Database Query Results : Celastrol, ,

Cela, Celastrol: Click to Expand ⟱
Features:

Celastrol — a quinone methide triterpenoid isolated from Tripterygium wilfordii (Thunder God Vine). Potent redox-active and pleiotropic signaling modulator studied in oncology, inflammation, and metabolic disease.

Primary mechanisms (conceptual rank):
1) Proteostasis stress induction (HSP90 inhibition; HSF1 activation)
2) NF-κB suppression (IKK inhibition; anti-survival transcription blockade)
3) ROS generation → mitochondrial apoptosis
4) STAT3 inhibition
5) PI3K/AKT/mTOR modulation (context-dependent)

Bioavailability / PK relevance: Poor aqueous solubility; narrow therapeutic index; rapid metabolism; dose-limiting toxicity in systemic use. Many mechanistic studies use micromolar concentrations.

In-vitro vs oral exposure: Anti-cancer cytotoxicity typically at concentrations unlikely achievable safely without advanced delivery systems (qualifier: high concentration only for direct tumor apoptosis).

Clinical evidence status: Preclinical oncology; early translational investigation; no approved cancer indication.

Celastrol—a bioactive compound extracted from traditional Chinese medicinal plants such as Tripterygium wilfordii (Thunder God Vine).

Pathways:
-inhibit NF-κB activation
-disrupt the function of chaperone proteins like HSP90 and HSP70, which are often overexpressed in cancer cells
-attenuate Akt phosphorylation and downstream mTOR signaling
-modulate components of the MAPK pathway, including ERK, JNK, and p38.
-increase intracellular ROS levels in cancer cells
-inhibiting STAT3

Celastrol — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 HSP90 / Proteostasis stress ↓ client proteins ↔ / ↑ stress (dose-dependent) R/G Oncoprotein destabilization HSP90 inhibition leads to degradation of AKT, HER2, EGFR and other client proteins.
2 NF-κB ↓ (primary) ↓ R/G Reduced inflammatory and survival transcription IKK inhibition suppresses NF-κB activation; central anti-survival axis.
3 ROS ↑ (primary; dose-dependent) ↑ (high concentration) P/R Oxidative stress induction Quinone methide structure enables redox cycling; contributes to apoptosis.
4 Intrinsic apoptosis (Bax↑, Bcl-2↓, caspases) ↑ ↑ (high dose) R/G Mitochondrial apoptosis Often ROS-mediated; cancer cells more vulnerable due to baseline oxidative stress.
5 STAT3 ↓ ↔ R/G Reduced proliferative signaling Inhibits STAT3 phosphorylation in multiple tumor models.
6 PI3K/AKT/mTOR ↓ (secondary) ↔ R/G Anabolic signaling suppression Often downstream of HSP90 inhibition and proteotoxic stress.
7 NRF2 ↑ (adaptive resistance; context-dependent) ↑ R/G Stress-response activation Low/moderate doses may activate NRF2; excessive ROS may overwhelm defense in tumors.
8 Ferroptosis ↑ (investigational; ROS-linked) ↔ R/G Lipid peroxidation vulnerability Oxidative stress environment may sensitize to ferroptotic pathways.
9 HIF-1α ↓ (model-dependent) ↔ G Reduced hypoxia adaptation Linked to suppression of angiogenesis-related signaling.
10 Ca²⁺ / ER stress ↑ (stress-mediated) ↑ (high dose) P/R UPR activation Proteostasis disruption induces ER stress response.
11 Clinical Translation Constraint ↓ (constraint) ↓ (toxicity) — Narrow therapeutic window Systemic toxicity and solubility challenges limit clinical oncology development.

TSF legend:
P: 0–30 min (direct redox/protein interactions)
R: 30 min–3 hr (acute stress and signaling shifts)
G: >3 hr (gene regulation and phenotype outcomes)
Scientific Papers found: Click to Expand⟱
2392- Cela,    The role of natural products targeting macrophage polarization in sepsis-induced lung injury
- Review, Sepsis, NA
TNF-α↓, IL1β↓, IL6↓, Warburg↓, PKM2↓, NRF2↑, HO-1↑, NF-kB↓, iNOS↓, M1↓,
2393- Cela,    Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect
- in-vivo, Sepsis, NA - in-vitro, Nor, RAW264.7
OS↑, PKM2↓, Glycolysis↓, Warburg↓, Inflam↓, HMGB1↓, ALAT↓, AST↓, TNF-α↓, IL1β↓, IL6↓,
2653- Cela,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
chemoPv↑, Catalase↑, ROS↑, HSP90↓, Sp1/3/4↓, AMPK↑, P53↑, JNK↑, ER Stress↑, MMP↓, TumCCA↑, TumAuto↑, Hif1a↑, Akt↑, other↓, Prx↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   HO-1↑, 1,   NRF2↑, 1,   Prx↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   Glycolysis↓, 1,   PKM2↓, 2,   Warburg↓, 2,  

Cell Death ⓘ

Akt↑, 1,   iNOS↓, 1,   JNK↑, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,  

Immune & Inflammatory Signaling ⓘ

HMGB1↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 1,   M1↓, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

chemoPv↑, 1,   OS↑, 1,  
Total Targets: 34

Pathway results for Effect on Normal Cells:


Total Targets: 0

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#:317  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page