Product name: Continentalic acid
Synonym name: Pimaradienoic acid
Catalogue No.: BP2057
Cas No.: 19889-23-7
Formula: C₂₀H₃₀O₂
Mol Weight: 302.458
Botanical Source: Acanthoppanax gracilistylus W. W. Smith.
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.

Description:

Continentalic acid and kaurenoic acid are quality control markers in Aralia continentalis. Continentalic acid has anti-inflammatory, anti-cancer, and anti-bacterial activities, it shows moderate cytotoxicity against A-549 (lung), THP-1 (leukemia) and MCF-7 (breast) cell lines; it has minimum inhibitory concentrations (MICs) of approximately 8-16 microg/mL against S. aureus, including the MSSA and MRSA standard strains.

References:

Indian J Pharm Sci. 2015 Nov-Dec;77(6):792-5.    

In vitro Cytotoxicity of Methanol Extract from Aerial Parts of Aralia cachemirica and Purified Continentalic Acid.   

The present study was designed to evaluate the in vitro cytotoxic effect of methanol extract of aerial parts including stems, leaves and twigs of Aralia cachemirica and purified Continentalic acidisolated from this extract against a panel of human cancer cell lines of varied tissues. 

METHODS AND RESULTS:

Percentage of growth inhibition was evaluated by sulphorhodamine B assay. Purified Continentalic acid showed moderate cytotoxicity against all the cell lines used. In contrast, the extract exhibited significant concentration dependant cytotoxicity against A-549 (lung), THP-1 (leukemia) and MCF-7 (breast) cell lines. 

CONCLUSIONS:

This work highlights cytotoxic potential of this extract, which can further be explored for different constituents for their possible use autonomously or in combined manner in cancer therapy. The detailed analysis of their cytotoxicity has been presented in this paper.    

Arch Pharm Res. 2009 Sep;32(9):1237-43.    

Anti-inflammatory activity of the constituents of the roots of Aralia continentalis.   

METHODS AND RESULTS:

To assess the anti-inflammatory activity of the constituents of the roots of Aralia continentalis, ent-pimara-8(14),15-diene-19-oic acid (Continentalic acid, pimaradienoic acid, compound I), 7beta-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (compound II), 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (compound III), 15alpha,16alpha-epoxy-17-hydroxy-ent-kauran-19-oic acid (compound IV) and ent-kaura-16-en-19-oic acid (kaurenoic acid, compound V), their inhibitory effects against cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide-treated RAW 264.7 cells were examined. 

CONCLUSIONS:

Taken together, the results of this study suggest that some constituents of A. continentalis, especially compounds I, III and V, exert significant anti-inflammatory activity, which suggests that these constituents contribute, at least in part, to the anti-inflammatory action of the roots of A. continentalis.   

Phytother Res. 2006 Jun;20(6):511-4.    

Continentalic acid from Aralia continentalis shows activity against methicillin-resistant Staphylococcus aureus.   

METHODS AND RESULTS:

In a continuing search for compounds with antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), a chloroform extract of roots of Aralia continentalis was found to contain Continentalic acid (CA, C(20)H(30)O(2)), a diterpenic acid. This compound exhibited potent activity against standard methicillin-susceptible Staphylococcus aureus (MSSA) as well as clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). It was determined that Continentalic acid had minimum inhibitory concentrations (MICs) of approximately 8-16 microg/mL against S. aureus, including the MSSA and MRSA standard strains. 

CONCLUSIONS:

Therefore, the results obtained in this study suggest that Continentalic acid might have potential as an adjunct in the treatment of antibiotic-resistant bacteria. 

HPLC of  Continentalic acid

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

Introduction/Overview

Continentalic acid (CAS No.: 19889-23-7) is a natural product derived from Aralia continentalis, a plant in the Araliaceae family. In recent years, it has attracted attention for its remarkable antibacterial and potential antitumor activity. As a uniquely structured diterpene compound, Changbai Quercus not only exhibits good inhibitory effects against various Staphylococcus aureus strains, especially the minimum inhibitory concentration (MIC) for methicillin-sensitive (MSSA) and MRSA-sensitive (MRSA) strains in the range of 8-16 μg/mL, demonstrating its potential as an antimicrobial drug candidate. Moreover, with further in-depth research into its molecular mechanisms, the regulatory role of Changbai Quercus on malignant tumor targets such as liver cancer has gradually been revealed, providing new ideas for the development of anti-tumor drugs.

This paper aims to systematically review the chemical structure and physicochemical properties of Changbai queratin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to conduct in-depth discussions in conjunction with its clinical application prospects, providing theoretical basis and research directions for subsequent drug development and clinical translation.

Chemical structure and physicochemical properties

The molecular formula of Changbai Quercolic acid is C_20H_30O_3, with a molecular weight of 302.4580 Da. Its structure belongs to the diterpenoid acidic compounds, featuring a typical terpene backbone and carboxylic acid functional groups. Its chemical structure contains multiple unsaturated bonds and fat-soluble groups, giving it high hydrophobicity. The LogP value was 5.1443, indicating strong lipid solubility that facilitates cell membrane penetration, but low water solubility (0.0115 mg/mL), which may affect its bioavailability. The topological pole surface area (TPSA) is 37.3 Ų, indicating low polarity and facilitating cell membrane penetration.

Additionally, Changbeihui has a high ability to penetrate the blood-brain barrier, suggesting its potential application in central nervous system diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating no significant genotoxicity and meeting the basic safety evaluation requirements.

In summary, the physicochemical properties of Changbai Quercus Acid indicate good membrane penetration and low risk of toxic side effects, but its low water solubility may limit oral absorption, so its bioavailability needs to be optimized through pharmaceutical formulation technology.

Plant Origins and Extraction Methods

Changbai Querellanic Acid mainly comes from Aralia continentalis, a plant in the Araliaceae family, which is used in traditional East Asian medicine to treat rheumatism, reduce inflammation, and enhance immunity. The roots and rhizomes of Aralia continentalis are the main accumulation sites for long altaric acid.

The extraction method typically uses organic solvent extraction combined with column chromatography separation technology. The specific steps include:

1. Raw material pretreatment: Fresh or dried Aralia continentalis rhizomes are collected and ground into fine powder.
2. Solvent extraction: Repeatedly extract the powder with ethanol or methanol to extract the crude extract containing long cylindric acid.
3. Liquid-liquid distribution: The crude extract is distributed through solvents such as petroleum ether and ethyl acetate to remove fat-soluble impurities.
4. Column chromatography separation: Using silica gel column chromatography combined with gradient elution to further purify Changbai queracin.
5. Crystallization purification: High-purity Changbai queraic acid is obtained through recrystallization technology.

In recent years, modern extraction technologies such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have also been applied to improve extraction efficiency and purity. In addition, analytical methods such as HPLC, mass spectrometry, and nuclear magnetic resonance (NMR) are widely used for qualitative and quantitative analysis of Changbai queraic acid.

Pharmacological activity research

Antibacterial activity

Changbai Quercolic acid exhibited significant antibacterial activity against Staphylococcus aureus, especially inhibiting both methicillin-sensitive (MSSA) and drug-resistant strains (MRSA), with a MIC value of about 8-16 μg/mL. This activity makes it a potential candidate for antibiotic-resistant bacterial infections. Its antibacterial mechanism may involve cell membrane destruction, protein synthesis inhibition, and metabolic interference, but the specific targets still need further clarification.

Antitumor activity

In solid tumor models such as liver cancer, Changbai Quercus showed certain cytotoxicity and proliferative inhibition effects. In vitro experiments have shown that it can induce apoptosis of liver cancer cells, inhibit cell migration and invasion, suggesting its anti-metastatic potential. Some studies suggest that Changbai Quercolic acid may exert anti-tumor effects by regulating multiple signaling pathways, including inhibiting key pathways such as STAT3, PI3K/AKT, NF-κB, thereby affecting tumor cell survival and proliferation.

Other pharmacological effects

In addition to its antibacterial and antitumor activities, Changbai Quercus also exhibits certain anti-inflammatory, antioxidant, and immunomodulatory effects, which may synergistically enhance its therapeutic effects. Its anti-inflammatory effects are related to inhibiting inflammatory factor expression and regulating immune cell function.

Mechanism of action and molecular targets

The molecular mechanism of Changbai Quercus involves multiple key targets, with particularly significant regulatory effects in liver cancer-related signaling pathways. The main targets include:

• BCL2: Oligosis can downregulate the expression of the anti-apoptotic protein BCL2, promoting tumor cell apoptosis.
• STAT3: By inhibiting STAT3 phosphorylation, it interferes with its transcriptional activity and blocks tumor cell proliferation and survival signals.
• TOP1: May affect the activity of DNA topoisomerase I, interfering with DNA replication and repair.
• TERT: Inhibits telomerase reverse transcriptase expression, limiting the unlimited proliferation capacity of tumor cells.
• PIK3CA/AKT1: Inhibits the PI3K/AKT signaling pathway, reduces cell proliferation, and promotes apoptosis.
• MMP9: Downregulates matrix metalloproteinase 9, inhibiting tumor cell invasion and metastasis.
• EGFR: Interferes with epidermal growth factor receptor signaling, blocking cell proliferation signaling.
• TP53: May activate tumor suppressor protein p53, promoting cell cycle arrest and apoptosis.
• NFKB1: Inhibits the NF-κB signaling pathway, reduces inflammatory responses, and inhibits tumor growth.

The multiple regulation of these targets gives Changbai Quercolic Acid the advantage of multi-target and multi-pathway synergistic effects in anti-tumor therapy, reflecting the multi-target pharmacological characteristics of natural products.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Changbai Quercolic acid shows it has good potential for drug development:

• The molecular weight (302.4580 Da) complies with the Lipinski rule, which facilitates oral absorption of the drug.
• The LogP value (5.1443) is slightly high, indicating strong lipid solubility, which may affect water solubility and bioavailability, but is beneficial for cell membrane penetration.
• Low TPSA (37.3 Ų), which facilitates transmembrane absorption.
• Water solubility (0.0115 mg/mL) is relatively low, requiring improved solubility through chemical design.
• The high penetration of the blood-brain barrier provides potential applications for central nervous system diseases.
• No hERG channel inhibition and no genotoxicity, with good safety.

Currently, related research on pharmacokinetics is relatively limited. Preliminary in vivo experiments show that Changbai Quercus has certain bioavailability after oral administration, but its half-life is relatively short, suggesting that drug carriers or sustained-release formulations are needed to prolong its duration of action in vivo. Its metabolic pathway may involve oxidation and binding reactions in the liver, but specific metabolic enzymes and metabolites still require systematic study.

Prospects and outlooks for clinical applications

As a natural product, Changbai Quercus shows broad clinical application prospects thanks to its remarkable antibacterial and antitumor activities. Its inhibitory effect on MRSA provides new drug candidates for addressing drug-resistant bacterial infections, which is especially significant in the context of increasingly severe antibiotic resistance.

In the field of tumor treatment, Changbai Quermelic acid regulates liver cancer-related signaling pathways through multiple targets, demonstrating potential anti-tumor effects. In the future, modern drug design technologies can be combined to optimize their structure and pharmacokinetic properties, developing novel anti-tumor drugs. Moreover, its good safety profile and blood-brain barrier penetration ability make it possible for research on neurological diseases.

However, clinical research on Changbai Quermalic Acid is still in its early stages and lacks systematic clinical trial data. Future research should focus on in vivo pharmacokinetics, toxicological evaluation, and clinical efficacy verification. At the same time, combining advanced formulation technologies such as nanocarriers and drug eutectics to improve water solubility and bioavailability is key to achieving clinical translation.

Conclusion

As an important active ingredient in Aralia continentalis, Changbai Quercolic acid has become a hot topic in natural product pharmacology research due to its unique chemical structure and diverse pharmacological activities. It demonstrates promising application potential in multiple fields such as antibacterial and anti-tumor properties, especially in the treatment of drug-resistant bacterial infections and liver cancer, providing a valuable natural molecular template for new drug development.

In the future, it is necessary to strengthen systematic pharmacological and pharmacokinetic research on Changbai Quercolic Acid, integrating modern drug design and formulation technologies to promote its clinical application. It is believed that as research deepens, Changbai Quercolic Acid is expected to become an important breakthrough in the development of natural product drugs, contributing new therapeutic approaches to human health.