Imperatorin

Biomol Ther (Seoul). 2015 Sep; 23(5): 421–427.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells.[Pubmed: 26336581]

Imperatorin has been known to exert many biological functions including anti-inflammatory activity.
METHODS AND RESULTS:
In this study, we investigated the inhibitory effects of Imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of Imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that Imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC.
CONCLUSIONS:
These results suggest that the effects of Imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Oncol Rep. 2016 Apr;35(4):1995-2002.

Imperatorin exhibits anticancer activities in human colon cancer cells via the caspase cascade.[Pubmed: 26794238 ]

Despite advances in medical treatments for colon cancer, it remains one of the leading causes of cancer-related mortality among men. Thus, more efficacious treatment strategies for colon cancer are needed. Imperatorin is one of the major ingredients present in the root of Angelica dahurica, and has been used in herbal formulations for the treatment of hypertension and cardiovascular diseases. However, the medical properties of Imperatorin remain unclear.
METHODS AND RESULTS:
In the present study, the anti‑proliferative activities of Imperatorin were investigated in the HT‑29 colon cancer cell line. The results showed that Imperatorin significantly inhibited HT‑29 colon cancer cell growth with an IC50 value of 78 μM. Imperatorin induced the apoptosis of colon cancer cells through upregulation of p53 and the caspase cascade. Our findings revealed that Imperatorin induced cell cycle arrest in the G1 phase. The apoptotic index showed a steady increment when the Imperatorin concentration was increased.
CONCLUSIONS:
The results suggest that Imperatorin exerts considerable anti‑proliferative activities in HT‑29 colon cancer cells and highlight the potential of Imperatorin as an anticancer agent for colon cancer.

Eur J Pharmacol. 2013 Dec 5;721(1-3):49-55.

Suppression of voltage-gated Na(+) channels and neuronal excitability by imperatorin.[Pubmed: 24113522]

Imperatorin is a naturally occurring furocoumarin compound isolated from plants such as Angelica archangelica and Cnidium monnieri. It has multiple pharmacological effects including anticonvulsant effects.
METHODS AND RESULTS:
Here we determined the effects of Imperatorin on voltage-gated Na(+) channels (VGSC) using whole-cell patch clamp techniques in differentiated neuronal NG108-15 cells. We showed that Imperatorin inhibited VGSC; such inhibition did not show state-dependence. Imperatorin caused a left shift in the steady-state inactivation curve without affecting activation gating. The inhibition of VGSC by Imperatorin displayed a mild frequency-dependence. Imperatorin was also shown to inhibit VGSC and action potential amplitude without affecting voltage-gated K(+) channels in rat hippocampal CA1 neurons.
CONCLUSIONS:
In conclusion, our results suggest that Imperatorin dampens neuronal excitability by inhibiting VGSC.

Pharmacol Rep. 2014 Apr;66(2):292-300.

The effect of quercetin and imperatorin on programmed cell death induction in T98G cells in vitro.[Pubmed: 24911084]

High expression of HSP27 and HSP72 in glioma cells has been closely associated with chemoresistance and decreased sensitivity to programmed cell death induction. Therefore, it is important to devise therapies that effectively target invasive cancer cells by inducing cell death. The aim of our study was to assess the effect of quercetin and Imperatorin applied separately and in combinations on the apoptosis and autophagy induction in human T98G cells cultured in vitro.
METHODS AND RESULTS:
Cell death induction was analyzed by the staining method. The Western blotting technique and fluorimetric measurements of activity were used to assess the expression of marker proteins of apoptosis and autophagy. The specific siRNA transfected method was used for blocking of the expression of HSP27 and HSP72 genes. The experiments revealed the highest percentage of apoptotic cells after using a 50?M concentration of both compounds. Simultaneous quercetin and Imperatorin administration induced apoptosis more effectively than incubation with single drugs. These results were accompanied with decreased HSP27 and HSP72 expression, and a high level of caspase-3 and caspase-9 activity. Autophagy was not observed. Additional experiments were performed on a cell line with blocked Hsp27 and Hsp72 expression and significant increase the sensitivity to apoptosis induction upon quercetin and Imperatorin treatment was noticed.
CONCLUSIONS:
The present study indicates that quercetin and Imperatorin are potent apoptosis inducers, especially when they act synergistically, which may be a promising combination useful in glioma therapy. Our results also demonstrated that blocking the HSP27 and HSP72 gene expression might serve as a therapeutic target for the human brain cancer.

Pharmacol Toxicol. 2002 Jul;91(1):40-8.

Imperatorin, a furanocoumarin from Angelica dahurica (Umbelliferae), induces cytochrome c-dependent apoptosis in human promyelocytic leukaemia, HL-60 Cells.[Pubmed: 12193260]

Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic leukaemia, HL-60 cells.
METHODS AND RESULTS:
DNA fragmentation assay, morphology-based evaluation, and flow cytometric analysis demonstrated that Imperatorin at micromolar concentrations was able to trigger apoptosis of HL-60 cells. Neither necrosis nor differentiation was observed at cytotoxic micromolar concentrations of Imperatorin. Further studies showed that the cytochrome c/caspase-9 pathway was responsible for Imperatorin-induced apoptosis; i.e., mitochondrial membrane was depolarized, Bcl-2 was down-regulated, cytochrome c was released from mitochondria, caspase-9 and caspase-3 were activated, and poly(ADP-ribose) polymerase was cleaved. Furthermore, Imperatorin-induced apoptosis was significantly blocked by Z-VAD-FMK (a broad spectrum caspase inhibitor), Z-LEHD-FMK (a caspase-9 inhibitor) and Ac-DMQD-CHO (a caspase-3 inhibitor), but not by Z-IEDT-FMK (a caspase-8 inhibitor).