Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Liquidabaric lactone, CAS number 185051-75-6, is a natural product isolated from plants and has received widespread attention in recent years due to its significant anti-inflammatory activity. As an important source of drug discovery, the structural diversity and biological activity of natural products provide abundant chemical space for the development of new drugs. As a class of lactone compounds, lulutolactone exhibits the ability to regulate various inflammation related targets, especially in regulating cytokines and signaling pathways, showing unique advantages. With the increase of incidence rate of inflammation related diseases, searching for efficient and safe anti-inflammatory drugs has become the focus of modern pharmacological research. The research of Lulutong lactone provides new ideas and potential candidate molecules for the development of natural anti-inflammatory drugs.
This article aims to systematically review the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity and mechanism of action, pharmacological evaluation and pharmacokinetic characteristics of lulutolactone. Combined with its clinical application prospects, it comprehensively evaluates its potential as an anti-inflammatory drug and provides theoretical basis and reference for subsequent basic and applied research.
The molecular formula of Lulutong lactone is C28H36O7, with a molecular weight of 468.6780, belonging to the lactone class of natural products. Its structural features include a typical lactone ring system and multiple hydroxyl substituents, which endow it with high chemical and biological activity. The lactone ring in the molecular structure is not only a key functional group for its biological activity, but also plays a decisive role in the stability of the molecule and its ability to bind to the target.
In terms of physicochemical properties, the LogP value of lulutolactone is 5.9417, indicating its strong lipophilicity, which helps it penetrate lipid membranes, especially the blood-brain barrier (BBB) with high permeability, supporting its potential application in central nervous system related inflammatory diseases. Its topological polar surface area (TPSA) is 55.9 Å ², and moderate polarity is beneficial for the binding and in vivo distribution of molecules and biological targets. Very low water solubility (0.0006 mg/mL) suggests limited solubility in aqueous phase, which may affect oral absorption and bioavailability.
The safety evaluation shows that lulutolactone has no hERG channel inhibitory effect, reducing its risk of cardiac toxicity, and the Ames test result is 0, indicating that it does not have mutagenicity and has high safety.
Lulutolactone is mainly isolated from the Liquidambar genus of plants in the Hamameliaceae family, which is widely distributed in East Asia and North America. It is traditionally used to treat rheumatism, inflammation, and skin diseases. Although the content of lactones in plants is not high, their unique biological activity makes them a research focus.
The extraction method usually uses organic solvent extraction combined with chromatographic separation technology. Common extraction solvents include ethanol, methanol, and ethyl acetate, which can effectively dissolve fat soluble components. The extraction process generally includes drying and crushing plant materials, solvent extraction, concentration, liquid chromatography separation and purification of crude extracts. High performance liquid chromatography (HPLC) and mass spectrometry (MS) techniques are used for purity detection and structural confirmation.
In recent years, green extraction techniques such as supercritical CO2 extraction and microwave-assisted extraction have also been attempted to be applied to the extraction of lactone, aiming to improve extraction efficiency and purity, reduce the use of organic solvents, and comply with the environmental trend of modern natural product extraction.
The pharmacological activity research of lulutolactone focuses on its anti-inflammatory effect, covering both in vitro cell models and in vivo animal models. Multiple studies have shown that lactone can significantly inhibit the production and release of inflammatory mediators, and alleviate inflammatory reactions.
At the cellular level, lactone exhibits inhibitory effects on inflammation related cells such as macrophages and fibroblasts, reducing the expression of pro-inflammatory cytokines such as IL-6 and TNF - α and weakening the transmission of inflammatory signals. Its inhibition of the inflammatory mediators PTGS1 (COX-1) and PTGS2 (COX-2) further reduces the production of prostaglandins and alleviates inflammatory symptoms.
In animal experiments, lactone has shown significant anti-inflammatory effects in various inflammatory models, such as mouse plantar swelling model and arthritis model, and can reduce tissue swelling, inflammatory cell infiltration, and tissue damage. In addition, lactone also has a regulatory effect on TRPV1 and TRPA1 channels related to neuroinflammation, indicating its potential application value in neuroinflammation and pain management.
The anti-inflammatory mechanism of lulutolactone involves multiple signaling pathways and molecular targets, mainly including:
IL-6/STAT3 pathway
IL-6, as an important pro-inflammatory cytokine, promotes inflammatory response by activating the STAT3 signaling pathway. Lulutong lactone can inhibit the expression of IL-6 and the phosphorylation of STAT3, block signal transduction, and reduce the transcriptional activity of pro-inflammatory genes.
NF - κ B signaling pathway
NF - κ B is a core transcription factor that regulates inflammatory responses. Lutone inhibits the activation of NFKB1, reduces the synthesis of inflammatory mediators, and alleviates inflammatory responses.
CASP1 (cysteine protease-1)
CASP1 participates in the activation of inflammasomes and promotes the maturation of pro-inflammatory cytokines such as IL-1 β. Lulutolactone reduces inflammasome mediated inflammatory response by inhibiting CASP1 activity.
TRPV1 and TRPA1 channels
These two types of transient receptor potential channels play important roles in pain and inflammation signaling. The regulatory effect of lactone on it helps alleviate neuroinflammation and pain.
NOS2 (inducible nitric oxide synthase)
NOS2 catalyzes the production of nitric oxide, and excessive NO participates in inflammatory reactions. Lutongtong lactone inhibits the expression of NOS2, reduces NO levels, and alleviates inflammation.
PTGS1 and PTGS2 (COX-1 and COX-2)
Inhibit the activity of these two enzymes, reduce prostaglandin synthesis, alleviate inflammation and pain.
In summary, the synergistic effect of lulutolactone on multiple targets and pathways enhances its anti-inflammatory effect, demonstrating its advantages as a multi-target drug.
The evaluation of drug properties is an important step in the development of natural product drugs. The physicochemical parameters of lulutolactone show that it has high lipid solubility (LogP 5.94), which is beneficial for cell membrane penetration and blood-brain barrier penetration, supporting its potential application in central nervous system inflammation. Its TPSA is moderate and meets the pharmacokinetic requirements of oral medications.
The extremely low water solubility may limit its oral absorption and bioavailability, and drug formulation techniques such as nanocarriers and liposome encapsulation are needed to improve solubility and stability. In terms of safety, there is no hERG inhibition and no mutagenicity, laying the foundation for clinical application.
In terms of pharmacokinetics, there are few existing studies, but its high lipid solubility and blood-brain barrier permeability suggest its widespread distribution in vivo, especially accumulation in brain tissue. The metabolic pathway may involve oxidative and reductive reactions in the liver, with excretion mainly through bile and urine. In the future, it is necessary to conduct systematic in vivo pharmacokinetic and toxicological studies to clarify their metabolic characteristics and safe dose ranges.
Given the inhibitory effects of lactone on various inflammation related targets, particularly its regulatory role in key inflammatory pathways such as IL-6/STAT3 and NF - κ B, it has broad application prospects in the treatment of rheumatoid arthritis, inflammatory bowel disease, neuroinflammation, and related pain diseases.
In addition, its excellent blood-brain barrier penetration ability makes it a potential candidate drug for treating inflammatory diseases of the central nervous system, such as multiple sclerosis and Alzheimer's disease-related inflammation. In the future, modern drug design technology can be combined to optimize its structure, improve its water solubility and bioavailability, and develop it into oral or injectable formulations.
Combining modern molecular biology and medicinal chemistry methods to deeply analyze its mechanism of action and molecular targets can help discover more indications and combination therapy strategies. At the same time, conducting systematic preclinical safety evaluations and clinical trials is a key step in promoting its clinical translation.
As a natural lactone compound with significant anti-inflammatory activity, lulutolactone has shown great potential as a new type of anti-inflammatory drug due to its multi-target regulatory ability and good pharmacological characteristics. Although research on its pharmacokinetics and clinical applications is still in its infancy, its unique molecular structure and extensive biological activity provide valuable examples for natural product pharmacology research.
In the future, it is necessary to strengthen the optimization of its extraction process, in-depth analysis of its pharmacological mechanism, and systematic research on its safety and pharmacokinetics, promote the transformation of lactone from laboratory research to clinical application, assist in the innovative development of natural anti-inflammatory drugs, and meet the urgent demand for efficient and safe anti-inflammatory drugs in clinical practice.
