Apigenin & Luteolin - Anti-Aging NAD+ Inflammatory Regulators & Brain Homeostasis

POWERFUL YELLOWS AND AGING. Apigenin and Luteolin. Many changes occur during the aging process, with the most profound being inflammation. Inflammation contradicts good health and becomes increasingly unregulated with age. Since inflammation is key in accelerating aging, it is important to modulate these effects, especially in the brain.

The gradual destruction of neurons by chronic inflammation (neuroinflammation) leads to brain deterioration and pathologies. In the arteries, inflammation facilitates the initiation and rapid onset of arteriosclerosis. It also is responsible for creating immune system dysfunction and autoimmune disease. Another affliction of the aging process is cancer, which is tightly associated with inflammation and cellular dysregulation. Apigenin and luteolin have both shown promise in supporting health aging including ensuring a healthy inflammatory response.  

      Longevity NAD+.

      • Apigenin increases levels of NAD+, which is a limiting factor in the ability of SIRT1 to enable numerous longevity effects. Apigenin works to increase NAD+ is via inhibition of CD38, which breaks down NAD+.(1)
      • High levels of NAD+ (via SIRT1 activation)  results in inhibition of obesity in high fat diets, metabolic syndrome and  glucose intolerance.
      • Degenerative brain disease associated with aging have high levels of CD38 and consequently low levels of NAD+. Therefore, apigenin may play an important role in increasing NAD+ in the brain and may mitigate brain degeneration. Biogerontology. 2014 Apr (2)

        Nrf2 Activation.

        • Nrf2 is a transcription factor is the trigger the cellular response to protect against damaging oxidative stress, including injury and inflammation as well as cellular homeostasis. Researchers suggest that Nrf2 may have a major impact on the health and lifespan.(3)
        • Apigenin and luteolin are both Nrf2 activators.(4)


          • Inflammatory diseases are prevalent in the aging population, as inflammation becomes a chronic condition with age. Moreover, inflammation is the  primary factor for the development of chronic ailments and skyrocketing health care costs with age.
          • Chronic inflammation destroys the body (including the brain). This is not the normal immune system response, but  a chronic overstimulation, which continuously exposes the body to destructive and age accelerating inflammation. Such inflammation is normally low grade and the effects may take years to be evident.
          •  Apigenin and luteolin have significant anti-inflammation properties, and may significantly reduce chronic inflammation.

            Cardiovascular Artery Inflammation

            • Oxidized LDL in arteries causes macrophage inflammation in the arteries which promotes arteriosclerosis. It is the survival and continued activation of the macrophages in the arteries which keep the arteries inflamed. Apigenin can induce autophagy of macrophages, thereby reducing inflammation and inhibit the progression of atherosclerosis.(5-6) 

              Brain Degeneration / Neuroinflammation

              • Inflammation. All Neurodegenerative diseases have chronic immune activation, in particular microglia inflammation, as a common feature. Over activation of microglia in the brain, creating a low grade chronic source of inflammation, slowly degenerates the neurons and other cognitive structures.
              • Importantly, in the brain, apigenin and luteolin suppress the chronic activation of microglia - a key cause of inflammation in the brain.(7-10)
              • Brain Fog. Includes symptoms "reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory." According to researchers much of this is attributed to inflammation and microglial activation in particular. Luteolin, inhibits many steps in the inflammation process in the brain, and, may be effective in in ameliorating brain fog.(9)
              • Neurogenesis. Apigenin induces neurogenesis by promoting neuronal differentiation of stem cells primarily in the hippocampus (the memory center).(11)
              • Apigenin reverses inflammation induced depression in lab animals. Effectively attenuated by apigenin were proinflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α). (12)
              • Protects neurovascular coupling. Apigenin maintains neurovascular coupling. This is an important relationship between the neurons and the vascular network in the brain. Maintenance of brain health depends on the ability to preserve and increase cerebral blood flow and oxygenation. Termed "white matter hypersensities" are the areas of the brain which developed micro vascular deficiencies, lack of blood flow, causing loss of neuro function. (13)

                 Immune System

                • Immune Allergic Response. Mast cells are primary to the immune allergic response which then releases a potent inflammatory response. Luteolin exhibits a modulatory effect on mast cell induced inflammatory response. (14) 
                • Immunity Balanced Restoration. Inflammation disrupts the balance of the immune system function. Apigenin via an effective anti-inflammatory response, is capable of restoring  the immune response.(15)


                  • Both apigenin and luteolin display potent ant-cancer properties.
                  • Apigenin:
                    • Prostate Cancer Cells. Studies indicate that apigenin may inhibit the progression of prostate cancer including tumor growth and invasiveness. (16)
                    • Colorectal Cancer Cells. Treated human colorectal cancer cells with apigenin, with extended exposure,  resulted in senescence of the cancer cells and attenuation of tumor formation. (17)
                    • Cancer Stem Cells. Apigenin inhibits the stimulation and self renewal of ovarian cancer stem cells.(18)  Furthermore, apigenin may inhibit other cancer stem cells via inhibition of the same chemical promoter (casein kinase 2α) thereby inhibiting other cancer stem cell self-renewal.(19)
                  • Luteolin:
                    • Anti-angiogenic - Cancer tumors grow by the creation of new bloods vessels, a process called angiogenesis. Luteolin inhibits the growth of new blood vessels in tumors.(20)
                    • Cancer Stem Cells.  Certain breast cancers have a high rate of recurrence due to the continued growth from cancer stem cells. Research indicates that luteolin blocks the pathway for cancer stem cell maintenance and may eliminate cancer stem cells.(21)
                    • Non-Small Cell Lung Cancer - Lab studies (in vitro) demonstrated the ability of luteolin to cause the cellular death of the cancer cells as well as inhibit migration.(22)

                    Anti-Diabetic Activity

                    • Apigenin and luteolin both inhibit gluconeogenic (glucose producing) and lipogenic (fat producing) gene expression.(23) 
                    • Apigenin improves glucose and lipid homeostasis.

                      Skin Rejuvenation

                      • Apigenin induces dermal collagen production, thereby serving as a potential agent improving collagen depleted skin. Collagen provides skin with youthful structure. Wrinkles are skin aging are the result of the loss of the collagen infrastructure.(24)


                        • Hypertension and low grade inflammation. Specifically, the link involves TLR4 - a protein involved with activation of  the innate immune response. Research indicates that TLR4 inflammatory response is key in the development and maintenance of hypertension.
                        • Apigenin was shown to significantly lower blood pressure in hypertensive rats, as well lowering inflammation, including reducing expression of TLR4 and inflammatory NF-KB and TNF-alpha.(25).


                            YELLOW LONGEVITY  (15 mg Apigenin plus 15mg Luteolin)

                            YELLOW NATURALLY  (10 mg Apigenin plus 10 mg Luteolin)

                            LONGEVITY NATURALLY (10 mg Apigenin plus 10 mg Luteolin)

                            CARTILAGE MAX (15 mg Apigenin plus 15 mg Luteolin)



                            1. Escande C, et al. Flavonoid Apigenin Is an Inhibitor of the NAD(+)ase CD38. Diabetes. 2013 Apr.

                            2. Braidy N, et al. Mapping NAD(+) metabolism in the brain of ageing Wistar rats: potential targets for influencing brain senescence. Biogerontology. 2014 Apr;

                            3. Blackwell TK, et al. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med. 2015 Aug.

                            4. Paredes-Gonzalez X, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos. 2015 Apr 

                            5. Wang Q, et al. Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis. Int Immunopharmacol. 2015 Jul;

                            6. Zeng P, et al. Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2. Oxid Med Cell Longev. 2015

                            7. Yuan Y, et al. Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci. 2014 Nov

                            8. Wang S, et al. Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation. Neuroscience. 2011 Jun

                            9. Theoharides TC, et al. Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Front Neurosci. 2015 Jul

                            10. Huang F, et al. The inhibitory effect of luteolin on inflammation in LPS-induced microglia. Zhong Yao Cai. 2011 Nov

                            11. Taupin P. Neurogenic drugs and compounds. Recent Pat CNS Drug Discov. 2010 Nov

                            12. Li R, et al. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci Lett. 2015 May

                            13. Liu R, et al. The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice. J Alzheimers Dis. 2011

                            14. Kritas SK, et al. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 2013 Oct-Dec

                            15. Arango D, et al. Dietary apigenin reduces LPS-induced expression of miR-155 restoring immune balance during inflammation. Mol Nutr Food Res. 2015 Apr
                            16. Shukla S, et al. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget. 2015 Sep.

                            17. Banerjee K, et al. Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells. Redox Biol. 2015 Apr

                            18. Tang AQ, et al. Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells. Mol Med Rep. 2015 Mar.

                            19. Liu J, et al. Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α. Mol Med Rep. 2015 Jan

                            20. Ambasta RK, et al. Comparative study of anti-angiogenic activities of luteolin, lectin and lupeol biomolecules .J Transl Med. 2015 Sep

                            21. Ma L, et al. Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis. Mol Med Rep. 2015 Sep

                            22. Davies AH, et al. Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells. Oncotarget. 2015 Aug

                            23. Bumke-Vogt C, et al. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One. 2014 Aug 

                            24 Zhang Y, et al. Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. Eur J Histochem. 2015 Apr 

                            25. Chen X, et al. Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B. Mediators Inflamm. 2013

                            Gail Paige
                            Gail Paige