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Synonym name: 20-Deoxyingenol
Catalogue No.: BP0046
Cas No.: 54706-99-9
Formula: C20H28O4
Mol Weight: 332.44
Botanical Source: Occurs as esters in Euphorbia kansui and Euphorbia paralias
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of 20-deoxyingenol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
74.6000
2.5000
2.5000
Low
No
No
No
Unknown
No
Unknown
20-deoxyingenol (CAS No.: 54706-99-9) is a diterpene natural product derived from the root of the traditional Chinese medicine Euphorbia kansui. As a derivative of giant alpha alcohol compounds, 20-deoxygiant alpha alcohol has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique molecular structure and diverse biological activities. In particular, in studies of chronic degenerative diseases such as osteoarthritis (OA), 20-deoxymacroterinol has shown potential therapeutic value by regulating autophagy and lysomal biogenesis. Moreover, based on its regulatory ability to target various disease-related molecules, 20-deoxymacroterol also shows broad research prospects in neurodegenerative diseases (such as Alzheimer's and Parkinson's) and metabolic diseases (such as non-alcoholic fatty liver disease and insulin resistance).
This paper will systematically review the chemical structure and physicochemical properties of 20-deoxymacroterinol, plant origin, and extraction methods, focusing on analyzing its pharmacological activity and mechanism of action, exploring its pharmacokinetic characteristics through druggability evaluation, and finally looking ahead to its clinical application potential, providing a theoretical foundation and research direction for the in-depth development and application of this natural product.
20-DeoxyMacroterpene Alcohol belongs to the diterpene class of compounds with a molecular formula of C20H28O5 and a molecular weight of 332.43. Its chemical structure is based on a giant alpha alcohol skeleton, with a 20-position deoxygenated group (deoxy modification) as a distinctive structural feature. This compound has four hydrogen bond acceptor sites, a polar surface area (TPSA) of 74.6 Ų, and a LogP value of about 2.5, indicating moderate lipid solubility and good membrane permeability.
Structural deoxy modifications may affect their binding affinity with biological targets and metabolic stability. The molecular structure of 20-deoxymacroterol gives it spatial conformational rigidity and stereoselectivity, which is of great significance for its biological activity. Its physicochemical properties, such as moderate molecular weight and lipid solubility, facilitate cell membrane penetration, but its low blood-brain barrier penetration suggests its direct role in the central nervous system may be limited.
20-Deoxymacroterol is mainly extracted from the roots of Euphorbia kansui. Gan Sui is a plant in the Euphorbiaceae family, widely used in traditional Chinese medicine to promote urination, reduce swelling, resolve phlegm, and relieve cough. Its roots are rich in diterpenoids, especially giant terpenoids and their derivatives.
Traditional extraction methods typically use organic solvents (such as ethanol, methanol, ethyl acetate) for extraction and then separation and purification through liquid-liquid partitioning, column chromatography (silica gel, reversed-phase C18), high-performance liquid chromatography (HPLC), and other techniques. In recent years, modern technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been used to improve extraction efficiency and purity.
During extraction, avoid high temperatures and strong acidic or alkaline conditions to prevent degradation of the 20-deoxymonoterol structure. The purified compounds undergo structural confirmation using methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).
The pharmacological activity of 20-deoxymacroterol is mainly reflected in its regulation of cellular autophagy and lysosomal function. Research shows that 20-deoxymacroteryl alcohol can promote nuclear translocation of the transcription factor EB (TFEB), activate the expression of autophagy-related genes, and enhance lysosomal biogenesis, thereby improving the efficiency of clearing intracellular metabolic waste.
In the osteoarthritis (OA) model, 20-deoxymacroterinol regulates inflammatory factors (such as IL-1β, IL-6, TNF-α), matrix metalloproteinases (MMP1, MMP3), and signaling pathways (NF-κB), reducing chondrocyte inflammation and matrix degradation, thereby delaying joint degeneration. Additionally, its role in activating the AMPK signaling pathway helps regulate chondrocyte energy metabolism and cell survival.
In neurodegenerative diseases, although 20-deoxymacroterol has a relatively low blood-brain barrier penetration, its regulatory potential for related targets such as BCL2, MCL1, APP, BACE1, suggests its value in peripheral or adjuvant therapy. Studies on non-alcoholic fatty liver disease and insulin resistance have shown that 20-deoxymacroterol may improve metabolic disorders and oxidative stress states by regulating key molecules such as AMPK, NFE2L2, and PTPN1.
The biological effects of 20-deoxymacroterol are mainly realized by regulating multiple signaling pathways and key molecular targets:
Promotes autophagy and lysosomal biogenesis
20-Deoxymacroterinol promotes the translocation of transcription factor EB (TFEB), activates transcription of autophagy-related genes, enhances autophagy activity and lysosomal function, and promotes intracellular waste clearance and metabolic homeostasis.
Anti-inflammatory effects
This compound can inhibit the NF-κB signaling pathway, reduce the expression of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, alleviate inflammatory responses, and play a protective role especially in osteoarthritis pathology.
Regulates matrix metalloproteinase expression
By downregulating matrix-degrading enzymes such as MMP1 and MMP3, 20-deoxymacroterol helps maintain the integrity of the articular cartilage matrix and slow the progression of osteoarthritis.
Energy metabolism regulation
Activates the AMPK (PRKAA1) signaling pathway, promotes energy metabolism balance, enhances cell viability, and inhibits pathological processes of metabolic diseases.
Multi-target regulatory potential
Combining bioinformatics and molecular docking analysis, 20-deoxymacroterinol may act on various disease-related targets, including BCL2, MCL1, APP, BACE1 in neurodegenerative diseases, and PTPN1 and NFE2L2 in metabolic diseases, demonstrating its pharmacological characteristics of multi-target and multi-pathway coordinated regulation.
From the perspective of druggability parameters, 20-deoxymacroterinol has an ideal molecular weight (332.43), moderate lipid solubility (LogP about 2.5), and polar surface area (TPSA 74.6), meeting the basic requirements of the Lipinski rule and indicating good oral bioavailability potential.
Its number of hydrogen bond receptors is 4, indicating that the molecule has a certain degree of hydrophilicity, which facilitates stable hydrogen bond interactions with target proteins. The blood-brain barrier has a relatively low penetration capacity, which may limit its direct application in central nervous system diseases, but it also reduces the risk of CNS side effects.
In terms of toxicity evaluation, 20-deoxymacroterinol showed no significant cardiotoxicity or hERG channel inhibition, indicating relatively high safety. Hepatotoxicity and genotoxicity (Ames test) are not yet clear and require further systemic toxicological studies.
Currently, systematic studies on its pharmacokinetics are limited, and it is expected that it may be metabolized by the liver in the body. The metabolites and their activity still require further exploration. In the future, research on absorption, distribution, metabolism, excretion (ADME), and toxicology should be strengthened to provide a basis for clinical development.
20-Deoxymacroterpenol, as a natural diterpenoid compound with multiple pharmacological activities, shows remarkable potential especially in the treatment of osteoarthritis. By promoting autophagy and lysosomal biogenesis, regulating inflammatory responses and matrix metabolism, it can effectively delay cartilage degeneration and improve joint function, showing potential as a novel treatment for osteoarthritis.
In addition, the regulatory ability of 20-deoxymacroterinol to target multiple diseases including Alzheimer's disease, Parkinson's disease, non-alcoholic fatty liver disease, and insulin resistance suggests its prospects for application in multi-disease and multi-mechanism collaborative treatments. Although its blood-brain barrier penetration capacity is relatively low, structural modification or optimization of drug delivery systems is expected to expand the therapeutic potential of its neurological diseases.
Future research should focus on:
Through multidisciplinary collaboration, 20-deoxymacroterinol is expected to become an important candidate in the development of natural product drugs, promoting the application of natural drugs in modern medicine.
In summary, 20-deoxymacroterpene alcohol, as an important diterpene active component in gansui, demonstrates broad application prospects in research on osteoarthritis and various metabolic and neurodegenerative diseases due to its unique chemical structure and diverse biological activities. By regulating autophagy, inflammation, and metabolic pathways, it exerts multi-target synergistic effects, providing a solid druggability foundation and safety potential.
However, current research on its pharmacokinetics, systemic toxicology, and clinical efficacy remains limited, urgently requiring in-depth exploration and validation. In the future, efforts should be made to strengthen the integration of basic and applied research, promote the clinical translation of 20-deoxycoterel, and foster innovative development of natural products in modern disease prevention and treatment.
Shenshuai
Wenjing
Hedandan
