GET 15% OFF FIRST SUBSCRIPTION ORDER (CLICK FOR DETAILS)

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]

 

CITRUS SINENSIS L. FRUIT EXTRACT CAN BE FOUND IN:

Morning Momentum

Get Instant Access To A Simple, Proven System That Has Helped

THOUSANDS of People

IGNITE Their Health and Energy

to Create The Life They Deserve!

Learn More

START HERE

 

OPTIMUM MIND PERFORMANCE

 

Optimum Health (Foundation)

 

Cleanse, Clear & Rejuvenate

 

Internal Body Balance

 

Build Healthy Cells

 

Fuel Your Mind & Body

 

Protect: Longevity & Immunity

 

Enhance: Biohacking

 

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).