The 8+ Benefits of Hederagenin (with Sources and Derivatives)

In this post, we will discuss the benefits and natural sources of hederagenin and hederagenin derivatives. 

Hederagenin is a triterpene derivative of oleanolic acid found in many plant sources (see sources below).

1. Has Strong Antidepressant Effects

Hedaragnin is a novel triple inhibitor of monoamine transporters and acts as a Serotonin (5-HT), Norepinephrine (NE) and Dopamine (DA) reuptake inhibitor. R

It can also increase the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor. R

Hedaragenin can also reduce stress hormones such as Adrenocorticotrophic Hormone (ACTH) and serum Corticosterone in rats exposed to chronic unpredicted mild stress. R

Behaviorally, it can mimic the antidepressant effects of escitalopram in rodents. R

2. May Combat Cancer

Hederagenin has anti-cancer activities against:

• Breast Cancer R
• Colon Cancer R
• Head and Neck Cancer (reduces NRF2/AREs) R
• Lung Cancer R

Other derivatives of hederagenin may be potent against some cancers. R R R R

Hedaragenin can also potentiate some chemotherapeutic agents. R

For example, H6 a derivative of hedaragenin can reverse Multidrug Resistance (MDR) by sensitizing KBV and MCF7/T cells to paclitaxel and vincristine (stimulates P-gp ATPase). R

3. May Fight Huntington's And Parkinson's Disease Development

Parkinson's Disease (PD) and Huntington's Disease (HD) pathologies contain protein aggregates and inclusion body (see proteopathy). R

Hederagenin can improve motor deficits in PD mice models. R

It can also promote autophagy and prevent the formation of α-synuclein and huntingtin (via AMPK-mTOR). R

4. May Protect Against Alcohol Exposure

Hederagenin may protect against alcohol-induced liver injury. R

For example, in rodent models, hedaragenin was able to reduce inflammation associated with alcohol use and improve alcohol metabolism. R

5. Has Antimicrobial Properties

Hederagenin has antibacterial against:

• B. cereus R
• E. coli R
• E. faecalis R
• K. pneumoniae R
• P. aeruginosa R
• S. aureus R
• S. epidermidis R
• S. typhimurium R

Hederagenin has antiparasitic activity against Leishmania infantum. R R

6. Reduces Inflammation

Hederagenin can reduce inflammatory responses. R

For example, treatment with hederagenin can in inhibited levels of protein expression of lipopolysaccharide-stimulated iNOS, COX-2, and NF-κB as well as production of NO, PGE2, TNF-α, IL-1β, and IL-6. R

Hederagenin can also mast cell degranulation. R

The hederagenin saponin SMG-1 is a natural FMLP receptor inhibitor that suppresses human neutrophil activation. R

7. Protects The Vascular System

Hederagenin has multiple pharmacological activities in the treatment of hyperlipidemia, antiplatelet aggregation, and atherosclerosis. R

For example, hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKβ/NF-κB signaling pathway to reduce the release of IL-6, IFN-γ, TNF-α, and other inflammatory factors. R

8. Has Antioxidant Properties

Derivatives of hederagenin can act as free-radical scavengers. R

...currently testing a few sources...

I have had positive experiences with Black Seed Oil, Quinoa, Red Beets, and Rambutan.

Sources of hederagenin and hederagenin derivatives:

• Akebia fruit (Fructus akebiae) R R
• Ann Ala Ivy (Hedera pastuchovii) R
• Barrelclover (Medicago truncatula) R
• Bittercress (Barbarea vulgaris) R
• Black Seed Oil (Nigella Sativa) R
• Blue cohosh (Caulophyllum robustum) R
• Castor Aralia (Kalopanax septemlobus) R
• Cephalaria species (e.g. - Cephalaria anthelminticum, C. balansae, C. elmaliensis, C. transsylvanica) R R R R R
• Chocolate vine (Akebia quinata) R
• Clematis species (e.g. - Clematis ganpiniana, C. lasiandra, C. mandshurica) R R R R
• Common Ivy (Hedera helix) R
• Hibberd (Hedera taurica) R
• Honeysuckle (Lonicera macranthoides) R
• Hybrid Alfalfa (Medicago hybrida) R
• Indian Elm (Holoptelea integrifolia) R
• Money Tree leaves (Cyclocarya Paliurus) R
• Paperplant (Fatsia japonica) R
• Persian Ivy (Hedera colchica) R
• Pulsatilla (Pulsatilla chinensis) R
• Quinoa (Chenopodium quinoa) R
• Red Beets (Beta vulgaris) R
• Rambutan (Nephelium lappaceum) R
• Soapberry (e.g. - Sapindus mukorossi, S. laurifolius, S. emarginatus, S. mukorossi, S. saponaria) R R R R
• Spotted medick (Medicago arabica) R
• Stelzneri (Weigela florida) R
• Teasel (Dipsacus asper) R

Hedaragenin may increase Lactate Dehydrogenase (LDH), although this has only shown to be in colon cancer cells. R

Simple:

• Increases ALDH2 R
• Increases AMPK R
• Increases Bax R R
• Increases Caspase-3 R R R
• Increases Caspase-9 R R
• Increases DA R
• Increases eNOS R
• Increases LDH R
• Increases NE R R
• Increases PARP R R
• Increases p53 (decreased in alcohol exposure) R R
• Increases 5-HT R R
• Increases 5-HT1A R
• Reduces ACTH R
• Reduces ADH R
• Reduces AKT R R
• Reduces Apaf-1 R
• Reduces Bcl-2 R
• Reduces Bcl-xL R
• Reduces Corticosterone R
• Reduces COX-2 R R
• Reduces Cyto C R
• Reduces ERK (seems to increase in cancer) R R
• Reduces FMLPR R
• Reduces IFN-gamma R
• Reduces IL-1b R
• Reduces IL-6 R R R
• Reduces iNOS R R
• Reduces JNK R
• Reduces MAPK R R
• Reduces mTOR R
• Reduces NF-kB R R
• Reduces NO R
• Reduces NRF2 R
• Reduces PGE2 R
• Reduces Procaspase-3 R
• Reduces Procaspase-9 R
• Reduces Survivin R
• Reduces TNF-α R R R
• Reduces 5-HTT R

Advanced:

• Hedaragnin can increase 5-HT, NE and DA in frontal cortex. R
  • Binding affinity (as Ki):
    SERT at cerebral cortex: 3.89±0.18 nm
    NET at hypothalamus: 0.22±0.04 nm
    DAT at striatum: 2.87±0.54 nm
• HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). R
• In cancer, Hedaragnin induces the apoptosis of tumor cells via the mitochondrial pathway. R
• Hederagenin or hederin lead to a reduced phosphorylation of p70S6K, which is a downstream target of mTOR. R
• SMG-1 inhibited FMLP binding to its receptor in a concentration-dependent manner...SMG-1 attenuated FMLP-induced increase of cytosolic calcium concentration and phosphorylation of p38 MAPK, ERK, JNK, and AKT. R