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

Hederagenin Sources And Derivatives

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

Contents:

  1. Basics Of Hederagenin
  2. Benefits Of Hederagenin
  3. My Experience With Hederagenin
  4. Natural Sources Of Hederagenin And Derivatives
  5. Caveats
  6. Mechanism Of Action

Basics Of Hederagenin

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

 
 

Benefits Of Hederagenin

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

 
 https://www.hindawi.com/journals/omcl/2017/5498908/

https://www.hindawi.com/journals/omcl/2017/5498908/

 

Hederagenin has anti-cancer activities against:

  • Breast Cancer R
  • Colon Cancer R
  • Head and Neck Cancer (reduces NRF2/AREsR
  • 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-6R

Hederagenin can also mast cell degranulationR

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

My Experience With Hederagenin

...currently testing a few sources...

I have had positive experiences with Black Seed OilQuinoaRed Beets, and Rambutan.

Natural Sources Of Hederagenin And Derivatives

 
 

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

Caveats

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

Mechanism Of Action

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