Introduction/Overview
Natural products, as important resources for drug discovery, attract much attention for their structural diversity and biological activity. Triterpenoids, as an important class of natural products, are widely found in plants and possess various pharmacological activities. Tormentic acid is a typical pentacyclic triterpene originally isolated from Rosa rugosa, a plant of the Rosaceae family. In recent years, with the deepening study of its biological activity, spirited acid has become a hot topic in natural medicine research due to its significant anti-inflammatory, lipid-lowering, and anti-atherosclerotic effects.
This paper aims to systematically review the chemical structure and physicochemical properties, plant origin, and extraction methods of Piccolic acid, focusing on analyzing its pharmacological activity and mechanism of action, evaluating its pharmacokinetic characteristics in combination with druggability parameters, exploring its clinical application potential and future research directions, and providing theoretical basis and research reference for natural product pharmacology and new drug development.
Chemical structure and physicochemical properties
Tormentic acid, CAS number 13850-16-3, chemical formula C30H48O4, molecular weight 488.7090. Its structure belongs to the pentacyclic triterpenic acid class, featuring a typical triterpene backbone, containing one carboxyl group and multiple hydroxyl functional groups, which impart certain polarity and biological activity. The carboxyl group in the molecular structure gives it acidic characteristics, while the hydroxyl group may participate in hydrogen bond formation, affecting its binding to biological targets.
In terms of physicochemical properties, the LogP value of Spiritulic acid is 4.4601, indicating high lipid solubility that facilitates cell membrane penetration, but its water solubility is relatively low (0.0099), which may limit its solubility and bioavailability in aqueous environments. Its topological pole surface area (TPSA) is 97.9900, indicating the presence of certain polar regions that facilitate interaction with protein targets. The blood-brain barrier has low permeability, suggesting its limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk.
Overall, the physicochemical properties of velvetic acid are suitable for oral administration, but its low water solubility and limited brain penetration suggest that administration methods or structural modifications need to be optimized to enhance efficacy and bioavailability.
Plant Origins and Extraction Methods
Potentilla acid is mainly found in Rosa rugosa, a plant of the Rosaceae family, and has also been reported in other medicinal materials such as Sanguisorba officinalis. As a traditional Chinese medicine and edible plant, rosehip is rich in various triterpene compounds, with Cincinic acid being one of its representative components.
The extraction method typically uses organic solvent extraction combined with column chromatography for separation. The specific steps include:
- Sample pretreatment: Crush dried rosehips into fine powder and screen for uniform particle size.
- Solvent extraction: Ethanol or methanol are commonly used as extraction solvents, and reflux or ultrasound assistance is employed to improve extraction efficiency.
- Crude extract concentration: Extract is obtained by removing solvent through vacuum concentration.
- Separation and purification: Using silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other technologies to separate potelina acid and further purify it to high purity.
- Identification and confirmation: Confirm the compound structure using modern analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).
In recent years, the application of green extraction methods such as supercritical CO2 extraction technology and microwave-assisted extraction has provided new ideas for improving the extraction efficiency and purity of Spirited acid.
Pharmacological activity research
Anti-inflammatory effects
Velvetic acid exhibits significant anti-inflammatory activity. Both in vitro cell models and in vivo inflammation models have confirmed that it can inhibit the generation and release of various inflammatory mediators. Its main manifestation is reduced expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide synthase 2 (NOS2), thereby alleviating inflammatory responses.
In the mouse acute inflammation model, velvetic acid significantly reduced edema and leukocyte infiltration at the inflamed site, inhibited the release of inflammatory mediators, and demonstrated good anti-inflammatory effects. Additionally, its inhibitory effect on inflammation-related enzymes such as cyclooxygenase 1 (PTGS1) and cyclooxygenase 2 (PTGS2) further illustrates the multi-target characteristics of its anti-inflammatory mechanism.
Lowers blood lipids and has anti-atherosclerosis effects
Velvetic acid has the potential to regulate blood lipids. Animal experiments have shown that velvetic acid can lower plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides, while also increasing high-density lipoprotein cholesterol (HDL-C) content. This lipid-regulating effect helps prevent and alleviate atherosclerosis.
In the atherosclerosis model, signulic acid reduces vascular endothelial damage and inhibits plaque formation and progression by inhibiting inflammatory responses and oxidative stress. Its antioxidant effects are achieved by scavenging free radicals and regulating antioxidant enzyme activity, further protecting vascular function.
Other pharmacological activities
In addition to the above effects, some studies have reported that velvianic acid has anti-tumor, antiviral, and immunomodulatory activities, but the related mechanisms require further elucidation.
Mechanism of action and molecular targets
The pharmacological effects of commissionic acid involve multiple signaling pathways and molecular targets, especially exhibiting multi-target coordinated regulation in anti-inflammatory effects.
Key target analysis
- IL-6 and TNF-α: As typical pro-inflammatory cytokines, IL-6 and TNF-α play a central role in the inflammatory response. Velvetic acid can significantly inhibit the expression of these two cytokines, reducing the inflammatory cascade.
- STAT3: Signal transduction and transcription activator factor 3 (STAT3) is an important transcription factor for inflammation and immune regulation. Veltrinic acid intervenes in inflammatory signaling by inhibiting STAT3 phosphorylation and activation.
- CASP1 (caspase-1): Involved in the activation of inflammasomes, regulating the maturation and release of pro-inflammatory cytokines. Velvetic acid inhibits CASP1 and reduces inflammatory responses mediated by inflammasomes.
- TRPV1 and TRPA1: These two transient receptor potential pathways play key roles in the transmission of inflammatory pain. Veltrinic acid alleviates inflammation-related pain by modulating the activity of TRPV1 and TRPA1.
- NOS2: Induced nitric oxide synthase, involved in the production of large amounts of NO during inflammation. Velvetic acid inhibits NOS2 expression and reduces NO-mediated inflammatory damage.
- PTGS1 and PTGS2: Cyclooxygenases 1 and 2 catalyze prostaglandin synthesis and are important enzymes in inflammatory responses. Pictrinal acid inhibits its activity, lowers prostaglandin levels, and alleviates inflammation.
- NFKB1: Member of the nuclear factor κB family, regulates the expression of various inflammatory genes. Velentine inhibits NFKB1 activation and blocks inflammatory signaling pathways.
Summary of molecular mechanisms
Veltrinic acid regulates the production and release of inflammatory mediators through multi-target and multi-pathway synergistic effects, inhibits inflammatory signal transduction, and reduces inflammatory responses. In addition, its regulation of lipid metabolism and antioxidant mechanisms work together to prevent and treat blood lipid levels and atherosclerosis.
Druggability evaluation and pharmacokinetics
Analysis of drug-dosable parameters
The molecular weight of charcanic acid is 488.7090, slightly above the 500 recommended by Lipinski's rules, but still within the acceptable range. The LogP is 4.4601, indicating good lipophile compatibility and facilitating cell membrane penetration, but may affect water solubility and oral absorption. TPSA is 97.9900, and moderate polarity aids target binding. Water solubility is extremely low (0.0099), suggesting that the solubility of oral formulations needs to be optimized to improve bioavailability.
The low permeability of the blood-brain barrier limits its application in the central nervous system, but it reduces the risk of CNS side effects. hERG channel inhibition is negative, indicating a low risk of cardiotoxicity. Ames test is negative, indicating relatively high safety.
Pharmacokinetic characteristics
Currently, pharmacokinetic research on pictrine is relatively limited. Existing data show that after oral administration, absorption is slow, and plasma concentration peaks last longer, possibly due to low water solubility and large molecular weight. Metabolic pathways mainly involve hepatic enzyme systems, involving oxidation and hydroxylation reactions, and the activity of these metabolites still requires further study.
The main excretion routes are bile and urine, with a moderate half-life. In the future, formulation improvements and structural modifications are needed to enhance pharmacokinetic properties and enhance bioavailability and targeting.
Prospects and outlooks for clinical applications
As a natural triterpenic acid with broad sources and significant pharmacological activity, it has good anti-inflammatory and lipid-regulating potential, making it suitable for adjunctive treatment for chronic inflammatory diseases, cardiovascular diseases, and metabolic syndrome.
Currently, Velvetic acid is still in the basic research and animal experiment stage, lacking systematic clinical trial data. Future research should focus on:
- Preclinical safety evaluation: Systematically evaluate its toxicological characteristics to ensure safety.
- Pharmacokinetics and dosage form development: optimizing delivery routes and formulations to enhance bioavailability.
- In-depth analysis of the mechanism of action: Using multi-omics technology to reveal its multi-target and multi-pathway regulatory network.
- Clinical trial design: Conduct clinical studies targeting inflammatory diseases and atherosclerosis to verify efficacy and safety.
- Structural modification and derivative development: Enhancing activity and pharmacokinetic properties through chemical modification, expanding application range.
Moreover, combining modern drug design with natural product chemistry, willelic acid is expected to become a leading compound for novel anti-inflammatory and cardiovascular protective drugs.
Conclusion
As a typical natural triterpenic acid, Velvetic acid shows broad application prospects in anti-inflammatory, lipid-lowering, and anti-atherosclerosis fields due to its unique structure and significant biological activity. Its multi-target mechanism of action offers new perspectives for pharmacological research of natural products. Although challenges remain in pharmacokinetics and clinical applications, with the support of modern drug development technologies, veltrinic acid is expected to become a key breakthrough in the development of natural product drugs. Future systematic research will further reveal its potential, drive its clinical application, and benefit human health.