生物活性

• 描述Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities^[6]. Naringenin, the aglycone formed by intestinal bacteria hydrolysis of naringin, competitively inhibits benzo(a)pyrene hydroxylase (AHH) activity with an estimated Ki of 39 microM^[7]. Naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. It also restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF-κB signaling pathway. Taken together, those results demonstrate that naringin effectively alleviates diabetic kidney disease (DKD), which provide theoretical basis for naringin clinically used to treatment of DKD^[6]. AGS cell proliferation was inhibited by Naringin in a dose- and time-dependent manner. Phosphorylation of PI3K and its activated downstream targets p-Akt and p-mTOR are significantly decreased at 2 mM in Naringin-treated AGS cells^[8]. Naringin protects pheochromocytoma cells (PC12 cells) from 3-NP neurotoxicity, as evaluated by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione^[9]. Treatment with naringin significantly alleviates renal injury in diabetic rats and increases diabetic rats body weight significantly. Administration of naringin effectively alleviates the collagen deposition and renal interstitial fibrosis in diabetic rats. Treatment with naringin could result in decreased levels of ROS and MDA and increased activities of SOD and GSH-Px^[6]. Naringin can also improve neuronal innsulin signaling, brain mitochondrial function, and cognitive function in high-fat diet-induced obese mice^[10].

• 动物研究
  剂量	Rat: 2.4 mg/kg, 9.4 mg/kg[3] (p.o.), 30 mg/kg[4] (p.o.), 200 mg/kg[5] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Rats[3] Dose 9.4 mg/kg Administration p.o. T1/2 1.0 ± 0.1 h AUC0-6 771 ± 81 ng·h/ml Tmax 2.0 ± 0.1 h Cmax 430 ± 64 ng/ml AUC0→∞ 797 ± 83 ng·h/ml

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03582553	Safety Issues ... more >> Pharmacokinetics Collapse <<	Early Phase 1	Completed	-	United States, Louisiana ... more >> Pennington Biomedical Research Center Baton Rouge, Louisiana, United States, 70808 Collapse <<
  NCT01423019	Weight Loss	Not Applicable	Completed	-	United States, Texas ... more >> Integrative Health Technologies, Inc. San Antonio, Texas, United States, 78209 Collapse <<
  NCT01272167	Post-menopausal Status	Not Applicable	Completed	-	France ... more >> CHU Clermont-Ferrand Clermont-Ferrand, France, 63003 Collapse <<

• 参考文献

• [1] Schindler R, Mentlein R. Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr. 2006 Jun;136(6):1477-82.

  [2] Ueng YF, Chang YL, et al. In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver. Life Sci. 1999;65(24):2591-602.

  [3] de Castro WV, Mertens-Talcott S, et al. Effect of grapefruit juice, naringin, naringenin, and bergamottin on the intestinal carrier-mediated transport of talinolol in rats. J Agric Food Chem. 2008 Jun 25;56(12):4840-5.

  [4] Punithavathi VR, Anuthama R, et al. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. J Appl Toxicol. 2008 Aug;28(6):806-13.

  [5] Li F, Sun X, et al. Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway. Biochem Biophys Res Commun. 2014 Sep 26;452(3):629-35.

  [6] Chen F, Zhang N, Ma X, Huang T, Shao Y, Wu C, Wang Q. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction. PLoS One. 2015 Nov 30;10(11):e0143868. doi: 10.1371/journal.pone.0143868. Retraction in: PLoS One. 2018 Feb 1;13(2):e0192465. PMID: 26619044; PMCID: PMC4664292.

  [7] Ueng YF, Chang YL, Oda Y, Park SS, Liao JF, Lin MF, Chen CF. In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver. Life Sci. 1999;65(24):2591-602. doi: 10.1016/s0024-3205(99)00528-7. PMID: 10619367.

  [8] Raha S, Yumnam S, Hong GE, Lee HJ, Saralamma VV, Park HS, Heo JD, Lee SJ, Kim EH, Kim JA, Kim GS. Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells. Int J Oncol. 2015 Sep;47(3):1061-9. doi: 10.3892/ijo.2015.3095. Epub 2015 Jul 20. PMID: 26201693.

  [9] Kulasekaran G, Ganapasam S. Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. Mol Cell Biochem. 2015 Nov;409(1-2):199-211. doi: 10.1007/s11010-015-2525-9. Epub 2015 Aug 18. PMID: 26280522.

  [10] Wang D, Yan J, Chen J, Wu W, Zhu X, Wang Y. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice. Cell Mol Neurobiol. 2015 Oct;35(7):1061-71. doi: 10.1007/s10571-015-0201-y. Epub 2015 May 5. PMID: 25939427.

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