Product name: Tetrahydromagnolol
Synonym name: Magnolignan
Catalogue No.: BP4363
Cas No.: 20601-85-8
Formula: C18H22O2
Mol Weight: 270.372
Botanical Source:
Type of Compound:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
HNMR of Tetrahydromagnolol
HPLC of Tetrahydromagnolol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Tetrahydromagnol (Tetrahydromagnol, CAS No.: 20601-85-8), as the main metabolite of Magnolol, has attracted widespread attention in the field of natural product pharmacology in recent years. Magnolia officinalis is a bisphenol natural product isolated from Magnolia officinalis, possessing significant anti-inflammatory, antifungal, and analgesic properties. Tetrahydromagnol, as its reducing metabolite, exhibits more unique biological characteristics, particularly in its selective activation of the cannabinoid receptor CB2. CB2 receptors are mainly distributed in the immune system and peripheral tissues, participating in regulating inflammatory responses and immune functions. Therefore, tetrahydromagnol has potential applications in anti-inflammation, immunomodulatory, and neuroprotective fields. Additionally, tetrahydromagnol also exhibits weak antagonistic activity against the GPR55 receptor, suggesting it may exert pharmacological effects through a multi-target mechanism. This paper will systematically review the chemical structure, physicochemical properties, sources and extraction methods, pharmacological activity and mechanism of action of tetrahydromagnomol, druggability evaluation, pharmacokinetic characteristics, and clinical application prospects, aiming to provide a theoretical foundation and reference for further research and development of this compound.
Tetrahydromagnomol has the molecular formula C18H18O2 and a molecular weight of 270.3720. Its chemical structure is based on the bisphenol framework of magnol, forming a tetrahydrogenated structure through partial hydrogenation of the aromatic ring, hence the name tetrahydromagnol. Structurally, tetrahydromagnol retains two phenolic hydroxyl groups, giving it certain polarity and antioxidant capacity. Its LogP value is 5.1744, indicating strong lipid solubility, which is beneficial for penetrating biofilms, especially the blood-brain barrier (BBB). TPSA (Topological Polar Surface Area) is 40.4600, indicating moderate molecular polarity and favorable membrane permeability. Low water solubility (0.0160 mg/mL) suggests limited solubility in the aqueous phase, possibly challenging formulation design. It is worth noting that tetrahydromagnol has a high blood-brain barrier penetration ability, which is beneficial for treating central nervous system diseases. The hERG suppression test result was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0.0, indicating no obvious genotoxicity.
Tetrahydromagnol mainly originates from the traditional Chinese medicinal material Magnolia officinalis and its related varieties. The main active ingredients of Magnolol (Magnolol) and curcumin (Honokiol) are tetrahydromagnol, a metabolite of Magnolol and is usually produced in the body through enzymatic reduction reactions. In the laboratory, tetrahydromagnol can be synthesized by catalytic hydrogenation of magnol, or by multiple steps of separation and purification from Magnolia officinal extracts.
Traditional extraction methods mainly rely on solvent extraction, commonly using ethanol or methanol as solvents, combined with ultrasound-assisted extraction or reflux extraction technologies to improve extraction efficiency. Subsequently, high-purity magnomol is obtained through liquid-liquid separation and column chromatography (such as silica gel columns and reversed-phase C18 columns). Further catalytic hydrogenation can convert magnool to tetrahydromagnomol. Modern extraction processes also use supercritical CO2 extraction technology, which offers advantages such as strong selectivity and environmental friendliness. During extraction and purification, care must be taken to avoid high temperatures and strong acidic or alkaline conditions to prevent structural damage of the compounds.
The pharmacological activity of tetrahydromagnol mainly focuses on its selective stimulating effect on the cannabinoid receptor CB2. In vitro experiments showed that tetrahydromagnophenol has an EC50 of 170 nM and a Ki of 416 nM for CB2 receptors, and its selectivity for CB2 receptors is about 20 times higher than that of CB1 receptors, indicating better targeting. CB2 receptor activation is typically associated with anti-inflammatory, immunomodulatory, and neuroprotective effects, and tetrahydromagnol thus shows potential therapeutic value in these areas.
Additionally, tetrahydromagnol exhibits weak antagonistic activity against the GPR55 receptor. As an emerging G protein-coupled receptor, GPR55 is involved in regulating inflammation, pain, and tumor biology, and its antagonists are considered to have anti-inflammatory and anticancer potential. The GPR55 antagonistic effect of tetrahydromagnol provides theoretical support for its multi-target pharmacological effects.
Magnol itself possesses antifungal, anti-inflammatory, and analgesic effects. As a metabolite, tetrahydromagnol is also believed to inherit and partially enhance these activities. Animal model studies have shown that tetrahydromagolol can alleviate inflammatory responses and relieve pain and anxiety symptoms through CB2 receptor-mediated signaling pathways. Its anti-anxiety effects have potential cross-regulation with various neurotransmitter system-related targets (such as MAOA, SLC6A4, HTR2A, DRD2, HTR1A, GABA receptor subunits, etc.), suggesting that it may exert comprehensive effects through complex neural regulatory networks.
The main molecular target of tetrahydromagnol is the cannabinoid receptor CB2. CB2 receptors belong to the G protein-coupled receptor family, mainly expressed in immune cells and peripheral tissues. After activation, they inhibit adenylate cyclase through Gi/o proteins, reduce cAMP levels, regulate cytokine secretion, and suppress inflammatory responses. Tetrahydromagnophenol, as a selective agonist of the CB2 receptor, can effectively regulate immune cell function and reduce inflammatory damage.
Additionally, the weak antagonism of tetrahydromagnol to GPR55 receptors may suppress inflammatory and pain-related pathways by blocking GPR55-mediated signaling. Activation of GPR55 is associated with various pathological states, and its antagonists are considered potential therapeutic agents.
In terms of anti-anxiety effects, tetrahydromagnophenol may achieve this by modulating various neurotransmitters and receptors, including:
Through the synergistic regulation of these targets, tetrahydromagnomol demonstrates the potential for anti-anxiety and neuroprotection.
The druggability parameters of tetrahydromagnol indicate that it has good potential for drug development. The molecular weight of 270.3720 conforms to the Lipinski rule, while the LogP of 5.1744 is slightly higher but still within the acceptable range, indicating good lipid solubility and favorable cell membrane penetration. TPSA 40.4600 is relatively low, which facilitates blood-brain barrier penetration and supports its application in central nervous system diseases. Low water solubility (0.0160 mg/mL) suggests that formulation design should consider strategies to improve solubility, such as nanocarriers or liposome encapsulation.
The blood-brain barrier has high penetration ability, meeting its role in neurological diseases. hERG channel inhibition negative, reducing the risk of cardiotoxicity. The Ames test result was 0.0, indicating no significant mutagenicity and good safety.
Pharmacokinetics, existing literature reports are limited, but based on its structure and physicochemical properties, tetrahydromagnol is well absorbed orally and widely distributed, especially at high concentrations in brain tissue. Metabolic processes may involve further transformation of hepatic enzyme systems, and excretion pathways still require further research. In the future, in vivo pharmacokinetic studies should be combined to clarify bioavailability, half-life, metabolites, and excretion characteristics, providing a basis for clinical development.
Based on tetrahydromagnophenol's highly selective agonizing effect on CB2 receptors and its multiple pharmacological activities including anti-inflammatory, anxiolytic, and neuroprotective effects, tetrahydromagnol shows broad application prospects in various disease fields.
Anti-inflammatory and immunomodulatory diseases
CB2 receptor agonists have potential therapeutic value in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Tetrahydromagnomol may become a candidate for new anti-inflammatory drugs by regulating immune cell function and inhibiting the release of inflammatory mediators.
Neuropsychiatric disorders
Its excellent blood-brain barrier penetration and regulation of various neurotransmitter systems support its application in neuropsychiatric disorders such as anxiety and depression. Tetrahydromagnol may improve neural function and alleviate mood disorders through multi-target mechanisms.
Analgesic treatment
As a CB2 receptor agonist, tetrahydromagolol has potential in alleviating chronic and neuropathic pain, especially for patients with poor tolerance to or high dependence on traditional opioids.
Anti-tumor potential
GPR55 receptors are abnormally expressed in various tumors, and the GPR55 antagonistic activity of tetrahydromagnofol suggests its possible antitumor effects, warranting further exploration.
Future research should focus on preclinical safety evaluation, pharmacokinetic optimization, and formulation development of tetrahydromagnophenol, while integrating modern drug design techniques to improve its water solubility and bioavailability. Multicenter clinical trials will be a key step in verifying its efficacy and safety.
As the main metabolite of magnol, tetrahydromagnol demonstrates significant potential in anti-inflammatory, analgesic, and neuroprotective effects due to its highly selective stimulating effect on the CB2 receptor and multi-target pharmacological activity. Its excellent druggability parameters and safety evaluation lay the foundation for clinical development. In the future, combining systematic pharmacokinetic research and preclinical trials, tetrahydromagnophenol is expected to become a new highlight in the development of natural product drugs, promoting the application of natural bisphenol compounds in modern medicine. By deeply analyzing its mechanism of action and optimizing drug properties, tetrahydromagnol may offer new strategies and options for treating various diseases.
