Lipoxygenases are a family of iron-containing enzymes that catalyze the formation of hydroperoxides from polyunsaturated fatty acids. Esculetin is an inhibitor of both 5- and 12-lipoxygenases with ID50 values of 4 and 2.5 μM, respectively[3]. It shows inhibitory effect on platelet lipoxygenase and platelet cyclooxygenase with respective IC50 values of 0.65 and 0.45 μM[4]. Treatment of colon cancer cells with esculetin (20-80 μMol/L) for 24h effectively suppressed TOP-luciferase activity in a dose-dependent manner. In HCT116, HCT15, and DLD1 colon cancer cells, 24h- treatment of esculetin at the doses of 20 - 80 μM substantially inhibited the protein levels of c-Myc and cyclin D1, but had no effect on the expressions of β-catenin or Tcf. Consistently, the mRNA levels of c-myc and cyclin D1 in esculetin-treated human colon cancer cells was downregulated compared to control group. Moreover, esculetin at 20 - 80 μM decreased the viability of colon cancer cells, and significantly repressed anchorage-independent cell growth in a dose-dependent manner. In athymic nude mice, intraperitoneal injection of esculetin at 20 and 100 mg/kg (3 times per week) for 2 weeks suppressed HCT116 tumor size by 44% and 64%, respectively, compared to vehicle-treated group[5].
Esculetin/七叶亭 细胞实验
Cell Line
Concentration
Treated Time
Description
References
colonic crypt epithelium
500 μM
10 minutes
Completely abolished DOC-induced increases in chemiluminescence (CL)
J Clin Invest. 1986 Mar;77(3):850-9
colonic mucosal scrapings
100 μM
10 minutes
Suppressed basal and DOC-induced increases in chemiluminescence (CL) by 40-50%, and reduced accumulation of PGE2, LTB4, 5-HETE, 12-HETE, and 15-HETE
J Clin Invest. 1986 Mar;77(3):850-9
Sorted ATMs
25 μg/mL DIL-ox-LDL
24 hours
Esculetin significantly increased the percentage of CD36+ cells and CD36+ DIL-ox-LDL+ cells, indicating enhanced phagocytosis in ATMs.
Theranostics. 2025 Apr 28;15(12):5910-5930
RAW 264.7 cells
25 μg/mL DIL-ox-LDL
3 to 24 hours
Esculetin significantly increased the fluorescence intensity of intracellular DIL-ox-LDL, indicating enhanced phagocytosis in macrophages.
Theranostics. 2025 Apr 28;15(12):5910-5930
PC12 cells
25 μM or 50 μM
24 hours
Esculetin functions as an ERR agonist, enhancing glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels
EBioMedicine. 2017 Aug;22:225-241
Bovine chondrocytes
31 μM–500 μM
6 days
Esculetin inhibited IL-1-induced cartilage degradation and significantly blocked the accumulation of ADAMTS4 and MT4-MMP proteins
Osteoarthritis Cartilage. 2005 Apr;13(4):269-77
T/C28a4 chondrocytes
100–500 µM
24 hours
To evaluate the inhibitory effect of Esculetin on MMP-1, MMP-3, and MMP-13 mRNA expression. Results showed that 250 µM EST reduced MMP-1, MMP-3, and MMP-13 mRNA expression to control levels, while TIMP-1 mRNA levels were unaffected.
Ann Rheum Dis. 2001 Feb;60(2):158-65
Human articular cartilage cells
50–500 µM
21 days
To evaluate the inhibitory effect of Esculetin on IL1 á and OSM-induced degradation in human articular cartilage. Results showed that 50 µM EST significantly inhibited proteoglycan and collagen degradation (p<0.01) and reduced MMP-1 levels (p<0.001).
Ann Rheum Dis. 2001 Feb;60(2):158-65
Bovine nasal cartilage cells
10–330 µM
14 days
To evaluate the inhibitory effect of Esculetin on IL1 á and OSM-induced collagen and proteoglycan degradation. Results showed that 66 µM EST significantly inhibited collagen degradation (p<0.001), and 100 µM EST significantly inhibited proteoglycan degradation (p<0.05).
Ann Rheum Dis. 2001 Feb;60(2):158-65
Phytophthora sojae zoospores
100 μM
30 min
To evaluate the inhibitory effect of Esculetin on the chemotaxis of Phytophthora sojae zoospores. Results showed that Esculetin competitively binds to the PsIRK1 receptor, disrupting zoospore chemotaxis toward genistein and thereby inhibiting infection.
Sci Adv. 2025 Jan 10;11(2):eadt0925
Esculetin/七叶亭 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Colonic epithelial proliferation model
Intracolonic instillation
50 μmol (25 mM)
Single administration, observed at 4 hours (ODC activity) or 24 hours ([3H]TdR incorporation)
Inhibited DOC-induced increases in ornithine decarboxylase (ODC) activity and [3H]TdR incorporation into DNA
J Clin Invest. 1986 Mar;77(3):850-9
C57BL6J male mice
High-fat diet-induced postprandial dyslipidemia model
Oral gavage
30, 90, 180 mg/kg/d
Once daily for 7 days
Esculetin significantly elevated postprandial HDL cholesterol levels and increased bile acid content in bile, promoting cholesterol excretion.
Theranostics. 2025 Apr 28;15(12):5910-5930
C57BL/6N Slc mice
MPTP-induced Parkinson's disease model
Oral
50 mg/kg/day
4 days per week for 5 months
Esculetin protected dopaminergic neurons by maintaining ATP levels and reducing ER stress, mitigating Parkinson's disease symptoms
EBioMedicine. 2017 Aug;22:225-241
Soybean (Glycine max)
Soybean seedlings
Root dipping
100 μM
Single treatment, lasting 30 minutes
To evaluate the preventive effect of Esculetin on Phytophthora sojae infection in soybean seedlings. Results showed that Esculetin treatment significantly increased the survival rate of soybean seedlings and reduced pathogen biomass in the roots.
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