Two-step continuous flow process of sodium tanshinone ⅡA sulfonate using a 3D circular cyclone-type microreactor

A sustainable and practical process is presented for the direct synthesis of sodium tanshinone IIA sulfonate(STS).Our approach was inspired by the well-established and industrially applied batch synthetic route for STS production.We constructed a telescoped two-step continuous flow platform.This involved a continuous tanshinone IIA sulfonation and in-line salt formation.For the setup,we constructed a 3D circular cyclone-type microreactor using femtosecond laser micromachining.Compared to the 68%yield for 2 h in batch,the two-step continuous flow had an STS yield of 90%,achieved for a total residence time of<3.0 min under optimal conditions.The proposed continuous flow method vastly simplified the operation and improved procedural safety,while significantly reducing the required acid content and wastewater production.

Sodium tanshinone ⅡA sulfonate prevents radiation-induced damage in primary rat cardiac fibroblasts

This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts(CFs) and its potential mechanism, as well as whether sodium tanshinone ⅡA sulfonate(STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin Ⅱ(Ang Ⅱ) and brain natriuretic peptide(BNP). STS inhibited the X-ray-induced increases in Ang Ⅱ and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38,cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2(ERK1/2)/ERK 1/2 and B cell lymphoma 2(Bcl-2)/Bcl-2 associated X protein(BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.

Protective Effect of Sodium Tanshinone ⅡA Sulfonate on Injury of Small Intestine in Rats with Sepsis and Its Mechanism

Objective： To explore the protective effect of sodium tanshinone ⅡA sulfonate （STS） on small intestine injury in rats with sepsis and its possible mechanism. Methods： According to a random number table, 24 Tats were randomly divided into 3 groups： sham operation group （sham group）, sepsis model group （model group） and STS treatment group （STS group）, with 8 Tats in each group. A rat model of sepsis was induced by cecal ligation and puncture （CLP） for 5 h. STS （1 mg/kg） was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestine tissue were observed under a light microscope, and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase （TdT）-mediated dUTP nick-end labeling （TUNEL） method. The expressions of Bcl-2, Bax and nuclear factor κB （NF- κ B） p65 in the intestinal tissue was determined by Western blot. The levels of tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay （ELISA）. Results： Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF- K B p65 and the levels of TNF- α and IL-6 were up-regulated after CLP, the apoptosis of intestinal epithelial cells was increased after CLP, and the ratio of Bcl-2 to Bax was decreased. STS post- treatment could attenuate the injury on the intestinal tissue induced by CLP, decrease the apoptosis of intestinal epithelial cells and the levels of NF- κ B p65, TNF-α and IL-6, and increase the ratio of Bcl-2 to Bax. Conclusion： STS can protect the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.

Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

Intervaginal space injection(ISI)is a novel mode of administration investigated over the last decade.After injecting nanoparticles into the intervaginal space,they can be transported along low flow resistance channels into the interstitial space.This transport has a certain delivery direction,and site-specific injection can work on specific organs or tissues.In this study,the thorax,a new ISI site in the interstitial surrounding the internal thoracic artery named the thoracic interstitial injection(tISI)was investigated.To prove the targeting ability of the tISI,two sizes of gold nanoparticles(AuNPs)(47 and 87 nm)were administered to mice.After 1 h,the biodistribution of AuNPs in the tissues was measured via single particle inductively coupled plasma mass spectrometry(spICP-MS).The results showed that the concentration of AuNPs in the aorta after tISI injection was significantly higher than that after intravenous injection.Moreover,fewer nanoparticles with larger particle sizes were observed to have entered the blood and were better targeted to the aorta.Thereafter,tanshinone IIa sodium sulfonate liposomes were administered for the treatment of aortic atherosclerosis.The proportion of aortic plaques in atherosclerotic Apoe-/-mice administered via tISI was significantly lower than that in other model animals(P<0.001).Furthermore,the proteoglycan content and CD68-positive cell count in the plaques were significantly reduced.The vascular elastic fibers at the plaque site were thickened,and fractures were reduced.tISI was,therefore,determined to be an effective strategy for the treatment of atherosclerotic aortic plaques.