Dihydrotanshinone I

Dihydrotanshinone I at a Glance

Dihydrotanshinone I is one of the four tanshinones — the orange-red, fat-soluble diterpene quinones that give dan shen root its colour and carry the lipophilic half of its pharmacology. It is by some distance the least famous of the four. Tanshinone IIA is the Chinese Pharmacopoeia marker compound and has a semi-synthetic injectable derivative in clinical use; cryptotanshinone has the larger cancer literature and the STAT3 headline. Dihydrotanshinone I has neither, and it is the least abundant of the four in the root ^{2,34Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →Reference 34Ayvazyan A et al. · 2023In vitroCytotoxic diterpenoids from Salvia glutinosa and comparison with the tanshinone profile of danshen (Salvia miltiorrhiza) — phytochemical and in vitro studyView study →}.

What it does have is the single most striking number in the tanshinone literature. It binds the RNA-binding protein HuR and blocks HuR’s association with target mRNA at a Ki of 3.74 nM ^{3Reference 3D’Agostino VG et al. · 2015In vitroDihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function — in vitro and cell studyView study →} — three orders of magnitude tighter than anything else here, and tight enough that a whole medicinal-chemistry programme of “tanshinone mimics” was built from its scaffold ^{5Reference 5Manzoni L et al. · 2018Interfering with HuR-RNA interaction: design, synthesis and biological characterization of tanshinone mimics as novel, effective HuR inhibitors — medicinal chemistry studyView study →}. On acetylcholinesterase, in the one clean head-to-head, it is seven times more potent than cryptotanshinone (IC50 1.0 µM vs. 7.0 µM) ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}.

The rest of the page is an attempt to be honest about what that does and does not mean. The molecule is chemically unstable — it oxidises to tanshinone I, in the plant by a characterised enzyme ^{6Reference 6Pan X et al. · 2023Chromosome-level genome assembly of Salvia miltiorrhiza with orange roots uncovers the role of Sm2OGD3 in catalyzing 15,16-dehydrogenation of tanshinones — genome and enzyme characterisationView study →} and in DMSO by simple standing ^{7Reference 7Roth A et al. · 2023In vitroChemical stability and bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems — comparative studyView study →} — so some fraction of its reported activity may belong to its own oxidation product. In a 63-compound Salvia cytotoxicity screen it was flagged as highly toxic to the healthy cell line, not selectively toxic to the cancer lines ^{10Reference 10Irtegun Kandemir S et al. · 2022In vitroInvestigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species — in vitro screen including a healthy cell lineView study →}. And measured plasma concentrations after oral dosing in rats sit at 12–41 nM ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}, which is below almost every in-vitro concentration used to demonstrate anything about it. HuR is the conspicuous exception, and that is interesting.

No human has been given this molecule in a trial.

Where It Sits in the Tanshinone Series

The four common tanshinones are two structural changes away from each other, and getting the axes straight makes the whole comparative literature legible.

	Furan D-ring (aromatic)	Dihydrofuran D-ring (C15–C16 reduced)
Aromatic A-ring	Tanshinone I	Dihydrotanshinone I
gem-Dimethyl A-ring	Tanshinone IIA	Cryptotanshinone

So dihydrotanshinone I is the 15,16-dihydro congener of tanshinone I, and cryptotanshinone stands in exactly the same relation to tanshinone IIA — which is why cryptotanshinone’s formal name is 15,16-dihydrotanshinone IIA. That is not a taxonomic nicety — it is a live chemical reaction that runs in both directions of the story:

• In the plant it is the precursor. A 2023 chromosome-level genome assembly of an orange-rooted S. miltiorrhiza line identified Sm2OGD3, a 2-oxoglutarate-dependent dioxygenase acting as a tanshinone 15,16-dehydrogenase. The recombinant enzyme converts the C15–C16 single bond to a double bond, taking 15,16-dihydrotanshinone I → tanshinone I and cryptotanshinone → tanshinone IIA. In the orange-root mutant, tanshinones with the C15–C16 single bond accumulated while those with the double bond fell sharply ^{6Reference 6Pan X et al. · 2023Chromosome-level genome assembly of Salvia miltiorrhiza with orange roots uncovers the role of Sm2OGD3 in catalyzing 15,16-dehydrogenation of tanshinones — genome and enzyme characterisationView study →}. (A separate group independently characterised a 2-oxoglutarate-dependent dioxygenase performing the cryptotanshinone → tanshinone IIA half of the same chemistry, naming it Sm2-ODD14 / tanshinone IIA synthase ^{49Reference 49Song JJ et al. · 2022A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids — identification of tanshinone IIA synthaseView study →}; the two enzymes are described in the tanshinone IIA and cryptotanshinone entries. Whether they are the same protein under two names has not been settled in print.)
• In the test tube it does the same thing spontaneously. A German comparative study of all four tanshinones found that dihydrotanshinone and cryptotanshinone concentrations “decreased rapidly” in DMSO, converting to tanshinone I and tanshinone IIA respectively; all four declined in aqueous solution within 24 h ^{7Reference 7Roth A et al. · 2023In vitroChemical stability and bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems — comparative studyView study →}.

That second finding is the uncomfortable one. Long incubations of dihydrotanshinone I in cell culture are, to an unquantified degree, incubations of tanshinone I. The same authors concluded on their own endpoints — oestrogen-receptor activity, anabolic activity in C2C12 cells, cytotoxicity, genotoxicity — that tanshinone I and tanshinone IIA are “the most relevant bioactive tanshinones in Danshen” ^{7Reference 7Roth A et al. · 2023In vitroChemical stability and bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems — comparative studyView study →}. That is a direct counter to the folk claim that dihydrotanshinone I is simply the strongest of the four.

One more structural consequence: dihydrotanshinone I is the least lipophilic of the series. Calculated logP values run 2.4 (dihydrotanshinone I), 3.4 (cryptotanshinone), 4.8 (tanshinone I) and 5.8 (tanshinone IIA) ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}. Least lipophilic is not water-soluble — see Does Any Danshen Preparation Deliver It? — but it does mean it is the tanshinone most plausibly able to cross the blood–brain barrier, which is why the cholinesterase work exists at all.

The “Most Potent Tanshinone” Claim, Examined

Dihydrotanshinone I is often described as the most potent member of the series. It is worth testing that against the studies that actually put the four side by side, because they do not agree with each other.

Comparison	Result	What it supports
Acetylcholinesterase inhibition, isolated compounds 2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →	DHT1 IC50 1.0 µM vs. cryptotanshinone 7.0 µM; tanshinone I and IIA inactive enough not to be quantified	DHT1 clearly strongest
HuR:RNA disruption 3,5Reference 3D’Agostino VG et al. · 2015In vitroDihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function — in vitro and cell studyView study →Reference 5Manzoni L et al. · 2018Interfering with HuR-RNA interaction: design, synthesis and biological characterization of tanshinone mimics as novel, effective HuR inhibitors — medicinal chemistry studyView study →	DHT1 Ki 3.74 nM; the scaffold became the reference natural-product HuR inhibitor	DHT1 uniquely potent — no sibling comparator published
Anti-inflammatory, LPS-stimulated RAW264.7 + three mouse models 9Reference 9Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →	The total tanshinone fraction (>97% tanshinones) outperformed dihydrotanshinone, tanshinone I, cryptotanshinone and tanshinone IIA individually	Fraction beats every isolate — a negative for all four
Cytotoxicity/apoptosis, 63 Salvia metabolites, MCF-7 / HT-29 / healthy fibroblast 10Reference 10Irtegun Kandemir S et al. · 2022In vitroInvestigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species — in vitro screen including a healthy cell lineView study →	DHT1 grouped with carnosic acid and carnosol as “high toxic effects on healthy cell line”; cryptotanshinone and several royleanones had the better cancer-vs-healthy ratio	DHT1 potent but not selective
Chemical stability + bioactivity panel 7Reference 7Roth A et al. · 2023In vitroChemical stability and bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems — comparative studyView study →	DHT1 unstable, converts to tanshinone I; authors conclude tanshinone I and IIA are the most relevant bioactives	Directly against the claim
Antibacterial, Gram-positive panel 8Reference 8Lee DS et al. · 1999In vitroAntibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge — in vitro studyView study →	DHT1 and cryptotanshinone both active across a broad Gram-positive range; no potency ranking reported	Undetermined

The defensible version of the claim is narrow: on the two molecular targets where a direct comparison exists — acetylcholinesterase and HuR — dihydrotanshinone I is the most potent tanshinone, and on HuR it is potent by a margin nothing else in the genus approaches. On general cytotoxicity it is potent but poorly selective. On anti-inflammatory activity the whole fraction beats it. And where stability is controlled for, the case reverses.

A further point from the cholinesterase study is easy to miss and applies to every “danshen extract” result on the internet: dihydrotanshinone and cryptotanshinone “in mixture.. appear to be less active than as isolated compounds” ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}. Whatever the tanshinones do together, it is not additive.

HuR — The Target That Made It a Chemical Tool

This is the one place where dihydrotanshinone I is not a second-tier tanshinone but a first-rank reference compound, and it is worth setting out properly.

HuR (human antigen R, gene ELAVL1) is an RNA-binding protein that recognises U/AU-rich elements in the 3′ untranslated regions of mRNAs and stabilises them. Its client list is a roll-call of inflammation and tumour biology — TNF-α among them — and it had long been considered undruggable, as protein–RNA interfaces generally are.

In 2015 a high-throughput screen of anti-inflammatory agents for compounds that prevent HuR:RNA complex formation returned dihydrotanshinone I. It interferes with the association step between HuR and RNA with an equilibrium dissociation constant in the nanomolar range (Ki = 3.74 ± 1.63 nM). In breast cancer cell lines, short exposure changed TNF mRNA stability and translational efficiency in a HuR-dependent manner, and both migration and drug sensitivity tracked HuR expression — the signature of genuine on-target activity rather than generic cytotoxicity ^{3Reference 3D’Agostino VG et al. · 2015In vitroDihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function — in vitro and cell studyView study →}.

A 2017 structural follow-up in Nucleic Acids Research mapped the interaction: NMR titration and molecular dynamics located the contact residues within HuR’s RRM1 and RRM2 domains, and showed that the compound occupies the same binding regions as the target RNA, locking HuR in a closed conformation that competitively blocks RNA binding. Transcriptome-wide RIP-chip showed it preferentially strips HuR from its weaker targets. In vivo, it inhibited xenograft tumour growth in a HuR-dependent model without systemic toxicity ^{4Reference 4Lal P et al. · 2017Regulation of HuR structure and function by dihydrotanshinone-I — NMR, molecular dynamics, RIP-chip and xenograft studyView study →}.

The medicinal chemistry then took over. A 2018 J. Med. Chem. paper used dihydrotanshinone I as the template for a designed array of ortho-quinone “tanshinone mimics”; two analogues were more effective than the natural product, and the series produced the first structure–activity relationships for HuR disruption ^{5Reference 5Manzoni L et al. · 2018Interfering with HuR-RNA interaction: design, synthesis and biological characterization of tanshinone mimics as novel, effective HuR inhibitors — medicinal chemistry studyView study →}. Work on the scaffold continues, including conjugates built for mechanism-of-action studies, and independent groups now use it as the natural-product benchmark alongside the synthetic HuR inhibitor CMLD-2 ^{46Reference 46Dev AJR et al. · 2025In vitroBiophysical and molecular characterization of HuR inhibitors, CMLD-2 and dihydrotanshinone I (DHTS), in triple negative breast cancer — in vitro studyView study →}.

Two of its other reported effects are plausibly downstream of the same mechanism rather than separate discoveries: suppression of HIF-1 by interfering with post-transcriptional processing in haemangioendothelioma cells ^{19Reference 19Duan P et al. · 2021In vitroDuan P, Huang Y, Chen K, Cheng C, Wu Z, Wu Y (2021). 15,16-dihydrotanshinone I inhibits EOMA cells proliferation by interfering in posttranscriptional processing of hypoxia-inducible factor 1 — in vitro study. International Journal of Medical Sciences. https://pubmed.ncbi.nlm.nih.gov/34400891/View study →}, and its various effects on cytokine mRNA levels. HuR is a well-documented regulator of HIF-1α message.

Why this matters for exposure. A Ki of 3.74 nM sits below the 12–41 nM plasma Cmax measured after oral dosing in rats ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}. Of everything here, HuR engagement is the only mechanism whose biochemical potency is not obviously out of reach of achievable blood levels. That is an arithmetic observation, not a demonstration — biochemical Ki is not cellular IC50, the cellular experiments used higher concentrations, and plasma protein binding is unmeasured — but it is the right way round, and nothing else here is.

What It's Used For

A large and fast-growing preclinical literature — 373 PubMed records for “dihydrotanshinone”, 251 of them alongside Salvia miltiorrhiza — with a dedicated 2019 review ^{1Reference 1Chen X et al. · 2019Systematic reviewPharmacological activities of dihydrotanshinone I, a natural product from Salvia miltiorrhiza Bunge — systematic reviewView study →} and no human data whatsoever.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row shares one ceiling: no human has ever taken this molecule in a study.

01AntibacterialShaky44%In-vivo mouse eradication of drug-resistant H. pylori beating triple therapy, plus a broad Gram-positive panel with a stated mechanism ^{8,11Reference 8Lee DS et al. · 1999In vitroAntibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge — in vitro studyView study →Reference 11Luo P et al. · 2021In vitroDihydrotanshinone I is effective against drug-resistant Helicobacter pylori in vitro and in vivo — in vitro and mouse studyView study →}

02Anti-Inflammatory & AutoimmuneShaky40%Direct IRF3 binding with three disease models; DSS colitis; mast-cell Syk inhibition — all rodent ^{9,12,13Reference 9Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →Reference 12Shi W et al. · 2025AnimalDihydrotanshinone I, a main compound of Salvia miltiorrhiza, alleviates autoimmune and inflammatory diseases by directly targeting IRF3 — cell and mouse studyView study →Reference 13Guo Y et al. · 2018AnimalDihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice — mouse studyView study →}

03CardioprotectionShaky34%Mechanistically deep rodent ischaemia work (PKM2 glutathionylation, lymphangiogenesis, HIF-1α preconditioning) ^{14,15Reference 14Wu X et al. · 2023AnimalDihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS — cell and mouse studyView study →Reference 15Wang YC et al. · 2025Dihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury — animal studyView study →}

04AnticancerShaky32%Large in-vitro literature plus HuR-dependent xenograft inhibition; undercut by poor selectivity against healthy cells ^{4,10,16,17,18Reference 4Lal P et al. · 2017Regulation of HuR structure and function by dihydrotanshinone-I — NMR, molecular dynamics, RIP-chip and xenograft studyView study →Reference 10Irtegun Kandemir S et al. · 2022In vitroInvestigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species — in vitro screen including a healthy cell lineView study →Reference 16Wang L et al. · 2015In vitroDihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer — in vitro studyView study →Reference 17Cao Y et al. · 2017In vitroSalvia miltiorrhiza extract dihydrotanshinone induces apoptosis and inhibits proliferation of glioma cells — in vitro studyView study →Reference 18Zhao H et al. · 2022AnimalDihydrotanshinone I inhibits the lung metastasis of breast cancer by suppressing neutrophil extracellular traps formation — mouse studyView study →}

05Metabolic & LiverShaky26%Two independent 2025 mouse NAFLD/NASH mechanisms (IRG1, free-cholesterol handling); complicated by a cholestasis finding ^{12,38,39Reference 12Shi W et al. · 2025AnimalDihydrotanshinone I, a main compound of Salvia miltiorrhiza, alleviates autoimmune and inflammatory diseases by directly targeting IRF3 — cell and mouse studyView study →Reference 38Xiang Y et al. · 2025AnimalDihydrotanshinone I attenuates diet-induced nonalcoholic fatty liver disease via up-regulation of IRG1 — mouse studyView study →Reference 39Shou JW et al. · 2025AnimalFree cholesterol-induced liver injury in non-alcoholic fatty liver disease: mechanisms and a therapeutic intervention using dihydrotanshinone I — mouse studyView study →}

06AntiplateletShaky24%One rabbit-platelet study, IC50 8.7 µM via calcium mobilisation — real but ~200× above measured plasma levels ^{30Reference 30Park JW et al. · 2008Park JW, Lee SH, Yang MK, et al. (2008). 15,16-dihydrotanshinone I, a major component from Salvia miltiorrhiza Bunge, inhibits rabbit platelet aggregation by suppressing intracellular calcium mobilization — ex vivo study. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/18277607/View study →}

07Cholinesterase & CognitionShaky22%Best-characterised enzymology on the page (IC50 1.0 µM, crystal structure, P-site specific) but only one thin animal model ^{2,21,22,23Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →Reference 21Cheung J et al. · 2014Acetylcholinesterase complexes with the natural product inhibitors dihydrotanshinone I and territrem B: binding site assignment and validation through crystal structure determination — structural studyView study →Reference 22Wong KK et al. · 2010In vitroInteraction study of two diterpenes, cryptotanshinone and dihydrotanshinone, to human acetylcholinesterase and butyrylcholinesterase by molecular docking and kinetic analysis — in vitro studyView study →Reference 23Bao Z et al. · 2020Clinical trialDihydrotanshinone I increases amyloid-β clearance and decreases tau phosphorylation via enhancing autophagy — preclinical studyView study →}

08AntiviralShaky18%Two 2024–25 mechanism papers (SARS-CoV-2 spike NTD; viral glycoprotein trafficking); no animal efficacy for the virus claims ^{37,41Reference 37Yang C et al. · 2025In vitroDihydrotanshinone I targets the spike N-terminal domain to inhibit SARS-CoV-2 entry and spike-induced inflammation — in vitro studyView study →Reference 41Muroi M · 2024In vitroInhibitory effects of cryptotanshinone and dihydrotanshinone I on intracellular trafficking of viral glycoproteins — in vitro studyView study →}

Mechanisms

Pharmacokinetics

The numbers here bound almost everything above.

• Plasma concentrations are nanomolar. After oral dosing in rats, reported Cmax values are 0.012 µM at 1.91 mg/kg (tmax 0.79 h, t½ 1.69 h) and 0.041 µM at 3.58 mg/kg (tmax 0.74 h, t½β 0.54 h, t½γ 3.65 h) ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}. No absolute oral bioavailability figure has been published for this molecule; for comparison, cryptotanshinone’s was estimated at 2.1% oral in rats ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}.
• The extract matrix raises exposure substantially. In a direct comparison, giving rats the liposoluble danshen extract rather than the pure compounds significantly increased AUC and Cmax for all four tanshinones, and increased tissue AUC in lung, heart, kidney, liver and brain — the co-occurring constituents “particularly promoted the distribution of tanshinones into tissues that the drug cannot sufficiently penetrate” ^{31Reference 31Wang D et al. · 2020AnimalComparative pharmacokinetics and tissue distribution of cryptotanshinone, tanshinone IIA, dihydrotanshinone I and tanshinone I after oral administration of pure tanshinones and liposoluble extract of Salvia miltiorrhiza to rats — rat studyView study →}. This is the rare case where the plant matrix demonstrably helps.
• Metabolism is extensive and oxidative. Seventeen metabolites of tanshinone I and dihydrotanshinone I were identified in rat bile: fifteen phase I products via dehydrogenation, hydroxylation, furan-ring cleavage and oxidation, plus two sulfate conjugates ^{33Reference 33Wang M et al. · 2010AnimalStructural elucidation of metabolites of tanshinone I and its analogue dihydrotanshinone I in rats by HPLC-ESI-MSn — rat metabolism studyView study →}. Note that dehydrogenation of dihydrotanshinone I yields tanshinone I, so the two molecules’ metabolic fates overlap by construction.
• The practical rule. Treat any in-vitro result at ≥1 µM as unreachable in plasma at plausible intakes. The mechanisms with a credible route to a real effect are (a) HuR engagement, whose Ki is below measured Cmax, and (b) the gut-luminal antibacterial activity against H. pylori, which does not require systemic absorption at all.

Clinical Trials

None. No trial has administered isolated dihydrotanshinone I to a human being for any indication. The human danshen literature — angina, ischaemic stroke — tests compound formulas, water-based dripping pills and injectable preparations, none of which is this molecule and most of which do not contain it in meaningful quantity.

Last checked: August 2026.

Isolate vs. Plant Studies

Unusually for a herbal constituent, essentially all of the evidence here is isolate evidence — which is a strength for attribution and a weakness for relevance.

Every study cited for a pharmacological effect used the purified molecule, generally sourced commercially or isolated by the authors from S. miltiorrhiza root ^{2,8,9Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →Reference 8Lee DS et al. · 1999In vitroAntibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge — in vitro studyView study →Reference 9Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}. There is no whole-herb human trial that can be credited to it, and there is no danshen preparation standardised to it.

Two comparisons cut against simple attribution:

• The fraction beat the isolate. In the only anti-inflammatory head-to-head, a >97%-pure total-tanshinone fraction outperformed dihydrotanshinone I and each of its three siblings individually, in LPS-stimulated macrophages and in three mouse models ^{9Reference 9Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}.
• The isolates antagonise each other on cholinesterase. Dihydrotanshinone and cryptotanshinone “in mixture appear to be less active than as isolated compounds” ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}.

And one that cuts in its favour:

• The extract improves its own delivery. Tanshinone AUC and tissue distribution were markedly higher from the liposoluble extract than from pure compound at matched dose ^{31Reference 31Wang D et al. · 2020AnimalComparative pharmacokinetics and tissue distribution of cryptotanshinone, tanshinone IIA, dihydrotanshinone I and tanshinone I after oral administration of pure tanshinones and liposoluble extract of Salvia miltiorrhiza to rats — rat studyView study →}.

The honest reading is that this molecule’s identified molecular targets are its own — HuR, IRF3, AChE, PKM2 are all direct-binding results on the pure compound — while its functional activity in any real preparation is inseparable from the tanshinone fraction it travels in.

Does Any Danshen Preparation Deliver It?

Danshen root is chemically two herbs in one. The tanshinones, including this molecule, are lipophilic diterpene quinones extracted by ethanol, ethyl acetate, acetone or supercritical CO₂. The salvianolic acids and their precursor rosmarinic acid are hydrophilic caffeic-acid oligomers, and they are what a water decoction extracts. The two fractions barely overlap.

Dihydrotanshinone I is squarely on the lipophilic side. Its calculated logP is 2.4 — the least lipophilic of the four tanshinones, but still a compound recovered by acetone and ethanol rather than water ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}, and the tanshinones as a class are described as poorly soluble in aqueous medium ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}. A functional demonstration of the split comes from the warfarin work: a danshen ethyl acetate extract containing the tanshinones inhibited warfarin hydroxylation in rat liver microsomes, while the aqueous extract containing salvianolic acid B and danshensu had no effect at all ^{28Reference 28Wu WW · 2010In vitroInhibition of warfarin hydroxylation by major tanshinones of Danshen (Salvia miltiorrhiza) in the rat in vitro and in vivo — rat studyView study →}.

The practical consequences:

• A traditional water decoction of danshen delivers essentially none of this molecule. Any claim built on the pharmacology above does not transfer to a tea or a water-based preparation.
• The Chinese Pharmacopoeia marker is not this compound. The ≥0.25% combined-tanshinone specification for dried root counts tanshinone IIA, cryptotanshinone and tanshinone I — dihydrotanshinone I is not one of the three ^{42Reference 42Su CY et al. · 2015ReviewSalvia miltiorrhiza: traditional medicinal uses, chemistry, and pharmacology — reviewView study →}.
• “Tanshinone capsules” and ethanol extracts do contain it, at whatever ratio the source material and extraction gave; the anti-cholestasis toxicology was done on exactly such a preparation ^{27Reference 27Li Y et al. · 2023In vitroLi Y, Wang Q, Jin J, et al. (2023). 15,16-dihydrotanshinone I in Danshen ethanol extract aggravated cholestasis by inhibiting Cyp3a11 mediated bile acids hydroxylation — mouse and in vitro study. Toxicology Letters. https://pubmed.ncbi.nlm.nih.gov/36804361/View study →}.
• Tanshinone IIA sodium sulfonate — the injectable used in China — is irrelevant here. It is a semi-synthetic water-soluble derivative of a different tanshinone. Its clinical data belong to neither tanshinone IIA nor to this molecule.

Prevalence in Nature

Dihydrotanshinone I is a genus-restricted compound. It is essentially a Salvia marker, and within Salvia it is concentrated in the roots of the tanshinone-producing species.

• Salvia miltiorrhiza (danshen) is the principal source and the material behind every study here. The two published assays disagree by sevenfold, and the honest thing is to print both. Ren and colleagues measured it in dried root by HPLC at 0.054% w/w, against 0.23% w/w for cryptotanshinone in the same sample set ^{2Reference 2Ren Y et al. · 2004In vitroNovel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza — in vitro study with HPLC quantification of root contentView study →}; a 2023 UHPLC-DAD-MS assay of authenticated root reported 76 mg/kg — 0.0076% — alongside 895 mg/kg tanshinone IIA, 764 mg/kg cryptotanshinone and 88 mg/kg tanshinone I ^{34Reference 34Ayvazyan A et al. · 2023In vitroCytotoxic diterpenoids from Salvia glutinosa and comparison with the tanshinone profile of danshen (Salvia miltiorrhiza) — phytochemical and in vitro studyView study →}. Whichever figure is right, the ranking is the same: dihydrotanshinone I is the least abundant of the four majors, by a wide margin. A validated LC-MS/MS method quantifying all four across seven batches of root from different Chinese regions exists and is the standard tool for settling this ^{35Reference 35Hu P et al. · 2005Quantitative determination of four diterpenoids in Radix Salviae Miltiorrhizae using LC-MS-MS — analytical methodView study →}.
• Salvia przewalskii is named alongside S. miltiorrhiza as a source of both tanshinone I and dihydrotanshinone I ^{33Reference 33Wang M et al. · 2010AnimalStructural elucidation of metabolites of tanshinone I and its analogue dihydrotanshinone I in rats by HPLC-ESI-MSn — rat metabolism studyView study →}.
• Salvia glutinosa (sticky sage) is the only tanshinone-bearing Salvia widely distributed in Europe, and a 2023 UHPLC-DAD-MS comparison confirmed dihydrotanshinone I in its roots. S. miltiorrhiza carried the higher concentration of most tanshinones; the notable European finding was danshenol A, present only in S. glutinosa and considerably more antiproliferative and cytotoxic than dihydrotanshinone I ^{34Reference 34Ayvazyan A et al. · 2023In vitroCytotoxic diterpenoids from Salvia glutinosa and comparison with the tanshinone profile of danshen (Salvia miltiorrhiza) — phytochemical and in vitro studyView study →}.

Content in cultivated danshen is manipulable: tetraploid lines produced by chromosome doubling gave increased biomass and increased dihydrotanshinone I ^{44Reference 44Chen EG et al. · 2018Chromosome doubling-enhanced biomass and dihydrotanshinone I production in Salvia miltiorrhiza, a traditional Chinese medicinal plant — plant studyView study →}, and continuous cropping alters the spatial distribution of tanshinones within the root.

Its Role in Plants

The tanshinones are root-localised, coloured, redox-active quinones — the profile of a defensive metabolite — and dihydrotanshinone I is an intermediate in the pathway rather than an endpoint.

Its position is now known enzymatically. Sm2OGD3, a 2-oxoglutarate-dependent dioxygenase, acts as a tanshinone 15,16-dehydrogenase, converting the C15–C16 single bond of the dihydrofuran D-ring to the double bond of the aromatic furan. Its confirmed conversions are 15,16-dihydrotanshinone I → tanshinone I, cryptotanshinone → tanshinone IIA, and 1,2,15,16-tetrahydrotanshinone I → 1,2-dihydrotanshinone I. The gene was identified through an orange-rooted S. miltiorrhiza line in which single-bond tanshinones accumulated and double-bond tanshinones fell sharply — root colour tracks the oxidation state of the D-ring ^{6Reference 6Pan X et al. · 2023Chromosome-level genome assembly of Salvia miltiorrhiza with orange roots uncovers the role of Sm2OGD3 in catalyzing 15,16-dehydrogenation of tanshinones — genome and enzyme characterisationView study →}.

That makes dihydrotanshinone I the direct biosynthetic precursor of tanshinone I, and gives the whole series a clean two-axis map: A-ring oxidation state distinguishes the I series from the IIA series, and Sm2OGD3 activity distinguishes the dihydro members from the fully aromatic ones.

Discovery & Synthesis

First isolation. The tanshinones were first isolated from danshen root in the 1930s by Nakao and colleagues ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}, and the name is simply tanshen (the Chinese name for the root) plus the ketone suffix. The series was structurally re-examined by A. C. Baillie and R. H. Thomson at Aberdeen in “Naturally occurring quinones. Part XI. The tanshinones” (J. Chem. Soc. C, 1968) ^{36Reference 36Baillie AC · 1968Naturally occurring quinonesView study →}, which is the standard citation for the mid-century structural work. A specific, verifiable first-isolation date for dihydrotanshinone I itself could not be established — it is not stated in the major reviews of the compound ^{1Reference 1Chen X et al. · 2019Systematic reviewPharmacological activities of dihydrotanshinone I, a natural product from Salvia miltiorrhiza Bunge — systematic reviewView study →} or the series ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}, and the literature reaches it as “one of the tanshinones” rather than as a discrete discovery event. The systematic name records the point of difference: 15,16-dihydrotanshinone I is tanshinone I with the furan ring’s 15,16 double bond reduced.

Synthesis. Total syntheses of the danshen diterpenoid quinones as a family are established chemistry, and the ortho-quinone core has been used as a design template rather than a target in its own right — the 2018 tanshinone-mimic programme built a designed array of ortho-quinones around it and produced analogues more potent than the natural product at HuR ^{5Reference 5Manzoni L et al. · 2018Interfering with HuR-RNA interaction: design, synthesis and biological characterization of tanshinone mimics as novel, effective HuR inhibitors — medicinal chemistry studyView study →}. Supply for research is by extraction from S. miltiorrhiza root; the compound is a standard commercial reference material.

Patents: not yet researched.

Toxicity & Safety

There is real toxicology here, and it is not reassuring in the way silence would be. The findings below are why it is graded moderate rather than low or unknown.

Cholestasis & the Non-Monotonic Dose Response

The most direct toxicity finding: in mice, low-dose dihydrotanshinone I ameliorated cholestatic liver injury while high-dose dihydrotanshinone I did not. The mechanism was worked out — it inhibits Cyp3a11-mediated hydroxylation of lithocholic acid, taurolithocholic acid and taurochenodeoxycholic acid with IC50 values of 0.81, 0.36 and 1.29 µM, while simultaneously up-regulating Cyp3a11 protein. As hepatic concentration rises, enzyme inhibition overwhelms protein induction and cholestasis worsens ^{27Reference 27Li Y et al. · 2023In vitroLi Y, Wang Q, Jin J, et al. (2023). 15,16-dihydrotanshinone I in Danshen ethanol extract aggravated cholestasis by inhibiting Cyp3a11 mediated bile acids hydroxylation — mouse and in vitro study. Toxicology Letters. https://pubmed.ncbi.nlm.nih.gov/36804361/View study →}. This was the mechanism behind an earlier observation that high-dose tanshinone capsules aggravated cholestasis in mice.

Enzyme Inhibition & Drug Interactions

Dihydrotanshinone I is a sub-micromolar, promiscuous inhibitor of drug-metabolising enzymes — the clearest interaction liability of any tanshinone, and it is not the enzyme set most people assume.

• CYP1 family. IC50 values of 0.56 µM (CYP1A1), 0.44 µM (CYP1A2) and 0.11 µM (CYP1B1) — competitive at CYP1A1 and CYP1B1, non-competitive at CYP1A2, NADPH- and time-independent. The same study notes an arguably favourable consequence: preferential inhibition of CYP1B1-mediated 4-hydroxylation of oestradiol, the genotoxic branch of oestrogen metabolism ^{24Reference 24Liu Y et al. · 2024In vitroDihydrotanshinone I-induced CYP1 enzyme inhibition and alteration of estradiol metabolism — in vitro enzyme kinetic studyView study →}.
• CYP2D6. Inhibition characterised by molecular docking and enzyme kinetics against a model probe substrate in human liver microsomes ^{25Reference 25Zhou X et al. · 2012In vitroMolecular docking and enzyme kinetic studies of dihydrotanshinone on metabolism of a model CYP2D6 probe substrate in human liver microsomes — in vitro studyView study →}.
• UGT. Competitive inhibition of human-liver-microsomal propofol glucuronidation, Ki 1.7 µM, with the authors estimating a ~10% increase in propofol exposure at reported Cmax ^{26Reference 26Cong M et al. · 2013In vitroCryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome-catalyzed propofol glucuronidation — in vitro studyView study →}.

Every one of those is in vitro. None has been tested clinically. But the CYP1A2 and CYP2D6 findings in particular cover a large share of prescription drugs, and the concentrations are low enough to be worth stating plainly.

The Danshen–Warfarin Interaction — Correct Attribution

Danshen has one of the better-documented herb–drug interactions in the materia medica: human case reports of over-anticoagulation and bleeding in patients on warfarin who took danshen ^{29Reference 29Chan TY · 2001Case reportInteraction between warfarin and danshen (Salvia miltiorrhiza) — review of case reportsView study →}, catalogued in systematic reviews of warfarin interactions, plus rat pharmacokinetic and pharmacodynamic studies showing danshen raises steady-state warfarin concentrations. This is real and must not be soft-pedalled. But the attribution needs stating precisely:

• The case reports are herb-level. They describe patients taking danshen preparations, not this molecule ^{29Reference 29Chan TY · 2001Case reportInteraction between warfarin and danshen (Salvia miltiorrhiza) — review of case reportsView study →}.
• The mechanistic study is fraction-level and sibling-specific. Wu and Yeung tested the danshen ethyl acetate extract and the individual tanshinones tanshinone I, tanshinone IIA and cryptotanshinone — not dihydrotanshinone I — and found they inhibited CYP1A1-, CYP2C6- and CYP2C11-mediated warfarin hydroxylation in rat microsomes; the aqueous extract had no effect. Steady-state plasma warfarin rose 23% with co-administration ^{28Reference 28Wu WW · 2010In vitroInhibition of warfarin hydroxylation by major tanshinones of Danshen (Salvia miltiorrhiza) in the rat in vitro and in vivo — rat studyView study →}.
• Dihydrotanshinone I was not among the tanshinones tested in that study. Its own CYP inhibition profile ^{24,25Reference 24Liu Y et al. · 2024In vitroDihydrotanshinone I-induced CYP1 enzyme inhibition and alteration of estradiol metabolism — in vitro enzyme kinetic studyView study →Reference 25Zhou X et al. · 2012In vitroMolecular docking and enzyme kinetic studies of dihydrotanshinone on metabolism of a model CYP2D6 probe substrate in human liver microsomes — in vitro studyView study →} partly overlaps (CYP1A1) and partly does not.
• It does have independent antiplatelet activity — IC50 8.7 µM on collagen-induced platelet aggregation ^{30Reference 30Park JW et al. · 2008Park JW, Lee SH, Yang MK, et al. (2008). 15,16-dihydrotanshinone I, a major component from Salvia miltiorrhiza Bunge, inhibits rabbit platelet aggregation by suppressing intracellular calcium mobilization — ex vivo study. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/18277607/View study →} — which compounds the bleeding concern in principle, though at 200×+ above its measured plasma Cmax ^{32Reference 32Zhang Y et al. · 2012ReviewTanshinones: sources, pharmacokinetics and anti-cancer activities — reviewView study →}.

The correct statement is therefore: the warfarin interaction belongs to danshen the herb and, mechanistically, to the lipophilic tanshinone fraction — with the molecule-level demonstration resting on this compound’s three siblings rather than on it. Anyone on warfarin, an antiplatelet drug or an anticoagulant should treat danshen preparations as interacting; that instruction is about the herb, and the herb monograph is where it belongs.

Selectivity

In a screen of 63 secondary metabolites from Salvia species across MCF-7, HT-29 and a healthy fibroblast line, dihydrotanshinone I was named among the diterpenes exhibiting high toxic effects on the healthy cell line, and was not among the compounds whose cytotoxic effects exceeded their toxic effects ^{10Reference 10Irtegun Kandemir S et al. · 2022In vitroInvestigation of cytotoxic and apoptotic effects of 63 compounds obtained from Salvia species — in vitro screen including a healthy cell lineView study →}. Its cytotoxicity is potency without selectivity.

Reproductive & Other Gaps

No reproductive or developmental toxicity study of isolated dihydrotanshinone I has been published, and no repeat-dose or genotoxicity dataset exists for it specifically. A comparative panel that included it found no cytotoxicity or genotoxicity for tanshinone I and tanshinone IIA but did not report clean equivalents for the unstable dihydro compounds ^{7Reference 7Roth A et al. · 2023In vitroChemical stability and bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems — comparative studyView study →}. Decisions about danshen intake during pregnancy or lactation belong on the dan shen monograph, where the preparation and dose are actually chosen.

Safety at a Glance

⚠️ Moderate toxicity

• Targeted mechanisms, not just cytotoxicity. HuR, IRF3, AChE and PKM2 are direct-binding results with structural or genetic confirmation — this is a real pharmacological agent, not an assay artefact.
• Low systemic exposure. Rat plasma Cmax of 12–41 nM after oral dosing means most in-vitro concerns are also out of reach at realistic intakes.
• Documented dose-dependent liver harm. High-dose dihydrotanshinone I worsened cholestasis in mice by inhibiting Cyp3a11-mediated bile-acid hydroxylation; the dose–response is not monotonic.
• Potent, broad in-vitro enzyme inhibition. CYP1A1/1A2/1B1 at 0.11–0.56 µM, CYP2D6, and UGT-mediated glucuronidation at Ki 1.7 µM. Untested clinically, but a wide interaction surface.
• Danshen interacts with warfarin and antiplatelet drugs. The case-report evidence is herb-level and the microsomal mechanism was shown for this molecule’s three siblings; this compound has its own antiplatelet activity in vitro. Treat danshen preparations as interacting.
• Not selectively cytotoxic. In the one screen with a healthy control line, it was among the compounds most toxic to healthy cells. Anticancer results without a healthy comparator mean little.
• Chemically unstable. It oxidises to tanshinone I in DMSO and in aqueous solution; long in-vitro exposures are partly exposures to a different molecule.
• No human data of any kind. No trial, no reproductive toxicology, no repeat-dose study. Silence is not safety.

Dosage

There is no human dose. Nothing below is a recommendation — these are the amounts research has used, given only for orientation.

Rodent doses do not scale to a human dose, and the constraint on translation here is absorption rather than tolerability. A danshen water decoction delivers essentially none of this compound; an ethanol or CO₂ extract delivers an unstandardised amount. These are doses studied in research and are not a personal recommendation.

References

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