Ligustilide

• CAS: 4431-01-0
• Catalog Number: ACM4431010-1
• Category: Main Products
• Molecular Weight: 190.24
• Molecular Formula: C12H14O2
• Synonyms: 3-[(Z)-Butylidene]-4,5-dihydrophthalide
• IUPAC Name: (3Z)-3-Butylidene-4,5-dihydro-2-benzofuran-1-one
• SMILES: CCCC=C1C2=C(C=CCC2)C(=O)O1
• InChI: InChI=1S/C12H14O2/c1-2-3-8-11-9-6-4-5-7-10(9)12(13)14-11/h5,7-8H,2-4,6H2,1H3/b11-8-
• InChI Key: IQVQXVFMNOFTMU-FLIBITNWSA-N
• Boiling Point: 377.9±11.0 °C
• Melting Point: 297-298ºC
• Flash Point: 158.6ºC
• Density: 1.10±0.1 g/cm³
• Appearance: Oil
• Exact Mass: 190.099379685
• Isomeric SMILES: CCC/C=C\1/C2=C(C=CCC2)C(=O)O1
• Monoisotopic Mass: 190.099379685
• Physical State: Liquid
• Topological Polar Surface Area: 26.3 Ų

Case Study

Ligustilide for the Activation of TRPA1 to Alleviate Functional Constipation

Zhang K, et al. Journal of Ethnopharmacology, 2025, 338, 119018.

In a targeted study on Angelica sinensis, Ligustilide was identified as the primary active pharmaceutical ingredient responsible for alleviating functional constipation via TRPA1 activation in colonic tissues. Using a loperamide-induced mouse constipation model, researchers demonstrated the therapeutic efficacy of Ligustilide through enhanced colonic mucus secretion. Periodic acid-Schiff (PAS) staining and immunofluorescence in HT-29 cells verified mucus induction. Target identification employed an alkynyl-modified Ligustilide probe (AM-Lig), followed by colocalization imaging to confirm TRPA1 engagement. Binding interactions were characterized via molecular docking, microscale thermophoresis (MST), and fluorescence quenching, revealing that Ligustilide non-covalently binds to Thr684 in the TRPA1 pre-S1 region. The Fluo-4/Ca²⁺ influx assay further confirmed TRPA1-mediated calcium entry post-Ligustilide exposure. These precise methodologies established Ligustilide as a selective TRPA1 agonist, elucidating its mechanistic role in stimulating mucus secretion and improving constipation, providing a valuable framework for the development of novel TRPA1-targeted therapies.

Targeting RXFP1 for Alcoholic Hepatic Steatosis: Experimental Application of Ligustilide

Yang H-Y, et al. International Immunopharmacology, 2024, 127, 111460.

In a murine model of alcoholic hepatic steatosis induced by chronic and binge ethanol feeding, Ligustilide (Lig) demonstrated therapeutic efficacy by attenuating hepatic lipid accumulation and inflammation. Experimental interventions included Lig administration, followed by histopathological assessments and immunoblotting to evaluate lipid metabolism markers, notably PPARα and SREBP1, in liver tissue and AML12 hepatocytes. Lig suppressed RXFP1 expression and inhibited NLRP3 inflammasome activation in liver macrophages and LPS/ATP-stimulated mouse peritoneal macrophages (MPMs), as confirmed by Western blotting and ELISA for inflammatory cytokines. Furthermore, Lig mitigated neutrophil extracellular trap (NET) formation and immune cell infiltration, assessed via immunofluorescence and flow cytometry. These findings reveal that Lig exerts protective effects against alcoholic steatosis by targeting the RXFP1-NLRP3 axis, modulating lipid metabolism, and curbing inflammatory cascades in hepatic tissues.

Ligustilide for Preventing Thymic Immune Senescence via Thymosin β15-Actin Pathway Modulation

Xu X, et al. Phytomedicine, 2024, 123, 155216.

In a murine model of adriamycin (ADM)-induced thymic immune senescence, Ligustilide (5 mg/kg) demonstrated significant protection against thymic atrophy and functional decline. SA-β-gal staining, H&E, immunofluorescence, and flow cytometry characterized TEC senescence and spatial disorganization. In vitro, organotypic cultures and immortalized TECs (iTECs) confirmed that ADM disrupted cytoskeletal integrity by reducing microfilament content and cytoskeletal protein expression. Ligustilide treatment restored TEC proliferation, enhanced reticular differentiation, and facilitated CD4+ T cell maturation. Mechanistic studies employing qPCR, Western blotting, fluorescence labeling, and β Thymosin-G-actin cross-linking assays established that Ligustilide inhibits the formation of the Tβ15-G-actin complex, thereby promoting actin polymerization. Molecular docking further confirmed Ligustilide's affinity for Tβ15. These findings reveal the capacity of Ligustilide to preserve thymic architecture and immune competence by targeting the Tβ15-dependent cytoskeletal assembly in TECs.

Inhibition of Postharvest Apple Ring Rot by Ligustilide: Experimental Application Against Botryosphaeria dothidea

Tong X, et al. Postharvest Biology and Technology, 2025, 228, 113671.

(Z)-Ligustilide, derived from Ligusticum jeholense, demonstrates potent antifungal activity against Botryosphaeria dothidea, the causative agent of apple ring rot. In vitro assays revealed an IC50 of 43.1 nL/mL against fungal growth. Detached apple fruit assays across multiple cultivars confirmed LIG's efficacy in suppressing infection while maintaining fruit quality. Structural disruptions in B. dothidea cells were visualized via scanning and transmission electron microscopy. Proteomic analysis coupled with molecular docking indicated LIG's interference with energy metabolism, targeting acetyl-CoA synthetase, malate dehydrogenase, and citrate synthase. Complementary assays measured membrane integrity, oxidative stress markers (malondialdehyde, hydrogen peroxide), relative conductivity, ATPase activity, and intracellular ATP levels, substantiating the proposed mechanism. These experimental methodologies collectively support Ligustilide as a promising botanical antifungal agent for postharvest disease management in apples.