Tanshinone IIA

Tanshinone IIA is a lipophilic diterpene quinone extracted from Salvia miltiorrhiza (Danshen) root that exerts cardioprotective effects primarily by suppressing NF-κB signaling and activating AMPK phosphorylation. Most evidence derives from preclinical models, with limited human clinical trial data available to date.

Origin & History

Tanshinone IIA is a fat-soluble abietane diterpenoid quinone extracted from Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicinal plant. First isolated by Japanese scholars in the 1930s, it represents the most chemically representative and highest-content diterpenoid quinone in Salvia miltiorrhiza.

Historical & Cultural Context

Tanshinone IIA derives from Salvia miltiorrhiza (Danshen), a cornerstone herb in Traditional Chinese Medicine with centuries of documented use for cardiovascular conditions, including angina and blood stasis-related disorders. Multiple clinical preparations incorporating tanshinone IIA are used in TCM practice, including tablets, capsules, and injections.

Health Benefits

• Cardiovascular protection through NF-κB suppression and AMPK phosphorylation (animal studies only) • Antioxidant activity by increasing superoxide dismutase (SOD) activity (in vitro evidence) • Anti-atherosclerotic effects via reduction of plaque formation (preclinical research) • Potential anticancer properties through modulation of gene expression and apoptosis (cell line studies) • Vulnerable plaque stabilization through RAGE axis suppression (animal models)

How It Works

Tanshinone IIA inhibits the NF-κB signaling pathway by blocking IκB kinase (IKK) activation, thereby reducing downstream pro-inflammatory cytokine expression including TNF-α and IL-6. It also activates AMP-activated protein kinase (AMPK) phosphorylation at Thr172, promoting mitochondrial biogenesis and reducing oxidative stress, in part by upregulating superoxide dismutase (SOD) and catalase enzyme activity. Additionally, tanshinone IIA modulates the PI3K/Akt survival pathway and inhibits smooth muscle cell proliferation by downregulating cyclin D1 and CDK4, contributing to its anti-atherosclerotic properties.

Scientific Research

The available research consists primarily of in vitro studies using cell lines (HeLa, KB-3-1, NCI-H460, PC3, MCF-7, K562) and animal model research. No human clinical trials, randomized controlled trials, or meta-analyses with specific PMIDs were found in the provided research dossier.

Clinical Summary

The majority of tanshinone IIA research consists of in vitro cell studies and rodent models, where oral doses of 10–80 mg/kg have demonstrated reductions in atherosclerotic plaque area and serum LDL-cholesterol in ApoE-knockout mice. A small number of Chinese clinical trials involving Danshen-based formulations (not isolated tanshinone IIA) in coronary artery disease patients have reported modest improvements in cardiac function markers, though these studies are limited by small sample sizes (typically under 100 participants) and lack of rigorous blinding. Isolated tanshinone IIA has poor oral bioavailability due to its lipophilic nature, which complicates translation of preclinical dosing to human settings. Overall, evidence in humans for isolated tanshinone IIA supplementation remains insufficient to establish clinical efficacy.

Nutritional Profile

Tanshinone IIA is not a nutrient but a lipophilic abietane diterpene compound (C₁₉H₁₈O₃, MW 294.34 g/mol) isolated primarily from the dried root of Salvia miltiorrhiza (Danshen). It is one of the most pharmacologically active constituents of Danshen, typically present at approximately 0.1–0.9% w/w of the dried root material depending on extraction method, cultivar, and growing conditions. Key bioactive profile: • Chemical class: Abietane-type diterpenoid quinone (phenanthrene-ring structure with a furan ring) • Typical concentration in Danshen root: 0.5–5.0 mg/g dried root (highly variable by source and preparation) • Concentration in standardized Danshen extracts: Often standardized to 5–20% tanshinone IIA by weight in pharmaceutical-grade extracts • Related co-occurring tanshinones: Tanshinone I (C₁₈H₁₂O₃), Cryptotanshinone (C₁₉H₂₀O₃), Dihydrotanshinone I (C₁₈H₁₄O₃) — all sharing the orthoquinone/paraquinone pharmacophore • Caloric/macronutrient contribution: Negligible (consumed in microgram-to-milligram pharmacological doses, not as a food) • Vitamins/minerals/fiber/protein: Not applicable — this is a single purified or semi-purified phytochemical, not a whole food • Bioavailability notes: Oral bioavailability is very poor (estimated <2–4% in animal pharmacokinetic studies) due to high lipophilicity (log P ~4.8), low aqueous solubility (~16.7 µg/mL at 25°C), extensive first-pass hepatic metabolism (CYP3A4/CYP2C-mediated oxidation), and rapid biliary excretion. Peak plasma concentrations after oral dosing in humans are typically in the low nanomolar range. Strategies to improve bioavailability include nanoparticle encapsulation, solid lipid nanoparticles, cyclodextrin inclusion complexes, and co-administration with sodium tanshinone IIA sulfonate (STS, a water-soluble derivative used intravenously in Chinese clinical practice, achieving much higher plasma levels). Protein binding in plasma is >95%, primarily to albumin. Half-life is approximately 1.5–4 hours depending on formulation and route.

Preparation & Dosage

The research mentions a lipid emulsion formulation containing 0.05% (w/v) tanshinone IIA, but no clinically studied therapeutic dosage ranges are available. No human clinical dosing protocols were found in the available research. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Salvia miltiorrhiza extract, Omega-3 fatty acids, Coenzyme Q10, Hawthorn extract, Garlic extract

Safety & Interactions

Tanshinone IIA has demonstrated low acute toxicity in animal models, but human safety data for isolated supplementation are limited and no standardized safe dosage range has been established. Because it inhibits CYP3A4 and CYP2C9 hepatic enzymes in vitro, tanshinone IIA may increase plasma concentrations of co-administered drugs including warfarin, statins, and certain benzodiazepines, raising the risk of adverse effects. It may potentiate the anticoagulant effects of warfarin and other blood-thinning agents, so concurrent use should be avoided without medical supervision. Tanshinone IIA is contraindicated in pregnancy due to its documented uterotonic effects in animal studies, and safety during breastfeeding has not been established.