Phellopterin

Phellopterin, an orally active furocoumarin with multiple biological activities. Phellopterin is a partial agonist of the central benzodiazepine receptors. Phellopterin exerts anti-inflammatory effects by upregulating SIRT1, downregulating ICAM-1 (reducing chronic inflammation, aiding diabetic ulcer healing), inhibiting STAT3 phosphorylation (easing atopic dermatitis inflammation), regulating Akt/PKC pathways (lowering TNF-α-induced VCAM-1 to block monocyte adhesion), and inhibiting TLR4/NF-κB pathway and macrophage M2 polarization (alleviating colitis-related cancers). Phellopterin suppresses ovarian cancer progression via inhibiting the PU.1/CLEC5A/PI3K-AKT loop (inducing cell cycle arrest, apoptosis, DNA damage). Phellopterin alleviates murine diabetes by promoting adipocyte differentiation and increasing PPARγ. Phellopterin also has anti-HSV-1 activity. Phellopterin can be used for studying anti-inflammation, anti-cancer (e.g., ovarian cancer, colitis cancer), blood glucose lowering, anti-diabetes, and anti-virus^{[1][2][3][4][5][6][7][8]}. In Vitro:Phellopterin (1-50 μM, 24 h) significantly inhibits VCAM-1 expression and Akt and PKC phosphorylation in a dose-dependent manner in TNF-α-stimulated HUVECs, and effectively prevents monocyte adhesion to TNF-α-stimulated ECs by regulating VCAM-1 expression^[1].
Phellopterin (1-25 μM, 24 h) upregulates the expression of SIRT1 and downregulates the expression of ICAM-1 in HaCaT cells, thereby reversing the proliferation inhibition caused by IFN-γ^[2].
Phellopterin (1-16 μM, 24 h) inhibits IL-4-induced activation of STAT3, which leaded to suppress the STAT3-mediated transcription of TSLP and IL-33 in HaCaT cells^[3].
Phellopterin (1-100 μg/mL, 48 h) attenuates the proliferation of ovarian cancer cells with IC₅₀s for OV90 and SKOV3 cells of 18.67 and 27.75 μg/mL^[4].
Phellopterin (25-50 μg/mL) attenuates ovarian cancer progression by inhibiting cell proliferation through modulating DNA replication, cell cycle (G0/G1), and apoptosis in OV90 cells and SKOV3 cells^[4].
Phellopterin (25 μg/mL, 48 h) inactivates CLEC5A/PI3K/AKT signaling in OV90 cells and SKOV3 cells ^[4].
Phellopterin (12.5-100 μg/mL) induces adipocyte differentiation and increases the mRNA expression of peroxisome proliferator-activated receptors γ (PPARγ)^[5].
Phellopterin (1-500 μg/mL, 72 h) reduces the HSV-1 replication by 3.01 log at the concentration of 7.81 mg/mL, and has a significant cytotoxicity towards Vero cells with CC₅₀ of 14.61 μg/mL^[6].
Phellopterin (40 min) inhibits [³H]diazepam and [³H]Ro 15-1788 binding to the benzodiazepine site of the rat brain 3,-aminobutyric acid_A (GABA_A) receptor in vitro with IC₅₀ values of 400 and 680 nM, respectively^[7].
In Vivo:Phellopterin (0.6-2.4 mg/kg, i,v., for 14 days) significantly accelerated the wound healing by downregulating ICAM-1 expression via SIRT1 in diabetic mice^[2].
Phellopterin (0.5-4.5 mg/kg, ear topically spread, twice a day for 10 days) improves the atopic dermatitis (AD)-like lesions in mice^[3].
Phellopterin (50 mg/kg, i,g., five times a week for 4 weeks) suppresses cancer growth in mice ovarian cancer xenograft model^[4].
Phellopterin (0.5-2 mg/kg, i,g., once daily for 4 weeks) significantly lowers blood sugar levels thus prevents High-fat diet/Streptozotocin (HFD/STZ) (HY-13753)-induced type Ⅱ diabetes in mice^[5].
Phellopterin (0.5-2 mg/kg, i,g.) improves the symptoms and inflammatory response of colitis-associated cancer (CAC) and inhibits the occurrence of colon cancer by inhibiting M2 polarization of macrophages and activation of the TLR4/NF-κB pathway in mice^[8].