Product name: Feretoside
Synonym name: Scandoside methyl este; 6-beta-Hydroxygeniposide
Catalogue No.: BP1708
Cas No.: 27530-67-2
Formula: C₁₇H₂₄O₁₁
Mol Weight: 404.368
Botanical Source:
Physical Description: Powder
Type of Compound: Iridoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of  Feretoside

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

In the field of natural product chemistry and pharmacology research, iridoid glycosides have attracted much attention due to their extensive biological activities. Among them, 6- β - hydroxygeniposide, also known as chicken vine glycoside methyl ester, chemical name Feretoside (CAS: 27530-67-2), as a phenolic iridoid glycoside isolated from traditional medicinal plants, has shown significant cell protective and anti-inflammatory potential in recent years. This compound has been identified as a heat shock protein (HSP) inducer, which gives it unique value in responding to pathological processes such as cellular stress, inflammation, and tissue damage. As a common gastrointestinal inflammatory disease, enteritis involves the overactivation of multiple key inflammatory mediators such as tumor necrosis factor (TNF), cyclooxygenase-2 (PTGS2/COX-2), nuclear factor kappa B (NF - κ B), and interleukin (IL-6, IL-1 β), as well as the disruption of signaling pathways. Therefore, finding natural active molecules that can intervene in these inflammatory pathways with multiple targets has become an important direction for new drug development. This article aims to systematically review the chemical properties, plant sources, pharmacological activities of 6- β - hydroxygeniposide, especially its mechanism of action against enteritis related targets, pharmacological characteristics, and prospects for its clinical application prospects, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of 6- β - hydroxygeniposide (Feretoside) is C17H24O11, with a molecular weight of 404.3680. Its structure belongs to the iridoid glycoside class, with a core of a cyclopentanopyran (iridoid) skeleton and a β - configured hydroxyl group connected at the C-6 position, which is the structural basis for its name and partial activity. This molecule is linked to a molecule of glucose through a glycosidic bond, forming a glycosidic structure that increases its water solubility. The molecule also contains multiple hydroxyl groups, making its overall polarity strong.

Based on its chemical structure, the compound exhibits typical hydrophilic characteristics. The calculated lipid water partition coefficient (LogP) is -1.5944, indicating that its hydrophilicity is much greater than its lipophilicity. The topologically polar surface area (TPSA) is as high as 175.37 Å ², mainly attributed to the abundant hydroxyl groups and oxygen atoms on sugar units in the molecule, further confirming its strong polarity. Its water solubility value is 63.3290 (usually measured in mg/L or μ M, depending on the model), indicating that it has good solubility in water. These physicochemical properties determine its distribution characteristics within the organism, for example, its polarity and larger TPSA result in a lower ability to penetrate the blood-brain barrier, predicted as a "low" level. In addition, preliminary pharmacological risk assessment showed that it has no inhibitory activity on hERG potassium channels (predicted as "no"), and the Ames mutagenicity test predicted a result of 0.0 (negative), suggesting that it may have good cardiac safety and low genetic toxicity risk, laying a favorable physicochemical and safety foundation for subsequent development.

Plant sources and extraction methods

6- β - hydroxygeniposide is mainly derived from Eucommia ulmoides（Eucommia ulmoides Obtained from the bark of Oliv. Eucommia ulmoides is a traditional precious medicinal plant in China. Its bark (Eucommia ulmoides bark) has the effects of nourishing liver and kidney, strengthening muscles and bones, etc. Modern research has shown that it is rich in various active ingredients, including lignans, cyclohexene ether terpenes, phenylpropanoids, etc. Feretoside is one of the characteristic iridoid glycosides in Eucommia ulmoides.

Its extraction and separation usually follow the conventional process of natural product chemistry. Firstly, the dried bark of Eucommia ulmoides is crushed and subjected to reflux extraction or ultrasound assisted extraction using polar solvents such as methanol, ethanol, or aqueous ethanol to fully extract the glycoside components. After vacuum concentration, the obtained crude extract was preliminarily enriched and purified using macroporous adsorption resins (such as D101, AB-8, etc.). After washing with water to remove high polarity impurities, it was eluted with appropriate concentration of ethanol to collect the elution site containing the target compound. Subsequently, further separation and purification were performed using chromatographic techniques such as silica gel column chromatography, reverse phase silica gel column chromatography (such as ODS-C18), and high performance liquid chromatography (HPLC). During the separation process, thin-layer chromatography (TLC) or high-performance liquid chromatography-mass spectrometry (HPLC-MS) are often used for online monitoring and identification. Finally, the chemical structure of 6- β - hydroxygeniposide was confirmed by spectroscopic methods such as nuclear magnetic resonance (NMR, including 1H-NMR and 13C-NMR) and mass spectrometry (MS), and compared with literature data. Optimizing the extraction process (such as solvent ratio, temperature, time) and adopting modern separation techniques (such as high-speed countercurrent chromatography) are key to improving its yield and purity.

Pharmacological activity research

Numerous in vitro and in vivo pharmacological studies have revealed the multifaceted biological activities of 6- β - hydroxygeniposide, with its core being its cell protective and anti-inflammatory effects.

1. Cell protection and HSP induction activity The most prominent feature of this compound is its use as a heat shock protein (HSP) inducer. HSP is a type of protective protein produced by cells under stress conditions such as heat, oxidation, and inflammation, which assists in the correct folding, repair, or clearance of damaged proteins and maintains cellular homeostasis. Research has shown that 6- β - hydroxygeniposide can upregulate the expression of proteins such as HSP70, thereby enhancing cells' resistance to various damage factors (such as hydrogen peroxide, high temperature, chemotherapy drugs) and reducing cell apoptosis. This characteristic is the molecular basis for its extensive cellular protective effects.

2. anti-inflammatory activity In various inflammatory models, 6- β - hydroxygeniposide exhibits strong anti-inflammatory effects. In the lipopolysaccharide (LPS) - induced macrophage (such as RAW264.7) inflammation model, it can dose dependently inhibit the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2). In animal models, especially in experimental colitis mouse or rat models induced by chemical substances such as dextran sulfate sodium DSS and trinitrobenzenesulfonic acid TNBS, oral or intraperitoneal administration of 6- β - hydroxygeniposide can significantly alleviate pathological damage to colon tissue, manifested as improved colon length shortening, reduced tissue edema, congestion, and inflammatory cell infiltration, and decreased disease activity index.

3. antioxidant activity As a phenolic compound, it has certain free radical scavenging ability, which can reduce intracellular reactive oxygen species (ROS) levels, alleviate oxidative stress damage, and complement anti-inflammatory and cell protective effects.

4. Other potential activities Some studies also suggest that it may have positive effects on bone health (related to the traditional efficacy of Eucommia ulmoides), neuroprotection, and other aspects, but further research is needed.

Mechanism of action and molecular targets

The anti-inflammatory and cell protective effects of 6- β - hydroxygeniposide, especially in colitis models, are achieved through multi-target and multi pathway synergistic effects, mainly focusing on its core HSP induction ability and regulation of key inflammatory signaling pathways.

1. The core mechanism induced by HSP As a chemical inducer, it may activate heat shock factor (HSF), transforming it from an inactive monomer to an active trimer and transferring it to the nucleus, where it binds to heat shock elements (HSE) and initiates transcriptional expression of genes such as HSP70 and HSP27. High levels of HSP70 can inhibit the activation of key inflammatory transcription factors such as NF - κ B, forming an endogenous protective network against inflammation.

2. Regulation of colitis related targets：

   • NF - κ B signaling pathway NF - κ B is the core transcription factor of inflammatory response. Research has shown that 6- β - hydroxygeniposide can inhibit the degradation and phosphorylation of I κ B α protein induced by LPS and other stimuli, thereby preventing the translocation of NF - κ B p65 subunit to the nucleus and downregulating the expression of downstream target genes.
   • Pro-inflammatory cytokines By inhibiting the NF - κ B pathway, this compound can effectively reduce the mRNA and protein expression levels of key pro-inflammatory cytokines such as TNF - α, IL-6, and IL-1 β. These cytokines form a cascade amplification effect in the pathology of enteritis, and their downregulation directly alleviates inflammatory response and tissue damage.
   • PTGS2 (COX-2) pathway COX-2 is a key enzyme that mediates the synthesis of PGE2 in inflammatory sites. 6- β - hydroxygeniposide can significantly inhibit the expression and activity of COX-2, reduce the production of PGE2, thereby alleviating inflammation, pain, and edema.
   • MAPK signaling pathway There are studies suggesting that it may also inhibit the phosphorylation of stress/inflammation related protein kinases such as p38 MAPK and JNK, which interact with the NF - κ B pathway to jointly regulate inflammatory responses.

In summary, the mechanism of action of 6- β - hydroxygeniposide can be summarized as follows: inducing HSP to produce endogenous protection, while exogenously inhibiting the overactivation of signaling pathways such as NF - κ B and MAPK, thereby downregulating the expression of inflammatory mediators such as TNF - α, IL-6, IL-1 β, COX-2/PGE2, forming a multi-level anti-inflammatory and cell protective network, and exerting therapeutic effects in inflammatory diseases such as enteritis.

Evaluation of drug properties and pharmacokinetics

Based on the physical and chemical properties and preliminary toxicity prediction mentioned earlier, 6- β - hydroxygeniposide shows certain potential for drug development, but its comprehensive pharmacokinetic characteristics still need to be further explored.

1. Prediction and Challenges of Absorption, Distribution, Metabolism, and Excretion (ADME)：

   • absorb Good water solubility is beneficial for its dissolution and absorption in the gastrointestinal tract. However, as highly polar glycosides, their transmembrane passive diffusion may be limited, and their absorption may depend on transporters in the intestine, such as glucose transporters. The bioavailability needs to be clarified through in vivo pharmacokinetic studies.
   • distribution Moderate molecular weight but high polarity, large TPSA, predicted tissue distribution more inclined towards blood and extracellular fluid, difficult to penetrate the blood-brain barrier, which is disadvantageous for treating central nervous system diseases, but may reduce central side effects. At the site of inflammation, due to increased vascular permeability, its distribution may be enhanced.
   • Metabolism As glycoside compounds, they are likely to be first hydrolyzed by intestinal microbiota or glycosidases on the intestinal mucosa in the body, producing aglycones. The lipid solubility of aglycones is enhanced and may be more easily absorbed, but their activity and toxicity may be altered. Subsequent metabolism may involve liver phase I (such as oxidation) and phase II (such as glucuronidation, sulfation) reactions.
   • excretion Polar prototype drugs and their metabolites may mainly be excreted through the kidneys in urine.

2. Analysis of drug properties parameters：

   • Advantage Good water solubility, no hERG inhibition and Ames mutagenicity risk predicted, with a high safety threshold. The clear HSP induction and multi-target anti-inflammatory mechanisms provide a clear pharmacological basis for it.
   • potential challenges Oral bioavailability may be low; Poor blood-brain barrier penetration; As a natural product, the structure may need to be optimized to improve stability or enhance pharmacokinetic properties; The specific metabolites, enzymatic mechanisms, and interactions of it in the complex human metabolic system are still unknown.

3. Pharmacokinetic research needs Currently, there is a lack of publicly available pharmacokinetic studies, such as blood concentration time curves, absolute bioavailability, tissue distribution, and identification of major metabolites in rats or beagle dogs. This is a key gap that must be filled to advance towards drug development.

Clinical application prospects and prospects

6- β - hydroxygeniposide, as a natural compound with a unique mechanism of action (HSP induction) and multi-target anti-inflammatory properties, has broad application prospects in the prevention and treatment of various diseases, but also faces a series of challenges.

1. Potential clinical application directions：

   • Inflammatory bowel disease Based on its significant therapeutic effect in experimental colitis, it is expected to be developed as an adjuvant or therapeutic drug for the treatment of ulcerative colitis or Crohn's disease, especially its HSP induction ability may help repair damaged intestinal mucosal barriers.
   • Other inflammation related diseases Its extensive anti-inflammatory mechanism is also applicable to the adjuvant treatment of other chronic inflammatory diseases, such as arthritis, dermatitis, hepatitis, etc.
   • Chemical Prevention and Cellular Protection As an HSP inducer, it can be used to alleviate nephrotoxicity, neurotoxicity, or intestinal mucosal inflammation caused by chemotherapy drugs such as cisplatin, and improve the tolerance and quality of life of cancer patients.
   • Functional foods and health products Derived from the traditional medicinal and edible plant Eucommia ulmoides, it has high safety and can be considered as a functional food ingredient for people with chronic inflammation or those who need daily cellular health care.

2. challenges faced：

   • Drug efficacy intensity and selectivity It is necessary to validate its efficacy in disease models that are closer to humans, such as humanized models, and clarify its treatment window.
   • Pharmacokinetic optimization Its natural form may have problems such as poor oral absorption and fast metabolism. It is necessary to optimize its ADME properties through pharmaceutical methods such as nanomedicine, phospholipid complexes, prodrug design, or structural modification (improving lipid solubility while retaining pharmacophores).
   • Deep analysis of the mechanism of action Further clarification is needed on the specific upstream signaling events that induce HSP, as well as the causal relationship and weights between its anti-inflammatory effects and HSP induction.
   • Preclinical and clinical research It is necessary to complete a systematic GLP toxicology evaluation and ultimately validate its safety and efficacy in humans through rigorous clinical trials.

3. Future research prospects：
   Future research should focus on: ① conducting systematic preclinical pharmacokinetic and toxicological studies; ② Using proteomics, metabolomics and other technologies to comprehensively reveal its functional network; ③ Explore its synergistic effects with other anti-inflammatory drugs; ④ Reasonably modify drug chemistry based on the structure activity relationship to obtain derivatives with stronger activity and better drug properties.

Conclusion

6- β - hydroxygeniposide (Feretoside) is an active iridoid glycoside derived from Eucommia ulmoides. With its unique HSP induction ability and effective regulation of multiple inflammatory targets such as TNF, NF - κ B, COX-2, IL-6, etc., it has shown remarkable potential in cell protection and anti-inflammatory, especially in the treatment of enteritis. Its good water solubility and preliminary predicted safety provide a favorable basis for its medicinal properties. However, its poor membrane permeability, unknown in vivo metabolic fate, and lack of systematic pharmacokinetic data are the main obstacles to pushing it from a lead compound to a clinical candidate drug. Future research needs to focus on addressing its pharmacokinetic shortcomings while delving into the details of its molecular mechanisms, and optimize its development through interdisciplinary strategies. With the continuous deepening of research, 6- β - hydroxygeniposide is expected to become an important candidate molecule for new drugs or health products in the treatment of inflammatory bowel disease and related diseases, demonstrating the sustained value of natural products in modern pharmaceutical research and development.