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FOOD CHEMISTRY · 2023 · IF 8.8

Small molecules interfacial assembly regulate the crystallization transition process for nobiletin stabilization

Xiaojuan Chen,Bojia Li,Sicheng Ji,Di Wu,Bing Cui,Xingling Ren,Bin Zhou,Bin Li,Hongshan Liang

Many bioactive nutraceuticals naturally occurring in food materials possess beneficial biological activities, while their use as functional supplements is subjected to hydrophobicity and crystallinity. Currently, inhibiting crystallization for such nutrients is of immense scientific interest. Here, we exploited diverse structural polyphenols as potential inhibitors for restraining Nobiletin crystallization. Specifically, the crystallization transition process could be influenced by the polyphenol gallol density, Nobiletin supersaturation (1, 1.5, 2, 2.5 mM), temperature (4, 10, 15, 25 and 37 ℃), and pH (3.5, 4, 4.5, 5), important factors for regulating the binding attachment and interactions. The optimized samples could be guided by NT100 lied in 4 ℃ at pH 4. Besides, the main assembly driving force was hydrogen-bonding cooperated with π-π stacking and electrostatic interaction, leading to a Nobiletin/TA combination ratio of ∼ 3:1. Our findings proposed an innovative synergistic strategy for inhibiting crystallization and broaden potential applications of polyphenol-based materials in advanced biological fields.

研究领域: 食品科学 · 分子生物学 · 材料科学
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Journal of Functional Foods · 2023 · IF 5.6

Nobiletin inhibits hypoxia-induced placental redox imbalance and subsequent offspring brain damage by regulating the one-carbon metabolism

Meng-ling Zhang,Qian Yang,Xiao-peng Li,Jia-hao Chen,Zi-jun Bi,Yang Shan,Li-fang Gao,Huan-ling Yu

Nobiletin (NOB) is one of the major polymethoxyflavone in citrus peels, which has antioxidant activities. The purpose of this study was to investigate the effects of NOB on hypoxia-induced placental oxidative stress and its mechanism. In vitro experiments, JEG-3 hypoxic model was constructed, and treated with 100 μM NOB. In vivo experiment, pregnant rats were injected intraperitoneally with 50 mg/kg body weight NOB daily, and the placental hypoxia model was established by RUPP. NOB hampered the reducing of reducing power in hypoxic cells, promoted NADPH to provide hydrogen donors to regenerate antioxidants GPX and GSH, thereby promoting the decomposition of ROS. NOB alleviated the adverse reaction of hypoxic placental one-carbon metabolism disorder by regulating the levels of homocysteine, DNMTs and TETs. Moreover, NOB suppressed offspring brain damage induced by RUPP. Taken together, NOB attenuated hypoxia-induced placental redox perturbation and subsequent offspring brain injury by modulating one-carbon metabolism.

CAS / MDL: 7791-13-1
研究领域: 药理学 · 妇产科学 · 神经科学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2020 ·Vol. 24 ·期 9 ·5168-5184 · IF 4.486

A network pharmacology-based approach to explore the effects of Chaihu Shugan powder on a non-alcoholic fatty liver rat model through nuclear receptors

Huan Nie,Yuanjun Deng,Chuiyang Zheng,Maoxing Pan,Jiqian Xie,Yupei Zhang,Qinhe Yang

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is still not fully understood, and currently, no effective pharmacotherapy is available. Nuclear receptors (NRs) are important biological participants in NAFLD that exhibit great therapeutic potential. Chaihu Shugan powder (CSP) is a traditional Chinese medicine (TCM) formula that has a wide therapeutic spectrum including NAFLD, but the effective components and functional mechanisms of CSP are unclear. We adopted a network pharmacology approach using multiple databases for Gene Ontology (GO) enrichment analysis and the molecular complex detection (MCODE) method for a protein-protein interaction (PPI) analysis, and we used molecular docking method to screen the NR targets and determine the corresponding CSP components. The screening results were validated through a NAFLD rat model that was used to explain the possible relationship between CSP and NAFLD. Finally, we screened PPARγ, FXR, PPARα, RARα and PPARδ as target genes and quercetin , kaempferol , naringenin , isorhamnetin and nobiletin as target compounds. The five components were detected through high-performance liquid chromatography-mass spectrometry (HPLC-MS), the results of which aligned with the docking experiments of PPARγ, PPARα and PPARδ. After CSP intervention, the NAFLD rat model showed ameliorated effects in terms of bodyweight, hepatic histopathology, and serum and liver lipids, and the mRNA levels of PPARγ, FXR, PPARα and RARα were significantly changed. The results from this study indicate that CSP exhibits healing effects in an NAFLD model and that the network pharmacology approach to screening NR targets and determining the corresponding CSP components is a practical strategy for explaining the mechanism by which CSP ameliorates NAFLD.

研究领域: 药理学 · 中药学 · 分子生物学 · 病理学
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FITOTERAPIA · 2014 · IF 2.216

Characteristics of nobiletin-induced effects on jejunal contractility

Yong-Jian Xiong,Da-Peng Chen,Bo-Chao Lv,Fang-Fei Liu,Li Wang,Yuan Lin

Nobiletin , a citrus polymethoxylated flavone , exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segments in all 6 different low contractile states, and meanwhile significant inhibitory effects in all 6 different high contractile states, showing characteristics of bidirectional regulation (BR). Nobiletin-exerted BR on jejunal contractility was abolished in the presence of c-kit receptor tyrosine kinase inhibitor imatinib or Ca 2   + channel blocker verapamil . In the presence of neuroxin tetrodotoxin , nobiletin only exerted stimulatory effects on jejunal contractility in both low and high contractile states. Hemicholinium-3 and atropine partially blocked nobiletin-exerted stimulatory effects on jejunal contractility in low-Ca 2   + -induced low contractile state. Phentolamine or propranolol or l -NG-nitro-arginine significantly blocked nobiletin-exerted inhibitory effects on jejunal contractility in high-Ca 2   + -induced high contractile state respectively. The effects of nobiletin on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin light chain phosphorylation extent were also bidirectional. In summary, nobiletin-exerted BR depends on the contractile states of rat jejunal segments. Nobiletin-exerted BR requires the enteric nervous system, interstitial cell of Cajal, Ca 2   + , and myosin phosphorylation-related mechanisms.

研究领域: 药理学 · 胃肠病学 · 分子生物学
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