HA4824 Hederagenin (CAS: 465-99-6)

Hederagenin (CAS: 465-99-6) Description

Hederagenin (CAS: 465-99-6) is the aglycone portion of various saponins found in Hedera helix (Common Ivy), with Hederacoside C and Alpha-Hederin being the most prevalent. It is also one of the three primary triterpenoids obtained from the plant Chenopodium quinoa and is classified as a biopesticide by the EPA. In rodent models, Hederagenin has demonstrated antidepressant effects.

Hederagenin (CAS: 465-99-6) is a plant metabolite. It is a pentacyclic triterpenoid, a dihydroxy-monocarboxylic acid, and a sapogenin. It is functionally related to oleanolic acid.

Hederagenin (CAS: 465-99-6) Specifications

Hederagenin (CAS: 465-99-6) Applications

Anti-Tumour Activity

Hederagenin has demonstrated a broad range of potential anticancer effects both in vitro and in vivo across various cancers, including lung, colorectal, gastric, liver, ovarian, prostate, breast, and uterine cancers. The anti-tumour mechanisms of Hederagenin in specific tumours have been elucidated at the molecular level through gene or protein expression. In a study on anti-hepatoma effect, Hederagenin reduced tumour weight in mice bearing H22 tumours and increased the expression of P21, Bax, Fas, Fasl, Caspase-3, and Caspase-8 genes, as well as their corresponding mRNAs and proteins, whilst decreasing the expression of mutated P53 and Bcl-2 genes, Bcl-2 mRNA, and Bcl-2 proteins.

Anti-Inflammatory Effect

Since the 1970s, it has been noted that Hederagenin exhibits anti-inflammatory and anti-arthritic effects in rats. In a mouse oedema model triggered by either croton oil or arachidonic acid, Hederagenin at a dose of 100 mg/kg demonstrated an anti-inflammatory effect with 42% and 23% inhibition, respectively.

Antidepressant Effect

Previous studies have indicated that Hederagenin possesses an antidepressant effect by enhancing the signalling of central monoamines through the inhibition of the reuptake of extracellular monoamines, including serotonin (5-HT), norepinephrine (NE), and dopamine (DA). In ex vivo and in vitro experiments, Hederagenin showed affinity for monoamine transporters in rats and cloned humans. However, Hederagenin was found to have no affinity for a range of other central nervous system receptors. In uptake studies with rat synaptosomes and transfected cells, it was demonstrated that Hederagenin dose- and time-dependently inhibits 5-HT, NE, and DA, with potency comparable to or greater than that of their respective specific inhibitors. Additionally, Hederagenin increased extracellular concentrations of 5-HT, NE, and DA in the frontal cortices of freely moving rats, thereby identifying Hederagenin as a novel triple inhibitor of monoamine transporters.

Anti-Neurodegenerative Activity

The autophagy activated by Hederagenin through AMPK-mTOR signalling pathways and autophagy-related gene 7 (ATG 7) has been shown to accelerate the degradation of mutated huntingtin with 74 CAG repeats and A53T α-synuclein, and to inhibit the oligomerisation of α-synuclein in cell models. Due to its capacity to facilitate the degradation of neurodegenerative disease proteins in cell models and to ameliorate motor deficits in mice injected with neurotoxins, a potential neuroprotective effect of Hederagenin in the treatment of Parkinson’s and Huntington’s diseases has been proposed. It has been observed that Hederagenin at concentrations of 3.13 and 6.25 mM has a reparative effect in a PC-12 cell injury model induced by Ab25-35. A high dose of 270 mg/kg improved learning and memory in mice following cholinergic system damage induced by scopolamine, increased cerebrospinal superoxide dismutase (SOD) activity, and reduced TchE values, indicating potential for treating age-related dementia and brain nerve injuries.

Anti-Hyperlipidaemic Activity

In an atherosclerosis model using Wistar rats, Hederagenin at a dose of 20 mg/kg reduced total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, improved haem rheological parameters, and increased high-density lipoprotein cholesterol (HDL-C) levels and the viscosity index of whole blood under high shear conditions. The mechanism of action of Hederagenin may relate to the regulation of lipid metabolism, protection of liver function, improvement of blood rheology, and regulation of endothelial dysfunction.

Anti-Leishmaniasis Activity

Hederagenin is commonly used as a biopesticide. The leishmanicidal effect of Hederagenin sodium salt was studied in vitro against the promastigote and amastigote forms of two strains of Leishmania infantum isolated from dogs and one strain of Leishmania tropica isolated from humans. Hederagenin exhibited activity against the promastigote forms at concentrations ranging from 50.54 to 202.14 mm, and the activity against the amastigote forms was comparable to that of the reference compound N-methylglucamine antimoniate[1].

Reference

Jia Zeng, Ting Huang, Man Xue, Jianxing Chen, Linglin Feng, Ruofei Du, Yi Feng: Current knowledge and development of hederagenin as a promising medicinal agent: a comprehensive review. RSC Adv., 2018, 8, 24188

[1] Jia Zeng, Ting Huang, Man Xue, Jianxing Chen, Linglin Feng, Ruofei Du, Yi Feng: Current knowledge and development of hederagenin as a promising medicinal agent: a comprehensive review. RSC Adv., 2018, 8, 24188