Acetyl-11-keto-β-boswellic acid (AKBA), a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata (frankincense), is a Nrf2 activator against a large number of inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn’s disease, and bronchial asthma[3]. AKBA is as a novel, orally active, non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro[4]. AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-κB-regulated gene expression[3]. In tumor cells, AKBA suppressed both inducible and constitutive NF-κB activation examined by DNA binding. AKBA inhibited the TNF-induced activation of IκBα kinase (IKK), IκBα phosphorylation, IκBα ubiquitination, IκBα degradation, p65 phosphorylation, and p65 nuclear translocation[3]. AKBA inhibited the NF-κB-dependent reporter gene expression activated by TNFR type 1, TNFR-associated death domain protein, TNFR-associated factor 2, NF-κB-inducing kinase, and IKK[3]. Induction of apoptosis in HL-60 and CCRF-CEM by AKBA may be due to inhibition of topoisomerase I in these cells[5]. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA), whose inhibitory effect on tumor growth was well correlated with suppression of angiogenesis induced by VEGFR2 signaling pathways[6]. In mice, AKBA significantly inhibited blood vessel formation in the Matrigel plug assay and effectively suppressed vascular endothelial growth factor (VEGF)–induced microvessel sprouting in rat aortic ring assay ex vivo[6]. In vitro, AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC50 of 1.68 μmol/L[6]. At low micromolar concentrations, AKBA rapidly and potently inhibited the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells[7]. AKBA inhibits the motility of meningioma cells showing a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 - 8 μM[7].
AKBA 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse primary keratinocytes
20 μM
12 h
AKBA decreases H3K27me3 methylation level
EBioMedicine. 2019 Jan;39:575-590
HaCaT cells
20 μM
12 h
AKBA inhibits MAT2A function, decreases SAM level and SAM/SAH ratio
EBioMedicine. 2019 Jan;39:575-590
U87-MG cells
10 mM, 20 mM, 30 mM
24 h
To detect the inhibitory effect of AKBA on autophagy in U87-MG cells using transmission electron microscopy. Results showed that AKBA significantly inhibited autophagy in U87 cells.
Acta Pharm Sin B. 2020 Feb;10(2):301-312
HEK293 cells
25 μM
180 min
AKBA significantly increased the formation of 15-LOX products in cells expressing 15-LOX-1 and 15-LOX-2.
Adv Sci (Weinh). 2023 Feb;10(6):e2205604
M2-MDMs
10 μM
180 min
AKBA significantly increased the formation of 12/15-LOX-derived lipid mediators and SPMs, particularly in M2-MDMs.
Adv Sci (Weinh). 2023 Feb;10(6):e2205604
Human monocytes
10 μM
90 min
AKBA significantly elevated the levels of 15-LOX and 12-LOX products and increased the formation of SPMs, especially in M2-MDMs.
Adv Sci (Weinh). 2023 Feb;10(6):e2205604
M1-like macrophages
10 μM
90 min
AKBA significantly reduced the formation of LTB4 while increasing the production of 12-HETE.
Nat Chem Biol. 2020 Jul;16(7):783-790
Neutrophils
10 μM
90 min
AKBA significantly reduced the levels of 5-HETE and LTB4 while increasing the production of 12-HETE.
Nat Chem Biol. 2020 Jul;16(7):783-790
HEK293 cells
25 μM
15 min
AKBA significantly reduced the formation of 5-LOX products (e.g., 5-HETE and LTB4) while increasing the production of 12-HETE.
Nat Chem Biol. 2020 Jul;16(7):783-790
Human prostate cancer cells (PC-3)
50μM
AKBA inhibited PC-3 cell proliferation, requiring a higher concentration than that needed to suppress endothelial cell proliferation.
Cancer Res. 2009 Jul 15;69(14):5893-900
Human umbilical vascular endothelial cells (HUVECs)
5-10 μM
6-8 h
AKBA significantly suppressed or terminated VEGF-induced tubular formation of endothelial cells.
Cancer Res. 2009 Jul 15;69(14):5893-900
Human umbilical vascular endothelial cells (HUVECs)
1-5 μM
24 h
AKBA inhibited VEGF-induced HUVEC migration and invasion in a dose-dependent manner.
Cancer Res. 2009 Jul 15;69(14):5893-900
U87-MG human glioblastoma cells
10, 20, 30 μM
24 and 48 h
AKBA inhibited cell proliferation, caused the release of LDH, decreased DNA synthesis, and inhibited the migration, invasion, and colony formation of U87-MG human glioblastoma cells.
J Exp Clin Cancer Res. 2018 Jul 3;37(1):132
U251 human glioblastoma cells
10, 20, 30 μM
24 and 48 h
AKBA inhibited cell proliferation, caused the release of LDH, decreased DNA synthesis, and inhibited the migration, invasion, and colony formation of U251 human glioblastoma cells.
J Exp Clin Cancer Res. 2018 Jul 3;37(1):132
PC3 cells
5, 10, 20, 30, 40 μM
48 h
AKBA dose-dependently inhibited cell proliferation in PC3 cells, with an IC50 value of approximately 21μM.
Acta Pharmacol Sin. 2019 May;40(5):689-698
PC3/Doc cells
5, 10, 20, 30, 40 μM
48 h
AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells, with an IC50 value of approximately 17μM in anti-proliferation.
Acta Pharmacol Sin. 2019 May;40(5):689-698
LS174T cells
20 μM
72 h
AKBA inhibited growth of LS174T cells, resulting in a 40-50% reduction in cell numbers.
Br J Pharmacol. 2006 Aug;148(8):1099-107
HT-29 cells
30 μM
72 h
AKBA inhibited growth of HT-29 cells, resulting in a 40-50% reduction in cell numbers.
Br J Pharmacol. 2006 Aug;148(8):1099-107
HCT-116 cells
5-25 μM
24-72 h
AKBA inhibited cellular growth in a time- and dose-dependent manner in HCT-116 cells, leading to G1 phase cell cycle arrest accompanied by downregulation of cyclin D1, E, CDK2, CDK4, and phosphorylated Rb, and upregulation of p21 expression.
Br J Pharmacol. 2006 Aug;148(8):1099-107
Schwann cells
2 µg/mL
0, 6, 12, 24 h
AKBA treatment significantly increased p-ERK1/2 expression in a time-dependent manner.
Neural Regen Res. 2018 Mar;13(3):484-491
Schwann cells
1.25, 2.5, 5, 10, 20 µg/mL
24 h
AKBA significantly promoted SC proliferation at concentrations of 1.25–5 µg/mL, peaking at 2 µg/mL; inhibited proliferation at >5 µg/mL.
Neural Regen Res. 2018 Mar;13(3):484-491
AKBA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
Orthotopic U87-MG glioblastoma model
Oral administration
100 mg/kg, 200 mg/kg
Once daily for 21 days
To evaluate the anti-tumor effects of AKBA on orthotopic glioblastoma. MRI results showed that AKBA significantly inhibited tumor growth without obvious weight loss or abnormal behavior.
Acta Pharm Sin B. 2020 Feb;10(2):301-312
BALB/c-nu nude mice
U87-MG human glioblastoma xenograft model
Oral
100 mg/kg
Once daily for 14 days
Oral administration of AKBA significantly suppressed the tumorigenicity of U87-MG cells in a xenograft mouse model.
J Exp Clin Cancer Res. 2018 Jul 3;37(1):132
C57BL/6 mice
RM-1/Doc homograft model
Intraperitoneal injection
30 mg/kg
Once daily for 14 days
AKBA significantly suppressed the growth of RM-1/Doc homografts without decreasing body weight.
Acta Pharmacol Sin. 2019 May;40(5):689-698
BALB/cA nude mice
Human prostate tumor xenograft model
Subcutaneous injection
10 mg/kg
Once daily for 30 days
AKBA significantly suppressed tumor volume and weight growth and inhibited tumor angiogenesis.
Cancer Res. 2009 Jul 15;69(14):5893-900
Sprague-Dawley rats
Sciatic nerve injury model
Intraperitoneal injection
1.5, 3, 6 mg/kg
Once every 2 days for 30 days
3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity.
Neural Regen Res. 2018 Mar;13(3):484-491
Mice
Zymosan-induced peritonitis
Intraperitoneal injection
20 mg/kg
Single dose, lasting 24 hours
AKBA significantly elevated SPM levels and promoted the resolution of inflammation.
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