Introduction/Overview
Natural products, as an important source of drug discovery, play an indispensable role in the long history of human struggle against diseases. From the practice of traditional medicine to the precise certification of modern pharmacology, countless natural compounds derived from plants, animals, and microorganisms have provided valuable lead compounds and drug molecules for clinical treatment. Among these structurally diverse and active natural products, Anemonin has attracted widespread attention from researchers due to its unique chemical skeleton and significant biological activity, especially in the field of inflammation related diseases.
Whitehead hormone, also known as Whitehead hormone or Silver Lotus hormone, is a naturally occurring small molecule lactone compound. Its name comes from its main plant source - the genus Paeonia in the Ranunculaceae family（Pulsatilla）And the Silver Lotus genus（Anemone）Plants. These plants have a long history of application in the traditional Chinese medicine system, often used to treat dysentery, malaria, hemorrhoids, and various inflammatory diseases. Modern pharmacological research has gradually revealed the molecular basis for the traditional effects of paeoniflorin. Research has shown that paeoniflorin is a selective inducible nitric oxide synthase (iNOS) inhibitor and also an inhibitor of protein kinase C - θ (PKC - θ). These two targets are closely related to the key links of inflammatory response - excessive production of nitric oxide (NO) and T cell-mediated immune response. More importantly, paeoniflorin showed significant therapeutic effects in a mouse model of acute ulcerative colitis (UC) induced by dextran sulfate sodium (DSS), providing strong preclinical evidence for its therapeutic application in autoimmune and inflammatory diseases such as inflammatory bowel disease (IBD).
This article aims to provide a comprehensive professional review of paeoniflorin, starting from its chemical structure and physicochemical properties, tracing its plant origin and extraction methods, systematically sorting out its pharmacological activity, mechanism of action, and molecular targets, evaluating its pharmacological properties and pharmacokinetic characteristics, and finally looking forward to its clinical application prospects and future research directions, in order to provide a systematic scientific reference for the modern drug development of this ancient natural product.
Chemical structure and physicochemical properties
The chemical structure of Anemonin is the core basis of its biological activity. From a chemical classification perspective, it belongs to the class of dimeric lactones. Specifically, it is a dimer formed by the Diels Alder cycloaddition reaction of two molecules of Protoanemon. This unique structure endows it with physical and chemical properties that distinguish it from other natural products.
Chemical structure analysis:
The chemical name of paeoniflorin is (1R, 8S, 9R, 10S) -9,10-dimethyl-2,7-dioxycyclo [4.4.0.0 ³, ⁸] dec-4,11-diene-3,6-dione. Its molecular formula is C ₁₀ H ₈ O ₄, and its molecular weight is 192.17 g/mol. Its core skeleton is a highly symmetrical bicyclic system, consisting of two fused gamma lactone rings (pentagonal lactones) and a central cyclobutane ring. This rigid and compact tricyclic structure (bicyclic [4.2.0] octane skeleton combined with two lactone rings) is a key feature that distinguishes it from other simple lactones. The two lactone carbonyls (C=O) and two carbon carbon double bonds (C=C) in the molecule constitute the main active sites, which may participate in chemical reactions such as Michael addition, and thus interact covalently or non covalently with target proteins in the organism.
Physical and chemical properties parameters:
According to the provided pharmacological parameters, paeoniflorin exhibits the following key physicochemical properties:
- Molecular weight (MW): 192.17 Da. This is an ideal value that meets the Lipinski's Rule of Five requirement for molecular weight less than 500, which is beneficial for drug absorption and diffusion.
- Lipid water partition coefficient (LogP): 0.45. The LogP value reflects the distribution equilibrium of compounds between n-octanol and aqueous phase, and is an important indicator for measuring lipophilicity. A LogP value of 0.45 indicates that paeoniflorin has moderate hydrophilicity and is slightly inclined towards the aqueous phase. This characteristic enables it to have good solubility in aqueous environments such as blood and cytoplasm, while also being able to moderately penetrate the lipid bilayer, which is beneficial for transport and distribution in the body. Generally, compounds with LogP between 0-3 are considered to have good oral absorption potential.
- Topological Polarity Surface Area (TPSA): 52.6 Å ². TPSA is the total surface area of all polar atoms (mainly oxygen and nitrogen) in a molecule, closely related to the intestinal absorption and blood-brain barrier penetration ability of compounds. Generally, molecules with TPSA less than 60 Å ² are considered to have good oral bioavailability and high cell membrane permeability. The TPSA of paeoniflorin is 52.6 Å ², which meets this standard and suggests that it may have good oral absorption properties. At the same time, this also means that it has a certain potential to penetrate the blood-brain barrier, although its blood-brain barrier penetration ability is currently unknown.
- Number of hydrogen bond acceptors: 4. The four oxygen atoms in the molecule (two carbonyl oxygen atoms and two ether oxygen atoms) can serve as hydrogen bond acceptors. This value also conforms to the "Five Rules of Drug Analogy" (hydrogen bond receptor ≤ 10), indicating moderate potential for hydrogen bond interactions with biological targets.
Overall, the chemical structure of paeoniflorin is compact and rigid, with multiple reaction sites. Its physicochemical properties parameters (low molecular weight, moderate LogP and TPSA) all exhibit good drug like characteristics, laying a favorable foundation for its subsequent drug development. However, key ADMET (absorption, distribution, metabolism, excretion, toxicity) parameters such as blood-brain barrier penetration, hepatotoxicity, and cardiotoxicity are currently unclear, which will be a key area of focus and research in future pharmacological evaluations.
Plant sources and extraction methods
Baitousu is not widely present in all plants, and it mainly comes from specific genera and species in the Ranunculaceae family, especially the Baitousu genus（Pulsatilla）And the Silver Lotus genus（Anemone）Plants. These plants are often used as herbs in traditional medicine, and their medicinal parts are mostly dried whole plants or rhizomes.
Main plant sources:
1. White headed Weng genus（Pulsatilla）： This genus is the most important source of paeoniflorin. For example, the traditional Chinese medicine Bai Tou Weng（Pulsatilla chinensis The roots and stems of Bunge Regel are rich in paeoniflorin and its precursor, protopaeoniflorin. In addition, the European white headed Weng（Pulsatilla vulgaris）Waiting is also an important source of plants.
2. Silver Lotus Genus（Anemone）： Many plants of the Silver Lotus genus, such as the Broken Bowl Flower（Anemone hupehensis）The Great Fire Grass（Anemone tomentosa）Wait, its roots and stems also contain paeoniflorin.
3. Ranunculus genus（Ranunculus）： Some plants of the Ranunculus genus, such as the buttercup（Ranunculus japonicus）In its fresh state, it contains a high concentration of original paeoniflorin, which can be partially converted into paeoniflorin during drying or processing.
Extraction and Separation Purification Methods:
Due to the coexistence of paeoniflorin with highly active protopaeoniflorin in plants, and the instability and aggregation of protopaeoniflorin, special attention should be paid to the extraction process. The classic extraction method usually includes the following steps:
- Raw material pretreatment: Crush dry plant roots or whole plants to increase solvent contact area. The drying process helps to convert the unstable original paeoniflorin into more stable paeoniflorin.
- Solvent extraction: According to the polarity of paeoniflorin (LogP 0.45), organic solvents with higher polarity are usually selected for extraction. Common solvents include:
- Ethanol or methanol: It is the most commonly used extraction solvent that can effectively dissolve paeoniflorin from plant tissues. Usually, cold soaking, percolation, or reflux extraction methods are used.
- Ethyl acetate: Due to the solubility of paeoniflorin in ethyl acetate and its low solubility for many impurities such as sugars and proteins, it is often used as a solvent for extraction or liquid-liquid extraction.
- Concentration and preliminary purification: After filtration, the extract is concentrated to a paste under reduced pressure. Subsequently, the extract was dispersed in water and subjected to gradient extraction using organic solvents of different polarities, such as petroleum ether, chloroform, ethyl acetate, and n-butanol. Baitousu is usually enriched in the ethyl acetate or chloroform extraction layer.
- Chromatographic separation: This is a key step in obtaining high-purity paeoniflorin. Common chromatographic techniques include:
- Silica gel column chromatography: Gradient elution using mixed solvents such as chloroform methanol or petroleum ether acetone as the mobile phase is the most classic method for separating paeoniflorin.
- Preparation type high performance liquid chromatography (Prep HPLC): For impurities with similar structures that are difficult to separate, preparative HPLC can be used for fine separation to obtain a purity of over 98% for paeoniflorin monomer.
- Recrystallization: Baitousu can form crystals in specific solvents such as ethanol and acetone, and its purity can be further improved by recrystallization.
- Structural identification: The isolated compound needs to be structurally confirmed by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), infrared spectroscopy (IR), and ultraviolet spectroscopy (UV), and compared with literature data to ultimately confirm as paeoniflorin.
It is worth noting that due to the strong skin irritation and toxicity of the original white hair extract, strict safety precautions must be taken when extracting and processing fresh plant materials. Modern research has also explored the use of biotechnology (such as plant cell culture) or chemical synthesis methods to obtain paeoniflorin, but natural extraction remains the most important and economical source at present.
Pharmacological activity research
The pharmacological activity research of paeoniflorin mainly focuses on its anti-inflammatory, immune regulatory, and protective effects on various disease models derived from it. Its activity spectrum is broad and highly compatible with traditional Chinese medicine applications.
1. Anti inflammatory activity:
This is the core pharmacological effect of paeoniflorin. A large number of in vitro and in vivo experiments have confirmed its powerful anti-inflammatory effect.
- Inhibition of inflammatory mediators: Baitouwensu can significantly inhibit the production of key pro-inflammatory factors such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and interleukin-1 β (IL-1 β) in macrophages stimulated by lipopolysaccharide (LPS). The mechanism is closely related to the inhibition of iNOS and cyclooxygenase-2 (COX-2) expression.
- Anti ulcerative colitis (UC): This is a highlight in the research on the anti-inflammatory activity of paeoniflorin. In DSS induced acute UC model in mice, treatment with paeoniflorin can significantly reduce disease activity index (DAI), improve pathological changes such as colon length shortening, mucosal damage, and inflammatory cell infiltration. Its efficacy is comparable to or better than the first-line clinical drug 5-aminosalicylic acid (5-ASA), indicating its enormous potential in the treatment of IBD.
- Other inflammatory models: The study also found that paeoniflorin exhibited significant inhibitory effects in acute inflammation models such as carrageenan induced paw swelling and xylene induced ear swelling.
2. Immune regulatory activity:
Whitehead hormone has a regulatory effect on the immune system, especially T cell-mediated immune responses.
- Inhibition of T cell activation: As a selective inhibitor of PKC - θ, paeoniflorin can effectively block downstream signaling of T cell receptors (TCR), inhibit T cell proliferation, activation, and cytokine production (such as IL-2, IFN - γ). This makes it potentially valuable in the treatment of T cell-mediated autoimmune diseases such as rheumatoid arthritis, psoriasis, and graft-versus-host disease.
- Regulating macrophage function: In addition to inhibiting the pro-inflammatory function of macrophages, paeoniflorin may also affect its polarization direction, such as promoting the transformation of M2 type (anti-inflammatory) macrophages, thereby contributing to the resolution of inflammation and tissue repair.
3. Antitumor activity:
Some studies have reported the inhibitory effect of anemonin on the proliferation of many tumor cell lines (such as liver cancer, lung cancer, breast cancer, leukemia cells). The mechanism may involve inducing cell apoptosis, blocking the cell cycle, inhibiting angiogenesis, and so on. However, there are relatively few studies on this part, and the concentration of action is usually high. Its in vivo anti-tumor effect and selectivity need further verification.
4. Antibacterial and antiviral activity:
Traditionally, white haired Weng has been used to treat dysentery, which is related to the antibacterial activity of white haired Weng Su. In vitro experiments have shown that paeoniflorin has a certain inhibitory effect on various bacteria such as Staphylococcus aureus, Escherichia coli, and Shigella. In addition, studies have reported its antiviral activity, such as its inhibitory effect on herpes simplex virus (HSV).
5. Other activities:
- Antioxidant: Baitousu has a certain free radical scavenging ability and may exert a protective effect by reducing oxidative stress damage.
- Neuroprotection: Given its anti-inflammatory and antioxidant properties, as well as its potential ability to penetrate the blood-brain barrier, the protective role of paeoniflorin in neurodegenerative disease models such as Alzheimer's disease and Parkinson's disease has also begun to receive attention. Preliminary studies suggest that it may exert neuroprotective effects by inhibiting excessive activation of microglia and neuroinflammation.
Mechanism of action and molecular targets
The pleiotropic pharmacological activity of paeoniflorin originates from its interaction with specific molecular targets. The two most extensively studied targets at present are inducible nitric oxide synthase (iNOS) and protein kinase C - θ (PKC - θ).
1. Selective inhibition of iNOS:
INOS is a key enzyme that catalyzes the production of large amounts of NO in inflammatory reactions. Under LPS or cytokine stimulation, iNOS expression is induced in immune cells such as macrophages, producing high concentrations of NO as an inflammatory mediator to participate in killing pathogens. However, excessive production of NO can also lead to tissue damage and inflammation amplification.
- Mode of action: Whitehead hormone can selectively inhibit the activity of iNOS, with little effect on the constitutive expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). This selectivity is crucial because inhibiting nNOS and eNOS can cause serious neurological and cardiovascular side effects.
- Molecular mechanism: Research has shown that kaempferol does not directly bind to the active site of iNOS, but works by inhibiting the expression level of iNOS protein. Specifically, it may inhibit the transcription of iNOS gene by interfering with the activation of transcription factor NF - κ B. In addition, there is evidence to suggest that resveratrol may downregulate the protein expression of iNOS mRNA by affecting its stability or translation process. By inhibiting iNOS, paeoniflorin effectively blocks the excessive production of NO, thereby reducing the inflammatory response.
2. Inhibit PKC - θ:
PKC - θ is a subtype of protein kinase C (PKC) family that plays a crucial role in T cell activation. It is a key node in the T cell receptor (TCR) signaling pathway.
- Mode of action: Whitehead hormone has been identified as a specific inhibitor of PKC - θ. It can directly bind to PKC - θ and inhibit its kinase activity.
- Molecular mechanism: In T cells, after TCR activation, PKC - θ is recruited to immune synapses and activated. Activated PKC - θ further activates downstream transcription factors such as NF - κ B and AP-1, ultimately leading to the production of cytokines such as IL-2 and the proliferation of T cells. Whitehead hormone inhibits the activation and function of T cells by blocking this critical signaling pathway through the inhibition of PKC - θ. The study also showed that Chinese cabbage extract can significantly inhibit the translation of PKC - θ protein or reduce its protein stability, which may be another important mechanism for its long-term inhibition of T cell activity. Given the central role of PKC - θ in T cell-mediated immune responses, its inhibitors are considered ideal candidate drugs for treating autoimmune diseases and transplant rejection.
3. Other potential targets and signaling pathways:
In addition to the two main targets iNOS and PKC - θ, paeoniflorin may also exert its pharmacological effects by affecting other signaling pathways.
- NF - κ B pathway: As mentioned earlier, inhibiting the activation of NF - κ B is a common mechanism by which baicalin downregulates the expression of various pro-inflammatory factors, including iNOS, COX-2, TNF - α, IL-6, etc. This may be the core upstream event of its anti-inflammatory effect.
- MAPK pathway: Some studies have shown that paeoniflorin can inhibit the phosphorylation of p38 MAPK and JNK, which are also involved in the production of inflammatory factors.
- NLRP3 inflammasome: The latest research suggests that paeoniflorin may reduce the maturation and secretion of IL-1 β by inhibiting the assembly and activation of NLRP3 inflammasomes, providing a new explanation for its anti-inflammatory mechanism.
- Wnt/β - catenin pathway: In anti-tumor research, it has been found that paeoniflorin can inhibit the Wnt/β - catenin signaling pathway, which may be related to its inhibition of tumor cell proliferation and induction of apoptosis.
In summary, the mechanism of action of paeoniflorin is multi-target and multi pathway. Its core lies in regulating iNOS, COX-2, various cytokines, and chemokines by inhibiting key signaling nodes such as PKC - θ and NF - κ B, thereby exerting its anti-inflammatory and immunomodulatory effects. This multi-target mode of action not only has its advantages (which may result in synergistic effects), but also lays the groundwork for its potential side effects and complex pharmacological effects.
Evaluation of drug properties and pharmacokinetics
To promote the clinical application of paeoniflorin from the laboratory, a comprehensive evaluation of its drug like and pharmacokinetic (ADME) properties is necessary. At present, the data in this area is not yet complete, but the existing information provides us with a preliminary assessment.
Drug Evaluation:
Based on the "Five Rules of Similar Drugs" and the provided parameters, Baitousu exhibits a good pharmacological basis:
- Molecular weight: 192.17 Da (compliant with<500)
- LogP: 0.45 (meets<5)
- Hydrogen bond receptor: 4 (meets<10)
- Hydrogen bond donor: 0 (meets<5, with no hydrogen bond donors such as hydroxyl or amino groups in the molecule)
- TPSA: 52.6 Å ² (conforms to<140 Å ² and indicates good intestinal absorption and cell membrane permeability)
These parameters indicate that baicalin has the basic conditions for becoming an oral drug in terms of chemical structure, and it is unlikely to have absorption problems caused by excessive molecular weight or strong/weak lipid solubility. However, the evaluation of drug properties goes far beyond this, and attention also needs to be paid to its metabolic stability, water solubility, toxicity, and so on.
Pharmacokinetic (ADME) characteristics:
At present, research on the ADME process of paeoniflorin in vivo is very limited, with most data coming from animal experiments or in vitro predictions.
- Absorption: Based on its low molecular weight and moderate LogP, it is speculated that its oral absorption may be better. However, as lactone compounds, their stability in acidic environments of the gastrointestinal tract and whether they are affected by gut microbiota metabolism still require further research. It is also unknown whether it is a substrate for efflux transporters such as P-glycoprotein (P-gp).
- Distribution: Its TPSA is 52.6 Å ², indicating that it may have some tissue penetration ability, including the potential to penetrate the blood-brain barrier (although currently labeled as unknown). Key parameters such as plasma protein binding rate and apparent distribution volume have not been reported.
- Metabolism: This is the largest unknown area in the evaluation of the medicinal properties of Baitousu. As a lactone, the ester bonds in its structure are easily hydrolyzed by esterases in the body, generating corresponding acids or alcohols. In addition, its double bond may also be oxidized by the cytochrome P450 enzyme system (CYP450). Therefore, paeoniflorin is likely to have serious first pass effects, resulting in extremely low oral bioavailability. Whether its metabolites are active or toxic is also a key issue that needs to be closely monitored. At present, its liver toxicity is labeled as Unknown, indicating a lack of relevant data.
- Excretion: Metabolites and prototype drugs are mainly excreted through the kidneys (urine) and/or bile (feces). The specific excretion pathway and rate are still unclear.
Toxicity evaluation:
- Acute toxicity: Whitehead hormone has a certain degree of irritability, and its precursor, protoWhitehead hormone, is more toxic. In animal experiments, high doses of paeoniflorin may cause gastrointestinal irritation, liver and kidney function damage, etc. The therapeutic window (the ratio of effective dose to toxic dose) is not yet clear.
- Cardiac toxicity: Annotated as Unknown. Given that many natural products have hERG potassium channel inhibitory effects, which may cause QT interval prolongation and arrhythmia, this is a risk that must be ruled out in drug development. Currently, there is a lack of data on the effect of paeoniflorin on hERG channels.
- Genetic toxicity: The Ames test results are marked as Unknown. This is a standard test for evaluating whether a compound has mutagenicity, and its results are crucial for determining its carcinogenic risk.
Summary:
Baitousu has good pharmacological properties in terms of chemical structure, but there is a huge knowledge gap in its pharmacokinetics and toxicological properties. The metabolic instability caused by its lactone structure is the biggest challenge, which may lead to low oral bioavailability. Future pharmaceutical research must prioritize addressing the following issues: 1) establishing sensitive biological sample analysis methods to study their absorption, distribution, metabolism, and excretion processes in vivo; 2) Evaluate its impact on major CYP450 enzymes and hERG channels; 3) Conduct acute and chronic toxicity evaluations of the system to clarify its safety window. If the issue of oral bioavailability cannot be resolved, it may be necessary to consider promoting its clinical application through structural modifications (such as prodrug design) or developing non oral routes of administration (such as injection, rectal administration).
Clinical application prospects and prospects
Despite the challenges in drug development, the unique pharmacological activity of paeoniflorin, especially its dual effects in anti-inflammatory and immune regulation, has shown promising clinical application prospects in multiple disease fields.
1. Inflammatory bowel disease (IBD):
This is the closest indication for clinical translation of paeoniflorin. Its significant therapeutic effect in the DSS induced UC model is highly consistent with the experience of traditional Chinese medicine in treating dysentery. Its mechanism of action - simultaneously inhibiting iNOS (reducing NO damage to intestinal mucosa) and PKC - θ (inhibiting T cell-mediated intestinal immune response) - precisely targets two key links in the pathogenesis of IBD. In the future, if suitable formulations for local intestinal administration can be developed (such as enema and colon targeted oral preparations), it is expected to overcome the problem of systemic metabolic instability and become an effective drug for treating UC, especially mild to moderate UC.
2. T cell-mediated autoimmune diseases:
As a PKC - θ inhibitor, anemonin can theoretically be used to treat rheumatoid arthritis, psoriasis, multiple sclerosis, type I diabetes, etc. Compared with existing biologics such as TNF - α inhibitors, small molecule PKC - θ inhibitors have advantages such as oral administration, low production costs, and no immunogenicity. However, the central role of PKC - θ in T cell activation also implies that its inhibitors may cause immunosuppressive side effects, such as increased risk of infection. Therefore, it is necessary to accurately evaluate its therapeutic window and explore strategies for combined use with other drugs.
3. Neuroinflammatory related diseases:
The occurrence and development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are closely related to chronic neuroinflammation. The ability of paeoniflorin to inhibit the activation of microglia and reduce the production of neurotoxic inflammatory mediators such as NO and TNF - α makes it a potential candidate molecule for the treatment of these diseases. Whether it can effectively penetrate the blood-brain barrier is the key to determining its application prospects in this field. If the penetration is poor, brain targeted delivery can be achieved through technologies such as nanocarriers.
4. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS):
In cases of sepsis, severe pneumonia, etc., overactivated inflammatory response can lead to ALI/ARDS, with extremely high mortality rates. Whitehorse is expected to alleviate lung inflammation and oxidative stress, protect alveolar epithelium and vascular endothelial cells, and provide a new option for the treatment of ALI/ARDS by inhibiting the iNOS and NF - κ B pathways.
Outlook and Challenges:
- Research on Structural Optimization and Structure Performance Relationship: Modifying the structure of paeoniflorin, such as modifying the lactone ring to improve metabolic stability, or introducing specific functional groups to enhance selectivity towards PKC - θ or iNOS, is key to improving its pharmacological properties. The systematic study of its structure-activity relationship (SAR) will provide guidance for designing better derivatives.
- Drug delivery system development: Given its potential metabolic instability and potential irritability, developing advanced drug delivery systems is crucial. For example, liposomes, polymer nanoparticles, phospholipid complexes, etc. can enhance their bioavailability, achieve targeted delivery, and reduce toxic side effects.
- In depth mechanism research: More advanced chemical biology tools (such as knockout/knock in mouse models, proteomics, chemical proteomics) are needed to accurately depict its intracellular target map, elucidate the synergistic mechanism of its multi-target effects, and discover new targets of action.
- Toxicological evaluation of the system: It is necessary to complete a comprehensive toxicological evaluation of the drug in accordance with the requirements of Good Clinical Practice (GLP), including genetic toxicity, reproductive toxicity, carcinogenicity, and long-term toxicity tests, to evaluate its clinical safety.
- Clinical translational studies: After completing sufficient preclinical research, rigorous clinical trials should be designed to first validate their safety and efficacy in relatively clear indications such as UC.
Conclusion
Baitousu, a natural lactone compound derived from ancient herbs, is gradually revealing its enormous potential as an anti-inflammatory and immunomodulatory agent through modern pharmacological research methods. Its unique chemical structure, excellent drug like basis, and selective inhibition of iNOS and PKC - θ, two key targets, make it an attractive prospect in multiple therapeutic fields such as inflammatory bowel disease, autoimmune diseases, and even neurodegenerative diseases.
However, the road from natural products to clinical drugs has never been smooth sailing. The commercialization process of paeoniflorin faces severe challenges such as poor metabolic stability and lack of toxicological data. Future research requires collaborative efforts from multiple disciplines such as chemistry, biology, pharmacology, and pharmacy. Through structural optimization, dosage form innovation, and in-depth mechanism and toxicology research, these obstacles can be overcome to truly translate the therapeutic potential of this natural molecule into clinical drugs that benefit patients. The in-depth study of paeoniflorin is not only a modern interpretation of traditional medical wisdom, but also a successful practice of the "old medicine new use" and "natural product leading" strategies in modern drug discovery. We have reason to believe that with the continuous deepening of research, baicalin or its derivatives have the potential to become important weapons for treating inflammation and immune related diseases in the future.
