Acetyl zingerone is an analog of Zingerone. Acetyl zingerone downregulates the expression of ROS metabolism-related genes, fibroblast senescence-related genes, keratinocyte differentiation-related genes, and IL-17A target genes. Acetyl zingerone inhibits the activities of MMP-1, MMP-3, and MMP-12, as well as the activation of NLRP3 inflammasome, pyroptosis ( pyroptosis ), ferroptosis ( ferroptosis ), cartilage destruction, and UVA-induced cyclobutane pyrimidine dimer formation. Acetyl zingerone upregulates the expression of collagen, proteoglycan, extracellular matrix glycoprotein, Notch pathway, and GPX4 gene, activates Nrf2 and HO-1, induces extracellular matrix synthesis and PINK1 / Parkin -mediated mitophagy ( mitophagy ), and promotes chondrocyte survival. Acetyl zingerone alleviates the progression of osteoarthritis in mice. Acetyl zingerone can be used in research related to skin aging, inflammatory skin diseases, osteoarthritis, melanoma, and non-melanoma skin cancer [1] [2] [3] [4].
In Vivo, Acetyl zingerone (1 mg/kg; intra-articular injection; twice a week; for 8 consecutive weeks) alleviates osteoarthritis progression induced by the destabilization of the medial meniscus (DMM) model in mice by promoting PINK1/Parkin-mediated mitophagy, inhibiting chondrocyte pyroptosis, reducing cartilage damage, and restoring subchondral bone remodeling[2].
In Vitro, Acetyl zingerone alters gene expression in recombinant human epidermis, upregulating genes related to the core matrix group, Notch, and ERK1/ERK2 pathways, while downregulating inflammation-related genes, as well as genes associated with the TGF-β signaling pathway and AP-1/NF-κB[1]. Acetyl zingerone (10-200 µg/mL; 6 days) dose-dependently increases the abundance of extracellular matrix proteins per cell density in cultured human skin fibroblasts[1]. Acetyl zingerone (10 µL/cm2; once daily for 4 consecutive days) doubles the dermal collagen content in ex vivo human facial skin biopsy samples[1]. Acetyl zingerone (with 1:1 serial dilutions performed starting from a stock solution prepared by dissolving 0.1 g AZ in 1 mL DMSO; 10 min (MMP-1, MMP-3); 15 min (MMP-12)) inhibits the activities of MMP-1, MMP-3 and MMP-12 in cell-free assays, with the strongest inhibitory potency against MMP-12 (IC50 = 0.255 mg), followed by MMP-3 (IC50 = 0.505 mg) and MMP-1 (IC50 = 1.065 mg)[1]. Acetyl zingerone reverses gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation in reconstructed human epidermis[1]. Acetyl zingerone (25-200 μM; 2-48 h) exerts a protective effect on ATDC5 chondrocytes, protecting them from LPS + ATP -induced cytotoxic damage and restoring their proliferative capacity[2]. Acetyl zingerone (100 μM; 24 h) inhibits LPS + ATP-induced pyroptosis of ATDC5 chondrocytes by alleviating cell membrane damage, suppressing NLRP3 inflammasome activation, and reducing the expression of downstream pyroptosis-related proteins[2]. Acetyl zingerone (100 μM; 24 h) attenuates LPS + ATP-induced mitochondrial damage in ATDC5 chondrocytes by reducing ROS/mtROS production and restoring mitochondrial membrane potential and structural integrity[2]. Acetyl zingerone (100 μM; 24 h pretreatment, 24 h LPS + ATP induction) activates PINK1/Parkin-mediated mitophagy in LPS + ATP-treated ATDC5 chondrocytes[2]. Acetyl zingerone (25-100 μM; 24-48 h) increases the survival rate of primary rat chondrocytes treated with IL-1β and restores their proliferative capacity[3]. Acetyl zingerone (25-100 μM; 24 h) maintains ECM homeostasis in IL-1β-treated primary rat chondrocytes and mouse ATDC5 chondrogenic cells by upregulating aggrecan and COL2A1, and downregulating matrix-degrading enzymes and inflammatory factors[3]. Acetyl zingerone (25-100 μM; 24 h) inhibits IL-1β-induced apoptosis in IL-1β-treated primary rat chondrocytes and mouse ATDC5 chondrogenic cells by upregulating Notch1 and SOCS3 and reducing the level of activated caspase-3[3]. Acetyl zingerone (25-100 μM; 24 h) reduces IL-1β-induced ROS accumulation in primary rat chondrocytes[3]. Acetyl zingerone (100 μM; 24 h) inhibits IL-1β-induced ferroptosis in primary rat chondrocytes and mouse ATDC5 chondrogenic cells by increasing GSH levels, decreasing MDA levels, stabilizing mitochondrial structure, upregulating GPX4, and activating the Nrf2/HO-1 pathway[3]. Acetyl zingerone (25 µg/mL; administered 1-6 h post-UVA irradiation) significantly reduces the formation of dark-state cyclobutane pyrimidine dimers (dark-CPD) in melanocytes of C57BL/6 mice within the first 2 hours after UVA exposure, with an inhibition rate of approximately 82% at 1 h post-irradiation, without impairing DNA repair function or cell viability[4]. Acetyl zingerone (25-50 µg/mL; 20 min pre-incubation prior to 25 min UVA irradiation) dose-dependently reduces UVA-induced ROS production in normal human neonatal epidermal keratinocytes, with reduction rates of 35% and 46%, respectively[4].
References:
[1]. Swindell WR, et al. A Zingerone Analog, Acetyl Zingerone, Bolsters Matrisome Synthesis, Inhibits Matrix Metallopeptidases, and Represses IL-17A Target Gene Expression. J Invest Dermatol. 2020;140(3):602-614.e15.
[2]. Zhang Z, et al. Acetyl zingerone inhibits chondrocyte pyroptosis and alleviates osteoarthritis progression by promoting mitophagy through the PINK1/parkin signaling pathway. Int Immunopharmacol. 2025;161:115055.
[3]. Chen X, et al. Acetyl zingerone ameliorates osteoarthritis by inhibiting chondrocyte programmed cell death. Mol Med Rep. 2023;28(5):202.
[4]. Chaudhuri RK, et al. Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends. Int J Cosmet Sci. 2020;42(1):36-45.
In Vivo, Acetyl zingerone (1 mg/kg; intra-articular injection; twice a week; for 8 consecutive weeks) alleviates osteoarthritis progression induced by the destabilization of the medial meniscus (DMM) model in mice by promoting PINK1/Parkin-mediated mitophagy, inhibiting chondrocyte pyroptosis, reducing cartilage damage, and restoring subchondral bone remodeling[2].
In Vitro, Acetyl zingerone alters gene expression in recombinant human epidermis, upregulating genes related to the core matrix group, Notch, and ERK1/ERK2 pathways, while downregulating inflammation-related genes, as well as genes associated with the TGF-β signaling pathway and AP-1/NF-κB[1]. Acetyl zingerone (10-200 µg/mL; 6 days) dose-dependently increases the abundance of extracellular matrix proteins per cell density in cultured human skin fibroblasts[1]. Acetyl zingerone (10 µL/cm2; once daily for 4 consecutive days) doubles the dermal collagen content in ex vivo human facial skin biopsy samples[1]. Acetyl zingerone (with 1:1 serial dilutions performed starting from a stock solution prepared by dissolving 0.1 g AZ in 1 mL DMSO; 10 min (MMP-1, MMP-3); 15 min (MMP-12)) inhibits the activities of MMP-1, MMP-3 and MMP-12 in cell-free assays, with the strongest inhibitory potency against MMP-12 (IC50 = 0.255 mg), followed by MMP-3 (IC50 = 0.505 mg) and MMP-1 (IC50 = 1.065 mg)[1]. Acetyl zingerone reverses gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation in reconstructed human epidermis[1]. Acetyl zingerone (25-200 μM; 2-48 h) exerts a protective effect on ATDC5 chondrocytes, protecting them from LPS + ATP -induced cytotoxic damage and restoring their proliferative capacity[2]. Acetyl zingerone (100 μM; 24 h) inhibits LPS + ATP-induced pyroptosis of ATDC5 chondrocytes by alleviating cell membrane damage, suppressing NLRP3 inflammasome activation, and reducing the expression of downstream pyroptosis-related proteins[2]. Acetyl zingerone (100 μM; 24 h) attenuates LPS + ATP-induced mitochondrial damage in ATDC5 chondrocytes by reducing ROS/mtROS production and restoring mitochondrial membrane potential and structural integrity[2]. Acetyl zingerone (100 μM; 24 h pretreatment, 24 h LPS + ATP induction) activates PINK1/Parkin-mediated mitophagy in LPS + ATP-treated ATDC5 chondrocytes[2]. Acetyl zingerone (25-100 μM; 24-48 h) increases the survival rate of primary rat chondrocytes treated with IL-1β and restores their proliferative capacity[3]. Acetyl zingerone (25-100 μM; 24 h) maintains ECM homeostasis in IL-1β-treated primary rat chondrocytes and mouse ATDC5 chondrogenic cells by upregulating aggrecan and COL2A1, and downregulating matrix-degrading enzymes and inflammatory factors[3]. Acetyl zingerone (25-100 μM; 24 h) inhibits IL-1β-induced apoptosis in IL-1β-treated primary rat chondrocytes and mouse ATDC5 chondrogenic cells by upregulating Notch1 and SOCS3 and reducing the level of activated caspase-3[3]. Acetyl zingerone (25-100 μM; 24 h) reduces IL-1β-induced ROS accumulation in primary rat chondrocytes[3]. Acetyl zingerone (100 μM; 24 h) inhibits IL-1β-induced ferroptosis in primary rat chondrocytes and mouse ATDC5 chondrogenic cells by increasing GSH levels, decreasing MDA levels, stabilizing mitochondrial structure, upregulating GPX4, and activating the Nrf2/HO-1 pathway[3]. Acetyl zingerone (25 µg/mL; administered 1-6 h post-UVA irradiation) significantly reduces the formation of dark-state cyclobutane pyrimidine dimers (dark-CPD) in melanocytes of C57BL/6 mice within the first 2 hours after UVA exposure, with an inhibition rate of approximately 82% at 1 h post-irradiation, without impairing DNA repair function or cell viability[4]. Acetyl zingerone (25-50 µg/mL; 20 min pre-incubation prior to 25 min UVA irradiation) dose-dependently reduces UVA-induced ROS production in normal human neonatal epidermal keratinocytes, with reduction rates of 35% and 46%, respectively[4].
References:
[1]. Swindell WR, et al. A Zingerone Analog, Acetyl Zingerone, Bolsters Matrisome Synthesis, Inhibits Matrix Metallopeptidases, and Represses IL-17A Target Gene Expression. J Invest Dermatol. 2020;140(3):602-614.e15.
[2]. Zhang Z, et al. Acetyl zingerone inhibits chondrocyte pyroptosis and alleviates osteoarthritis progression by promoting mitophagy through the PINK1/parkin signaling pathway. Int Immunopharmacol. 2025;161:115055.
[3]. Chen X, et al. Acetyl zingerone ameliorates osteoarthritis by inhibiting chondrocyte programmed cell death. Mol Med Rep. 2023;28(5):202.
[4]. Chaudhuri RK, et al. Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends. Int J Cosmet Sci. 2020;42(1):36-45.