Tanshinone IIA sulfonate sodium (Tanshinone IIA sodium sulfonate) is a water-soluble derivative of tanshinone IIA extracted from Savia miltiorrhiza; a potent negative allosteric modulator of the human purinergic receptor P2X7. Tanshinone IIA sulfonate sodium (12.5 μM) inhibits hypoxia-induced PKG and PPAR-γ downregulation in PASMCs and distal pulmonary arteries of rats.

Sodium Tanshinone IIA sulfonate (12.5 μM) effectively inhibits hypoxia-induced downregulation of PKG and PPAR-γ in PASMCs and the distal pulmonary arteries of rats, indicating its role in preserving pulmonary vascular function. This compound also prevents the reduction of TRPC1 and TRPC6 expression in hypoxic PASMCs, a process that is reversible upon specific knockdown of PKG or PPAR-γ. This suggests the involvement of the PKG-PPAR-γ signaling axis in mitigating the proliferative response of PASMCs under hypoxic conditions. Furthermore, a PPAR-γ agonist enhances the compound's ability to maintain basal calcium levels and store-operated calcium entry (SOCE) in PASMCs. In terms of drug metabolism, Sodium Tanshinone IIA sulfonate dose-dependently inhibits CYP3A4 activity in human liver microsomes (HLMs) and CYP3A4 isoform, with minimal impact on other CYP enzymes, suggesting a specific interaction with the CYP3A4 pathway. The kinetic parameters for its inhibition of CYP3A4 are detailed for both HLMs and the CYP3A4 isoform. Due to its significant inhibitory effect on CYP3A4, Sodium Tanshinone IIA sulfonate has the potential for drug-drug interactions when administered with other CYP3A4 substrates.

Sodium Tanshinone IIA sulfonate administered at dosages of 10 mg/kg and 20 mg/kg, in conjunction with Donepezil, effectively reduces escape latency, enhances the number of times subjects crossed the original platform location, and extends the duration spent in the target quadrant in experimental settings. This compound notably diminishes acetylcholinesterase (AChE) activity while boosting choline acetyltransferase (ChAT) activity within the hippocampus and cortex of SCOP-treated mice, alongside increasing superoxide dismutase (SOD) activity and reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels in the same regions. At a preventive dosage of 30 mg/kg/day, Sodium Tanshinone IIA sulfonate mitigates the characteristic alterations induced by hypoxia in a chronic hypoxia PH rat model. Moreover, when administered intraperitoneally at dosages of 20, 10, and 5 mg/kg, it effectively prevents peritoneal adhesion without impeding anastomotic healing in rats, demonstrating increased peritoneal lavage fluid tPA activity and tPA/PAI-1 ratio, alongside decreased TGF-β1 and collagen I expressions in ischemic tissues.