytotoxicity but more potent therapeutic effect than andrographolide (AD), the major active extract of A. paniculata, which has been traditionally used to treat inflammation-related diseases. Taken together, our study clarified a novel role of ISA in attenuating inflammation and fibrosis in silicosis, and indicated a bright future of ISA as a lead compound for developing therapeutic drug for silicosis.

An optimal initial tension for rat basilar artery in wire myography.

AIMS: The aim of the present study was to determine the optimal initial tension for the rat basilar artery when using wire myography. METHODS: Rat basilar arteries were mounted in myograph baths. A normalization procedure was performed. K(+)-rich (60mM) buffer solution-induced tension was measured in different initial tensions. RESULTS: The initial tension of the basilar artery increased from 0.47 to 2.68mN/mm. Contractile tension was also elevated along with the initial tension. When the initial tension reached 1.63mN/mm, K(+)-induced contractile tension of basilar artery achieved its maximum. Thereafter, contractile tension declined as initial tension increased. The duration of equilibration time did not affect K(+)-induced contractile tension. CONCLUSION: The optimal initial tension is 1.63±0.01mN/mm in rat basilar arteries when using wire myography.