Curcumin. Anti-inflammatory.
Curcumin is a compound found within the spice turmeric, which is made by grinding the root of a turmeric plant. Ground turmeric has been used as an anti-inflammatory in Ayurvedic and Chinese medicine for centuries, and Western clinical research has begun to support the value of curcumin for inflammatory conditions, particularly arthritis.
Studies show that curcumin could also potentially treat inflammation relating to mood disorders. The spice decreases levels of inflammatory interleukin 1β and tumor necrosis factor α, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo.
Curcumin is the main biological active phytochemical component of turmeric which is a member of the Curcuma botanical group (Family Zingiberaceae). Extensive studies within the last half a century have demonstrated the protective action of curcumin in almost all the disorders of the body. The molecule is known to possess antimicrobial, antiinflammatory, antihypertensive, antihyperlipidemic, antitumor, anticancer, antiphlogistic, antidiabetic, antipsoriasis, antithrombotic, antihepatotoxic and many other useful properties. Besides its protective action in peripheral organ disorders, the molecule is known to possess neuroprotective properties as well. The low molecular weight and polar structure of curcumin allows it to penetrate the blood-brain barrier effectively.
Animal studies have indicated that curcumin can enhance the adult hippocampus neurogenesis process by increasing the number of newly generated cells in the dentate gyrus region of hippocampus. Moreover, it is a potent inhibitor of reactive astrocyte expression and thus, prevents hippocampal cell death induced by kainic acid. In one of the recent studies, low doses of curcumin has shown to effectively disaggregate beta amyloid as well as prevents fibril and oligomer formation and thus found to be protective in treating Alzheimer’s disease. Various experimental evidences have shown protective effect of curcumin in animal models of seizures.
Similarly, antidepressant activity of curcumin has been reported in animal models of depression. Recently, research on exploring antidepressant properties of curcumin is exponentially increasing. The molecule is effective in forced swim test and chronic unpredictable stress. Curcumin possess antidepressant activity through modulating the release of serotonin and dopamine. Curcumin enhances the level of neurotrophic factors such as brain derived neurotrophic factor (BDNF).
Another exciting use of curcumin is in the treatment of diabetic neuropathy. Curcumin enhanced the glucose lowering effect of insulin and protects against the onset of diabetic neuropathy.
Our earlier experience with curcumin has demonstrated its neuroprotective action in animal models of tardive dyskinesia.
Curcumin in major depression:
Despite the availability of various antidepressants, we are still not able to treat 20-30% of the depressed patients. Also, these antidepressants are associated with plethora of side-effects and drug-drug/drug-food interactions. Therefore, it is utmost important to find alternative drug therapies that is efficacious and safe in the treatment of major depression.
Curcumin has been found to possess antidepressant action in various animal models of depression. Curcumin at dose range of 10-80 mg/kg, i.p. demonstrated antiimmobility action in forced swim test during 6 min period. The maximum anti-immobility effect was observed at 90 min of its administrations. Moreover, curcumin at doses of 40 and 80 mg/kg also reversed the reserpine-induced behavioral despair in mice. Further studies have demonstrated that curcumin enhanced the anti-immobility effect of tranylcypromine (5 mg/kg, i.p.), and selegiline (5 mg/kg, i.p.), two monoamine oxidase (MAO) inhibitors in mouse forced swim test. This study suggests the involvement of monoamine oxidase enzyme in the antidepressant property of curcumin. It was further explored that curcumin inhibits the activity of both MAO-A and MAO-B enzymes. It is important to mention here that monoamine oxidase is the enzyme that is involved in the degradation of norepinephrine, serotonin and dopamine. By inhibiting the activity of MAO enzyme, curcumin increases the concentration of these neurotransmitters in the synapse and thus prolonging their action.
The antidepressant activity of curcumin was further explored by combining it with various conventional and newly discovered antidepressants. To this end, we found that curcumin enhanced the anti-immobility effect of sub-effective doses of f1uoxetine (selective serotonin reuptake inhibitor), bupropion (dopamine reuptake inhibitor) and venlafaxine (dual reuptake inhibitor of serotonin and norepinephrine). Interestingly, curcumin did not potentiate the antidepressant effect of desipramine (tricyclic antidepressant and norepinephrine reuptake inhibitor) and imipramine (tricyclic antidepressant). This gives an indication of the involvement of serotoninergic and dopaminergic system in the antidepressant action of curcumin. When the brain neurotransmitter levels were checked following curcumin administration, it increased the levels of serotonin and dopamine but not norepinephrine in the mouse brain. Further, curcumin potentiated the brain levels of serotonin when combined with various antidepressant agents. Therefore, from all the above findings, it can be concluded that the antidepressant action of curcumin majorly involves the serotoninergic neurotransmission. This is further confirmed from the study by Wang and colleagues, who have demonstrated that curcumin antidepressant action is blocked by p-chlorophenylalanine, a tryptophan hydroxylase inhibition. Moreover, it has been demonstrated that the antidepressant action of curcumin involves the participation of 5-HT(1A/1B) and 5-HT(2C) receptors. However, in contrast to these studies, Xu and colleagues have demonstrated an increase in noradrenaline levels in the frontal cortex and striatum regions of the rat brain following curcumin administration.
Another animal model of depression is unpredictable chronic stress. Our laboratory has demonstrated the protective action of curcumin in unpredictable chronic stress model. Animal challenged with chronic unpredictable stress demonstrates lower levels of norepinephrine, serotonin and dopamine in the brain. Chronic administration of curcumin did not affect depleted norepinephrine levels but restored levels of serotonin and dopamine. In one of the studies carried out by Li and colleagues, curcumin produced beneficial effects on the stressed rats by effectively improving chronic unpredictable mild stress -induced low sucrose consumption and reducing serum corticosterone levels in rats. The studies further demonstrate the participation of adenylyl cyclase (AC) and cyclic adenosine monophosphate (cAMP) pathway in the antidepressant activity of curcumin.
Curcumin has poor oral bioavailability. It has been demonstrated that piperine (2.5 mg/kg, i.p.) enhanced the antidepressant-like activity of curcumin (20 and 40 mg/kg, i.p.) in mouse challenged to unpredictable mild chronic stress.
Curcumin and Curcuminoids.
Curcumin is one of several curcuminoids, which are polyphonic compounds, present in turmeric. Turmeric contains approximately 2 percent curcumin by weight, so a tablespoon of turmeric, which weighs 6.8 grams, contains about 0.136 gram curcumin, or 136 milligrams. In addition to curcumin, turmeric also contains smaller amounts of the curcuminoids demethoxycurcumin and bisdemethoxycurcumin. Researchers believe curcumin to be the most biologically active curcuminoid in turmeric.
Dosages.
To gain health benefits from turmeric, the University of Maryland Medical Center recommends taking 1 to 3 grams of dried, powdered turmeric root per day, about 1/2 to 1.5 teaspoons. The recommended dosage for standardized curcumin powder is 400 to 600 milligrams, three times per day. Curcumin and turmeric are safe when eaten in foods and at recommended dosages, but larger doses may cause stomach upset. Exercise caution and check with your doctor before taking curcumin or turmeric supplements if you are diabetic, pregnant or breast-feeding or if you take medications that thin the blood, reduce stomach acid or lower blood sugar.
Turmeric Safety.
Turmeric use is safe for most adults, the National Center for Complementary and Alternative Medicine reports. If you take high doses of the herb, or take it for prolonged periods of time, however, you can develop symptoms that include diarrhea, nausea or indigestion. In severe cases, excess consumption of turmeric can lead to the development of gastrointestinal ulcers. In laboratory testing, animals given high doses of turmeric sometimes developed liver problems; however, these effects are not known to occur in human beings.
Turmeric and Stroke Medications.
People with ischemic stroke sometimes receive drugs called anticoagulants, or blood thinners, which achieve their effects by reducing the normal tendency of platelets — clotting components in your blood — to clump together. Common blood-thinning medications include clopidogrel, sold commercially as Plavix; warfarin, sold commercially as Coumadin; and aspirin. If you take turmeric in combination with any of these medications, the UMMC explains, it can potentially interfere with their effectiveness by changing your blood’s clotting characteristics. If you use any anticoagulant medication, speak with your doctor and get his advice before you use any supplement labeled as turmeric or curcumin. Also ask him for information on potential adverse interactions between turmeric and other medications.
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