AbMole丨Honokiol(和厚朴酚):一种具有多靶点调节活性的天然产物及其科研应用
Honokiol和厚朴酚AbMoleM3377是一种源自木兰属植物树皮的天然双酚类新木脂素化合物具有多靶点生物活性例如抑制Akt磷酸化以及促进ERK1/2磷酸化。Honokiol在肾癌细胞中能显著抑制细胞增殖与迁移[1]HonokiolCAS No.35354-74-6被用于处理异位子宫内膜间质细胞EESCs在低剂量时无明显细胞毒性但可抑制该细胞迁移、侵袭及上皮-间质转化EMT等过程[2]。Honokiol和厚朴酚在SKOV3与Caov-3卵巢癌细胞中的半抑制浓度IC₅₀分别为48.71±11.31 μM与46.42±5.37 μM能通过激活caspase-3/7/9诱导上述细胞的凋亡[3]。Honokiol和厚朴酚在SK-BR-3乳腺癌细胞中50–60 μmol/L处理后可显著提升其凋亡率下调PCNA、MMP-2、β-catenin及c-Myc表达抑制Wnt/β-catenin通路[4]。Honokiol和厚朴酚AbMoleM3377在U87 MG与U-87 MG-R9胶质瘤细胞中能促进caspase-9活化、Bax上调及Bcl-2下调并通过AMPK-mTOR通路诱导该细胞的自噬依赖性凋亡[5]。动物实验方面Honokiol和厚朴酚在SD大鼠子宫内膜异位症模型中腹腔注射给药后显著改善小鼠的病理形态[2]Honokiol和厚朴酚还在C57BL/6小鼠脉络膜新生血管模型中以20 mg/kg的剂量通过抑制HIF-1α/VEGF轴减轻小鼠病灶面积与渗漏[6]此外Honokiol在SD大鼠非酒精性脂肪性肝炎模型中通过PPARγ通路促进巨噬细胞M2极化[7]。Honokiol还能在氟化钠诱导的C57BL/6小鼠认知障碍模型中通过激活Sirt3提升SOD2活性、清除线粒体活性氧[8]。参考文献及鸣谢[1] Hamedani, Y.; Chakraborty, S.; Sabarwal, A.; et al. Novel Honokiol-eluting PLGA-based scaffold effectively restricts the growth of renal cancer cells.PloS one2020,15(12), e0243837.[2] Kong, X.; Lei, L. Honokiol inhibits cell migration and invasion by blocking EMT via Snail/Slug axis in endometriosis.Naunyn-Schmiedebergs archives of pharmacology2026,399(3), 4507-4517.[3] Lee, J. S.; Sul, J. Y.; Park, J. B.; et al. Honokiol induces apoptosis and suppresses migration and invasion of ovarian carcinoma cells via AMPK/mTOR signaling pathway.International journal of molecular medicine2019,43(5), 1969-1978.[4] Shi, H.; Wang, Y.; Yao, M.; et al. Honokiol inhibits the growth of SKBR3 cells.Translational cancer research2020,9(12), 7596-7604.[5] Lin, C. J.; Chen, T. L.; Tseng, Y. Y.; et al. Honokiol induces autophagic cell death in malignant glioma through reactive oxygen species-mediated regulation of the p53/PI3K/Akt/mTOR signaling pathway.Toxicology and applied pharmacology2016,304, 59-69.[6] Pan, N.; Shi, J.; Du, S.; et al. Honokiol Attenuates Choroidal Neovascularization by Inhibiting the Hypoxia-Inducible Factor-alpha/Vascular Endothelial Growth Factor Axis via Nuclear Transcription Factor-Kappa B Activation.Current eye research2024,49(1), 88-96.[7] Zhong, X.; Liu, H. Honokiol attenuates diet-induced non-alcoholic steatohepatitis by regulating macrophage polarization through activating peroxisome proliferator-activated receptor gamma.Journal of gastroenterology and hepatology2018,33(2), 524-532.[8] Wang, D.; Cao, L.; Zhou, X.; et al. Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1alpha/Sirt3.Journal of hazardous materials2022,437, 129381.细胞实验参考细胞系SKOV3, Caov-3 and NIH-3T3 cell方法Cells were seeded at 5×103 cells/ml in 96-well microplates and were cultured overnight to allow attachment. Honokiol (1-100 µM), compound C (20 µM), and AICAR (500 µM) were added to the medium.浓度1-100 µM处理时间24 h参考文献International Journal of Molecular Medicine, 2019, 43(5): 1969-1978.*上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。动物实验参考动物模型Male Institute of Cancer Research (ICR) mice配制Sterile saline containing 10% dimethyl sulfoxide (DMSO)剂量10 and 20 mg/kg给药处理i.p.参考文献Eur J Pharmacol. 2015 Aug 5;760:88-95.*上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。体内实验的工作液建议现用现配当天使用如在配制过程中出现沉淀、析出现象可以通过超声和或加热的方式助溶。切勿一次性将产品全部溶解。建议制定动物给药及实验方案时尽量参考已发表的相关实验文献溶剂种类及配比众多简单地溶解目的化合物并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题未必能保证目的化合物在动物体内充分发挥生物学效用。