Salvia miltiorrhiza / CYP2E1 Cancer Research Results

SM, Salvia miltiorrhiza: Click to Expand ⟱
Features:

Salvia miltiorrhiza (Danshen; SM) — a traditional Chinese medicinal root containing two major bioactive classes: lipophilic tanshinones (e.g., tanshinone IIA, cryptotanshinone) and hydrophilic phenolic acids (e.g., salvianolic acid A/B). Studied in oncology, cardiovascular, and neurovascular contexts.

Primary mechanisms (conceptual rank):
1) STAT3 / PI3K-AKT-mTOR suppression (anti-survival signaling; mainly tanshinones)
2) ROS modulation (often ↑ in cancer → apoptosis; ↓ oxidative injury in normal tissue)
3) NF-κB inhibition (anti-inflammatory, anti-proliferative)
4) Cell-cycle arrest (G0/G1 or G2/M; cyclin/CDK modulation)
5) Anti-angiogenic signaling (↓ VEGF / HIF-1α coupling)

Bioavailability / PK relevance: Tanshinones are lipophilic with poor oral bioavailability; phenolic acids more water-soluble but rapidly metabolized. Many in-vitro cancer effects occur at concentrations higher than typical plasma levels from oral preparations unless specialized formulations are used.

In-vitro vs oral exposure: Anti-cancer cytotoxicity frequently at micromolar range (qualifier: high concentration only for direct tumor apoptosis).

Clinical evidence status: Widely used in cardiovascular medicine (Asia); oncology evidence largely preclinical or adjunct-hypothesis; no major oncology RCT approval.

Red sage, redroot sage, Chinese sage or danshen.
Salvianolic Acid A (SAA) is predominantly isolated from Salvia miltiorrhiza, commonly known as Danshen.
Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as 'Danshen'

Salvianolic Acid A, primarily derived from Salvia miltiorrhiza (Danshen), shows promise in cancer research due to its ability to inhibit cell proliferation, induce apoptosis, reduce angiogenesis, and impact multiple signaling pathways involved in tumor progression.

Salvianolic Acid A may impact several intracellular signaling pathways involved in cancer progression:
NF-κB Pathway: SAA might inhibit the NF-κB pathway, reducing inflammation and cell proliferation signals.
MAPK Pathways (ERK, JNK, p38): By modulating these pathways, SAA can influence cell survival, differentiation, and apoptosis.
PI3K/Akt Pathway: Inhibition of this pathway is another mechanism through which SAA can reduce cancer cell survival and proliferation.
Oxidative Stress Reduction: SAA’s antioxidant properties may help in reducing oxidative stress, which is implicated in cancer progression and chemoresistance.
Synergistic Effects with Conventional Therapies:
Preliminary studies suggest that Salvianolic Acid A might enhance the effectiveness of various chemotherapeutic agents.

Some studies have observed anti-proliferative effects at concentrations around 10–50 µM. rodent models have been reported in the range of 10–100 mg/kg

Salvia miltiorrhiza (Danshen) — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 STAT3 signaling ↓ (primary; tanshinone-driven) ↔ R/G Reduced survival transcription Cryptotanshinone widely reported STAT3 inhibitor; central anti-proliferative axis.
2 PI3K/AKT/mTOR ↓ ↔ / ↑ metabolic protection R/G Suppressed anabolic signaling Often linked to reduced proliferation and enhanced apoptosis.
3 ROS ↑ (dose-dependent; apoptosis) ↓ (phenolic antioxidant) P/R Redox divergence Biphasic: pro-oxidant in tumors (tanshinones); antioxidant in normal tissues (salvianolic acids).
4 Intrinsic apoptosis (Bax↑, Bcl-2↓, caspases) ↑ ↔ R/G Mitochondrial apoptosis Common downstream outcome of STAT3/AKT suppression and ROS elevation.
5 NF-κB ↓ ↓ R/G Anti-inflammatory / anti-survival Contributes to both anti-cancer and cardiovascular protective roles.
6 Cell Cycle (Cyclin D1/CDK4, p21) ↓ proliferation ↔ G G0/G1 or G2/M arrest Model-dependent checkpoint enforcement.
7 HIF-1α / VEGF ↓ ↔ G Reduced angiogenesis Reported anti-angiogenic effect; linked to tumor growth inhibition in vivo models.
8 NRF2 ↔ / ↑ (context-dependent) ↑ R/G Stress-response activation Phenolic components may activate antioxidant pathways in normal tissues; cancer context variable.
9 Ca²⁺ / ER stress ↑ (stress-induced; model-dependent) ↔ P/R ER-mitochondrial coupling Observed in apoptosis models; not always primary mechanism.
10 Ferroptosis ↑ (investigational; ROS-linked) ↔ R/G Lipid peroxidation stress Possible secondary overlap via redox modulation; not universally established.
11 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — Bioavailability + heterogeneity Variable extract composition (tanshinone vs phenolic content); limited oncology clinical trials.

TSF legend:
P: 0–30 min (direct redox or signaling interactions)
R: 30 min–3 hr (acute stress and transcriptional modulation)
G: >3 hr (gene regulation and phenotype outcomes)
CYP2E1, cytochrome P450 2E1 (CYP2E1): Click to Expand ⟱
Source:
Type:
CYP2E1 is an enzyme belonging to the cytochrome P450 family that is primarily involved in the metabolism of small organic molecules, including drugs, toxins, and endogenous substrates. It plays a significant role in the biotransformation of various compounds through oxidation reactions.

Due to its role in metabolizing procarcinogenic compounds, elevated CYP2E1 activity has been linked to an increased risk of certain cancers, particularly in the context of chronic alcohol consumption or exposure to environmental toxins. In some studies, higher CYP2E1 levels have been associated with liver cancer and may also influence risk in other tissues.
Scientific Papers found: Click to Expand⟱
1193- SM,    Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways
- in-vivo, Alcohol, NA - in-vitro, Liver, HepG2
*p‑AMPK↑, *SIRT1↑, *NRF2↑, *CYP2E1↓, *lipoGen↓, *ROS↓, *Inflam↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

CYP2E1↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

p‑AMPK↑, 1,   lipoGen↓, 1,   SIRT1↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 7

Scientific Paper Hit Count for: CYP2E1, cytochrome P450 2E1 (CYP2E1)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:146  Target#:1040  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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