Nobiletin is a polymethoxylated flavone extracted from citrus plants[1]. Nobiletin has a variety of pharmacological effects, including antioxidant, anti-inflammatory, and anti-tumor properties[2]. Nobiletin can be used to improve metabolic syndrome and regulate lipid and blood glucose levels[3]. Nobiletin can also induce apoptosis in cancer cells, inhibit the proliferation and metastasis of tumor cells, and has potential applications in cancer therapy[4].
In vitro, Nobiletin (50–100μM) pre-treated RAW 264.7 macrophages for 16 hours, followed by stimulation with LPS (200ng/mL), significantly inhibited the expression of pro-inflammatory factors and promoted the polarization of macrophages towards the M2 phenotype by activating RORα and increasing Klf4 expression[5]. Nobiletin (2.5μM) pre-treated non-small-cell lung cancer (NSCLC) cell lines H460 and A549 for 24 hours, inhibited cell colony and sphere formation, and induced apoptosis by suppressing the activity of the WNT/β-catenin signaling pathway[6].
In vivo, Nobiletin (100mg/kg/day) was orally administered to D-galactose-induced aging C57BL/6J mice for 10 weeks. Nobiletin significantly increased mouse body weight, hindlimb muscle mass, and lean body mass, and improved skeletal muscle function. Nobiletin also improved muscle fiber size, increased the main protein components of skeletal muscle, and inhibited the production of inflammatory factors[7]. Nobiletin (100mg/kg/day) was intraperitoneally injected into C57BL/6N mice with alcohol-induced hepatic steatosis for 4 weeks. Nobiletin significantly attenuated alcohol-induced hepatic steatosis, endoplasmic reticulum stress, inflammation, and tissue damage in mice. Nobiletin reversed alcohol-induced hepatic mitochondrial dysfunction and oxidative stress[8].
References:
[1] Mileykovskaya E, Yoo SH, Dowhan W, et al. Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging. Biochemistry (Mosc). 2020 Dec;85(12):1554-1559.
[2] Huang J, Chang Z, Lu Q, et al. Nobiletin as an inducer of programmed cell death in cancer: a review. Apoptosis. 2022 Jun;27(5-6):297-310.
[3] Huang Q, Tian L, Zhang Y, et al. Nobiletin alleviates myocardial ischemia-reperfusion injury via ferroptosis in rats with type-2 diabetes mellitus. Biomed Pharmacother. 2023 Jul;163:114795.
[4] Moazamiyanfar R, Rezaei S, AliAshrafzadeh H, et al. Nobiletin in Cancer Therapy; Mechanisms and Therapy Perspectives. Curr Pharm Des. 2023;29(22):1713-1728.
[5] Wang SW, Lan T, Sheng H, et al. Nobiletin Alleviates Non-alcoholic Steatohepatitis in MCD-Induced Mice by Regulating Macrophage Polarization. Front Physiol. 2021 May 20;12:687744.
[6] Han SH, Han JH, Chun WJ, et al. Nobiletin Inhibits Non-Small-Cell Lung Cancer by Inactivating WNT/β-Catenin Signaling through Downregulating miR-15-5p. Evid Based Complement Alternat Med. 2021 Dec 30;2021:7782963.
[7] Wang HH, Zhang Y, Qu TQ, et al. Nobiletin Improves D-Galactose-Induced Aging Mice Skeletal Muscle Atrophy by Regulating Protein Homeostasis. Nutrients. 2023 Apr 7;15(8):1801.
[8] Lu D, Huang A, Tong X, et al. Nobiletin protects against alcohol-induced mitochondrial dysfunction and liver injury by regulating the hepatic NRF1-TFAM signaling pathway. Redox Rep. 2024 Dec;29(1):2395779.
Nobiletin是从柑橘类植物中提取的一种多甲氧基黄酮类化合物[1]。Nobiletin具有抗氧化、抗炎、抗肿瘤等多种药理作用[2]。Nobiletin可用于改善代谢综合征，调节血脂和血糖水平[3]。Nobiletin还可以诱导癌细胞凋亡，抑制肿瘤细胞的增殖和转移，在癌症治疗中具有潜在的应用价值[4]。
在体外，Nobiletin（50–100μM）预处理RAW 264.7巨噬细胞16h，随后以LPS（200ng/mL）刺激，Nobiletin显著抑制促炎因子的表达，还可通过激活RORα，增加Klf4表达，促进巨噬细胞向M2表型极化[5]。Nobiletin（2.5μM）预处理非小细胞肺癌（NSCLC）细胞系H460和A549 24小时，Nobiletin通过抑制WNT/β-catenin信号通路活性，抑制细胞集落形成和球体形成，诱导细胞凋亡[6]。
在体内，Nobiletin（100mg/kg/day）口服给药，用于处理D-半乳糖诱导的衰老C57BL/6J小鼠10周。Nobiletin显著增加了小鼠体重、后肢肌肉质量、瘦体质量，并改善了骨骼肌功能。Nobiletin还改善了肌纤维尺寸，增加了骨骼肌主要蛋白质成分，并抑制了炎症因子的产生[7]。Nobiletin（100mg/kg/day）腹腔注射，用于处理酒精诱导的小鼠肝脂肪变性C57BL/6N小鼠模型，持续4周。Nobiletin显著减轻了酒精诱导的小鼠肝脂肪变性、内质网应激、炎症和组织损伤。Nobiletin逆转了酒精诱导的小鼠肝脏线粒体功能障碍和氧化应激[8]。