Curcumin (Turmeric)

Curcumin is today one of the most thoroughly researched dietary phytochemicals (1), but its combination of anti-inflammatory and anti¬oxidant properties suggests potential also in other realms of medicine (2).

 

Neuroprotection

Within the various activities of curcumin, its neuroprotective effects on cognition have been extensively investigated in terms of epidemiology and in various preclinical and clinical models. Thus regular consumption of curcumin has been related to better cognitive function in the elderly (3), and in India incidence and prevalence of AD is indeed over four times lower than in the United States (4).

A correlation between curry consumption and cognitive level was identified studying a sample of more than 1000 Asians from their sixties to their nineties, and concluded that people on a curry diet performed better on a standard test (mini mental state examination) of cognitive function than those who never or rarely ate curry (3). As an attractive potential mechanism for the management of AD and other types of dementia, the anti-amyloidogenic properties of curcumin were investigated in terms of reduction of plaque burden, an end point related to the potential to reverse amyloid pathology (5-9). Curcumin’s direct radical scavenging activity has been investigated (10,11), but the compound can also reduce radical levels by improving mitochondrial function (12,13). In these studies, it was found that curcumin, by activating various phase II enzymes, can stimulate Nrf2/ ARE-signaling pathways that play a neuroprotective role, also upregulating the intrinsic antioxidant cell defenses (14-16).

 

Depression

An additional indication of curcumin is the management of depression, a major health problem affecting about 120 million people world wide, according to the World Health Organization. The use of curcumin to treat depression is being further supported by the latest research on depression, which emphasizes the importance of neurotoxicity and chronic inflammation (17). Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed drugs for depression. At the time of their launch, the potentiation of aminergic signaling was considered the major antidepressant mechanism for this class of compounds. However, the credibility of the monoamine theory and the therapeutic efficacy of these compounds in the treatment of depression has been questioned, and novel mechanism(s) of activity have been proposed. Thus it is now generally expected that the symptoms of depression are closely linked with disturbances in proinflammatory signaling, and SSRIs possess significant anti-inflammatory properties (18).

Preliminary human intervention studies have indeed suggested that curcumin has an antidepressant activity comparable to fluoxetine in the treatment of major depression (19). A mini meta-analysis has concluded curcumin administration reduces depressive symptoms in patients with major depression (20), with benefits occurring in one trial 4-8 weeks after treatment (21).

Anti-inflammatory effects Additionally, inflammation may also play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism, and post-traumatic stress disorder. Curcumin shows anti-inflammatory properties, has an excellent safety profile over extended periods of use, and can stimulate hippocampal neurogenesis, an important pathway to enhance neuroplasticity and repair.

 

References

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2 Aggarwal, B.B., Sung, B., 2009. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol. Sci. 30, 85–94.

3 Ng, T.P., Chiam, P.C., Lee, T., Chua, H.C., Lim, L., Kua, E.H., 2006. Curry consumption and cognitive function in the elderly. Am. J. Epidemiol. 164, 898–906.

4 Ganguli, M., Chandra, V., Kamboh, M.I., et al, 2000. Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US cross-national dementia study. Arch. Neurol. 57, 824–830.

5 Garcia-Alloza, M., Borrelli, L.A., et al, 2007. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites. J. Neurochem. 102, 1095–1104.

6 Lim, G.P., Chu, T., Yang, F., et al., 2001. The curry spice curcumin reduces oxidative damage and amy¬loid pathology in an Alzheimer transgenic mouse. J. Neurosci. 21, 8370–8377.

7 Ono, K., Hasegawa, K., Naiki, H., Yamada, M., 2004. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s b-amyloid fibrils in vitro. J. Neurosci. Res. 75, 742–750.

8 Shytle, R.D., Bickford, P.C., Rezai-Zadeh, K., et al., 2009. Optimized turmeric extracts have potent anti-amyloido¬genic effects. Curr. Alzheimer Res. 6, 564–571.

9 Yang, F., Lim, G.P., Begum, A.N., et al, 2005. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 280, 5892–5901

10 Ak, T., Gulcin, I., 2008. Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact. 174, 27–37.

11 Suwannateep, N., et al 2012. Encap¬sulated curcumin results in prolonged curcumin activity in vitro and radical scavenging activity ex vivo on skin after UVB-irradia¬tion. Eur. J. Pharm. Biopharm. 82, 485–490.

12 Barzegar, A., Moosavi-Movahedi, A.A., 2011. Intracellular ROS protec¬tion efficiency and free radical-scavenging activity of curcumin. PLoS One 6, e26012.

13 Fujisawa, S., Atsumi, T.,et al, 2004. Cytotoxic¬ity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds. Anticancer Res. 24, 563–569.

14 Balogun, E., Hoque, M., Gong, P., et al, 2003. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive ele¬ment. Biochem. J. 371, 887–895.

15 McNally, S.J., et al., 2007. Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition. Int. J. Mol. Med. 19, 165–172.

16 Yin, W., Zhang, X., Li, Y., 2012. Protective effects of curcumin in APPswe transfected SH-SY5Y cells. Neural Regen. Res. 7, 405–412.

17 Berk, M., Williams, L.J., Jacka, F.N., et al, 2013. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 11, 200.

18 Walker, F.R., 2013. A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression? Neuropharmacology 67, 304–317.

19 Sanmukhani, J., Satodia, V., Trivedi, et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phyto¬ther. Res. 28 (4), 579-585.

20 Al-Karawi D, Mamoori DA, Tayyar Y. 2015. The role of curcumin administration in patients with major depressive disorder: Mini Meta-analysis of clinical trials. Phytother Res. DOI 10.1002/ptr.5524

21 Lopresti A et al. Curcumin for the treatment of major depression: a randomised, double blind, placebo controlled study. In press