Synonym name: Ursonic acid;3-Ketone
Catalogue No.: BP0072
Cas No.: 6246-46-4
Formula: C₃₀H₄₆O₃
Mol Weight: 454.695
Botanical Source: dammar resin, Rubus fruticosus Hopea sp., Shorea sp., Xylanche himalaica and other plants

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 3-oxo-urs-12-en-28-oic acid

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

Introduction/Overview

Ursonic acid (CAS number: 6246-46-4) is a naturally occurring triterpene compound that has attracted widespread attention in pharmacology and natural product chemistry in recent years due to its diverse biological activities. As an important member of triterpenoids, ursolic acid not only shows significant potential in anti-tumor and antiviral effects but has also been found to interact with molecular targets related to various metabolic diseases, indicating its potential applications in metabolic regulation and the treatment of neuropsychiatric disorders. This paper will systematically review the chemical structure, natural origin, pharmacological activity, mechanism of action, druggability evaluation, and future clinical application prospects of urbutic acid, aiming to provide a theoretical foundation and reference for related research.

Chemical structure and physicochemical properties

Ursolone acid belongs to the triterpene class of compounds, with a molecular formula of C30H46O4 and a molecular weight of 454.68. Its structural features include a multi-ring framework and multiple oxygen functional groups, giving it unique physicochemical properties. The LogP value of ursolic acid is about 6.0, indicating strong hydrophobicity, which has an important impact on cell membrane penetration and drug distribution. Its polar surface area (TPSA) is 57.53, and the number of hydrogen bond acceptors is 3, suggesting that it has certain hydrophilic sites in intermolecular interactions. Arbutone acid has relatively low blood-brain barrier penetration ability, and no significant risks of hepatotoxicity, cardiotoxicity, or hERG channel inhibition have been observed, demonstrating good safety potential. However, the results of Ames-induced mutagenic tests are still unclear, and further research is needed to assess its genotoxicity risk.

Plant Origins and Extraction Methods

Arbutic acid is mainly found in the bark, leaves, and fruits of various plants, with Arbutaceae species (such as bearberry leaves) and certain Eucommiaceae plants as the primary sources. Traditional Chinese medicinal herbs containing ursolic acid are mostly used for anti-inflammatory, antibacterial, and metabolic regulation. The extraction method typically uses organic solvent extraction combined with column chromatography for purification, with commonly used solvents including ethanol, methanol, and ethyl acetate. In recent years, to improve extraction efficiency and purity, ultrasound-assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) purification technologies have gradually been applied to the separation and preparation of ursolone acid. In addition, chemical and semi-synthetic methods for ursolic acid are continuously developing to meet the demands of large-scale production.

Pharmacological activity research

Antitumor activity

Arbutone acid exhibits significant antiproliferative and pro-apoptotic effects in various human cancer cell lines. By regulating cell cycle-related proteins, activating endogenous apoptosis pathways, and inhibiting tumor cell migration and invasion, it demonstrates broad anti-cancer potential. In vitro studies have shown that urbutic acid can induce loss of mitochondrial membrane potential in cancer cells, activate the caspase cascade, and promote apoptosis. In addition, urbutic acid can enhance the sensitivity of chemotherapy drugs and has potential adjunctive therapeutic value.

Antiviral activity

Arbutone acid exhibits good inhibitory effects against herpes simplex virus (HSV) types I and II. Its antiviral mechanism may involve inhibiting viral replication and blocking the binding process between the virus and host cells. In vitro experiments show that ursolic acid can significantly reduce viral loads and alleviate virus-mediated cellular lesions, suggesting its potential for antiviral drug development.

Antidepressant effects

In recent years, research on urbutic acid in the field of neuropsychiatric disorders has gradually increased. It demonstrates antidepressant potential by regulating neurotransmitter balance, antioxidant stress, and inflammatory responses. Some studies indicate that urbutic acid can affect the metabolism of neurotransmitters such as serotonin (5-HT) and dopamine in the brain, improving depressive symptoms and becoming a candidate compound for developing new antidepressant drugs.

Metabolic disease regulation

Arbutone acid has a regulatory effect on metabolic diseases such as diabetes, obesity, and non-alcoholic fatty liver disease. By activating the AMPK signaling pathway, it improves energy metabolism, inhibits fat synthesis, promotes fatty acid oxidation, and reduces inflammatory responses, thereby improving metabolic abnormalities. Additionally, urbutone acid regulates key targets such as PTPN1, STAT3, and ABCB1, participating in insulin signaling and lipid metabolism regulation.

Mechanism of action and molecular targets

The multi-target mechanism of urbutic acid forms the basis of its broad biological activity. The main molecular targets and their mechanisms of action include:

• AMPK (PRKAA1): Arbutanoic acid activates AMPK, promotes cellular energy metabolism balance, inhibits fat production, enhances insulin sensitivity, and exerts metabolic regulation effects.
• PTPN1 (protein tyrosine phosphatase 1B): By inhibiting PTPN1, urbutic acid enhances insulin signaling and improves glucose metabolism disorders.
• STAT3: Arbutic acid inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and survival signals, and promoting apoptosis.
• ABCB1 (P-glycoprotein): Regulates drug efflux; ursolin may enhance intracellular accumulation of chemotherapy drugs by affecting ABCB1 expression.
• ALOX15 (lipoxygenase 15): involved in lipid metabolism and inflammatory responses; ursolic acid regulates its activity and reduces inflammatory damage.
• PRKCA (protein kinase Cα): regulates cell proliferation and apoptosis; ursolic acid influences cell fate by modulating PRKCA signaling.
• NFE2L2 (Nrf2): activates the Nrf2 antioxidant pathway, enhances cellular antioxidant capacity, and reduces oxidative stress damage.
• SHBG (sex hormone-binding globulin): regulates sex hormone activity. Arbutin may participate in endocrine regulation by affecting SHBG levels.
• TOP1 (Topoisomerase I): Affects DNA replication and repair; urdentic acid regulates TOP1 to help inhibit tumor cell proliferation.
• HIF1A (hypoxia-inducing factor 1α): regulates cellular adaptation to hypoxic environments. Arbutanoic acid blocks the tumor's hypoxia adaptation mechanism by inhibiting HIF1A.

In summary, ursolic acid exerts its multi-target and multi-pathway synergistic effects on anti-tumor, antiviral, and metabolic regulation.

Druggability evaluation and pharmacokinetics

The druggability evaluation of urbutic acid shows that it has certain advantages and challenges. Its high hydrophobicity (LogP=6.0) favors membrane penetration but may limit its water solubility and bioavailability. TPSA was 57.53, with 3 hydrogen bond receptors, indicating moderate molecular polarity and favorable binding to target proteins. Arbutone acid's blood-brain barrier penetration ability is relatively low, suggesting its direct effect in the central nervous system may be limited, but it can still exert antidepressant effects through peripheral mechanisms.

In terms of safety, urbutone acid did not show significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, reducing the risk of cardiovascular side effects. Ames-induced mutagenic test results are not yet clear, and further toxicological studies are needed to ensure genetic safety. Pharmacokinetic studies are relatively limited, with preliminary data suggesting that oral absorption may be limited. In vivo, metabolic pathways mainly involve the hepatic CYP450 enzyme system, and the metabolites and their activity require further investigation.

To enhance the drug properties of ursoloneic acid, future methods such as structural modification, nanocarrier encapsulation, and drug delivery systems can optimize its solubility and bioavailability, promoting its clinical translation.

Prospects and outlooks for clinical applications

As a versatile natural product, ursolic acid has broad clinical application potential. Its antitumor activity makes it a strong candidate for adjuvant cancer therapy, especially in overcoming chemotherapy resistance and regulating the tumor microenvironment, offering unique advantages. Its antiviral activity provides the foundation for developing novel anti-HSV drugs, meeting the diverse clinical needs of antiviral drugs.

In the field of metabolic diseases, urbutic acid is expected to become a new drug for treating diabetes, obesity, and fatty liver by regulating AMPK and related signaling pathways. Moreover, its antidepressant effects open new directions for treating neuropsychiatric disorders, especially for patients with depression accompanied by metabolic abnormalities.

Future research should focus on optimizing the pharmacokinetics, formulation development, and preclinical safety evaluation of urbutic acid, integrating modern drug design and precision medicine strategies to promote its translation into clinical application. At the same time, in-depth analysis of its mechanism of action and multi-target synergistic effects will help develop more selective and efficient ursolic acid derivatives.

Conclusion

Arbutanoic acid, as a naturally occurring triterpene compound with rich biological activity, exhibits multiple pharmacological effects including anti-tumor, antiviral, antidepressant, and metabolic regulation. Its multi-target and multi-pathway mechanisms provide a theoretical basis for the development of novel therapeutic drugs. Despite certain druggability challenges, its good safety profile and unique bioactivity make it an important candidate for natural product drug development. In the future, by combining structural optimization with drug delivery technology, urbutic acid is expected to play a broader role in clinical applications, driving the development and innovation of natural product pharmacology.