Nobiletin (BioDeep_00000002607)

 

Secondary id: BioDeep_00000270592

human metabolite PANOMIX_OTCML-2023 Endogenous


代谢物信息卡片


2-(3,4-Dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one, 9CI

化学式: C21H22O8 (402.1314612)
中文名称: 川陈皮素, 蜜橘黄素, 川皮亭, 川皮苷, 蜜橘黄素
谱图信息: 最多检出来源 Viridiplantae(plant) 0.63%

分子结构信息

SMILES: c1(c(c(c2c(c1OC)oc(cc2=O)c1cc(c(cc1)OC)OC)OC)OC)OC
InChI: InChI=1S/C21H22O8/c1-23-13-8-7-11(9-15(13)24-2)14-10-12(22)16-17(25-3)19(26-4)21(28-6)20(27-5)18(16)29-14/h7-10H,1-6H3

描述信息

Nobiletin is a methoxyflavone that is flavone substituted by methoxy groups at positions 5, 6, 7, 8, 3 and 4 respectively. It has a role as a plant metabolite and an antineoplastic agent. It is functionally related to a flavone.
Nobiletin is a natural product found in Citrus tankan, Citrus keraji, and other organisms with data available.
See also: Tangerine peel (part of); Citrus aurantium fruit rind (part of).
Isolated from peel of king orange (Citrus nobilis), seville orange (Citrus aurantium) and other Citrus subspecies, and the round kumquat (Fortunella japonica). Nobiletin is found in many foods, some of which are sweet bay, citrus, lemon, and grapefruit.
Nobiletin is found in citrus. Nobiletin is isolated from peel of king orange (Citrus nobilis), seville orange (Citrus aurantium) and other Citrus species, and the round kumquat (Fortunella japonica
A methoxyflavone that is flavone substituted by methoxy groups at positions 5, 6, 7, 8, 3 and 4 respectively.
D020011 - Protective Agents > D000975 - Antioxidants
Nobiletin is a poly-methoxylated flavone from the citrus peel that improves memory loss. Nobiletin is a retinoid acid receptor-related orphan receptors (RORs) agonist. Nobiletin can reduce reactive oxygen species (ROS) levels in differentiated C2C12 myotubes and has anti-inflammation and anti-cancer properties, including anti-angiogenesis, anti-proliferation, anti-metastasis and induced apoptosis[1][2][3][4].
Nobiletin is a poly-methoxylated flavone from the citrus peel that improves memory loss. Nobiletin is a retinoid acid receptor-related orphan receptors (RORs) agonist. Nobiletin can reduce reactive oxygen species (ROS) levels in differentiated C2C12 myotubes and has anti-inflammation and anti-cancer properties, including anti-angiogenesis, anti-proliferation, anti-metastasis and induced apoptosis[1][2][3][4].

同义名列表

34 个代谢物同义名

2-(3,4-Dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one, 9CI; 4H-1-Benzopyran-4-one, 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-; 2-(3,4-Dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one; 4H-1-Benzopyran-4-one,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-chromen-4-one; 2-(3,4-Dimethoxy-phenyl)-5,6,7,8-tetramethoxy-chromen-4-one; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-chromen-4-one; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one; 4,5,6,7,8,9,10,11,12,13-decahydrocyclododeca[d]oxazole; FLAVONE, 3,4,5,6,7,8-HEXAMETHOXY-; NOBILETIN, 20\\% (Technical Grade); Flavone, 5,6,7,8,3,4-hexamethoxy; 5,6,7,8,3,4-Hexamethoxyflavone; 3,4,5,6,7,8-Hexamethoxyflavone; Nobiletin (Hexamethoxyflavone); 5,6,7,8,3,4-hexamethoxyflavone; Nobiletin, analytical standard; 345,6,7,8-Hexamethoxyflavone; HEXAMETHOXYFLAVONE [WHO-DD]; NOBILETIN (USP-RS); NOBILETIN [USP-RS]; hexamethoxyflavone; Nobiletin, >=97\\%; NOBILETIN [INCI]; Spectrum4_001020; Spectrum2_001697; Spectrum3_000921; UNII-D65ILJ7WLY; MEGxp0_000930; NCI60_041691; ACon1_000921; KBio3_001922; D65ILJ7WLY; Nobiletin



数据库引用编号

20 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(0)

BioCyc(0)

PlantCyc(0)

代谢反应

0 个相关的代谢反应过程信息。

Reactome(0)

BioCyc(0)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(0)

PharmGKB(0)

82 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。



文献列表

  • Yulia N Cajas, Karina Cañón-Beltrán, Rosane Mazzarella, Carolina Nuñez-Puente, Encina M González, Heriberto Rodriguez-Martinez, Dimitrios Rizos, Cristina A Martinez-Serrano. Nobiletin as a novel agent to enhance porcine in vitro embryo development and quality. Theriogenology. 2024 Jul; 223(?):36-46. doi: 10.1016/j.theriogenology.2024.04.011. [PMID: 38669840]
  • Xingran Kou, Min Hong, Fei Pan, Xin Huang, Qingran Meng, Yunchong Zhang, Qinfei Ke. Inhibitory effects of nobiletin-mediated interfacial instability of bile salt emulsified oil droplets on lipid digestion. Food chemistry. 2024 Jun; 444(?):138751. doi: 10.1016/j.foodchem.2024.138751. [PMID: 38412567]
  • Menglin Chen, Huaizhi Li, Shanshan Zheng, Junyu Shen, Yuxuan Chen, Yaqi Li, Mengyun Yuan, Jian Wu, Qingmin Sun. Nobiletin targets SREBP1/ACLY to induce autophagy-dependent cell death of gastric cancer cells through PI3K/Akt/mTOR signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024 Jun; 128(?):155360. doi: 10.1016/j.phymed.2024.155360. [PMID: 38547624]
  • Qiqi Ran, Qianrong Gan, Ye Zhu, Li Song, Longyu Shen, Xinyi Duan, Xinyun Zhu, Wei Huang. Mechanism insights into the pleiotropic effects of nobiletin as a potential therapeutic agent on non-alcoholic fatty liver disease (NAFLD). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024 Apr; 173(?):116322. doi: 10.1016/j.biopha.2024.116322. [PMID: 38401524]
  • Heng Wang, Qinqin Tian, Ruijing Zhang, Qiujing Du, Jie Hu, Tingting Gao, Siqi Gao, Keyi Fan, Xing Cheng, Sheng Yan, Guoping Zheng, Honglin Dong. Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway. Lipids in health and disease. 2024 Mar; 23(1):76. doi: 10.1186/s12944-024-02049-5. [PMID: 38468335]
  • Jingchun Bai, Xinyu Wang, Yiqiu Chen, Qiongyu Yuan, Zhaoyu Yang, Yuling Mi, Caiqiao Zhang. Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy. Cells. 2024 Feb; 13(5):. doi: 10.3390/cells13050415. [PMID: 38474379]
  • Hongling Xu, Mingming Yuan, Kailin Niu, Wei Yang, Maoyuan Jiang, Lei Zhang, Jing Zhou. Involvement of Bile Acid Metabolism and Gut Microbiota in the Amelioration of Experimental Metabolism-Associated Fatty Liver Disease by Nobiletin. Molecules (Basel, Switzerland). 2024 Feb; 29(5):. doi: 10.3390/molecules29050976. [PMID: 38474489]
  • Chaowen Fan, Anli Ling-Hu, Dali Sun, Weiman Gao, Chenfang Zhang, Xueqing Duan, Haiyang Li, Weiyi Tian, Qi Yu, Zunli Ke. Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease. Journal of agricultural and food chemistry. 2023 Dec; 71(50):20105-20117. doi: 10.1021/acs.jafc.3c06498. [PMID: 38073108]
  • Areeg Almubarak, Sanghoon Lee, Il-Jeoung Yu, Yubyeol Jeon. Effects of Nobiletin supplementation on the freezing diluent on porcine sperm cryo-survival and subsequent in vitro embryo development. Theriogenology. 2023 Nov; 214(?):314-322. doi: 10.1016/j.theriogenology.2023.11.006. [PMID: 37956580]
  • Yueshan Pang, Juan Xiong, You Wu, Weijun Ding. A review on recent advances on nobiletin in central and peripheral nervous system diseases. European journal of medical research. 2023 Nov; 28(1):485. doi: 10.1186/s40001-023-01450-7. [PMID: 37932838]
  • Eunju Kim, Kazuaki Mawatari, Seung-Hee Yoo, Zheng Chen. The Circadian Nobiletin-ROR Axis Suppresses Adipogenic Differentiation and IκBα/NF-κB Signaling in Adipocytes. Nutrients. 2023 Sep; 15(18):. doi: 10.3390/nu15183919. [PMID: 37764703]
  • Wei Huang, Hui Chen, Qi He, Weidang Xie, Zanlin Peng, Qiang Ma, Qiaobing Huang, Zhongqing Chen, Yanan Liu. Nobiletin protects against ferroptosis to alleviate sepsis-associated acute liver injury by modulating the gut microbiota. Food & function. 2023 Aug; ?(?):. doi: 10.1039/d3fo01684f. [PMID: 37545398]
  • Menglin Chen, Ruijuan Zhang, Yaling Chen, Xu Chen, Yaqi Li, Junyu Shen, Mengyun Yuan, Yuxuan Chen, Jian Wu, Qingmin Sun. Nobiletin inhibits de novo FA synthesis to alleviate gastric cancer progression by regulating endoplasmic reticulum stress. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023 Jul; 116(?):154902. doi: 10.1016/j.phymed.2023.154902. [PMID: 37270969]
  • Konglong Feng, Yashan Duan, Huiting Zhang, Jie Xiao, Chi-Tang Ho, Qingrong Huang, Yong Cao. Influence of 1,3-diacylglycerol on physicochemical and digestion properties of nanoemulsions and its enhancement of encapsulation and bioaccessibility of hydrophobic nobiletin. Food & function. 2023 Jul; 14(13):6212-6225. doi: 10.1039/d3fo00543g. [PMID: 37345830]
  • Zhitian Lu, Xudong Li, Min Wang, Xiaojun Zhang, Runxuan Zhuang, Fan Wu, Wenxue Li, Wei Zhu, Bo Zhang. Liver-Specific Bmal1 Depletion Reverses the Beneficial Effects of Nobiletin on Liver Cholesterol Homeostasis in Mice Fed with High-Fat Diet. Nutrients. 2023 May; 15(11):. doi: 10.3390/nu15112547. [PMID: 37299510]
  • Cunzhen Zhao, Jiahua Guo, Chunyu Du, Yongjie Xu. Modulation of Fat Deposition-Gut Interactions in Obese Mice by Administrating with Nobiletin. Genes. 2023 May; 14(5):. doi: 10.3390/genes14051062. [PMID: 37239422]
  • Shang-Zhen Li, Ning-Ning Zhang, Xing Yang, Tian-Qing Huang, Yang Lin, Zheng-Meng Jiang, Yongxiang Yi, E-Hu Liu. Nobiletin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Myristoleic Acid Metabolism. Journal of agricultural and food chemistry. 2023 May; ?(?):. doi: 10.1021/acs.jafc.2c08637. [PMID: 37139957]
  • Xushan Yang, Linye Sun, Dongliang Feng, Yudi Deng, Wenzhen Liao. A Lipidomic Study: Nobiletin ameliorates hepatic steatosis through regulation of lipid alternation. The Journal of nutritional biochemistry. 2023 Apr; ?(?):109353. doi: 10.1016/j.jnutbio.2023.109353. [PMID: 37116815]
  • Xiaoshan Liao, Jiaxuan Zou, Mengting Wu, Yudi Deng, Jinwei Shi, Yuting Hao, Hong Deng, Wenzhen Liao. Hypoglycemic Effect of Nobiletin via Gut Microbiota-Metabolism Axis on Hyperglycemic Mice. Molecular nutrition & food research. 2023 Mar; ?(?):e2200289. doi: 10.1002/mnfr.202200289. [PMID: 36906890]
  • Zunli Ke, Chaowen Fan, Jun Li, La Wang, Haiyang Li, Weiyi Tian, Qi Yu. Nobiletin Intake Attenuates Hepatic Lipid Profiling and Oxidative Stress in HFD-Induced Nonalcoholic-Fatty-Liver-Disease Mice. Molecules (Basel, Switzerland). 2023 Mar; 28(6):. doi: 10.3390/molecules28062570. [PMID: 36985541]
  • Yanhong Sun, Xiaoyan Duan, Fenghe Wang, Huixin Tan, Jiahuan Hu, Wanting Bai, Xinbo Wang, Baolian Wang, Jinping Hu. Inhibitory effects of flavonoids on glucose transporter 1 (GLUT1): From library screening to biological evaluation to structure-activity relationship. Toxicology. 2023 Mar; ?(?):153475. doi: 10.1016/j.tox.2023.153475. [PMID: 36870413]
  • Chiara Corrado, Maria Magdalena Barreca, Stefania Raimondo, Patrizia Diana, Giacomo Pepe, Maria Giovanna Basilicata, Alice Conigliaro, Riccardo Alessandro. Nobiletin and xanthohumol counteract the TNFα-mediated activation of endothelial cells through the inhibition of the NF-κB signaling pathway. Cell biology international. 2023 Mar; 47(3):634-647. doi: 10.1002/cbin.11963. [PMID: 36378586]
  • Yuan Wu, Qiong Li, Ling-Ling Lv, Jing-Xian Chen, Hai-Feng Ying, Ming Ruan, Wen-Hua Zhu, Jia-Yue Xu, Chen-Yiyu Zhang, Kai-Yuan Zhang, Yuan-Biao Guo, Wei-Rong Zhu, Lan Zheng. Nobiletin inhibits breast cancer cell migration and invasion by suppressing the IL-6-induced ERK-STAT and JNK-c-JUN pathways. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023 Feb; 110(?):154610. doi: 10.1016/j.phymed.2022.154610. [PMID: 36584607]
  • Q-J Du, Q Li, R-H Zhou, H Wang, Q Yan, W-J Dang, J-J Guo. An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology. European review for medical and pharmacological sciences. 2023 Feb; 27(4):1553-1564. doi: 10.26355/eurrev_202302_31398. [PMID: 36876711]
  • Muhammad Umar Ijaz, Aqsa Ahmed, Khalid Abdullah Al-Ghanim, Fahad Al-Misned, Mian Nadeem Riaz, Zahid Ali Kaimkhani, Shahid Mahboob. Evaluation of the Possible Protective Role of Nobiletin against Arsenic-Induced Liver Damage in Male Albino Rats. Toxics. 2023 Jan; 11(2):. doi: 10.3390/toxics11020110. [PMID: 36850985]
  • Yun-Yi Chen, Jiao-Jiao Liang, Deng-Liang Wang, Jie-Biao Chen, Jin-Ping Cao, Yue Wang, Chong-De Sun. Nobiletin as a chemopreventive natural product against cancer, a comprehensive review. Critical reviews in food science and nutrition. 2023; 63(23):6309-6329. doi: 10.1080/10408398.2022.2030297. [PMID: 35089821]
  • Yueshan Pang, Ni Yang, Yali Zheng, Lu Zhang, Yan He, Weijun Ding. Nobiletin protects enteric nerves and ameliorates disordered bowel motility in diet-induced obese mice via increasing Trem2 expression. Biochemical and biophysical research communications. 2022 12; 635(?):19-29. doi: 10.1016/j.bbrc.2022.10.008. [PMID: 36252333]
  • Shiwei Su, Denggao Zhao, Bo Yuan, Yanyan Ma, Siyue Zhu, Kuangyu Xu, Grace Lee, Chi-Tang Ho, Qingrong Huang. Biosynthesis of 6- and 7-Mono-Demethylated Nobiletins by a Newly Isolated Strain of Yeast. Journal of agricultural and food chemistry. 2022 Dec; 70(49):15439-15448. doi: 10.1021/acs.jafc.2c03822. [PMID: 36454712]
  • Ching-Yen Lin, Pei-Yi Chen, Hao-Jen Hsu, Wan-Yun Gao, Ming-Jiuan Wu, Jui-Hung Yen. The Citrus Flavonoid Nobiletin Downregulates Angiopoietin-like Protein 3 (ANGPTL3) Expression and Exhibits Lipid-Modulating Effects in Hepatic Cells and Adult Zebrafish Models. International journal of molecular sciences. 2022 Oct; 23(20):. doi: 10.3390/ijms232012485. [PMID: 36293338]
  • Xushan Yang, Yudi Deng, Yali Tu, Dongliang Feng, Wenzhen Liao. Nobiletin mitigates NAFLD via lipophagy and inflammation. Food & function. 2022 Oct; 13(19):10186-10199. doi: 10.1039/d2fo01682f. [PMID: 36111578]
  • Sebastian Larion, Caleb A Padgett, Joshua T Butcher, James D Mintz, David J Fulton, David W Stepp. The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm. American journal of physiology. Gastrointestinal and liver physiology. 2022 Oct; 323(4):G387-G400. doi: 10.1152/ajpgi.00130.2022. [PMID: 35997288]
  • Metee Iampanichakul, Anuson Poasakate, Prapassorn Potue, Siwayu Rattanakanokchai, Putcharawipa Maneesai, Parichat Prachaney, Wannapa Settheetham-Ishida, Poungrat Pakdeechote. Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats. Scientific reports. 2022 06; 12(1):9289. doi: 10.1038/s41598-022-13513-6. [PMID: 35662276]
  • Ying Zhou, Hong-Liang Zeng, Xin-Yue Wen, Ling Jiang, Chu-Han Fu, Yi-Bo Hu, Xin-Xin Lei, Li Zhang, Xing Yu, Si-Yu Yang, Li-Hua Huang, Hong Xiang, Jin-Hua Huang, Jing Chen, Li Lei, Qing-Hai Zeng. Selaginellin Inhibits Melanogenesis via the MAPK Signaling Pathway. Journal of natural products. 2022 04; 85(4):838-845. doi: 10.1021/acs.jnatprod.1c00971. [PMID: 35290062]
  • Wen Chai, Ji Zhang, Zhengbing Xiang, Honglian Zhang, Zhujun Mei, Hongbing Nie, Renxu Xu, Ping Zhang. Potential of nobiletin against Alzheimer's disease through inhibiting neuroinflammation. Metabolic brain disease. 2022 04; 37(4):1145-1154. doi: 10.1007/s11011-022-00932-7. [PMID: 35267136]
  • Michio Hashimoto, Kentaro Matsuzaki, Koji Maruyama, Shahdat Hossain, Eri Sumiyoshi, Harumi Wakatsuki, Setsushi Kato, Miho Ohno, Yoko Tanabe, Yoko Kuroda, Shuhei Yamaguchi, Koji Kajima, Yasushi Ohizumi, Osamu Shido. Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly. Food & function. 2022 Mar; 13(5):2768-2781. doi: 10.1039/d1fo03508h. [PMID: 35171190]
  • Shuyu Li, Xi Li, Fangyuan Chen, Min Liu, Liuxin Ning, Yufeng Yan, Shuncai Zhang, Shaoping Huang, Chuantao Tu. Nobiletin mitigates hepatocytes death, liver inflammation, and fibrosis in a murine model of NASH through modulating hepatic oxidative stress and mitochondrial dysfunction. The Journal of nutritional biochemistry. 2022 02; 100(?):108888. doi: 10.1016/j.jnutbio.2021.108888. [PMID: 34695558]
  • Nadya M Morrow, Natasha A Trzaskalski, Antonio A Hanson, Evgenia Fadzeyeva, Dawn E Telford, Sanjiv S Chhoker, Brian G Sutherland, Jane Y Edwards, Murray W Huff, Erin E Mulvihill. Nobiletin Prevents High-Fat Diet-Induced Dysregulation of Intestinal Lipid Metabolism and Attenuates Postprandial Lipemia. Arteriosclerosis, thrombosis, and vascular biology. 2022 02; 42(2):127-144. doi: 10.1161/atvbaha.121.316896. [PMID: 34911361]
  • Liping You, Jiacheng Lin, Zhuo Yu, Yihan Qian, Yuting Bi, Fang Wang, Lei Zhang, Chao Zheng, Jinghao Zhang, Wenxuan Li, Yaxuan Cai, Yueqiu Gao, Xiaoni Kong, Xuehua Sun. Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β. International journal of biological sciences. 2022; 18(15):5698-5712. doi: 10.7150/ijbs.78345. [PMID: 36263164]
  • Marwa Salah, Khadiga Ahmed Ismail, Sally Mostafa Khadrawy. Nobiletin protects against diabetes-induced testicular injury via hypophysis-gonadal axis upregulation and amelioration of oxidative stress. Molecular biology reports. 2022 Jan; 49(1):189-203. doi: 10.1007/s11033-021-06858-0. [PMID: 34709572]
  • Jie Zhang, Meiling Fan, Xia Yu, Bin Zhang. The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro. Pharmaceutical biology. 2021 Dec; 59(1):1528-1532. doi: 10.1080/13880209.2021.1990355. [PMID: 34726569]
  • Mingzhu Xu, Ruifang Wang, Hui Fan, Ziyuan Ni. Nobiletin ameliorates streptozotocin-cadmium-induced diabetic nephropathy via NF-κB signalling pathway in rats. Archives of physiology and biochemistry. 2021 Aug; ?(?):1-9. doi: 10.1080/13813455.2021.1959617. [PMID: 34346259]
  • Takuya Nihei, Eri Ushiro, Hideyuki Sato, Satomi Onoue. Biopharmaceutical Study on Nobiletin-Loaded Amorphous Solid Dispersion with Improved Hypouricemic Effect. Molecules (Basel, Switzerland). 2021 Jul; 26(15):. doi: 10.3390/molecules26154447. [PMID: 34361599]
  • Ji-Guo Wang, Wen-Jing Jian, Yang Li, Jing Zhang. Nobiletin promotes the pyroptosis of breast cancer via regulation of miR-200b/JAZF1 axis. The Kaohsiung journal of medical sciences. 2021 Jul; 37(7):572-582. doi: 10.1002/kjm2.12371. [PMID: 33728753]
  • Karina Cañón-Beltrán, Yulia N Cajas, Serafín Peréz-Cerezales, Claudia L V Leal, Ekaitz Agirregoitia, Alfonso Gutierrez-Adán, Encina M González, Dimitrios Rizos. Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation. Scientific reports. 2021 06; 11(1):11796. doi: 10.1038/s41598-021-91158-7. [PMID: 34083641]
  • Hong-Ci Lan, Shang-Zhen Li, Kai Li, E-Hu Liu. In vitro human intestinal microbiota biotransformation of nobiletin using liquid chromatography-mass spectrometry analysis and background subtraction strategy. Journal of separation science. 2021 May; 44(10):2046-2053. doi: 10.1002/jssc.202001150. [PMID: 33682313]
  • Man Zhang, Xin Zhang, Jieyu Zhu, Deng-Gao Zhao, Yan-Yan Ma, Dongli Li, Chi-Tang Ho, Qingrong Huang. Bidirectional interaction of nobiletin and gut microbiota in mice fed with a high-fat diet. Food & function. 2021 Apr; 12(8):3516-3526. doi: 10.1039/d1fo00126d. [PMID: 33900329]
  • Yurong Song, Linlin Liu, Bin Liu, Rui Liu, Youwen Chen, Chenxi Li, Guangzhi Liu, Zhiqian Song, Cheng Lu, Aiping Lu, Yuanyan Liu. Interaction of nobiletin with methotrexate ameliorates 7-OH methotrexate-induced nephrotoxicity through endoplasmic reticulum stress-dependent PERK/CHOP signaling pathway. Pharmacological research. 2021 03; 165(?):105371. doi: 10.1016/j.phrs.2020.105371. [PMID: 33460792]
  • Muhammad Umar Ijaz, Arfa Tahir, Abdul Samad, Haseeb Anwar. Nobiletin ameliorates nonylphenol-induced testicular damage by improving biochemical, steroidogenic, hormonal, spermatogenic, apoptotic and histological profile. Human & experimental toxicology. 2021 Mar; 40(3):403-416. doi: 10.1177/0960327120950007. [PMID: 32815738]
  • Tingting Chen, Liu Liu, Yonghong Zou, Xiaoyan Hu, Wenfeng Zhang, Tao Zhou, Xi Luo, Weihua Fu, Jie Xu. Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma. Cancer biology & medicine. 2021 02; 18(1):227-244. doi: 10.20892/j.issn.2095-3941.2020.0186. [PMID: 33628597]
  • Guangning Kou, Peiyuan Li, Youchun Hu, Huanan Chen, Adwoa Nyantakyiwaa Amoah, Stanislav Seydou Traore, Zhenwei Cui, Quanjun Lyu. Nobiletin activates thermogenesis of brown and white adipose tissue in high-fat diet-fed C57BL/6 mice by shaping the gut microbiota. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021 02; 35(2):e21267. doi: 10.1096/fj.202002197r. [PMID: 33475201]
  • Kuntol Rakshit, Aleksey V Matveyenko. Induction of Core Circadian Clock Transcription Factor Bmal1 Enhances β-Cell Function and Protects Against Obesity-Induced Glucose Intolerance. Diabetes. 2021 01; 70(1):143-154. doi: 10.2337/db20-0192. [PMID: 33087455]
  • Sarawoot Bunbupha, Poungrat Pakdeechote, Putcharawipa Maneesai, Patoomporn Prasarttong. Nobiletin alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating AdipoR1 and gp91phox expression in rats. The Journal of nutritional biochemistry. 2021 01; 87(?):108526. doi: 10.1016/j.jnutbio.2020.108526. [PMID: 33096235]
  • Bo Liu, Quanhong Deng, Lei Zhang, Wen Zhu. Nobiletin alleviates ischemia/reperfusion injury in the kidney by activating PI3K/AKT pathway. Molecular medicine reports. 2020 Dec; 22(6):4655-4662. doi: 10.3892/mmr.2020.11554. [PMID: 33173956]
  • Hao Wang, Lin Dong, Fangfei Qu, Huimin He, Wei Sun, Yuqing Man, Hongjie Jiang. Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism. Pharmaceutical biology. 2020 Dec; 58(1):352-356. doi: 10.1080/13880209.2020.1751661. [PMID: 32298152]
  • Yue Wang, Yunyi Chen, He Zhang, Jiebiao Chen, Jinping Cao, Qingjun Chen, Xian Li, Chongde Sun. Polymethoxyflavones from citrus inhibited gastric cancer cell proliferation through inducing apoptosis by upregulating RARβ, both in vitro and in vivo. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2020 Dec; 146(?):111811. doi: 10.1016/j.fct.2020.111811. [PMID: 33058988]
  • Xin Huang, Junxiang Zhu, Li Wang, Huijuan Jing, Chaoyang Ma, Xingran Kou, Hongxin Wang. Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation. International journal of biological macromolecules. 2020 Dec; 164(?):1927-1938. doi: 10.1016/j.ijbiomac.2020.07.305. [PMID: 32795575]
  • Sarawoot Bunbupha, Kwanjit Apaijit, Putcharawipa Maneesai, Patoomporn Prasarttong, Poungrat Pakdeechote. Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats. Life sciences. 2020 Nov; 260(?):118398. doi: 10.1016/j.lfs.2020.118398. [PMID: 32920004]
  • Junjun Yang, Yang Yang, Lu Wang, Qiuchen Jin, Minghui Pan. Nobiletin selectively inhibits oral cancer cell growth by promoting apoptosis and DNA damage in vitro. Oral surgery, oral medicine, oral pathology and oral radiology. 2020 Oct; 130(4):419-427. doi: 10.1016/j.oooo.2020.06.020. [PMID: 32868254]
  • Man Zhang, Yanping Xin, Konglong Feng, Baoer Yin, Qixin Kan, Jie Xiao, Yong Cao, Chi-Tang Ho, Qingrong Huang. Comparative Analyses of Bioavailability, Biotransformation, and Excretion of Nobiletin in Lean and Obese Rats. Journal of agricultural and food chemistry. 2020 Sep; 68(39):10709-10718. doi: 10.1021/acs.jafc.0c04425. [PMID: 32880448]
  • Mao Seoka, Gang Ma, Lancui Zhang, Masaki Yahata, Kazuki Yamawaki, Toshiyuki Kan, Masaya Kato. Expression and functional analysis of the nobiletin biosynthesis-related gene CitOMT in citrus fruit. Scientific reports. 2020 09; 10(1):15288. doi: 10.1038/s41598-020-72277-z. [PMID: 32943728]
  • Zhenyu Xu, Ding Wu, Dian Fu, Chaopeng Tang, Jingping Ge, Zhengyu Zhang, Wenquan Zhou. Nobiletin inhibits viability of human renal carcinoma cells via the JAK2/STAT3 and PI3K/Akt pathway. Cellular and molecular biology (Noisy-le-Grand, France). 2020 Jul; 66(5):199-203. doi: . [PMID: 33040836]
  • Akira Nakajima, Kiyomitsu Nemoto, Yasushi Ohizumi. An evaluation of the genotoxicity and subchronic toxicity of the peel extract of Ponkan cultivar 'Ohta ponkan' (Citrus reticulata Blanco) that is rich in nobiletin and tangeretin with anti-dementia activity. Regulatory toxicology and pharmacology : RTP. 2020 Jul; 114(?):104670. doi: 10.1016/j.yrtph.2020.104670. [PMID: 32371103]
  • Balwinder Singh, Jatinder Pal Singh, Amritpal Kaur, Narpinder Singh. Phenolic composition, antioxidant potential and health benefits of citrus peel. Food research international (Ottawa, Ont.). 2020 06; 132(?):109114. doi: 10.1016/j.foodres.2020.109114. [PMID: 32331689]
  • Eman H Yousef, Mohamed E El-Mesery, Maha R Habeeb, Laila A Eissa. Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2020 Apr; 42(4):1010428320914475. doi: 10.1177/1010428320914475. [PMID: 32252611]
  • Zhongwen Hu, Jieli Hu, Fang Ren, Hongyan Xu, Ming Tan, Qing Wang, Jihua Ren. Nobiletin, a novel inhibitor, inhibits HBsAg production and hepatitis B virus replication. Biochemical and biophysical research communications. 2020 03; 523(3):802-808. doi: 10.1016/j.bbrc.2019.12.099. [PMID: 31954513]
  • Nadya M Morrow, Amy C Burke, Joshua P Samsoondar, Kyle E Seigel, Andrew Wang, Dawn E Telford, Brian G Sutherland, Conor O'Dwyer, Gregory R Steinberg, Morgan D Fullerton, Murray W Huff. The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK. Journal of lipid research. 2020 03; 61(3):387-402. doi: 10.1194/jlr.ra119000542. [PMID: 31964763]
  • Mehmet Güvenç, Mustafa Cellat, Ahmet Uyar, Hüseyin Özkan, İshak Gokcek, Cafer Tayer İsler, Akın Yakan. Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions. Inflammation. 2020 Feb; 43(1):336-346. doi: 10.1007/s10753-019-01123-w. [PMID: 31705353]
  • Sen-Ling Feng, Yun Tian, Shuai Huo, Biao Qu, Rui-Ming Liu, Peng Xu, Ya-Zhuo Li, Ying Xie. Nobiletin potentiates paclitaxel anticancer efficacy in A549/T xenograft model: Pharmacokinetic and pharmacological study. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2020 Feb; 67(?):153141. doi: 10.1016/j.phymed.2019.153141. [PMID: 31884406]
  • Mehmet Güvenç, Mustafa Cellat, İshak Gökçek, Hüseyin Özkan, Gözde Arkalı, Akın Yakan, Şule Yurdagül Özsoy, Mesut Aksakal. Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats. Journal of biochemical and molecular toxicology. 2020 Feb; 34(2):e22427. doi: 10.1002/jbt.22427. [PMID: 31777137]
  • Di Wu, Youyan Liang, Yaqiong Pei, Bin Li, Hongshan Liang. Plant exine capsules based encapsulation strategy: A high loading and long-term effective delivery system for nobiletin. Food research international (Ottawa, Ont.). 2020 01; 127(?):108691. doi: 10.1016/j.foodres.2019.108691. [PMID: 31882107]
  • Kazunari Nohara, Eunju Kim, Marvin Wirianto, Eugenia Mileykovskaya, William Dowhan, Zheng Chen, Seung-Hee Yoo. Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet. Oxidative medicine and cellular longevity. 2020; 2020(?):5304768. doi: 10.1155/2020/5304768. [PMID: 32617138]
  • Yiming Ouyang, Linhai Li, Ping Ling. Nobiletin Inhibits Helicobacterium pylori Infection-Induced Gastric Carcinogenic Signaling by Blocking Inflammation, Apoptosis, and Mitogen-Activated Protein Kinase Events in Gastric Epithelial-1 Cells. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer. 2020; 39(1):77-88. doi: 10.1615/jenvironpatholtoxicoloncol.2020031272. [PMID: 32479014]
  • Yue Sun, Yanhui Han, Mingyue Song, Noppawat Charoensinphon, Jinkai Zheng, Peiju Qiu, Xian Wu, Hang Xiao. Inhibitory effects of nobiletin and its major metabolites on lung tumorigenesis. Food & function. 2019 Nov; 10(11):7444-7452. doi: 10.1039/c9fo01966a. [PMID: 31664275]
  • Hae Jin Lee, Sung-Kwon Lee, Dong-Ryung Lee, Bong-Keun Choi, Bao Le, Seung Hwan Yang. Ameliorating effect of Citrus aurantium extracts and nobiletin on β‑amyloid (1‑42)‑induced memory impairment in mice. Molecular medicine reports. 2019 Oct; 20(4):3448-3455. doi: 10.3892/mmr.2019.10582. [PMID: 31432129]
  • Yongliang Cui, Jing Zhao, Jie Zhou, Guiyu Tan, Qiyang Zhao, Yaohai Zhang, Baomin Wang, Bining Jiao. Development of a sensitive monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay for analysing nobiletin in citrus and herb samples. Food chemistry. 2019 Sep; 293(?):144-150. doi: 10.1016/j.foodchem.2019.04.101. [PMID: 31151594]
  • Yin Xu, Xiaojian Lv, Guliang Yang, Jianfeng Zhan, Ming Li, Tao Long, Chi-Tang Ho, Shiming Li. Simultaneous separation of six pure polymethoxyflavones from sweet orange peel extract by high performance counter current chromatography. Food chemistry. 2019 Sep; 292(?):160-165. doi: 10.1016/j.foodchem.2019.04.031. [PMID: 31054661]
  • Kazunari Nohara, Travis Nemkov, Angelo D'Alessandro, Seung-Hee Yoo, Zheng Chen. Coordinate Regulation of Cholesterol and Bile Acid Metabolism by the Clock Modifier Nobiletin in Metabolically Challenged Old Mice. International journal of molecular sciences. 2019 Sep; 20(17):. doi: 10.3390/ijms20174281. [PMID: 31480535]
  • Huijuan Zhang, Guifang Tian, Chengying Zhao, Yanhui Han, Christina DiMarco-Crook, Chang Lu, Yuming Bao, Chengxiu Li, Hang Xiao, Jinkai Zheng. Characterization of polymethoxyflavone demethylation during drying processes of citrus peels. Food & function. 2019 Sep; 10(9):5707-5717. doi: 10.1039/c9fo01053j. [PMID: 31436765]
  • Qing Mao, Xiulin Liang, Yufu Wu, Yongxiang Lu. Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats. Naunyn-Schmiedeberg's archives of pharmacology. 2019 09; 392(9):1121-1130. doi: 10.1007/s00210-019-01661-y. [PMID: 31073648]
  • Bo-Fang Zhang, Hong Jiang, Jing Chen, Xin Guo, Yue Li, Qi Hu, Shuo Yang. Nobiletin ameliorates myocardial ischemia and reperfusion injury by attenuating endoplasmic reticulum stress-associated apoptosis through regulation of the PI3K/AKT signal pathway. International immunopharmacology. 2019 Aug; 73(?):98-107. doi: 10.1016/j.intimp.2019.04.060. [PMID: 31082728]
  • Di Wu, Xinyi Wang, Shishuai Wang, Bin Li, Hongshan Liang. Nanoparticle Encapsulation Strategy: Leveraging Plant Exine Capsules Used as Secondary Capping for Oral Delivery. Journal of agricultural and food chemistry. 2019 Jul; 67(29):8168-8176. doi: 10.1021/acs.jafc.9b02003. [PMID: 31268318]
  • Yvonne Hagenlocher, Sonja Gommeringer, Anna Held, Katharina Feilhauer, Jörg Köninger, Stephan C Bischoff, Axel Lorentz. Nobiletin acts anti-inflammatory on murine IL-10-/- colitis and human intestinal fibroblasts. European journal of nutrition. 2019 Jun; 58(4):1391-1401. doi: 10.1007/s00394-018-1661-x. [PMID: 29525889]
  • Prapassorn Potue, Chutamas Wunpathe, Putcharawipa Maneesai, Upa Kukongviriyapan, Parichat Prachaney, Poungrat Pakdeechote. Nobiletin alleviates vascular alterations through modulation of Nrf-2/HO-1 and MMP pathways in l-NAME induced hypertensive rats. Food & function. 2019 Apr; 10(4):1880-1892. doi: 10.1039/c8fo02408a. [PMID: 30864566]
  • Jie Bai, Shengyu Zhao, Xiaoqing Fan, Yonghui Chen, Xiaowen Zou, Minwan Hu, Baolian Wang, Jing Jin, Xiaojian Wang, Jinping Hu, Dan Zhang, Yan Li. Inhibitory effects of flavonoids on P-glycoprotein in vitro and in vivo: Food/herb-drug interactions and structure-activity relationships. Toxicology and applied pharmacology. 2019 04; 369(?):49-59. doi: 10.1016/j.taap.2019.02.010. [PMID: 30790579]
  • Yue Wang, Wenjing Zang, Shiyu Ji, Jinping Cao, Chongde Sun. Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway. Nutrients. 2019 Apr; 11(4):. doi: 10.3390/nu11040791. [PMID: 30959824]
  • Jung-Joon Kim, Keunyoung Kim, Ye-Ryeon Jung, Yiying Bian, Thien Ngo, Ok-Nam Bae, Kyung-Min Lim, Jin-Ho Chung. Co-Existence of Hypertensive and Anti-Hypertensive Constituents, Synephrine, and Nobiletin in Citrus unshiu Peel. Molecules (Basel, Switzerland). 2019 Mar; 24(7):. doi: 10.3390/molecules24071197. [PMID: 30934724]
  • Masazumi Iwashita, Kohjiro Hashizume, Masahiro Umehara, Takaaki Ishigami, Shintaro Onishi, Masaki Yamamoto, Kenjirou Higashi, Kunikazu Moribe. Development of nobiletin-methyl hesperidin amorphous solid dispersion: Novel application of methyl hesperidin as an excipient for hot-melt extrusion. International journal of pharmaceutics. 2019 Mar; 558(?):215-224. doi: 10.1016/j.ijpharm.2018.12.092. [PMID: 30654059]
  • Ping-Ping He, Qian-Qian Shen, Min Wen, Jie-Qiong Zou, Yan Wang, Jiao-Xing Yang, Li-Zhi Hu, Xi-Long Zheng, Ye-Shi Chen, Hua Su, Juan Liu, Xin-Ping Ouyang, Chao-Ke Tang. Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression. Biochemical and biophysical research communications. 2019 01; 508(1):97-101. doi: 10.1016/j.bbrc.2018.11.075. [PMID: 30471854]
  • Jeong Yong Moon, Le Van Manh Hung, Tatsuya Unno, Somi Kim Cho. Nobiletin Enhances Chemosensitivity to Adriamycin through Modulation of the Akt/GSK3β/β⁻Catenin/MYCN/MRP1 Signaling Pathway in A549 Human Non-Small-Cell Lung Cancer Cells. Nutrients. 2018 Nov; 10(12):. doi: 10.3390/nu10121829. [PMID: 30486290]
  • Takahiro Matsumoto, Takahiro Kitagawa, Stephen Teo, Yuuka Anai, Risa Ikeda, Daisuke Imahori, Haji Sapuan Bin Ahmad, Tetsushi Watanabe. Structures and Antimutagenic Effects of Onoceranoid-Type Triterpenoids from the Leaves of Lansium domesticum. Journal of natural products. 2018 10; 81(10):2187-2194. doi: 10.1021/acs.jnatprod.8b00341. [PMID: 30335380]
  • Di Wu, Youyan Liang, Kai Huang, Xinyi Jing, Bin Li, Hongshan Liang. Leveraging plant exine capsules as pH-responsive delivery vehicles for hydrophobic nutraceutical encapsulation. Food & function. 2018 Oct; 9(10):5436-5442. doi: 10.1039/c8fo01665h. [PMID: 30280748]
  • Guoyuan Qi, Rui Guo, Haoyu Tian, Lixia Li, Hua Liu, Yashi Mi, Xuebo Liu. Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2018 Jun; 1863(6):549-562. doi: 10.1016/j.bbalip.2018.02.009. [PMID: 29501626]
  • Rui Guo, Xiaoxiao Zhang, Jin Su, Haiyu Xu, Yanqiong Zhang, Fangbo Zhang, Defeng Li, Yi Zhang, Xuefeng Xiao, Shuangcheng Ma, Hongjun Yang. Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap, ADME prediction and network target analysis. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018 May; 44(?):117-128. doi: 10.1016/j.phymed.2018.01.019. [PMID: 29526583]
  • Mark S Butler, Peter C Healy, Paul I Forster, Gordon P Guymer, Ronald J Quinn. 5,6,7,3',4',5'-Hexamethoxyflavone from the Australian plant Eremophila debilis (Myoporaceae). Fitoterapia. 2018 Apr; 126(?):90-92. doi: 10.1016/j.fitote.2017.07.014. [PMID: 28774690]
  • Jameel Lone, Hilal Ahmad Parray, Jong Won Yun. Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1 adipocytes. Biochimie. 2018 Mar; 146(?):97-104. doi: 10.1016/j.biochi.2017.11.021. [PMID: 29217172]
  • Maik Behrens, Ming Gu, Shengjie Fan, Cheng Huang, Wolfgang Meyerhof. Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors. Chemical biology & drug design. 2018 02; 91(2):422-433. doi: 10.1111/cbdd.13089. [PMID: 28834122]
  • Inês Silva, Marta F Estrada, Carolina V Pereira, Andreia Bento da Silva, Maria R Bronze, Paula M Alves, Catarina M M Duarte, Catarina Brito, Ana Teresa Serra. Polymethoxylated Flavones from Orange Peels Inhibit Cell Proliferation in a 3D Cell Model of Human Colorectal Cancer. Nutrition and cancer. 2018 Feb; 70(2):257-266. doi: 10.1080/01635581.2018.1412473. [PMID: 29313727]
  • Xian Wu, Mingyue Song, Peiju Qiu, Fang Li, Minqi Wang, Jinkai Zheng, Qi Wang, Fei Xu, Hang Xiao. A metabolite of nobiletin, 4'-demethylnobiletin and atorvastatin synergistically inhibits human colon cancer cell growth by inducing G0/G1 cell cycle arrest and apoptosis. Food & function. 2018 Jan; 9(1):87-95. doi: 10.1039/c7fo01155e. [PMID: 29063088]
  • Manami Yamaguchi, Keita Shigeyama, Masato Yoshikawa, Takuya Matsumoto, Yasushi Yonezawa, Hironori Shiota, Taketeru Ueyama, Ikuyo Sakaguchi. Effects of Cultivation Month and Genetic Background on Phenolic Content of Citrus tachibana Peel. Biological & pharmaceutical bulletin. 2018; 41(8):1277-1281. doi: 10.1248/bpb.b17-00970. [PMID: 30068877]