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CITRUS SINENSIS L. FRUIT EXTRACT (40% NOBILETIN)

TOP BENEFITS OF CITRUS BIOFLAVONOIDS

    • Supports body clock function (i.e., circadian system)*
    • Supports healthy weight*
    • Supports mitochondrial biogenesis, structure, and function*
    • Supports healthy metabolism and insulin signaling*
    • Supports cellular responses and antioxidant defenses*
    • Supports brain function*
    • Supports the protection of organs and systems *
    • Supports healthy gut microbiota*  

WHAT ARE CITRUS BIOFLAVONOIDS?

Citrus × sinensis, which includes sweet oranges and blood oranges, is regularly consumed in the diet. The peels and fruit are a rich source of the polymethoxylated flavones nobiletin and tangeretin. They also contain the flavanone hesperidin and lesser amounts of other citrus bioflavonoids. Citrus bioflavonoids were once called vitamin P and have been used to support healthy blood vessels and veins. Flavonoids tend to promote antioxidant defenses and a balanced cellular response. Citrus flavonoids share these properties. This citrus bioflavonoid extract has been concentrated for the unique polymethoxylated flavone nobiletin, a clock-enhancing small molecule used to support body clock function and metabolic health.


CITRUS BIOFLAVONOIDS KEY MECHANISMS

Circadian rhythms

 

  • Nobiletin and tangeretin are clock amplitude-enhancing small molecules (CEM) — modulate the circadian system [1, 2]
  • Nobiletin and tangeretin upregulate circadian rhythm protein Period 2 (PER2) [1–3]
  • Promotes metabolic function through a circadian-dependent mechanism [1, 4]

 

Mitochondrial biogenesis

 

  • Supports healthy body fat levels [21]
  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) [4–7]
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (nuclear respiratory factor 1 [NRF1], NRF2, mitochondrial transcription factor A [TFAM]) [6, 8–10]

 

Mitochondrial structure and function

 

  • Protects from mitochondrial dysfunction [11, 12]
  • Protects from complex I-V inhibition [4, 13]
  • Upregulates ATP production [14]
  • Supports mitochondrial membrane potential [11]

 

Signaling pathways

 

  • Upregulates AMP-activated protein kinase (AMPK) signaling [4, 8, 15, 16]
  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) and delta PPARδ [6, 8, 17–19]
  • Regulates PPARγ signaling [6, 15, 17–20]
  • Downregulates glycogen synthase kinase 3 beta (GSK-3β) [4, 13, 21]
  • Downregulates mTOR signaling [21]
  • Upregulates SIRT-1 signaling [4, 6]

 

Metabolism

 

  • Supports healthy blood glucose levels [1, 5, 7, 17, 18, 22]
  • Supports healthy insulin sensitivity [1, 4, 5, 7, 18, 19, 22]
  • Upregulates GLUT-1 and GLUT-4 [17, 18]
  • Balances the respiratory quotient [1]
  • Regulates the urea cycle [23]

 

Body weight

 

  • Supports healthy body weight [1, 5, 7, 17, 22]
  • Downregulates fat accumulation in the blood and liver [1, 5, 7, 19, 22, 24]
  • Supports healthy blood triglyceride and cholesterol levels  [7, 19, 24, 25]
  • Upregulates adiponectin levels [17, 18]
  • Promotes the differentiation of brown adipose tissue [6, 22]
  • Upregulates UCP-1 and UCP-2 [6, 7, 17, 22]
  • Promotes thermogenesis [22]

 

Cellular signaling

 

  • Downregulates the expression of proinflammatory mediators – cyclooxygenase-2 (COX-2), nitric oxide (NO) inducible NO synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), IL-6, nuclear factor-kappa B (NF-κB), interferon-gamma (IFN-ɣ) [7–10, 17–21, 26–28]
  • Regulates immune cell activity [7, 29]

 

Antioxidant defenses

 

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])  [8, 9, 12, 27]
  • Downregulates the generation of reactive oxygen species [4, 8, 11, 12, 27]
  • Replenishes glutathione (GSH) levels [8, 9, 12, 27]
  • Upregulates heme oxygenase-1 (HO-1) [10, 20]

 

Brain function

 

  • Neuroprotective against ischemia/hypoxia [9, 21, 30, 31]
  • Neuroprotective against neurotoxic agents [11, 12, 32]
  • Protects cognitive function [3, 13, 33]
  • Supports emotional memory [34]
  • Regulates neural cytokine signaling [26, 28]
  • Supports hippocampal mitochondrial bioenergetics [14]
  • Upregulates BDNF signaling [31, 35]

 

Protection of organs and systems

 

  • Protects cardiovascular structure and function [5, 7, 36–38]
  • Protects liver structure and function [8]
  • Protects gastrointestinal structure and function [27]

 

Gut microbiota

 

  • Regulates the composition of the gut microbiota [39–42]
  • Regulates gut microbial metabolism [41]
  • Supports gut barrier function [39]

 

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REFERENCES

[1] B. He et al., Cell Metab. 23, 610–621 (2016).
[2] A. Shinozaki et al., PLoS One. 12, e0170904 (2017).
[3] J. Gile, B. Scott, T. Eckle, Crit. Care Med. 46, e600–e608 (2018).
[4] G. Qi et al., Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 1863, 549–562 (2018).
[5] E. E. Mulvihill et al., Diabetes. 60, 1446–1457 (2011).
[6] J. Lone, H. A. Parray, J. W. Yun, Biochimie. 146, 97–104 (2018).
[7] A. C. Burke et al., J. Lipid Res. 59, 1714–1728 (2018).
[8] B.-K. Choi et al., Phytother. Res. 29, 1577–1584 (2015).
[9] L. Zhang et al., Brain Res. 1636, 130–141 (2016).
[10] X. Wu et al., J. Nutr. Biochem. 42, 17–25 (2017).
[11] J. H. Lee et al., Korean J. Physiol. Pharmacol. 22, 311–319 (2018).
[12] K. Tamilselvam et al., Oxid. Med. Cell. Longev. 2013, 102741 (2013).
[13] D. Wang, L. Liu, X. Zhu, W. Wu, Y. Wang, Cell. Mol. Neurobiol. 34, 1209–1221 (2014).
[14] N. Jojua, N. Sharikadze, E. Zhuravliova, E. Zaalishvili, D. G. Mikeladze, Nutr. Neurosci. 18, 225–231 (2015).
[15] Y. Choi et al., J. Agric. Food Chem. 59, 12843–12849 (2011).
[16] T. Yuk et al., Evid. Based. Complement. Alternat. Med. 2018, 7420265 (2018).
[17] Y.-S. Lee et al., J. Nutr. Biochem. 24, 156–162 (2013).
[18] Y.-S. Lee et al., Biochem. Pharmacol. 79, 1674–1683 (2010).
[19] Y.-J. Kim et al., Mol. Nutr. Food Res. 61 (2017), doi:10.1002/mnfr.201600889.
[20] S. Namkoong et al., J. Med. Food. 20, 873–881 (2017).
[21] Y. Zheng, J. Bu, L. Yu, J. Chen, H. Liu, Biomed. Pharmacother. 91, 494–503 (2017).
[22] Y.-C. Chou, C.-T. Ho, M.-H. Pan, J. Agric. Food Chem. 66, 9697–9703 (2018).
[23] K. Nohara et al., Nutr. Metab. . 12, 23 (2015).
[24] E. M. Kurowska, J. A. Manthey, J. Agric. Food Chem. 52, 2879–2886 (2004).
[25] J. M. Roza, Z. Xian-Liu, N. Guthrie, Altern. Ther. Health Med. 13, 44–48 (2007).
[26] Y. Cui et al., Biol. Pharm. Bull. 33, 1814–1821 (2010).
[27] W. Li et al., Immunopharmacol. Immunotoxicol. 39, 354–363 (2017).
[28] S.-C. Ho, C.-T. Kuo, Food Chem. Toxicol. 71, 176–182 (2014).
[29] G. Yang et al., J. Agric. Food Chem. 66, 8299–8306 (2018).
[30] N. Yasuda et al., Brain Res. 1559, 46–54 (2014).
[31] L. Zhang et al., Brain Res. Bull. 96, 45–53 (2013).
[32] Y. Yabuki, Y. Ohizumi, A. Yokosuka, Y. Mimaki, K. Fukunaga, Neuroscience. 259, 126–141 (2014).
[33] A. Nakajima et al., Behav. Brain Res. 250, 351–360 (2013).
[34] J. Kang et al., J. Nat. Med. 71, 181–189 (2017).
[35] J. Li et al., Evid. Based. Complement. Alternat. Med. 2013, 359682 (2013).
[36] N. Zhang et al., Cell. Physiol. Biochem. 42, 1313–1325 (2017).
[37] P. Cirillo et al., Biochem. Pharmacol. 128, 26–33 (2017).
[38] N. A. Parkar, L. K. Bhatt, V. Addepalli, Food Funct. 7, 3121–3129 (2016).
[39] D. Li, H. Wu, H. Dou, L. Guo, W. Huang, Biochem. Biophys. Res. Commun. (2018), doi:10.1016/j.bbrc.2018.10.035.
[40] Y.-C. Tung et al., Food Funct. 9, 3363–3373 (2018).
[41] T. Unno, T. Hisada, S. Takahashi, J. Agric. Food Chem. 63, 7952–7957 (2015).
[42] A. Cuervo et al., Nutrients. 7, 1301–1317 (2015).