Curcumin Abstracts 5

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The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials.
(Al-Karawi et al., 2016) Download
Major depression is a common, recurrent, and chronic disease that negatively affects the quality of life and increases the risk of mortality. Several studies have demonstrated that curcumin, the yellow-pigmented substance of the turmeric, possesses antidepressant properties. The aim of this review is to meta-analytically assess the antidepressant effect of curcumin in patients with major depressive disorders. We extensively searched the literature until August 2015. The random-effect model was used to calculate the pooled standardized difference of means (SMD). Subgroup analyses were also performed to examine the effect of different study characteristics on the overall model. Six clinical trials met the inclusion criteria. Overall, curcumin administration showed a significantly higher reduction in depression symptoms [SMD = -0.34; 95% confidence interval (CI) = -0.56, -0.13; p = 0.002]. Subgroup analyses showed that curcumin had the highest effect when given to middle-aged patients (SMD = -0.36; 95% CI = -0.59; -0.13; p = 0.002), for longer duration of administration (SMD = -0.40; 95% CI = -0.64, -0.16; p = 0.001), and at higher doses (SMD = -0.36; 95% CI = -0.59, -0.13; p = 0.002). The administration of new formulation of curcumin (BCM-95) had non-significantly higher effect on depression as compared with the conventional curcumin-piperine formula. We conclude that there is supporting evidence that curcumin administration reduces depressive symptoms in patients with major depression.

Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.
            (Antiga et al., 2015) Download
Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.

Effects of Curcuma extract and visible light on adults with plaque psoriasis.
            (Carrion-Gutierrez et al., 2015) Download
INTRODUCTION:  We conducted a phase IV randomized, double-blind, placebo-controlled, pilot clinical trial to investigate the safety and efficacy of oral curcumin together with local phototherapy in patients with plaque psoriasis. MATERIALS AND METHODS:  Patients with moderate to severe psoriasis received Curcuma extract orally with real visible light phototherapy (VLRT) or simulated visible light phototherapy (VLST) in the experimental area, while the rest of the body surface was treated with ultraviolet A (UVA) radiation. The endpoints were the number of responders and the temporal course of the response. The secondary outcomes were related to safety and adverse events. RESULTS:  Twenty-one patients were included in the study. In the intention-to-treat analysis, no patients included in the VLRT group showed "moderate" or "severe" plaques after the treatment, in contrast to the patients included in the VSLT group (p<0.01). Parallelisms in the evolution of PGA, BSA, and PASI scores were observed in the two groups following the treatment. At the end of the study period, 76% of all patients showed a response in the BSA exposed to UVA. Lesions on the experimental area showed a response in 81% of the patients in the VLRT group and 30% of the patients in the VLST group. There were no study-related adverse events that necessitated participant withdrawal. CONCLUSION:  The results suggested that moderate to severe plaque psoriasis should show a therapeutic response to orally administered Curcuma if activated with visible light phototherapy, a new therapeutic method that would be safer for patients than existing treatments.

Antidepressant activity of curcumin: involvement of serotonin and dopamine system.
            (Kulkarni et al., 2008) Download
RATIONALE:  Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. OBJECTIVE:  The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. METHODS AND OBSERVATIONS:  Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. CONCLUSION:  The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.
            (Kuptniratsaikul et al., 2014) Download
OBJECTIVE:  To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement. METHODS:  367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded. RESULTS:  185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010, respectively), except for the WOMAC stiffness subscale, which showed a trend toward significance (P=0.060). The number of patients who developed AEs was no different between groups. However, the number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group (P=0.046). Most subjects (96%-97%) were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment. CONCLUSION:  C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal AE reports in the C. domestica extracts group.

Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress.
            (Liu et al., 2014) Download
Accumulating evidence suggests that cognitive processes, such as learning and memory, are affected in depression and antidepressant treatment may ameliorate cognitive impairments. Recent studies have shown that curcumin exhibits antidepressant-like effects. The aim of the present study was to determine whether curcumin administration influences chronic unpredictable stress (CUS)-induced cognitive deficits and explores underlying mechanisms. Male Wistar rats were subjected to CUS protocol for a period of 5 weeks to induce depression. The depressive-like behavior was tested using sucrose preference test, open field test and Morris water maze test. Effects of curcumin on brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) levels in the hippocampus were also examined. Chronic treatment with curcumin significantly reversed the CUS-induced behavioral and cognitive parameters (reduced sucrose preference and impaired learning and memory function) in stressed rats. Additionally, CUS reduced hippocampal BDNF and ERK levels, while curcumin effectively reversed these alterations. Taken together, our results indicate that the antidepressant-like effects of curcumin in CUS rats are related to its aptitude to promote BDNF and ERK in the hippocampus.

Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study.
            (Lopresti et al., 2014) Download
BACKGROUND:  Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in individuals with major depressive disorder. METHODS:  In a randomised, double-blind, placebo-controlled study, 56 individuals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks. The primary measure was the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI). RESULTS:  From baseline to week 4, both curcumin and placebo were associated with improvements in IDS-SR30 total score and most secondary outcome measures. From weeks 4 to 8, curcumin was significantly more effective than placebo in improving several mood-related symptoms, demonstrated by a significant group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS-SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was identified in a subgroup of individuals with atypical depression. CONCLUSIONS:  Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment. LIMITATIONS:  Investigations with larger sample sizes, over extended treatment periods, and with varying curcumin dosages are required.

Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study.
            (Lopresti and Drummond, 2017) Download
BACKGROUND:  Several studies have supported the antidepressant effects of curcumin (from the spice turmeric) and saffron for people with major depressive disorder. However, these studies have been hampered by poor designs, small sample sizes, short treatment duration, and similar intervention dosages. Furthermore, the antidepressant effects of combined curcumin and saffron administration are unknown. METHODS:  In a randomised, double-blind, placebo-controlled study, 123 individuals with major depressive disorder were allocated to one of four treatment conditions, comprising placebo, low-dose curcumin extract (250mg b.i.d.), high-dose curcumin extract (500mg b.i.d.), or combined low-dose curcumin extract plus saffron (15mg b.i.d.) for 12 weeks. The outcome measures were the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) and Spielberger State-Trait Anxiety Inventory (STAI). RESULTS:  The active drug treatments (combined) were associated with significantly greater improvements in depressive symptoms compared to placebo (p=.031), and superior improvements in STAI-state (p<.001) and STAI-trait scores (p=.001). Active drug treatments also had greater efficacy in people with atypical depression compared to the remainder of patients (response rates of 65% versus 35% respectively, p=.012). No differences were found between the differing doses of curcumin or the curcumin/saffron combination. LIMITATIONS:  Investigations with larger sample sizes are required to examine the efficacy of differing doses of curcumin and saffron/curcumin combination. Its effects in people with atypical depression also require examination in larger scale studies. CONCLUSIONS:  Active drug treatments comprising differing doses of curcumin and combined curcumin/saffron were effective in reducing depressive and anxiolytic symptoms in people with major depressive disorder.

Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS).
            (Nicol et al., 2015) Download
INTRODUCTION:  Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice. PURPOSE:  To determine effects of curcumin on muscle damage, inflammation and delayed onset muscle soreness (DOMS) in humans. METHOD:  Seventeen men completed a double-blind randomized-controlled crossover trial to estimate the effects of oral curcumin supplementation (2.5 g twice daily) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise. Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise, separated by 14-d washout. Measurements were made at baseline, and 0, 24 and 48-h post-exercise comprising: (a) limb pain (1-10 cm visual analogue scale; VAS), (b) muscle swelling, (c) single-leg jump height, and (d) serum markers of muscle damage and inflammation. Standardized magnitude-based inference was used to define outcomes. RESULTS:  At 24 and 48-h post-exercise, curcumin caused moderate-large reductions in pain during single-leg squat (VAS scale -1.4 to -1.7; 90 %CL: ±1.0), gluteal stretch (-1.0 to -1.9; ±0.9), squat jump (-1.5 to -1.1; ± 1.2) and small reductions in creatine kinase activity (-22-29 %; ±21-22 %). Associated with the pain reduction was a small increase in single-leg jump performance (15 %; 90 %CL ± 12 %). Curcumin increased interleukin-6 concentrations at 0-h (31 %; ±29 %) and 48-h (32 %; ±29 %) relative to baseline, but decreased IL-6 at 24-h relative to post-exercise (-20 %; ±18 %). CONCLUSIONS:  Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance. Further study is required on mechanisms and translational effects on sport or vocational performance.

Relevance of the anti-inflammatory properties of curcumin in neurodegenerative diseases and depression.
            (Tizabi et al., 2014) Download
This review is an attempt to summarize our current understanding of curcumin's potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin's pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson's disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD). It is concluded that curcumin, or better yet, an analog with better and longer bioavailability could be of important therapeutic potential in PD and/or major depression.


 

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.
            (Xu et al., 2006) Download
Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.
            (Xu et al., 2007) Download
Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicine, which has been used to effectively manage stress and depression-related disorders in China. As the active component of curcuma longa, curcumin possesses many therapeutic properties; we have previously described its antidepressant activity in our earlier studies using the chronic unpredictable stress model of depression in rats. Recent studies show that stress-induced damage to hippocampal neurons may contribute to the phathophysiology of depression. The aim of this study was to investigate the effects of curcumin on hippocampal neurogenesis in chronically stressed rats. We used an unpredictable chronic stress paradigm (20 days) to determine whether chronic curcumin treatment with the effective doses for behavioral responses (5, 10 and 20 mg/kg, p.o.), could alleviate or reverse the effects of stress on adult hippocampal neurogenesis. Our results suggested that curcumin administration (10 and 20 mg/kg, p.o.) increased hippocampal neurogenesis in chronically stressed rats, similar to classic antidepressant imipramine treatment (10 mg/kg, i.p.). Our results further demonstrated that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. In addition, curcumin significantly prevented the stress-induced decrease in 5-HT(1A) mRNA and BDNF protein levels in the hippocampal subfields, two molecules involved in hippocampal neurogenesis. These results raise the possibility that increased cell proliferation and neuronal populations may be a mechanism by which curcumin treatment overcomes the stress-induced behavioral abnormalities and hippocampal neuronal damage. Moreover, curcumin treatment, via up-regulation of 5-HT(1A) receptors and BDNF, may reverse or protect hippocampal neurons from further damage in response to chronic stress, which may underlie the therapeutic actions of curcumin.

Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress.
            (Xu et al., 2009) Download
Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously we demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown. This study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity. Furthermore, the portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated CaMKII, pCaMKII), and the glutamate receptor sub-type (NMDA(2B)) expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or imipramine treatment. Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and glutamate receptor levels.


 

Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial.
            (Yang et al., 2014) Download
Human studies of curcumin extract on lipid-lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty-five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high-density lipoprotein cholesterol (HDL-C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The triglyceride-lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL-C effect in female patients, both of which result in a decrease of T-Chol/HDL-C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid-lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol-related parameters, especially in metabolic syndrome patients.


 

References

Al-Karawi, D, DA Al Mamoori, and Y Tayyar (2016), ‘The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials.’, Phytother Res, 30 (2), 175-83. PubMed: 26610378
Antiga, E, et al. (2015), ‘Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.’, Biomed Res Int, 2015 283634. PubMed: 26090395
Carrion-Gutierrez, M, et al. (2015), ‘Effects of Curcuma extract and visible light on adults with plaque psoriasis.’, Eur J Dermatol, 25 (3), 240-46. PubMed: 26066761
Kulkarni, SK, MK Bhutani, and M Bishnoi (2008), ‘Antidepressant activity of curcumin: involvement of serotonin and dopamine system.’, Psychopharmacology (Berl), 201 (3), 435-42. PubMed: 18766332
Kuptniratsaikul, V, et al. (2014), ‘Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.’, Clin Interv Aging, 9 451-58. PubMed: 24672232
Liu, D, et al. (2014), ‘Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress.’, Behav Brain Res, 271 116-21. PubMed: 24914461
Lopresti, AL, et al. (2014), ‘Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study.’, J Affect Disord, 167 368-75. PubMed: 25046624
Lopresti, AL and PD Drummond (2017), ‘Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study.’, J Affect Disord, 207 188-96. PubMed: 27723543
Nicol, LM, et al. (2015), ‘Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS).’, Eur J Appl Physiol, 115 (8), 1769-77. PubMed: 25795285
Tizabi, Y, et al. (2014), ‘Relevance of the anti-inflammatory properties of curcumin in neurodegenerative diseases and depression.’, Molecules, 19 (12), 20864-79. PubMed: 25514226
Xu, Y, et al. (2006), ‘Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.’, Brain Res, 1122 (1), 56-64. PubMed: 17022948
Xu, Y, et al. (2007), ‘Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.’, Brain Res, 1162 9-18. PubMed: 17617388
Xu, Y, et al. (2009), ‘Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress.’, Neuropharmacology, 57 (4), 463-71. PubMed: 19540859
Yang, YS, et al. (2014), ‘Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial.’, Phytother Res, 28 (12), 1770-77. PubMed: 25131839