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Hederagenin

Hederagenin is a pentacyclic triterpenoid saponin found in quinoa, ivy (Hedera helix), and various plants. Structurally similar to ursolic acid and oleanolic acid. NO GRADED OUTCOMES - limited research exists. Preclinical studies suggest anti-inflammatory, anti-cancer, and hepatoprotective effects, but human research is lacking. Not commonly available as an isolated supplement - typically consumed through quinoa or ivy-containing cough remedies. Research is too preliminary for recommendations.

Quick Answer

What it is

Hederagenin is a pentacyclic triterpenoid saponin found in quinoa, ivy (Hedera helix), and various plants. Structurally similar to ursolic acid and oleanolic acid.

Key findings

  • Grade C: Alzheimer's Disease Biomarkers
  • Grade C: Inflammation
  • Grade D: Cancer Cell Proliferation

Safety

No specific caution or interaction language was detected in the current summary/outcome notes.

ℹ️ Quick Facts: Hederagenin

Quick Facts: Hederagenin

  • Best Evidence:Grade C
  • Conditions Studied:4
  • Research Outcomes:9
  • Key Effect:Alzheimer’s Disease
Outcomes by grade:
A0
B0
C2
D7
4 conditions · 9 outcomes

Detailed Outcomes

|
C
Alzheimer's Disease Biomarkers
In APP/PS1 transgenic Alzheimer's mice, hederagenin (25–50 mg/kg/day for 2 months) improved cognitive performance in Morris water maze, object recognition, and Y-maze tests while promoting amyloid-beta degradation via PPARα/TFEB-mediated autophagy. Additional studies in SH-SY5Y cells and C. elegans models confirmed reduced Aβ deposition, decreased oxidative damage via PI3K/Akt and PTPN1 signaling.
moderate↓Improves
C
Inflammation
In rodent models, hederagenin (30 mg/kg) dose-dependently inhibited NF-κB, iNOS, COX-2, and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in LPS-stimulated macrophages and carrageenan-induced paw edema. A rat atherosclerosis model showed comparable anti-inflammatory effects to atorvastatin via IKKβ/NF-κB inhibition.
moderate↓Improves
D
Cancer Cell Proliferation
In vitro studies across colon (IC50 1.39 μM), lung (IC50 26.23 μM), breast, head/neck, ovarian, and pancreatic cancer cell lines demonstrate hederagenin induces apoptosis via mitochondrial pathways and modulates autophagy context-dependently. In xenograft models, hederagenin potentiated cisplatin and paclitaxel cytotoxicity in lung cancer cells by impairing autophagic flux, and showed efficacy against cisplatin-resistant head/neck cancer tumors in vivo.
moderate↓Worsens
D
Parkinson's Disease Biomarkers
In MPTP-induced Parkinson's mice, hederagenin promoted degradation of mutant α-synuclein via AMPK-mTOR-dependent autophagy and improved motor deficits. A separate C. elegans study confirmed mitophagy induction via PINK1/Parkin pathway, reducing α-synuclein aggregation and mitigating dopaminergic neuron loss. Hederagenin was shown to cross the blood-brain barrier.
moderate↓Improves
D
Depressive Symptoms
In mice and rats, hederagenin (5–20 mg/kg daily for 3 weeks) significantly decreased immobility in forced swim and tail suspension tests and increased sucrose preference in an unpredictable chronic mild stress model. Mechanism identified as triple monoamine reuptake inhibition (serotonin, norepinephrine, dopamine) with increased hippocampal monoamine levels.
small↓Improves
D
Stroke/Cerebral Ischemia Damage
In a mouse MCAO (middle cerebral artery occlusion) model, hederagenin (26.5–106 μmol/kg i.p. for 3 days) significantly reduced brain infarct volumes, attenuated ischemia/reperfusion-induced apoptosis, and suppressed inflammatory cytokine expression through inhibition of MLK3 signaling. MLK3 overexpression abolished the neuroprotective effects, confirming the mechanism.
moderate↓Improves
D
Alcohol-Induced Liver Damage
In rats, hederagenin supplementation (50 mg/kg/day for 21 days) decreased serum AST, ALT, triglycerides, TNF-α, and IL-6 following chronic ethanol exposure, while reducing hepatic apoptosis markers. However, an earlier mouse study found hederagenin did NOT protect against CCl4- or acetaminophen-induced hepatotoxicity, indicating the hepatoprotective effect may be specific to alcohol-induced injury.
small↓Improves
D
Blood Lipids
In hyperlipidemic rats, hederagenin reduced total cholesterol, triglycerides, LDL-C, and MDA while increasing HDL-C, SOD, and GSH-PX via p38 MAPK pathway inhibition. A separate rat atherosclerosis model confirmed reductions in serum lipids comparable to atorvastatin (positive control).
moderate↓Improves
D
Atherosclerosis Progression
In a Wistar rat atherosclerosis model (high-lipid diet + vitamin D3), hederagenin improved blood rheology and endothelial function, corrected iNOS/eNOS imbalance, and inhibited IKKβ/NF-κB signaling with results comparable to atorvastatin at statistical significance (P < 0.01).
moderate↓Improves

Research Citations (16)

Hederagenin reduces Aβ-induced oxidative damage, decreases Aβ deposition and promotes cell survival by the PI3K/Akt signaling pathway
(2025)
PMID: 38814954
Hederagenin promotes lung cancer cell death by activating CHAC1-dependent ferroptosis pathway
(2024)
PMID: 38735142
Advances in the anti-tumor potential of hederagenin and its analogs
(2023)
PMID: 37742813
Hederagenin improves Alzheimer's disease through PPARα/TFEB-mediated autophagy
(2023)
PMID: 36809694
Hederagenin Exerts Potential Antilipemic Effect via p38MAPK Pathway in Oleic Acid-induced HepG2 cells and in Hyperlipidemic Rats
(2022)
PMID: 36102390
Hederagenin potentiated cisplatin- and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells
(2020)
PMID: 32792495
Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling
(2020)
PMID: 32848779
A hederagenin saponin isolated from Clematis ganpiniana induces apoptosis in breast cancer cells via the mitochondrial pathway
(2018)
PMID: 29434869
Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells by Inhibiting the Nrf2-ARE Antioxidant Pathway
(2017)
PMID: 29456786
Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats
(2017)
PMID: 28067819

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