Most research has focused on a series of curcumin constituents found in the herb. Many of the animal studies; however, involve parenteral administration and oral curcumin or turmeric is likely to be far less active because curcumin is poorly absorbed by the gastrointestinal tract and only trace amounts appear in the blood after oral intake (Ammon & Wahl 1991). Curcumin may, however, have significant activity in the gastrointestinal tract, and systemic effects may take place as a consequence of local gastrointestinal effects or be associated with metabolites of the curcuminoids. antioxidant
Studies have shown that turmeric, as well as curcumin, has significant antioxidant activity (Shalini & Srinivas 1987, Soudamini et al 1992). Turmeric not only exerts direct free radical scavenging activity, it also appears to enhance the antioxidant activity of endogenous antioxidants, such as glutathione peroxidase, catalase and quinine reductase. Curcumin has been shown to induce phase II detoxifying enzymes (glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and catalase) (Iqbal et al 2003). Additionally, its antioxidant effects are 10-fold more potent than ascorbic acid or resveratrol (Song et al 2001). In addition to curcumin, turmeric contains the antioxidants protocatechuic acid and ferulic acid and exhibits significant protection to DNA against oxidative damage in vitro (Kumar et al 2006).
Turmeric's antioxidant activity may mediate damage produced by myocardial ischaemia and diabetes. Turmeric has been shown to restore myocardial antioxidant status, inhibit lipid peroxidation and protect against ischaemia-reperfusion induced myocardial injuries in an animal model with enhancement of functional recovery (Mohanty et al 2004). Curcumin has also been found to prevent protein glycosylation and lipid peroxidation caused by high glucose levels in vitro (Jain et al 2006) and to improve diabetic nephropathy (Srinivasan 2005). Turmeric has also been shown to suppress cataract development and collagen cross-linking, promote wound healing, and lower blood lipids and glucose levels (Jain et al 2006).
The many and varied effects of curcumin may be partly associated with the inhibition of transcription factor nuclear factor-kappa beta (NF-kappa-B) and induction of heat shock proteins. NF-kappa-B is a transcription factor pivotal in the regulation of inflammatory genes and is also closely associated with the heat shock response, which is a cellular defence mechanism that confers broad protection against various cytotoxic stimuli. Inhibition of NF-kappa-B may reduce inflammation and protect cells against damage (Chang 2001) and curcumin has been found to attenuate experimen
tal colitis in animal models through a mechanism correlated with the inhibition of NF-kappa-B (Salh et al 2003). The clinical significance of this is unclear.
There have been a large number of studies examining the anti-inflammatory effects of curcumin. Turmeric is a dual inhibitor of the arachidonic acid cascade. Curcumin has been shown to exert anti-inflammatory effects via phospholipase, lipo-oxygenase, COX-2, leukotrienes, thromboxane, PGs, NO, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, IFN-inducible protein, TNF and IL-12 (Chainani-Wu 2003, Lantz et al 2005).
The anti-inflammatory effect of curcumin was tested in adjuvant-induced chronic inflammation rats which found that curcumin significantly reduced C-reactive protein, TNF-alpha, IL-1 and NO, with no significant changes observed in PGE2 and leukotriene B4 levels or lymphocyte proliferation (Banerjee et al 2003). Curcumin has also been shown to inhibit inflammation in experimental pancreatitis via inhibition of NF-kappa-B and activator protein-1 in two rat models (Gukovsky et al 2003).
Hepatoprotective Curcumin prevents carbon tetrachloride-induced liver injury both in vivo and in vitro (Deshpande et al 1998, Kang et al 2002), reverses aflatoxin-induced liver damage in experimental animals (Soni et al 1992) and effectively suppresses the hepatic microvascular inflammatory response to lipopolysaccharides in vivo (Lukita-Atmadja et al 2002). An ethanol soluble fraction of turmeric was shown to contain three antioxidant compounds, curcumin, demethoxycurcumin and bisdemethoxycurcumin, which exert similar hepatoprotective activity to silybin and silychristin in vitro (Song et al 2001).
Several different mechanisms may contribute to turmeric's hepatoprotective activity. Curcumin has been shown to prevent lipoperoxidation of subcellular membranes in a dosage-dependent manner, due to an antioxidant mechanism (Quiles et al 1998) and turmeric may also protect the liver via inhibition of NF-kappa-B (see above), which has been implicated in the pathogenesis of alcoholic liver disease. Curcumin also blocked endotoxin-mediated activation of NF-kappa-B and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells (Nanji et al 2003).
Cholagogue and hypolipidaemic Turmeric extract or curcumin extract has shown dose-dependent hypolipidaemic activity in vivo (Asai & Miyazawa 2001, Babu & Srinivasan 1997, Keshavarz 1976, Ramirez-Tortosa et al 1999, Soudamini et al 1992). One in vivo study suggests that curcumin may stimulate the conversion of
cholesterol Into bile acids, and therefore, Increase the excretion of cholesterol (Srlnlvasan & Sambalah 1991). A further study demonstrated that supplementation with turmeric reduces fatty streak development and oxidative stress (Qulles et al 2002). Oral curcumln has also been shown to stimulate contraction of the gall bladder and promote the flow of bile In healthy subjects (Rasyld & Lelo 1999). Antispasmodic Curcumlnolds exhibit smooth muscle relaxant activity possibly mediated through calcium-channel blockade, although additional mechanisms cannot be ruled out (Gllanl et al 2005). Curcumlnolds produced antispasmodic effects on Isolated guinea pig Ileum and rat uterus by receptor-dependent and Independent mechanisms (Itthlpanlchpong et al 2003).
Curcumln has been studied for Its wide-ranging effects on tumorlgenesls, anglogenesls, apoptosls and signal transduction pathways (Gururaj et al 2002, Mohan et al 2000, Thaloor et al 1998). It Is known to Inhibit oncogenesis during both the promotion and progression periods In a variety of cancers (Anto et al 1996, Kuttan et al 1985, Menon et al 1999, Ruby et al 1995). Recently, curcumln was found to possess chemopreventlve effects against skin cancer, stomach cancer, colon cancer and oral cancer In mice.
Chemoprevention Chemopreventlon refers to reversing, suppressing or preventing the process of carcinogenesis. Carcinogenesis results from the accumulation of multiple sequential mutations and alterations In nuclear and cytoplasmic molecules, culminating In Invasive neoplasms. These events have traditionally been separated Into three phases: Initiation, promotion and progression. Typically, Initiation Is rapid, whereas promotion and progression can take many years. Ultimately, chemopreventlon alms at preventing the growth and survival of cells already committed to becoming malignant (Gescher et al 1998, 2001).
Curcumln has been found to effectively block carcinogen-Induced skin (Azulne & Bhlde 1992), colon (Rao et al 1995, 1999) and liver (Chuang et al 2000) carcinogenesis In animals. It has been suggested that the chemoprotectlve activity of curcumln occurs via changes In enzymes Involved In both carcinogen bloactlvatlon and oestrogen metabolism. This Is supported by the findings that curcumln treatment produced changes In CYP1A, CYP3Aand GST In mice (Valentine et al 2006) and alleviated the CCI4-lnduced Inactlvatlon of CYPs 1 A, 2B, 2C and 3A Isozymes In rats, possibly through Its antioxidant properties, without Inducing hepatic CYPs (Suglyama et al 2006).
Oral curcumln Inhibited chemically Induced skin carcinogenesis In mice (Huang et al 1992) and curcumln prevented radiation-Induced mammary and pituitary tumors © 2007 Elsevier Australia
in rats (Inano & Onoda 2002). Curcumin and genistein (from soybeans) inhibited the growth of oestrogen-positive human breast MCF-7 cells induced individually or by a mixture of the pesticides endosulfane, DDT and chlordane, or 17-beta oestradiol (Verma et al 1997).
Apoptosis Apoptosis (programmed cell death) plays a crucial role in regulating cell numbers by eliminating damaged or cancerous cells. Curcumin induced apoptosis in vitro (Kim et al 2001, Kuo et al 1996) and may act via reactive oxygen species and other mechanisms. Curcumin has been demonstrated to induce apoptosis in human basal cell carcinoma cells associated with the p53 signalling pathway, which controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis (Jee et al 1998). Curcumin has also been found to induce apoptosis in human mutant p53 melanoma cell lines and block the NF-kappa-B cell survival pathway and suppress the apoptotic inhibitor known as XIAP. Because melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment (Bush et al 2001).
Curcumin has also been found to inhibit prostate cancer cell growth in mice (Dorai et al 2001) and decrease proliferation and induce apoptosis in androgen-dependent and androgen-independent prostate cancer cells in vitro. This was found to be mediated through modulation of apoptosis suppressor proteins and interference with growth factor receptor signalling pathways (Dorai et al 2000). In a further study with rats, however, curcumin did not prevent prostate carcinogenesis (Imaida et al 2001). Antiproliferative Reduction in proliferation and/or increased apoptosis will lead to tumour regression; however, a more potent effect will be achieved if the two mechanisms occur simultaneously. Curcumin has been shown to do this. The inhibition of cell proliferation is partly related to inhibition of various kinases, such as protein kinase and phosphorylase kinase (Reddy and Aggarwal 1994), and inhibition of several oncogenes and transcription factors. For example, turmeric inhibited epidermal growth factor receptor (EGF-R) signalling via multiple mechanisms including downregulation of the EGF-R protein, inhibition of intrinsic EGF-R tyrosine kinase activity and inhibition of ligand-induced activation of the EGF-R (Dorai et al 2000). These mechanisms may be particularly important in preventing prostate cancer cells from progressing to a hormone refractory state (Dorai et al 2000). Curcumin has also been found to suppress the growth of multiple breast cancer cell lines and deplete p185neu, the protein product of the HER2/neu proto-oncogene that is thought to be important in human carcinogenesis (Hong et al 1999).
Antimetastatic Curcumin demonstrated the ability to reduce lung metastases from melanoma cells in mice. The activity of curcumin is varied.
• In cell adhesion assays, curcumin-treated cells showed a dose-dependent reduction in their binding to four extracellular matrix proteins (binding to proteins is associated with the spreading of the cancer).
• Curcumin-treated cells showed a marked reduction in the expression of integrin receptors (integrins functionally connect the cell interior with the extracellular matrix, another process necessary for metastases).
• Curcumin also enhanced the expression of antimetastatic proteins, tissue inhibitor metalloproteinase, non-metastatic gene 23 and E-cadherin (a cell adhesion factor) (Ray et al 2003).
Chemotherapy Curcumin enhanced the cytotoxicity of chemotherapeutic agents in prostate cancer cells in vitro by inducing the expression of certain androgen receptor and transcription factors and suppressing NF-kappa-B activation (Hour et al 2002). Curcumin also enhanced the antitumour effect of cisplatin against fibrosarcoma (Navis et al 1999).
Curcumin, however, was found to significantly inhibit cyclophosphamide-induced tumour regression in an in vivo model of human breast cancer. It is suspected that this occurred as a result of inhibition of free radical generation and blockade of JNK function. As such, curcumin intake should be limited in people undergoing treatment for breast cancer with cyclophosphamide until further investigation can clarify the significance of these findings (Somasundaram et al 2002).
Immunomodulation Curcumin administration was found to significantly increase the total white blood cell count and circulating antibodies in mice. A significant increase in macrophage phagocytic activity was also observed in curcumin-treated animals (Antony et al 1999). However, curcumin has also been demonstrated to have some immunosuppressive activity. Curcumin inhibits PAR2-and PAR4-mediated human mast cell activation by block of ERK pathway (Baek et al 2003).
An in vivo study using a cardiac transplant model found that curcumin also significantly reduced expression of IL-2, IFN-gamma and granzyme B (a serine protease associated with the activity of killer T-lymphocytes and NK cells) and increased mean survival time. Curcumin was further shown to work synergistically with the anti-rejection drug cyclosporine (Chueh et al 2003).
Curcumin also modulates other interleukins and has been shown in vitro to be a potent inhibitor of the production of the pro-inflammatory cytokine IL-8, thereby reducing tumour growth and carcinoma cell viability. Curcumin not only inhibited IL-8 production but also inhibited signal transduction through IL-8 receptors (Hidaka et al
2002) and to inhibit cell proliferation, cell-mediated cytotoxicity and cytokine production most likely by inhibiting NF-kappa-B target genes (Gao et al 2004).
Antiplatelet Curcumin has been shown to inhibit platelet aggregation in vivo (Srivastava et al 1985, 1986) and in vitro (Srivastava 1989, 1995). The anticoagulant effect of curcumin is weaker than that of aspirin, which is four-fold more potent than curcumin in treatment of collagen- and noradrenalin-induced thrombosis. Curcumin 100 mg/kg and aspirin 25 mg/kg resulted in 60% protection from thrombosis (Srivastava et al 1985).
Anti-atherogenic A hydro-ethanolic extract of turmeric was found to decrease LDL oxidation, have a vitamin E-sparing effect and lower the oxidation of erythrocyte and liver membranes in rabbits fed a diet high in saturated fat and cholesterol (Mesa et al 2003, Ramirez-Tortosa et al 1999). The atheroscleroprotective potential of turmeric was further demonstrated by an animal study that found turmeric lowered blood pressure and reduced the atherogenic properties of cholesterol (Zahid Ashraf et al 2005).
Dietary curcumin has also been shown to significantly lower blood cholesterol in diabetic animals. Cholesterol decrease was exclusively from the LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids was also brought about by dietary curcumin in diabetic rats (Babu & Srinivasan 1997). In a parallel study in which diabetic animals were maintained on a high cholesterol diet, curcumin lowered cholesterol and phospholipid and countered the elevated liver and renal cholesterol and triglyceride levels seen in the diabetic animals (Babu & Srinivasan 1997).
Wound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors, of which transforming growth factor-beta (TGF-beta) is one of the most important. Nitric oxide is also an important factor in healing, and its production is regulated by iNOS. Topical application of curcumin accelerated wound healing in normal and diabetic rats. The wound healing is partly associated with the regulation of the growth factor TGF-beta-1 and iNOS (Mani et al 2002). Curcumin's wound healing ability has been confirmed in several other animal studies (Sidhu et al 1998, 1999). Wounds of animals treated with curcumin showed earlier re-epithelialisation, improved neovascularisation, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content (Sidhu et al 1999). It appears to be effective when used orally or as a local application.
Curcumin has also demonstrated powerful Inhibition against hydrogen peroxide damage In human keratlnocytes and fibroblasts (Phan et al 2001) and pretreatment with curcumin significantly enhanced the rate of wound contraction, decreased mean wound healing time, Increased synthesis of collagen, hexosamlne, DNA and NO, and Improved fibroblast and vascular densities In full thickness wounds In mice exposed to whole-body [gamma]-radlatlon (Jagetla & Rajanlkant 2004).
Turmeric Is used as an antimicrobial for preserving food (Jayaprakasha et al 2005) and has been found to have antifungal activity, as well as Inhibiting asperglllus growth and aflatoxln production In feeds (Gowda et al 2004).
Curcumin has also been found to have dose-dependent, antlprotozoan activity against Giardia lamblia with Inhibition of parasite growth and adherent capacity, Induction of morphological alterations and apoptosls-llke changes In vitro (Perez-Arrlaga et al 2006). Curcumin has also shown In vitro and In vivo activity against malaria, with Inhibition of growth of chloroqulne-reslstant Plasmodium falciparum In vitro and enhancement of survival In mice Infected with P. berghei (Reddy et al 2005).
Topical curcumin reduced the severity of active, untreated psoriasis as assessed by clinical, histological and Immunohlstochemlcal criteria In an observational study of 10 patients. Curcumin was also found to decrease phosphorylase kinase, which Is Involved In signalling pathways, Including those Involved with cell migration and proliferation (Heng et al 2000). Topical administration of curcumin also Induced normal skin formation In the modified mouse tall test (Bosman 1994). The effects are thought to be due to Immune-modulating, anti-Inflammatory and cyclo-oxygenase Inhibitory actions. The downregulatlon of pro-Inflammatory cytokines supports the view that turmeric antioxidants may exert a favourable effect on psoriasis-linked inflammation. Moreover, because IL-6 and IL-8 are growth factors for keratinocytes, their inhibition by those antioxidants may reduce psoriasis-related keratinocyte hyperproliferation (Miquel etal 2002).
Was this article helpful?
Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.