Daphnoretin

Daphnoretin (Dephnoretin; Thymelol) is a protein kinase C (PKC) activator that inhibits the expression of hepatitis B virus (HBV) surface antigen (HBsAg) and exhibits antiviral activity. Daphnoretin exerts its antitumor effects by inhibiting the activation of the PI3K/AKT signaling pathway and triggers the mitochondrial apoptosis pathway. Daphnoretin alleviates chondrocyte apoptosis and inflammatory responses by inhibiting endoplasmic reticulum stress and activation of the NLRP3 inflammasome. Daphnoretin regulates the differentiation and maturation of dendritic cells, inhibits their immunostimulatory function by downregulating the phosphorylation level of JNK, and thus exerts a protective effect in skin graft rejection^{[1][2][3][4]In Vitro:Daphnoretin (0.1-1.0 μM; 48 h) inhibits the expression of hepatitis B surface antigen gene at the mRNA level in human hepatocellular carcinoma Hep3B cells, with an IC₅₀ of 0.1 μM after 48 h of treatment[1].
Daphnoretin (1 μM; 4 h) induces the translocation of protein kinase C (PKC) from the cytosol to the cell membrane, and treatment of human hepatocellular carcinoma Hep3B cells with 800 nM daphnoretin for 24 h downregulates the total intracellular PKC level[1].
Daphnoretin (0.1-8.0 μM; 24-48 h) inhibits the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner, with IC₅₀ values of 2.0 μM and 1.0 μM, respectively[2].
Daphnoretin (0.5-4 μM; 24 h) induces S-phase cell cycle arrest in human breast cancer MCF-7 and MDA-MB-231 cells by downregulating the protein levels of cyclin E and CDK2[2].
Daphnoretin (0.5-4 μM; 24 h) induces apoptosis in human breast cancer MCF-7 and MDA-MB-231 cells via a mitochondria-dependent pathway, and reduces BCL-2 levels while increasing the levels of BAX, activated caspase-9 and activated caspase-3[2].
Daphnoretin (0.5-4 μM; 24 h) inhibits the PI3K/AKT pathway in human breast cancer MCF-7 and MDA-MB-231 cells at 24 h post-treatment by reducing the protein levels of p-PI3K and p-AKT[2].
Daphnoretin (0.5-512 μM; 48 h) reduces the viability of ATDC5 chondrocytes, with an IC₅₀ of 72.97 μM after 48 h of treatment[3].
Daphnoretin (1-4 μM; 48 h) increases the viability of IL-1β-induced ATDC5 chondrocytes and reduces their apoptosis rate in a dose-dependent manner[3].
Daphnoretin (1-4 μM) dose-dependently inhibits IL-1β-induced ERS in ATDC5 chondrocytes[3].
Daphnoretin (1-4 μM; 48 h) dose-dependently inhibits IL-1β-induced production of inflammatory mediators and activation of the NLRP3 inflammasome in ATDC5 chondrocytes[3].
Daphnoretin (1.1-30 μM; 6 days) reduces the viability of human CD14+ monocyte-derived dendritic cells in a dose-dependent manner, with an IC₅₀ of approximately 30 μM; at a concentration of 10 μM, it inhibits dendrite formation without significant cytotoxicity[4].
Daphnoretin (1.1-30 μM; 6 days) dose-dependently downregulates the expression of differentiation and maturation markers, including CD1a, CD40, CD83, DC-SIGN and HLA-DR, on mature dendritic cells derived from human CD14+ monocytes, without inducing their dedifferentiation into macrophages[4].
Daphnoretin (1.1-30 μM; 6 days) dose-dependently impairs the allostimulatory function of mature dendritic cells derived from human CD14+ monocytes and reduces the proliferative capacity of allogeneic naive CD4+CD45RA+ T cells[4].
Daphnoretin (10 μM) specifically downregulates the LPS-induced upregulated expression of phosphorylated JNK in human CD14+ monocyte-derived dendritic cells[4]. In Vivo:Daphnoretin (10 mg/kg; i.p.; administered daily for the first week post-surgery, then once every 3 days for the subsequent 7 weeks; total duration of 8 weeks) alleviates the progression of osteoarthritis induced by destabilization of the medial meniscus (DMM) in mice by attenuating cartilage damage, regulating the expression of apoptosis-related proteins, inhibiting endoplasmic reticulum stress and inactivating the NLRP3 inflammasome, significantly reducing the OARSI score and improving the thickness of the subchondral cortical bone plate[3].
Daphnoretin (0.5-1.0 mg/kg; i.p.; administered daily until graft rejection) inhibits acute skin allograft rejection in mice without altering body weight or white blood cell counts, and exhibits no obvious dose-dependent effect[4].}