Curcumin

Category: polyphenol

Aliases: Diferuloylmethane, Turmeric extract, Curcuma longa

Pharmacological Mechanism

Inhibits nfkb signaling, arachidonic acid cascade COX-2, 5-LOX, and STAT3 — broad anti-inflammatory profile. Anti-oxidant via direct ROS scavenging + nrf2 keap1 antioxidant response Nrf2 activation. Extensively glucuronidated + sulfated in the gut / liver — circulating aglycone is minimal without a bioavailability enhancer (piperine inhibits glucuronidation). Most clinical effects at supplemental doses are modest; symptomatic OA improvement is the best-established endpoint.

Half-Life (t½)

PO: 6h

Dosing Guidelines

• PO: Typical 1000 mg (Range: 500–2000 mg)

Target Organ Systems

• immune-hematologic

Interactions

• Piperine (synergistic): Canonical bioavailability-enhancer pair.

Pathways It Modulates

• Alzheimer disease (inhibitor) — Aβ aggregation (preclinical anti-amyloid)
• AMPK energy sensor (activator) — AMPK (anti-inflammatory + metabolic)
• Atherosclerosis plaque pathology (inhibitor) — oxLDL + plaque inflammation (preclinical)
• BDNF / TrkB neurotrophic signaling (activator) — BDNF (chronic; HDAC + 5-HT pathways)
• Brown adipose thermogenesis (activator) — BAT activation + WAT browning (preclinical)
• CD4 T-helper differentiation (inhibitor) — Th17 + Treg balance modulation (preclinical)
• Cellular senescence / SASP / senolytics (inhibitor) — NF-κB-driven SASP
• Estrogen phase-2 clearance (activator) — Nrf2 → phase-2 induction
• Estrogen receptor (ERα / ERβ / GPER) (inhibitor) — ER (modest; cancer chemoprevention)
• Ferroptosis (inhibitor) — ferroptosis (preclinical; iron chelation + antioxidant)
• GSH / GSSG redox cycle (activator) — Nrf2 → GPx + GR upregulation
• Hedgehog / Smoothened signaling (inhibitor) — Hedgehog (chronic; tumor models)
• Hepcidin / ferroportin iron regulation (inhibitor) — IL-6 → hepcidin axis
• Hippo / YAP-TAZ signaling (inhibitor) — YAP/TAZ-TEAD (preclinical anti-cancer)
• Kynurenine pathway (inhibitor) — IDO1 + IFN-γ → KP suppression in tumor microenvironment
• MAPK / ERK (RAS-RAF-MEK-ERK) cascade (inhibitor) — MAPK (chronic anti-inflammatory)
• Microbiome short-chain fatty acid signaling (activator) — beneficial SCFA producers (poorly absorbed → reaches colon)
• Mitophagy (activator) — mitophagy (preclinical neuroprotection)
• NAFLD / MASH (inhibitor) — hepatic NF-κB + lipogenesis (preclinical + small trials)
• Necroptosis (inhibitor) — necroptosis (anti-inflammatory; preclinical)
• Neuroinflammation (inhibitor) — NF-κB + NLRP3 (chronic, modest clinical signal in CNS)
• Notch signaling (inhibitor) — Notch (chronic; tumor models)
• Nrf2 / Keap1 antioxidant response (activator) — Nrf2 + NF-κB + COX-2 (multi-target)
• p53 / MDM2 DNA-damage response (activator) — restores / amplifies WT p53 (preclinical anti-cancer)
• Parkinson disease (inhibitor) — α-synuclein aggregation (preclinical anti-fibril)
• Pyroptosis (inhibitor) — NLRP3 / NF-κB priming
• Telomere maintenance + shelterin complex (activator) — telomerase + telomere length (preclinical)
• TLR (Toll-like receptor) innate signaling (inhibitor) — TLR4 / NF-κB
• Transsulfuration → cysteine → glutathione (activator) — Nrf2 → γ-GCS upregulation
• Unfolded protein response / ER stress (inhibitor) — CHOP-driven apoptosis (preclinical neuroprotection)
• Wnt / β-catenin canonical signaling (inhibitor) — β-catenin (chronic, anti-tumor)
• Wound healing cascade (activator) — wound healing (anti-inflammatory + collagen modulation; diabetic-wound clinical signal)

Chemical Identifiers

• PubChem CID: 969516
• Formula: C21H20O6
• Molecular weight: 368.38 g/mol
• InChIKey: VFLDPWHFBUODDF-FCXRPNKRSA-N
• SMILES: COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O

References

• PMID 9619120