Costunolide, a natural sesquiterpene lactone, is found commonly in many species such as Saussurea lappa and Artemisia balchanorum. Besides, it has a variety of biological activities, such as chemopreventive and antitumor activity, anti-inflammatory, antibiotic, anti-fungal and anti-viral activity of costunolide[3]. Costunolide caused inhibition of cell growth of human breast carcinoma cell lines MCF-7 cells and MDA-MB-231 cells with IC50 of 90 mM and 50 mM, respectively, and this effect was mediated at least in part by costunolide-induced significant reduction in telomerase activity[4]. Costunolide treatment at 40 mg/kg on acute liver injury (ALI) mice significantly improved the pathological changes of hepatic tissue, and reduced the LPS and D-galactosamine-induced increases of alanine aminotransferase (from 887.24 ± 21.72 to 121.67 ± 6.56 IU/L) and aspartate aminotransferase (from 891.01 ± 45.24 to 199.94 ± 11.53 IU/L) activities in serum, remarkably reduced malondialdehyde content (from 24.56 ± 1.39 to 9.17 ± 0.25 nmol/ml) and reactive oxygen species (from 203.34 ± 7.68 to 144.23 ± 7.12%), increased the activity of anti-oxidant enzymes superoxide dismutase (from 153.74 ± 10.33 to 262.27 ± 8.39 U/ml), catalase (from 6.12 ± 0.30 to 12.44 ± 0.57 U/ml), and total anti-oxidant capacity (from 0.64 ± 0.06 to 6.29 ± 0.11 U/ml) in hepatic tissues[5]. CHO cells treated with 5.01 μM Costunolide showed slightly higher micronuclei compared to the untreated cells, and Costunolide at 5.01, 7.56, and 10.12 μM concentrations significantly inhibited tubulin polymerization by 64.89, 50.86, and 41.63%, respectively, in comparison to the control[6].
Costunolide/木香烃内酯 细胞实验
Cell Line
Concentration
Treated Time
Description
References
YD-10B
9.2 µM (IC50)
24 hours
Inhibited cell proliferation and induced apoptosis
Int J Mol Sci. 2021 Jul 13;22(14):7509.
HOMF
20 µM
24 hours
Evaluated in vitro toxicity
Int J Mol Sci. 2021 Jul 13;22(14):7509.
YD-9
39.6 µM (IC50)
24 hours
Inhibited cell proliferation and induced apoptosis
Int J Mol Sci. 2021 Jul 13;22(14):7509.
Ca9-22
7.9 µM (IC50)
24 hours
Inhibited cell proliferation and induced apoptosis
Int J Mol Sci. 2021 Jul 13;22(14):7509.
RAW264.7 cells (mouse macrophage cell line)
2.5, 5, 10 µM
1 hour pretreatment, followed by stimulation for 6 hours
CTD dose-dependently reduced oxLDL-induced NF-κB activity, as validated in RAW264.7 cells stably expressing NF-κB EGFP reporter.
Acta Pharmacol Sin. 2023 Jan;44(1):58-70.
Mouse primary peritoneal macrophages (MPMs)
2.5, 5, 10 µM
1 hour pretreatment, followed by stimulation for 6 or 24 hours
CTD pretreatment significantly inhibited oxLDL-induced inflammatory responses, including reducing mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6), decreasing transcriptional levels of chemokines and adhesion molecules, and suppressing oxLDL uptake and foam cell formation.
Acta Pharmacol Sin. 2023 Jan;44(1):58-70.
JB6 cells
5, 10, 20 µM
14 days
Assess the inhibitory effect of COS on TPA-induced cell transformation, showing concentration-dependent inhibition of cell transformation and proliferation.
Cancer Cell Int. 2025 Mar 20;25(1):106.
JB6 cells
5, 10, 20 µM
18 hours
Evaluate the effect of COS on the cell cycle, showing induction of G2/M phase cell cycle arrest.
Cancer Cell Int. 2025 Mar 20;25(1):106.
Primary rat hepatic stellate cells
10, 20, 30 µM
24 hours
To evaluate the effects of Costunolide on HSC activation and glycolysis. Results showed that Costunolide reduced HSC viability, inhibited the expression of α-SMA and collagen I, decreased glucose uptake and consumption, reduced lactate levels, and suppressed HK2 expression and activity.
Cell Mol Biol Lett. 2019 Aug 14;24:52.
T98G
30 µM
24 hours
Costunolide had no effect on the viability of p53 mutant glioma cell T98G.
Cell Death Dis. 2016 May 5;7(5):e2213.
U87MG
30 µM
24 hours
Costunolide induced glioma cell apoptosis in an ROS-dependent manner, increased p53 levels, and abrogated telomerase activity.
Cell Death Dis. 2016 May 5;7(5):e2213.
A172
30 µM
24 hours
Costunolide induced glioma cell apoptosis in an ROS-dependent manner, increased p53 levels, and abrogated telomerase activity.
Cell Death Dis. 2016 May 5;7(5):e2213.
Human erythrocytes
1-80 µM
24 hours
To investigate the effects of Costunolide on eryptosis, results showed that Costunolide dose-dependently increased phosphatidylserine exposure and cell shrinkage, and completely inhibited G6PDH activity.
Apoptosis. 2020 Oct;25(9-10):674-685.
JB6 cells
5, 10, 20 µM
24 hours
Evaluate the effect of COS on apoptosis, showing a concentration-dependent increase in apoptotic cell proportion.
Cancer Cell Int. 2025 Mar 20;25(1):106.
SH-SY5Y cells
50 µg/mL
24 hours
Investigation of the neuroprotective effects of Costunolide against MPP+-induced cytotoxicity, showing that 50 µg/mL Costunolide significantly improved cell viability.
Cells. 2023 Mar 24;12(7):992.
SH-SY5Y cells
100 µg/mL
24 hours
Investigation of the neuroprotective effects of Costunolide against MPP+-induced cytotoxicity, showing that 100 µg/mL Costunolide significantly improved cell viability.
Cells. 2023 Mar 24;12(7):992.
MCF-7 cells
15 µM
24 hours
CTL activated PINK1/Parkin-dependent mitophagy to remove damaged mitochondria, preventing ROS elevation and reducing sensitivity to CTL.
Int J Mol Sci. 2023 Feb 16;24(4):4009.
SK-BR-3 cells
15 µM
24 hours
CTL significantly increased intracellular ROS levels, leading to lysosomal membrane permeabilization and cathepsin D release, subsequently activating the mitochondrial-dependent apoptotic pathway.
Int J Mol Sci. 2023 Feb 16;24(4):4009.
A549 cells
0.39 µM, 1.56 µM, 6.26 µM, 25 µM, 100 µM
24 hours
To evaluate the effect of CTD and CTD-GNE on the viability of A549 cells. CTD-GNE significantly reduced cell viability with an IC50 value of 6.1 ± 0.8 µM, while CTD had an IC50 value of 13.4 ± 1.5 µM.
Pharmaceutics. 2022 Jan 19;14(2):227.
JB6 cells
5, 10, 20 µM
24, 48 hours
Evaluate the cytotoxicity of COS on JB6 cells, showing no cytotoxicity at all tested concentrations.
Cancer Cell Int. 2025 Mar 20;25(1):106.
Bone marrow-derived macrophages (BMDMs)
1, 2, 5 µM
30 minutes
Inhibited NLRP3 inflammasome activation, reduced IL-1β and p20 secretion
Acta Pharm Sin B. 2023 Feb;13(2):678-693.
Alveolar macrophages (AMs)
10 µM
30 minutes
Costunolide significantly inhibited HKSA-induced production of IL-6, TNF-α, IL-1β, and KC.
Acta Pharmacol Sin. 2019 Aug;40(8):1040-1048.
Mouse bone marrow-derived macrophages (BMDMs)
0, 3, 10, and 30 µM
30 minutes
Costunolide significantly inhibited HKSA-induced production of IL-6, TNF-α, IL-1β, and KC in a dose-dependent manner.
Acta Pharmacol Sin. 2019 Aug;40(8):1040-1048.
HEKn cells
0.2, 0.4, 0.6, 0.8, 1 µM
48 hours
Costunolide showed no significant impact on the viability of HEKn cells at concentrations below 1 µM.
Int J Mol Sci. 2021 Feb 19;22(4):2075.
A431 cells
0.2, 0.4, 0.6, 0.8, 1 µM
48 hours
Costunolide significantly reduced the viability of A431 cells with an IC50 value of 0.8 µM.
Int J Mol Sci. 2021 Feb 19;22(4):2075.
H1975-Osi
0, 5, 10, 20 µM
6 hours
Inhibited the kinase activity of MEK1 and AKT1/2, restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis
Mol Cancer. 2022 Oct 6;21(1):193.
HCC827-Osi
0, 5, 10, 20 µM
6 hours
Inhibited the kinase activity of MEK1 and AKT1/2, restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis
Mol Cancer. 2022 Oct 6;21(1):193.
PC9-Osi
0, 5, 10, 20 µM
6 hours
Inhibited the kinase activity of MEK1 and AKT1/2, restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis
Mol Cancer. 2022 Oct 6;21(1):193.
MDA-MB-436
10 µM, 25 µM
6 hours
Costunolide significantly reduced detyrosinated tubulin levels without inducing apoptosis.
Breast Cancer Res. 2013;15(5):R83.
Bt-549
10 µM, 25 µM
6 hours
Costunolide significantly reduced detyrosinated tubulin levels without inducing apoptosis.
Breast Cancer Res. 2013;15(5):R83.
MDA-MB-157
10 µM, 25 µM
6 hours
Costunolide significantly reduced detyrosinated tubulin levels without inducing apoptosis.
Breast Cancer Res. 2013;15(5):R83.
Costunolide/木香烃内酯 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR female mice
DMBA/TPA-induced skin cancer model
Topical administration
0.5 µmol/200 µL, 1 µmol/200 µL
Twice a week for 21 weeks
Evaluate the preventive effect of COS on skin cancer, showing significant reduction in papilloma formation and inhibition of tissue hyperplasia.
Cancer Cell Int. 2025 Mar 20;25(1):106.
Nude mice
Cell-derived xenograft model
Intraperitoneal injection
10 mg/kg
Once every two days for 21 days
Inhibited tumor growth
Int J Mol Sci. 2021 Jul 13;22(14):7509.
ApoE−/− mice
High-fat diet-induced atherosclerosis model
Intragastric administration
10, 20 mg/kg
Every 2 days for 8 weeks
CTD dose-dependently alleviated atherosclerosis in HFD-fed ApoE?/? mice, reducing aortic plaque area and collagen deposition, inhibiting infiltration of inflammatory cells (macrophages, neutrophils, monocytes), and decreasing expression of pro-inflammatory cytokines (TNF-α, IL-6).
Acta Pharmacol Sin. 2023 Jan;44(1):58-70.
NOD/SCID mice
HLG57-Osi PDX model
Oral
20 mg/kg
Once daily, continuous treatment
Costunolide inhibited tumor growth, and combination treatment with osimertinib showed a more obvious growth inhibitory effect
Mol Cancer. 2022 Oct 6;21(1):193.
C57BL/6J mice
HKSA-induced acute lung injury model
Intraperitoneal injection
30 mg/kg
Single dose, evaluated after 8 hours
Costunolide significantly attenuated HKSA-induced lung tissue damage, reduced lung edema and neutrophil infiltration, and significantly decreased the production of pro-inflammatory cytokines.
Acta Pharmacol Sin. 2019 Aug;40(8):1040-1048.
C57BL/6J mice
Gouty arthritis model
Intraperitoneal injection
40 mg/kg
Twice, 30 minutes apart
Reduced joint swelling, decreased IL-1β and p20 production
Acta Pharm Sin B. 2023 Feb;13(2):678-693.
Nude mice
Heterotypic xenograft glioma mouse model
Intraperitoneally
5 mg/kg
Every alternate day for 20 days
Costunolide significantly reduced tumor volume and weight, downregulated telomerase activity, increased ROS levels, and elevated caspase 3/8 activity.
Cell Death Dis. 2016 May 5;7(5):e2213.
Sprague-Dawley rats
Bile duct ligation (BDL)-induced hepatic fibrosis model
Oral gavage
80 mg/kg
Once daily for 14 days
COS administration significantly attenuated hepatic histopathological injury and collagen accumulation and reduced the expression of fibrogenic genes.
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