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Synonym name: Ligusticum lactone
Catalogue No.: BP0061
Cas No.: 551-08-6
Formula: C12H12O2
Mol Weight: 188.226
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 3-Butylidenephthalide
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
34.1400
2.8100
2.8100
High
No
No
No
No
Butylidenephthalidide (3-Butylidenephthalidide, CAS No.: 551-08-6) is a natural isobenzofurone compound with multiple biological activities, first isolated and identified from the traditional Chinese medicine Ligusticum chuanxiong. As a phthalic anhydride derivative, butenylphthalein has attracted widespread attention in the field of natural product pharmacology due to its significant antihyperglycemic, analgesic, and insecticidal activities. In addition, the potential regulatory role of butenylphthalein on viral disease-related targets also provides new directions for research on its multi-target pharmacological mechanisms. This paper will systematically review the chemical structure and physicochemical properties of butenylphthalein, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and explore its clinical application prospects and future research directions, aiming to provide a theoretical foundation and practical guidance for drug development and application of this compound.
The chemical structure of butenylphthalein belongs to the isobenzofuran class, with a molecular formula of C_12H_12O_2 and a molecular weight of 188.22. Its structural core is a furanone ring derived from phthalate anhydride, with three positions linked to the butyl side chain (Butylidene), giving it unique chemical properties. The LogP value of butenylphthalein is 2.81, indicating moderate lipid solubility, which facilitates membrane penetration and distribution in vivo. The polar surface area (TPSA) is 34.14, and the number of hydrogen bond acceptors is 2, indicating that it has a certain affinity for binding to biomacromolecules. This compound crosses the blood-brain barrier, suggesting its potential application value in central nervous system diseases. In vitro safety evaluations showed that butenylphthalein had no hepatotoxicity, cardiotoxicity, or hERG channel inhibitory effects, and Ames-induced mutagenic tests were negative, indicating high safety and a solid druggability.
Butenylphthalein mainly comes from Ligusticum chuanxiong Hort., a traditional medicinal plant widely used in traditional Chinese medicine. The rhizomes of Ligusticum chuanxiong contain abundant volatile oils and various bioactive components, among which butenylphthalic phthalate, as one of the main phthalic anhydrides, holds significant pharmacological significance. Common methods for extracting buteneylphthalein include solvent extraction with ultrasound-assisted extraction, and column chromatography separation techniques. Generally, ethanol or methanol is used as the extraction solvent, and high-purity butenylphthalein is obtained through a multi-step separation and purification process. In recent years, the application of supercritical fluid extraction and high-performance liquid chromatography (HPLC) technology has further improved extraction efficiency and purity, providing technical support for the industrial production of butenylphthalein.
Butenylbenzphthalein exhibits significant antihyperglycemic activity, mainly by inhibiting intestinal β-glucosidase. This enzyme catalyzes the cleavage of glycosidic bonds during carbohydrate digestion, inhibiting its activity, which can delay glucose absorption and reduce postprandial blood sugar peaks. In vitro experiments showed that butenylphthalein inhibited yeast β-glucosidase non-competitively, with a IC_50 of 2.35 mM and an inhibition constant of 4.86 mM K_i, demonstrating strong enzyme activity regulation ability. Its mechanism of action is similar to existing glycosidase inhibitors such as acarbose, but the natural origin of butenylphthalein and its lower risk of side effects offer potential as a novel antidiabetic drug.
In animal models, butenylphthalein exhibited dose-dependent analgesic effects. The hot plate test showed that doses of 10 mg/kg and 31.6 mg/kg of butenylphthalein significantly prolonged the latency of mice and reduced pain responses caused by thermal stimuli. Additionally, this compound also demonstrated good analgesic activity in models of chemically stimulated-induced pain, suggesting it may regulate pain signaling through multiple mechanisms. The specific molecular mechanisms of analgesic effects require further study, but their good blood-brain barrier penetration makes central analgesic effects possible.
Buene phthalein showed significant insecticidal activity against the larvae of the agricultural pest Spodoptera litura, with a LC_50 of 1.56 mg/g. This activity makes it a potential natural insecticide with environmental friendliness and biodegradability advantages. The insecticidal mechanism may involve interference with the insect's nervous system or metabolic pathways, and related research is underway to develop butenylphthalein as a green pesticide.
The multi-target mechanism of butenylphthalein is the basis of its pharmacological activity. Besides β-glucosidase, butenylphthalein has potential interactions with various viral disease-related targets, including DNA repair enzyme BLM, anti-apoptotic protein MCL1, immunomodulatory enzyme IDO1, cell cycle regulator enzyme CDC25A/B, DNA repair enzyme APEX1, telomerase WRN, deubiquitinizing enzyme USP1, ion channel TRPA1, and chromatin protein CBX1. These targets involve key biological processes such as cell proliferation, apoptosis, DNA repair, immune regulation, and ion channel regulation, suggesting that butenylphthalein may exert broad biological effects by regulating multiple signaling pathways.
For example, IDO1, as a key enzyme for immunosuppression, plays an important role in various viral infections and tumor immune evasion. Regulation of IDO1 by butenylphthalein may enhance antiviral immune responses. TRPA1 ion channels are involved in the transmission of pain and inflammation, and the effect of butenylphthalein on them may explain the molecular basis for its analgesic effects. Regulation of DNA repair-related enzymes such as BLM, APEX1, and WRN may be linked to studies on their impact on cellular stress responses and antitumor potential.
The druggability parameters of butenylphthalein are good. Molecular weight is 188.22, meeting the Lipinski rule, LogP is 2.81, indicating moderate lipid solubility, which is beneficial for oral absorption and cell membrane penetration. The TPSA is 34.14, and its low polarity helps cross the blood-brain barrier, supporting its potential application in central nervous system diseases. In vivo safety, there was no hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and the Ames test was negative, indicating a low risk of mutagenic induction.
Pharmacokinetic research is still in its early stages, but its high blood-brain barrier permeability suggests that butenylphthalein is widely distributed in the body, especially in the central nervous system. In the future, systematic ADME (Absorption, Distribution, Metabolism, Excretion) studies are needed to clarify its bioavailability, metabolic pathways, and excretion modes, providing a basis for clinical dosage formulation design and dose optimization.
As a versatile natural product, butenylphthalein has broad clinical application potential. Its antihyperglycemic effects offer new ideas for the treatment of diabetes and its complications, especially through intestinal enzyme inhibition mechanisms, which may reduce the side effects of traditional glycosidase inhibitors. Its analgesic effect makes it promising for the management of chronic and neuropathic pain. Combined with its good blood-brain barrier penetration, butenylphthalein may become a candidate molecule for central analgesics.
Additionally, butenyl benzenephthalein modulates targets related to viral diseases suggest its potential in antiviral therapy. Combined with its immunomodulatory effects, future applications of it can be explored in viral infections and related immune diseases. Insecticidal activity provides a natural, environmentally friendly alternative to insecticides in agriculture, aligning with the trend of green agriculture.
Future research should focus on in-depth analysis of the mechanism of action of butenylphthalein, structural optimization, and pharmacokinetic improvement, combined with modern drug design technologies to promote clinical translation. At the same time, safety evaluation and preclinical research are key steps in its development process.
As an important active ingredient in Ligusticum chuanxiong, butenyl phthalein exhibits diverse pharmacological activities and good druggability. Its antihyperglycemic, analgesic, and insecticidal activities have been widely confirmed, and its potential role on viral disease-related targets offers new directions for multi-target drug development. Considering its chemical properties, biological activity, and safety, butenylphthalein has the potential to become an important candidate molecule for new natural medicines. In the future, through systematic pharmacological mechanism research, pharmacokinetic optimization, and preclinical evaluation, it is expected that the application of butenylphthalein in multiple fields such as diabetes, pain management, antiviral, and agricultural insecticide will be promoted, fostering innovative development of natural product drugs.
Shenshuai
Wenjing
Hedandan
