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].
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 acidA (GABAA) receptor in vitro with IC50 values of 400 and 680 nM, respectively[7].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Did not inhibit TNF-α-induced ICAM-1 expression, whereas it inhibited VCAM-1 expression from 5 μM, and completely suppressed it at 50 μM concentration.
Had no effect on ERK1/2 phosphorylation, whereas they significantly inhibited the phosphorylation of Akt and PKC in dose-dependent manner.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Streptozotocin (STZ) -induced diabetic model established in five-week-old C57BL/6J male mice[2]
Dosage:
0.6, 1.2 and 2.4 mg/kg
Administration:
Intravenous injection (i.v.), for 14 days
Result:
Seemed to have the greatest effect on wound healing at medium dose.
Promoted diabetic wound healing by accelerating epidermic re-epithelialization.
Downregulated ICAM-1 expression via SIRT1 in mice with diabetic ulcers.
Animal Model:
Calcipotriol (MC-903) (HY-10001) induced AD like skin model established in male C57BL/6 mice around 8 to 10 weeks of age[3]
Dosage:
0.5, 1.5 and 4.5 mg/kg
Administration:
Ear topically spread, twice a day for 10 days
Result:
The concentration at 1.5 mg/kg showed the optimal therapeutic effect.
Exhibited significant reduction in epidermal thickness and scales as well as serum IgE levels.
Decreased the infiltrated eosinophils and mast cells.
The protein levels of TSLP and IL-33 in epidermal keratinocytes were decreased.
The expression of IL-4 was remarkably elevated in the AD-like skin lesions, but not significantly changed its expression.
Animal Model:
SKOV3 cells induced ovarian cancer xenograft model established in nude mice[4]
Dosage:
50 mg/kg
Administration:
Intragastric administration (i.g.), five times a week for 4 weeks
Result:
Attenuated cancer growth.
No significant difference in mice body weight and the histopathological changes of the liver and kidney.
Ki67 levels were also downregulated in tumor.
Animal Model:
High-fat diet/Streptozotocin (HFD/STZ)-induced diabetic established in male ICR strain mice[5]
Dosage:
0.5, 1 and 2 mg/kg
Administration:
Intragastric administration (i.g.), once daily for 4 weeks
Result:
Total cholesterol decreased from 1154.8 to 630.4 mg/dL.
Triglycerides dropped from 541.6 to 346.7 mg/dL.
No obvious toxic reactions were observed and the organ coefficients were within the normal range.
Animal Model:
Azoxymethane (AOM) (HY-111375)/DSS (Dapsone) (HY-B0688) induced colitis-associated cancer (CAC) model established in C57BL/6 mice[8]
Dosage:
0.5, 1 and 2 mg/kg
Administration:
Intragastric administration (i.g.)
Result:
Dose-dependently improved the weight loss in mice and increased the length of their colons.
Reduced the rate of tumor formation.
Increased CD4+ and CD8+, and decreased pro-inflammatory factors (IL-6, IL-1β, TNF-α).
Reduced the levels of M2-type markers (such as CD163, CD206, etc.)
Decreased the expression of TLR4 and NF-κB p65.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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