Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside

Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside is a TRPV1 antagonist and HDAC7 inhibitor. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside blocks TRPV1-mediated calcium influx, suppresses phosphorylation of p65, IκBα, p38, JNK, and ERK1/2, inhibiting NF-κB and MAPK signaling cascades. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside reduces production and gene expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside exhibits potent analgesic activity, elevates thermal pain threshold and mechanical pain threshold in murine models. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside restores CD8⁺ T cell infiltration into bladder cancer tumors and improves bladder cancer immunotherapy efficacy. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside can be used for the researches of painand bladder cancer^[1][2]. In Vitro:Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (100 ns) forms a more stable complex with human TRPV1 than capsazepine, with a binding free energy of -117.696 kJ/mol^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (1-10 μM; 1 h) inhibits Capsaicin (HY-10448)-induced calcium influx in human TRPV1-expressing HEK293 cells^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (6.25-100 μM; 24 h) is non-toxic to RAW264.7 macrophage cells at concentrations up to 100 μM after 24 h treatment^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (2.5-10 μM; 1 h) inhibits TNF-α-induced inflammatory gene expression in RAW264.7 macrophage cells^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (10 μM; 1 h pre-incubation before TNF-α stimulation, 1 h) inhibits TNF-α-induced activation of the NF-κB and MAPK signaling pathways in RAW264.7 macrophage cells at 10 μM, an effect that is attenuated by capsaicin co-treatment, suggesting TRPV1-mediated activity^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (Compound PINO) (3.13 µM-0.38 nM) binds to recombinant human HDAC7 protein with a K_d of 76.7 nM^[2].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (10-200 µM; 48 h) specifically inhibits HDAC activity in HDAC7-overexpressing T24 and MB49 bladder cancer cells, with no significant effect on other HDAC subtypes or their non-histone substrates^[2].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (10-200 µM) activates the SRSF7-CCL5 pathway in T24 and UMUC3 bladder cancer cells by increasing SRSF7 acetylation and expression, and upregulating CCL5 expression^[2]. In Vivo:Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (20 mg/kg; i.p.; single dose) exhibits potent analgesic activity in a Mus musculus mouse model of Acetic acid (HY-Y0319)-induced acute inflammatory pain^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (20 mg/kg; i.p.; single dose) increases the thermal pain threshold in mice, as demonstrated by prolonged tail-flick latency in the hot water tail-flick test^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (10-20 mg/kg; i.p.; single dose) exhibits dose-dependent analgesic activity in a mouse model of CFA (HY-153808)-induced chronic inflammatory pain, with the 20 mg/kg dose significantly increasing the mechanical withdrawal threshold and exerts anti-inflammatory effects in a mouse model of CFA-induced chronic inflammatory pain, reducing serum levels of IL-1β, IL-6, and TNF-α^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (20 mg/kg; i.p.; single dose) effectively alleviates both thermal and mechanical bone cancer pain in mice, restoring mechanical withdrawal threshold to near pre-inoculation levels^[1].
Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside (Compound PINO) (50 µg/g; i.p.; daily for 2 weeks) enhances BCa sensitivity to anti-PD1 immunotherapy by increasing CD8⁺ T cell tumor infiltration and reducing tumor growth^[2].