Product name: Tulipalin A
Synonym name: 2-Methylene-gamma-butyrolactone
Catalogue No.: BP0031
Cas No.: 547-65-9
Formula: C₅H₆O₂
Mol Weight: 98.1
Botanical Source:

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 Tulipalin A

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

Introduction/Overview

Tulipalin A (CAS No.: 547-65-9) is a natural compound belonging to the 4-butylenolactone compound with a methylene group at the 3-position. As a small molecule with a unique structure, tulip A has attracted widespread attention for its remarkable anti-ulcer and gastrointestinal pharmacological activity. In recent years, with the deepening pharmacological research of natural products, the potential value of tulip A in the prevention and treatment of gastrointestinal diseases has gradually emerged, becoming a research hotspot in the field of drug development.

This paper aims to systematically review the chemical structure and physicochemical properties of Tulip A, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, as well as its clinical application prospects and development trends. By integrating existing literature, a comprehensive assessment of the research progress and future potential of Tulip A can be provided as a reference for researchers in related fields.

Chemical structure and physicochemical properties

Tulipin A is a 4-butynolactone derivative with a methylene bridging structure, molecular formula C6H8O3, and molecular weight 100.10. Its core structure is a butyllactone ring, with a methylene group attached to the 3-position carbon atom, giving it a unique spatial configuration and chemical activity. The LogP value of this compound is -0.09, indicating strong hydrophilicity and good water solubility, which is beneficial for absorption and distribution in the body. The topological pole surface area (TPSA) is 37.3 Ų, indicating moderate polarity, which may affect its cell membrane penetration capability.

Tulip A contains two hydrogen bond receptor sites that may form stable hydrogen bonds with biological targets, enhancing their biological activity. There is currently no definitive data on safety indicators such as blood-brain barrier penetration, hepatotoxicity, cardiotoxicity, and hERG channel inhibition, and further research is needed for verification.

Plant Origins and Extraction Methods

Tulipin A is mainly found in Tulipa spp. plants, with higher levels in tulip petals and bulbs. As a secondary metabolite of plants, this compound participates in plant defense mechanisms and possesses certain antibacterial and antioxidant functions.

Traditional extraction methods mostly use organic solvent extraction combined with column chromatography separation. Common solvents include ethanol, methanol, and ethyl acetate, which use their polarity differences to achieve preliminary separation of crude extracts. It is then purified by silica gel column chromatography or high-performance liquid chromatography (HPLC) to obtain high-purity tulipin A. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, reducing solvent usage and extraction time.

In addition, research on plant cell culture technology and biosynthetic pathways provides new ideas for large-scale production of tulip A, especially showing promising prospects in optimizing yield under controlled environmental conditions.

Pharmacological activity research

The pharmacological activity of Tulipin A mainly focuses on anti-ulcer and gastrointestinal protective effects. Multiple in vitro and in vivo experiments have shown that this compound can effectively inhibit gastric mucosal damage, promote mucosal repair, and alleviate symptoms of gastric ulcers caused by excessive gastric acid secretion.

1. Anti-ulcer effect
   Tulip A exerts anti-ulcer effects through multiple mechanisms, including strengthening the gastric mucosal barrier, inhibiting gastric acid secretion, promoting mucus secretion, and anti-oxidative stress response. Animal model experiments have shown that tulip A can significantly reduce the area of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol, and decrease infiltration of inflammatory cells in the gastric mucosa.

2. Gastrointestinal regulation
   This compound also demonstrates the potential to regulate gastrointestinal motility and protect the intestinal mucosa. Research has found that tulip A can regulate the contractile function of intestinal smooth muscle, improve gastrointestinal motility, and relieve gastrointestinal dysfunction. Additionally, its anti-inflammatory effects help reduce intestinal inflammation and promote intestinal barrier repair.

3. Antioxidant and anti-inflammatory effects
   Tulip A has certain antioxidant activity, can eliminate free radicals, and reduce oxidative stress damage to gastrointestinal tissues. At the same time, its anti-inflammatory effect reduces gastrointestinal inflammatory responses by inhibiting the release of inflammatory mediators and inflammatory signaling pathways.

Mechanism of action and molecular targets

The pharmacological effects of tulip A involve multiple signaling pathways and molecular targets, with specific mechanisms still under in-depth research. Existing evidence indicates that its main mechanisms of action include:

1. Regulates gastric acid secretion
   Tulip A may reduce acid secretion by inhibiting H+/K+-ATPase activity in gastric parietal cells, thereby decreasing acidic damage to the gastric mucosa. Additionally, it may regulate histamine H2 receptors and cholinergic receptors, indirectly affecting gastric acid secretion levels.

2. Enhances the defense of the gastric mucosa
   This compound promotes the secretion of gastric mucus and bicarbonate, strengthens the gastric mucosal barrier function, and prevents the invasion of the stomach lining by stomach acid and digestive enzymes. At the same time, tulip A can activate prostaglandin synthesis pathways, promote blood flow to the gastric mucosa, and maintain mucosal integrity.

3. Antioxidant stress
   Tulipin A upregulates antioxidant enzyme activity (such as superoxide dismutase and glutathione peroxidase), scavenging reactive oxygen species (ROS) and reducing cellular damage caused by oxidative stress.

4. Regulation of anti-inflammatory signaling pathways
   Tulipin A can inhibit activation of the nuclear factor κB (NF-κB) signaling pathway, reducing the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, thereby alleviating gastrointestinal inflammation.

5. Regulates intestinal smooth muscle function
   By affecting calcium channels and neurotransmitter release, Tulipin A regulates the contraction and relaxation of intestinal smooth muscle, improving gastrointestinal motility abnormalities.

Although the above mechanisms are currently the mainstream view, the specific molecular targets of tulip A are not yet fully understood. Future efforts will require further elucidation of its functional network through molecular docking, proteomics, and gene editing technologies.

Druggability evaluation and pharmacokinetics

The druggability parameters of Tulipin A indicate that it has certain potential for drug development. The molecular weight is only 100.10, meeting the requirements for drug molecular weight under the Lipinski rule. The LogP value was -0.09, indicating strong hydrophilicity, which is beneficial for oral absorption but may affect the ability to penetrate lipid membranes. TPSA is 37.3 Ų, suitable for cell membrane penetration, and has 2 hydrogen bond receptors, indicating certain specificity for target binding.

Currently, there is a lack of safety evaluation data on Tulipin A's blood-brain barrier penetration, hepatotoxicity, cardiotoxicity (including hERG channel inhibition), and genotoxicity (Ames assay), which limits its preclinical development progress. Systematic toxicological studies are needed in the future to assess safety risks.

Regarding pharmacokinetics, there are few existing literature reports. Based on its physicochemical properties, tulip A is expected to be well absorbed orally, but its metabolic pathways, half-life, distribution, and excretion mechanisms in the body remain unclear. Given its simple molecular structure, it may be metabolized via hepatic enzyme systems; specific enzyme species and metabolites require further identification.

Prospects and outlooks for clinical applications

Tulip A, as a natural anti-ulcer and gastrointestinal protectant, has broad clinical application potential. Currently, the incidence of gastrointestinal diseases continues to rise, especially for gastric ulcers, gastritis, and functional gastrointestinal diseases, urgently requiring safe and effective treatment drugs. The multi-target mechanism of tulip A and its promising safety assumptions make it a strong candidate for the development of novel gastrointestinal drugs.

Future research directions include:

1. In-depth mechanism research
   Using modern molecular biology techniques, key molecular targets and signaling pathways of tulip A have been identified, revealing the substance basis of its pharmacotherapeutic properties.

2. Safety and toxicological assessment
   Systematically conduct acute, subchronic, and chronic toxicity tests to assess hepatorenal toxicity, cardiotoxicity, and genotoxicity, providing safety assurance for clinical application.

3. Pharmacokinetics and formulation development
   Clarify its absorption, distribution, metabolism, and excretion characteristics in vivo, optimize administration routes and dosage forms, and improve bioavailability and therapeutic efficacy.

4. Preclinical and clinical trials
   Based on animal models, preclinical efficacy and safety evaluations are conducted, gradually advancing to human clinical trials to verify the efficacy and safety of gastrointestinal diseases.

5. Combination medication strategies
   Exploring the synergistic effects of Tulip A with existing anti-ulcer drugs to reduce drug dosage, minimize side effects, and improve treatment outcomes.

Conclusion

Tulip A, as a unique natural product, demonstrates significant anti-ulcer and gastrointestinal protective effects, showing promising potential for drug development. Although research on its mechanism of action and safety is still incomplete, as research deepens, Tulip A is expected to become an important candidate for the treatment of next-generation gastrointestinal diseases. In the future, research on its pharmacological mechanisms, toxicology, and pharmacokinetics needs to be strengthened to promote its clinical translational application, providing more safe and effective treatment options for patients with gastrointestinal diseases.