Zederone

Zederone is a sesquiterpene. Zederone inhibits ovarian cancer cell proliferation through mTOR/p70s6K signalling pathway. Zederone inhibits CYP activities with IC₅₀s of 2.9 μM (CYP2B6), 9.2 μM (CYP2C9), 11,2 μM (CYP2C19) and >30 μM (CYP1A2 and CYP2D6). Zederone is hepatotoxic with LD₅₀ value at 24 hours in mice of approximately 223 mg/kg and cytotoxic against the KG1a cell line. Zederone shows antibacterial activity against a number of multi-drug resistant and Methicillin (HY-121544)-resistant Staphylococcus aureus strain. Zederone shows cognition improving capacity and assists in the modulation of gut bacterial dysbiosis^{[1][2][3][4][5][6]}. In Vitro:Zederone (0-80 μg/mL, 24 h) can inhibit the proliferation of human ovarian cancer cell line SKOV3 and arrest SKOV3 cells at G1 phase, and it may regulate the proliferation of SKOV3 cells through inhibiting mTOR/p70s6K signalling pathway^[2].
Zederone (0-30 μM, 24 h) significantly activates mouse PXR, significantly activates human PXR and CAR, and AhR shows no response in human hepatoma C3A cells^[3].
Zederone exhibits IC₅₀s in HLM incubations of 3.9 μM (CYP2B6), 9.9 μM (CYP3A4/M) and >50 μM (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/T)^[3].
Zederone shows antibacterial activity against SA1199B, ATCC25923, XU212, RN4220 and EMRSA15 with MICs of 128, 64, 128, 64 and 128 μg/ml^[4].
Zederone (0-100 μg/mL, 48 h) selectively kills leukemia stem cells (KG1a) with an IC₅₀ of 56.8 μg/mL and low cytotoxicity toward normal peripheral blood mononuclear cells (PBMCs) ^[5].
In Vivo:Zederone (50-300 mg/kg, i.p., single dose) increases the expression of cytochrome P450 (Cyp) and leads to the formation of biological reactive metabolites and that cause the oxidative stress and liver cell injuries in mice^[1].
Zederone (10 mg/kg, p.o.) improves the fecal microbial profile in dementia induced rat model, showing a increased shift towards Lactobacillus genera from Bacteroides^[6].