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. 2015 May;1852(5):951-61.
doi: 10.1016/j.bbadis.2014.12.005. Epub 2014 Dec 27.

Curcumin Boosts DHA in the Brain: Implications for the Prevention of Anxiety Disorders

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Free PMC article

Curcumin Boosts DHA in the Brain: Implications for the Prevention of Anxiety Disorders

Aiguo Wu et al. Biochim Biophys Acta. .
Free PMC article

Abstract

Dietary deficiency of docosahexaenoic acid (C22:6 n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18:3 n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissues. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.

Keywords: ALA; Curcumin; DHA synthesis; DPA; Docosahexaenoic acid; Omega 3 fatty acid.

Figures

Figure 1
Figure 1. Curcumin combined with ALA increases DHA in the brain, which correlates with reduced anxiety-like behavior
ALA alone and CUR alone did not increase DHA in the hippocampus (A). A1LA plus CUR significantly increased DHA levels at both 250 and 500 ppm doses of CUR. The time in open arm was significantly higher in ALA+CUR groups compared with CTL or ALA alone (B). DHA in the brain was positively correlated with time spent in the open arm (C). CTL: control, ALA: α-linolenic acid, CUR: curcumin. *compared with control (p<0.05); # compared with indicated p<0.05 (n=5–6)
Figure 2
Figure 2. Curcumin increases FADS2 and Elov2 in the brain
Curcumin significantly increased the levels of FADS2 (A) and Elov2 (B) with or without ALA as detected by immunoblotting. Combined, ALA + CUR 500 ppm increased both enzymes more than 500pm CUR alone or ALA +250 ppm (A, B). FADS2: delta 6 desaturase, Elov2: elongase, HIP: hippocampus, CTL: control, ALA: α-linolenic acid, CUR: curcumin. *compared with control (p<0.05); # compared with indicated p<0.05 (n=5–6).
Figure 3
Figure 3. The n-3 precursor ALA supports the antioxidant action of curcumin in the brain
In combination with dietary ALA, however, CUR significantly reduces the lipid peroxidation product 4 hydroxynonenol (4-HNE). Representative bands from Western blot are shown. CTL: control, ALA: α-linolenic acid, CUR: curcumin *compared with control (p<0.05); # compared with indicated p<0.05 (n=5–6).
Figure 4
Figure 4. Curcumin and ALA combined increases DHA and DHA-synthesis-related enzymes in the liver
ALA alone increase DHA in the liver, which is further elevated when ALA is combined with CUR at both 250 and 500 ppm doses, whereas CUR alone did not elevate liver DHA content (A). FADS2 was significantly increased in both ALA+CUR groups compared to other groups (B). Elov2 was higher in all CUR groups compared to other groups (C). Representative bands for FADS2 and Elov2 (D). FADS2: delta 6 desaturase, Elov2: elongase, CTL: control, ALA: α-linolenic acid, CUR: curcumin. *compared with control (p<0.05); # compared with indicated p<0.05 (n=5–6).
Figure 5
Figure 5. The DHA precursor ALA supports the antioxidant action of curcumin in the liver
In combination with dietary ALA, CUR significantly reduces the lipid peroxidation product 4 hydroxynonenol (4-HNE). Representative bands from Western blot are shown. CTL: control, ALA: α-linolenic acid, CUR: curcumin *compared with control (p<0.05); # compared with indicated p<0.05 (n=5–6).
Figure 6
Figure 6. DHA and DHA-synthesis-related enzymes are elevated by curcumin in cultured liver cells (HepG2)
The combination of DPA (50 μM) and CUR (20μM) significantly increased DHA levels compared to DPA treatment alone (A). CUR significantly increased the enzyme FADS2 (B) and Elov2 (C) at all doses compared with DPA (50 μM) alone. DPA plus CUR at dose of 20 μM significantly increase FADS2 (B) and Elov2 (C) compared to other doses of curcumin treatment. Representative bands for FADS2 and Elov2 (D). FADS2: delta 6 desaturase, Elov2: elongase, CTL: control, DPA: Docosapentaenoic acid, CUR: curcumin. *compared with control (p<0.05); # compared with indicated p<0.05.
Figure 7
Figure 7. FADS2 is essential to curcumin effects on DHA synthesis in hepatic HepG2 cells
SC-26196, an inhibitor of FADS2, significantly reduced the DHA levels in cells treated with DPA plus curcumin compared to the cells with similar treatment except inhibitor SC-26196. * p<0.05
Figure 8
Figure 8. Schematic of the mammalian DHA synthesis pathway and the influence of curcumin
Curcumin elevates the enzymes FASD2 and Elov2 in both liver and brain tissues and increases DHA levels in these tissues when fed in combination with ALA. In cultured liver cells, curcumin + DPA increases DHA production, an action which is prevented by inhibiting the FASD2 enzyme. Thus we propose that curcumin enhances DHA synthesis by increasing levels of DHA processing enzymes in the liver and brain, though we cannot say for sure whether the increased DHA content in the brain is a product of elevated DHA synthesis in the brain tissue or whether DHA produced in the liver is transported to the brain. FADS2: delta 6 desaturase, Elov2: elongase, ALA: α-linolenic acid DPA: Docosapentaenoic acid, DHA: Docosahexaenoic acid.

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