Tanshinone IIA is a naturally occuring cardioprotective agent which can inhibit NF-κB and AP-1 DNA binding and display antioxidant and anti-inflammatory properties. Tanshinone IIA showed inhibitory effect on PL(pro) with IC50 value of 1.6μM and less inhibitory effect on 3CLpro with IC50 value of 89.1μM.
Sodium tanshinone IIA sulfonate (STS) is one of the derivatives of tanshinone IIA (Tan IIA) which is a main lipophilic constitute of Chinese Materia Medica Salvia miltiorrhiza Bge. (Danshen)[3].Tan-IIA reduces the production of inflammatory mediators and restores abnormal signaling pathways via regulating the function and activation of immune cells. It can also regulate signal transduction pathways, ie, TLR/NF-κB pathway and MAPKs/NF-κB pathway, thereby tan-IIA has an anti-inflammatory, anticoagulant, antithrombotic and neuroprotective role[4]. In vivo , echocardiography results showed that Tanshinone IIA could significantly improve heart function. Western Blot result showed that Tanshinone IIA treatment enhanced autophagy and regulated expressions of key autophagy-related molecules, including protein 1 light chain 3 (LC3), p62 and Beclin1. Tanshinone IIA also inhibited apoptosis and regulated expressions of key apoptotic protein, including B cell lymphoma-2 (Bcl-2) and Bcl-2 Associated X Protein (Bax) and cleaved caspase-3 and -7. Further experiments demonstrated that the effects of Tanshinone IIA were mediated through upregulation of AMPK and downregulation of mTOR simultaneously. The mTOR agonist MHY1485 could abrogate the therapeutic effect of Tanshinone IIA in vitro [5]. Tanshinone IIA has anti-adipogenic effects on 3T3-L1 cells and zebrafish, and its anti-adipogenic effect on 3T3-L1 cells is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3/5[6].Tan IIA treatment of high-fat diet fed ApoE-/- mice significantly attenuated NLRP3 inflammasome activation In vivo . Consistently, Tan IIA also potently inhibited oxLDL-induced NLRP3 inflammasome activation in mouse macrophages[7].
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