Product name: 12-O-Methylcarnosic acid
Synonym name:
Catalogue No.: SBP03616
Cas No.: 62201-71-2
Formula: C₂₁H₃₀O₄
Mol Weight: 346.467
Botanical Source: Rosmarinus officinalis
Type of Compound: Diterpenoids

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.

HPLC of 12-O-Methylcarnosic acid

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

12-O-Methylcarnitine: a multi-target natural active molecule extracted from rosemary

1. Overview

12-O-Methylcarnosic acid, also known as 12-methoxycarnosic acid, is a diterpenoid compound with significant biological activity. Its CAS number is 62201-71-2. The compound was initially isolated and identified from the acetone extract of Salvia miltiorrhiza, but subsequent studies have confirmed that its primary natural source is the well-known medicinal and edible plant, rosemary（Salvia rosmarinus Lipstick family). As a methoxylated derivative of Carnosic acid, 12-O-methylCarnosic acid inherits the core active skeleton of the parent compound and the introduction of methoxy groups (- OCH ∝) at specific positions may have profound effects on its biological activity, stability, and metabolic characteristics.

Modern pharmacological research has revealed that 12-O-methylcarnitine is a typical multi-target, multifunctional natural product. Its biological activity spectrum is extensive, covering Antioxidant, anti-inflammatory, anti-cancer, antimicrobial, anti diabetes and inhibition of 5 α - reductase Waiting for multiple aspects. Of particular note is that it has been identified as an active ingredient that inhibits 5 α - reductase (IC ₅₀=61.7 μ M) and can effectively inhibit the proliferation of prostate cancer cells (such as LNCaP cells). In addition, it can inhibit melanin production by down regulating tyrosinase expression, and show potential anti diabetes activity by activating peroxisome proliferator activated receptor γ (PPAR γ). These diverse biological effects make it a bridge connecting traditional herbal applications with modern precision pharmacology research, attracting sustained attention in the fields of natural product chemistry, pharmacology, and new drug development. This article will systematically interpret this promising natural molecule from its chemical nature, origin, mechanism of action, medicinal properties, and prospects.

2. Chemical structure and physicochemical properties

The molecular formula of 12-O-methylcarnitine is C ₂₁ H ∝₀ O ₄, with a molecular weight of 346.4670 g/mol. Structurally, it belongs to Rosin type diterpenes（abietane diterpenoid）， Its core skeleton is a highly functionalized tricyclic phenanthrene structure, with a methoxy group (- OCH ∝) attached at the C-12 position, a key phenolic hydroxyl group at the C-11 position, and a carboxyl group at the C-20 position. Its SMILES string (COc1c (C (C) C) cc2c (c1O) [C @ @] 1 (C (=O) O) CCCC (C) (C) [C @ @ H] 1CC2) accurately describes its atomic connection order and chiral center (two chiral carbon atoms, usually in a specific stereoconfiguration), indicating that it is a compound with a clear three-dimensional spatial structure.

Analyzing its physicochemical properties from the parameters of drug properties:
- fat-soluble The calculated LogP value is 4.7646 and the LogD value is 2.6520. This indicates that the compound has Moderate to high lipophilicity A higher LogP value is usually beneficial for transmembrane passive diffusion, but excessive lipid solubility (LogP>5) may lead to poor water solubility and rapid metabolism. Its LogD (distribution coefficient at a specific pH) is lower than LogP, indicating that its carboxylic acid groups may be partially ionized at physiological pH, thereby increasing its hydrophilicity.
- Water solubility The predicted water solubility is 0.0221 mg/mL, belonging to slightly soluble Level. This is consistent with high LogP values and is a common characteristic of many diterpenoid compounds, which may affect their oral bioavailability and formulation development.
- Polar Surface Area The topological polar surface area (TPSA) is 66.76 Å ². This value is moderate, and compounds with TPSA<140 Å ² are generally considered to have good membrane permeability.
- Permeability The predicted permeability of Caco-2 cells is 6.42 × 10 ⁻⁶ cm/s, and the Peff value is 6.0244, both indicating that the compound has Good intestinal permeability potential This is a positive signal for its oral absorption.

In summary, 12-O-methylcarnitine is a medium-sized molecule with certain lipophilicity but retaining some polar groups (carboxyl and phenolic hydroxyl). Its physicochemical properties lay the foundation for its biological activity, but also pose challenges to its pharmacological properties.

3. Plant sources and traditional applications

The main natural source of 12-O-methylcarnitine is rosemary（Salvia rosmarinus, formerly known as Rosmarinus officinalis）It belongs to the Lamiaceae family and the Salvia genus. Rosemary is an evergreen aromatic shrub native to the Mediterranean region, and its leaves have been widely used for their unique aroma and various health benefits, with a long history.

In traditional medicine and folk applications, rosemary has been endowed with various benefits:
- Antioxidant and anti-corrosion Its strong antioxidant properties are used to preserve food, especially high-fat foods, to prevent spoilage. This is closely related to its high content of phenolic diterpenes such as carnitine, salvianolic acid, rosmarinic acid, and 12-O-methyl carnitine.
- Brain health and alertness Traditionally used to improve memory, enhance attention, and alleviate nerve fatigue. Modern research supports its potential to improve cognitive function, which may be related to antioxidant, anti-inflammatory, and effects on the neurotransmitter system.
- Digestive aid Used to relieve indigestion, bloating, and abdominal pain.
- Anti inflammatory and analgesic effects Used topically or orally to relieve muscle pain, arthritis, and headache.
- Antibacterial Used for treating minor wound infections and respiratory problems.

12-O-methylcarnitine, as an important member of the active ingredient group in rosemary, is one of the scientific material foundations for these traditional applications. Extracting and isolating such diterpenes from rosemary is a key step in elevating it from traditional experience to modern pharmaceutical research. Rosemary, as a medicinal and edible plant, has a long history of safe use, which also provides important safety references for the development of drugs or health products based on its active ingredients.

4. Pharmacological activity and mechanism of action

12-O-methylcarnitine exhibits a wide range of pharmacological activities, and its mechanism of action is complex, involving Multi target regulation Current research suggests that its core biological effects may revolve around Antioxidant, anti-inflammatory, and hormone regulation The three main lines are unfolded and achieved by influencing key signaling pathways.

Core pharmacological activity

1. antioxidant activity As a phenolic diterpene, the phenolic hydroxyl group in its structure is a powerful hydrogen donor that can effectively scavenge free radicals (such as ROS) and inhibit lipid peroxidation. This is not only the basis for its protection of gastric mucosa and prevention of gastric damage, but also the upstream mechanism for its downstream effects such as anti-inflammatory and neuroprotective effects.
2. anti-inflammatory activity This is one of the most prominent characteristics of 12-O-methylcarnitine. Its anti-inflammatory effect is not achieved through a single target, but rather through Systematically regulate the inflammatory network The database target information clearly points to multiple core inflammatory mediators and regulatory factors:
   • TNF (tumor necrosis factor)、IL6 (interleukin-6)、IL1B (interleukin-1 β)These are all key pro-inflammatory cytokines. Inhibiting their production or activity can directly alleviate inflammatory reactions and tissue damage.
   • PTGS2 (prostaglandin endoperoxide synthase 2, also known as COX-2)Induced cyclooxygenase is the rate limiting enzyme for prostaglandin synthesis during inflammation, closely associated with pain, fever, and swelling. Inhibition of COX-2 is a classic mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs).
   • NFKBIA (nuclear factor kappa B inhibitory protein alpha)It is a key negative regulator of the NF - κ B signaling pathway. NF - κ B is the "master switch" that regulates the gene expression of numerous inflammatory factors, including TNF - α, IL-6, IL-1 β, COX-2. Upregulation or stabilization of NFKBIA can inhibit the activation of NF - κ B, thereby comprehensively downregulating the inflammatory response at the transcriptional level.
     Integration of mechanism of action 12-O-methylcarnitine is likely to reduce the activation of cells by oxidative stress through its antioxidant effect, while directly or indirectly intervening in signaling pathways such as NF - κ B, ultimately leading to downregulation of pro-inflammatory cytokines (TNF, IL6, IL1B) and inflammatory enzymes (COX-2) expression, thereby achieving a powerful anti-inflammatory effect. This multi-target mode of action may have therapeutic potential for chronic inflammation related diseases such as metabolic inflammation and neuroinflammation.
3. anticancer activity：
   • Inhibition of 5 α - reductase This enzyme can convert testosterone into the more active dihydrotestosterone (DHT), which is closely related to the occurrence and development of prostate hyperplasia and prostate cancer. 12-O-methylcarnitine, as an inhibitor of this enzyme (IC ₅₀ 61.7 μ M), can reduce DHT levels, thereby inhibiting the proliferation of hormone dependent prostate cancer (such as LNCaP cells).
   • Multi pathway anti proliferation Its anti-inflammatory and antioxidant effects themselves help create a microenvironment that is unfavorable for tumor growth. In addition, it may directly act on cancer cells by inducing cell cycle arrest, promoting apoptosis, and other pathways.
4. Anti diabetes potential: Through Activate PPAR γMake an impact. PPAR γ is a core nuclear receptor that regulates glucose and lipid metabolism, and is the target of thiazolidinedione insulin sensitizers (such as Rosiglitazone). Activation of PPAR γ can enhance insulin sensitivity and improve glucose and lipid metabolism disorders.
5. Other activities Including:antimicrobial(Related to its destruction of microbial membrane structure) and Inhibit melanin production By downregulating the expression of tyrosinase, its application prospects in the field of dermatology were demonstrated.

5. Evaluation of drug properties

Based on the provided pharmacological parameters, combined with classic Lipinski's Five Rules The development potential of 12-O-methylcarnitine can be preliminarily evaluated based on the Rule of Five (Ro5) and modern drug design concepts

1. Lipinski Five Rule Compliance：

   • Molecular weight (MW): 346.47 Da<500 Da (compliant)
   • Hydrogen bond donor (HBD): Structurally, the phenolic hydroxyl and carboxyl groups each provide one dissociable hydrogen, totaling approximately 2<5 (compliant)
   • Hydrogen bond acceptor (HBA): There are 4 oxygen atoms in the molecule (1 methoxy group, 1 phenolic hydroxyl group, 2 carboxyl groups), totaling about 4<10 (compliant)
   • Lipid water partition coefficient (LogP): 4.76 (slightly higher than the recommended value<5, but acceptable, belonging to the "boundary" compound)
   • Number of rotatable keys: Based on the structure, the quantity is moderate and not significantly exceeded.
     Conclusion 12-O-methylcarnitine basically conforms to Lipinski's five rules, indicating its good performance Oral absorption potential。

2. Analysis of Absorption, Distribution, Metabolism, and Excretion (ADME) Characteristics：

   • absorb Good Caco-2 permeability (6.42) and Peff value (6.02) support its good intestinal absorption potential. Moderate TPSA (66.76 Å ²) is also beneficial for transmembrane transport.
   • distribution The plasma protein binding rate (PPB) is as high as 92.17%, which means that most drugs in the blood bind to proteins and may affect their free drug concentration and tissue distribution, but this is also a common characteristic of many highly active natural products.Prediction of blood-brain barrier (BBB) penetration as' low 'This limits its potential to directly act on the central nervous system, but it may not be the main obstacle for the treatment of peripheral system diseases.
   • Metabolism and toxicity The predicted results of Ames test, chromosomal aberration, hERG inhibition, skin/respiratory sensitization, phototoxicity, etc. are all negative or "none/no",Preliminary indications suggest that its genetic toxicity and cardiotoxicity risks are relatively low The security features are good. But the prediction of "Ser_LK" (serum alkaline phosphatase) is "yes", indicating that its potential impact on the liver may need to be studied and experimentally verified.

3. Main challenges and optimization directions：

   • Poor water solubility(0.0221 mg/mL): This is one of the main bottlenecks for its drug development. Solubilization techniques may be required in formulation development, such as making salts (utilizing their carboxyl groups), nanocrystals, liposomes, or cyclodextrin inclusion complexes.
   • High plasma protein binding rate Higher doses may be required to achieve effective free blood drug concentrations.
   • Metabolic stability unknown The metabolic rate and main metabolic pathways need to be evaluated through in vitro liver microsomal experiments.

Overall evaluation 12-O-Methylcarnitine is a lead compound that conforms to the basic rules of drug likeness, with clear multi-target pharmacological activity and good preliminary safety prediction. Its main optimization direction lies in Improve solubility and bioavailability And further optimization of its activity, selectivity, and pharmacokinetic properties may be achieved through structural modifications (such as preparation of prodrugs or analogues).

6. Research Status and Application Prospects

At present, research on 12-O-methylcarnitine is still ongoing Preclinical stage Mainly focused on activity screening, preliminary exploration of mechanism of action, and preliminary isolation and preparation. Its research data mostly comes from cell models and a few animal experiments, lacking systematic pharmacokinetic, toxicological, and clinical efficacy evaluation.

Future research and application directions：
1. Deepening the mechanism of action Using chemical biology techniques such as molecular docking, surface plasmon resonance, proteomics, to accurately elucidate its direct interaction mode and affinity with predicted targets (TNF, PTGS2, NFKBIA, etc.), and explore whether it affects other unknown targets or signaling pathways (such as the Nrf2/ARE antioxidant pathway).
2. Structural optimization and derivative development Using it as the mother nucleus for systematic analysis Structure Activity Relationship (SAR) Study For example, modifying carboxyl, phenolic hydroxyl, or methoxy groups aims to improve water solubility, metabolic stability, target selectivity (such as enhancing selectivity for PPAR γ or 5 α - reductase), or BBB penetration (if needed for central nervous system diseases).
3. Pharmacokinetic and Formulation Research Conduct comprehensive ADME research to clarify its in vivo processes. Focus on tackling the problem of low solubility formulations and developing efficient delivery systems suitable for oral or topical use.
4. Disease model validation: Verify its efficacy and safety in animal models closer to human diseases (such as prostate cancer models, diabetes models, chronic inflammation models), and provide solid evidence for its possible clinical application.
5. Application scenario expansion：
- drug development: As anti prostatic hyperplasia/prostate cancer, anti type 2 diabetes or anti chronic inflammation New lead compounds。
- Functional food/health products As one of the standardized marker components of rosemary extract, it is used to develop health products with antioxidant, anti-inflammatory, liver protective, and sugar control functions.
- cosmetic ingredient Develop anti-aging and brightening cosmetic additives by utilizing their antioxidant and whitening (inhibiting melanin) activities.

Conclusion 12-O-methylcarnitine is a treasure molecule discovered from the traditional medicinal plant rosemary. It has demonstrated remarkable potential in various modern disease fields, such as anti-inflammatory, anticancer, and metabolic disease intervention, due to its unique multi-target mechanism of action. Although it still faces scientific challenges such as solubility and systemic efficacy verification before becoming a mature drug, its clear biological activity, good drug like basis, and abundant plant resources make it a highly valuable candidate for innovative natural product drug development and health product development. With the deepening of systematic research, this "green molecule" originating from the Mediterranean is expected to bring new choices for human health in the future.