Supplement
Hederagenin is a plant compound found in ivy leaves and Clematis roots, studied mainly for its effects on inflammation. The evidence is limited, but in rodents and cell studies it dampened NF-κB inflammatory signaling and lowered inflammatory messengers, and in Alzheimer's mice it improved memory and thinking tests. Most of this work was in animals or lab cells, so how it applies to people is unclear.
Sources: PMID 26481049; PMID 26557859; PMID 36809694
- Updated
- How we grade
- 16 studies cited
- Best evidence
- Grade C
- Conditions studied
- 4
- Outcomes
- 9
- Graded outcomes
- 0027
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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. | Improves (the measure goes down) | Moderate effect | 3 studies | |||
Studies that measured alzheimer's disease biomarkers
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General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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. | Improves (the measure goes down) | Moderate effect | 2 studies | |||
| 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. | Changes; see studies | Moderate effect | 6 studies | |||
Studies that measured cancer cell proliferation
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| 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. | Improves (the measure goes up) | Moderate effect | 1 study | |||
Studies that measured parkinson's disease biomarkers | ||||||
| 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. | Improves (the measure goes down) | Small effect | 1 study | |||
Studies that measured depressive symptoms | ||||||
| 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. | Improves (the measure goes down) | Moderate effect | 1 study | |||
Studies that measured stroke/cerebral ischemia damage | ||||||
Alcoholic Hepatitis
- Alcohol-Induced Liver Damage: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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. | Improves (the measure goes down) | Small effect | 2 studies | |||
Studies that measured alcohol-induced liver damage | ||||||
Cardiovascular Health
- Blood Lipids: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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). | Improves (the measure goes down) | Moderate effect | 2 studies | |||
Atherosclerosis
- Atherosclerosis Progression: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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). | Improves (the measure goes up) | Moderate effect | 1 study | |||
Studies that measured atherosclerosis progression | ||||||
Key findings
- Alzheimer's Disease BiomarkersImproves (the measure goes down)
- InflammationImproves (the measure goes down)
- Cancer Cell ProliferationChanges; see studies
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- Grade C
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Studies cited
16 studies from PubMed
- Hederagenin reduces Aβ-induced oxidative damage, decreases Aβ deposition and promotes cell survival by the PI3K/Akt signaling pathway
- Hederagenin promotes lung cancer cell death by activating CHAC1-dependent ferroptosis pathway
- Advances in the anti-tumor potential of hederagenin and its analogs
- Hederagenin improves Alzheimer's disease through PPARα/TFEB-mediated autophagy
- Hederagenin Exerts Potential Antilipemic Effect via p38MAPK Pathway in Oleic Acid-induced HepG2 cells and in Hyperlipidemic Rats
- Hederagenin potentiated cisplatin- and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells
- Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling
- A hederagenin saponin isolated from Clematis ganpiniana induces apoptosis in breast cancer cells via the mitochondrial pathway
- Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells by Inhibiting the Nrf2-ARE Antioxidant Pathway
- Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats
- Hederagenin and alpha-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice
- Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice
- Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats
- Hederagenin as a novel antidepressant-like compound identified from Clematis chinensis Osbeck
- Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway
- The effects of 10 triterpenoid compounds on experimental liver injury in mice