Garcinol is an nonspecificity inhibitor of the histone acetyltransferases (HATs) p300 and PCAF, IC50 values are 7μM and 5μM respectively[1-3]. It is also an nonspecificity inhibitor of potent histone deacetylase 11(HDAC11), IC50 value is 5μM[4].
Garcinol Suppresses CAL-27 cells (10μM, 24h) Proliferation and Colony Formation, inhibits Cell Cycle G1 Phase[5]. And Garcinol induces SCC-15 cells (20μM, 24h) Apoptosis[5]. Garcinol(100μM, 2h) could inhibit the elevated ROS level in H2O2 stimulation-induced Mouse Bone Marrow Mesenchymal Stem Cells(BMSCs) as well[6].
Garcinol(20mg/kg/d for 3days dissolved in 0.1% DMSO by intraperitoneal injection) could decrease inflammation and oxidative stress in cerebral ischemia-reperfusion (I/R) rats, and decreased cerebral injury of I/R rats and improved its neurological function[7]. Garcinol(20mg/kg for 5min dissolved in 0.1% DMSO and intraperitoneally injected)exhibits antithrombotic activity without impacting bleeding time under an efficacious dosage in a model of adenosine diphosphate(ADP)-induced acute pulmonary thromboembolism in mice[8].
Garcinol can prevent ischemia-reperfusion brain injury by inhibiting the TLR4/NF-ĸB signaling pathway to reduce inflammation and oxidative stress and improve nerve function[7].
References:
[1] KOPYTKO P, PIOTROWSKA K, JANISIAK J, et al. Garcinol-A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug [J]. Int J Mol Sci, 2021, 22(6):
[2] BALASUBRAMANYAM K, ALTAF M, VARIER R A, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression [J]. J Biol Chem, 2004, 279(32): 33716-26.
[3] CAO H, AL MAMUN BHUYAN A, UMBACH A T, et al. Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis [J]. Toxins, 2019, 11(7):
[4] SON S I, SU D, HO T T, et al. Garcinol Is an HDAC11 Inhibitor [J]. ACS Chem Biol, 2020, 15(11): 2866-71.
[5] ZHANG G, FU J, SU Y, et al. Opposite Effects of Garcinol on Tumor Energy Metabolism in Oral Squamous Cell Carcinoma Cells [J]. Nutrition and Cancer, 2019, 71(8): 1403-11.
[6] ZOU J, CHEN H, FAN X, et al. Garcinol prevents oxidative stress-induced bone loss and dysfunction of BMSCs through NRF2-antioxidant signaling [J]. Cell Death Discov, 2024, 10(1): 82.
[7] KANG Y, SUN Y, LI T, et al. Garcinol protects against cerebral ischemia-reperfusion injury in vivo and in vitro by inhibiting inflammation and oxidative stress [J]. Mol Cell Probes, 2020, 54(101672.
[8] HSIA C W, HUANG W C, JAYAKUMAR T, et al. Garcinol acts as a novel integrin alpha(IIb)beta(3) inhibitor in human platelets [J]. Life Sci, 2023, 326(121791.
Garcinol是组蛋白乙酰转移酶p300和PCAF的非特异性抑制剂，IC50分别为7μM和5μM[1-3]。它也是强效的组蛋白脱乙酰酶11（HDAC11）的非特异性抑制剂（IC50为5μM）[4]。
Garcinol抑制CAL-27细胞（10μM，24小时）的增殖与克隆形成，使细胞周期停留在G1期[5]。Garcinol还诱导SCC-15细胞（20μM，24小时）凋亡[5]。Garcinol（100μM，2小时）能够抑制由H2O2刺激引起的骨髓间充质干细胞（BMSCs）中升高的活性氧水平[6]。
Garcinol（20mg/kg，三天，0.1% DMSO溶解腹腔注射）能减少脑缺血再灌注大鼠的炎症与氧化应激，并减轻脑缺血再灌注大鼠的脑损伤，改善其神经功能[7]。Garcinol（20mg/kg，5分钟，0.1% DMSO溶解腹腔注射）在二磷酸腺苷诱导的小鼠急性肺栓塞模型中，在有效剂量下表现出抗血栓活性而不影响出血时间[8]。
Garcinol可以通过抑制TLR4/NF-ĸB信号通路减轻炎症和氧化应激以及改善神经功能来预防缺血再灌注脑损伤[7]。