Database Query Results : Salvia miltiorrhiza, ,

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)
Scientific Papers found: Click to Expand⟱
1068- SM,    Danshen Improves Survival of Patients With Breast Cancer and Dihydroisotanshinone I Induces Ferroptosis and Apoptosis of Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, BC, NA - Human, BC, NA
TumCG↓, Ferroptosis↑, GPx4↓, TumVol↓, OS↑, GSH/GSSG↓,
1133- SM,    Salvianolic Acid A, a Component of Salvia miltiorrhiza, Attenuates Endothelial-Mesenchymal Transition of HPAECs Induced by Hypoxia
- in-vitro, Nor, HPAECs
*ROS↓, *p‑Smad1↑, *p‑SMAD5↑, *SMAD2↓, *SMAD3↓, *p‑ERK↓, *p‑Cofilin↓,
1191- SM,    Salvia miltiorrhiza extract inhibits TPA‑induced MMP‑9 expression and invasion through the MAPK/AP‑1 signaling pathw
- in-vitro, BC, MCF-7
Inflam↓, MMP9↓, TumCI↓, AP-1↓, lipidLev↓,
1192- SM,    Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1
- in-vitro, GC, AGS - in-vitro, Liver, HepG3
Hif1a↓, VEGF↓,
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↓,
1194- SM,    Salvia miltiorrhiza protects against diabetic nephropathy through metabolome regulation and wnt/β-catenin and TGF-β signaling inhibition
- in-vivo, Diabetic, NA
β-catenin/ZEB1↓, TGF-β↓,
1195- SM,    Salvia miltiorrhiza polysaccharide activates T Lymphocytes of cancer patients through activation of TLRs mediated -MAPK and -NF-κB signaling pathways
- in-vitro, Lung, A549 - in-vitro, Liver, HepG2 - in-vitro, CRC, HCT116
T-Cell↑, TumCP∅, IL4↑, IL6↑, IFN-γ↑, TLR4↑, TLR1↑, TLR2↑, p‑JNK↑, p‑ERK↑, IKKα↑,
1291- SM,    Tanshinone IIA inhibits human breast cancer cells through increased Bax to Bcl-xL ratios
- in-vitro, BC, MDA-MB-231
TumCP↓, TumCCA↑, BAX↑, Bcl-2↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH/GSSG↓, 1,  

Core Metabolism/Glycolysis ⓘ

lipidLev↓, 1,  

Cell Death ⓘ

BAX↑, 1,   Bcl-2↓, 1,   Ferroptosis↑, 1,   p‑JNK↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↑, 1,   TumCG↓, 1,  

Migration ⓘ

AP-1↓, 1,   MMP9↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 1,   TumCP∅, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IFN-γ↑, 1,   IKKα↑, 1,   IL4↑, 1,   IL6↑, 1,   Inflam↓, 1,   T-Cell↑, 1,   TLR1↑, 1,   TLR2↑, 1,   TLR4↑, 1,  

Clinical Biomarkers ⓘ

IL6↑, 1,  

Functional Outcomes ⓘ

OS↑, 1,   TumVol↓, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

CYP2E1↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Core Metabolism/Glycolysis ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,  

Migration ⓘ

p‑Cofilin↓, 1,   p‑Smad1↑, 1,   SMAD2↓, 1,   SMAD3↓, 1,   p‑SMAD5↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 13

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

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