Role of Curcumin in Disease Prevention and Treatment.

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases.

Introduction

The plants and its constituents based remedies are very popular in health management since ancient time. Numerous studies based on animal model and clinical trials have shown beneficial effect of medicinal plants in diseases control through modulation of various biological activities. Natural products or natural products based remedies are very popular in health management and its importance in health cure documented in religious literatures including Bible and Quran. In this vista, Prophet Mohammad (Peace Be Upon Him) has recommended various plants in the diseases cure and prevention.[12] In this view, turmeric and its constituents curcumin derived from turmeric (Curcumin longa) has been used for thousands of years in the treatment of various diseases due to efficacy, affordable, and rich source of antioxidant. In addition, toxicity studies showed that it is quite safe even in high doses (up to 12 g in humans).[34] Curcumin, a chief constituents of turmeric has been proven to have clinical therapeutic and its antioxidant properties play an important role in the management of chronic inflammation diseases.[5] Previous finding has proven that curcumin has a therapeutic potential as antifungal, antiviral, antioxidant, anti-inflammatory, and management of other pharmacological activities.[56789] In this review, we summarized the therapeutics role of curcumin in diseases prevention such as cancer, diabetes, cardiovascular, and other diseases together with modulation of biological activities.

Possible Mechanism of Action of Curcumin in Health Management

Curcumin shows a pivotal role in the diseases prevention through the modulation of biological processes. It shows role in the prevention of pathogenesis due its effective scavenger of reactive oxygen species (ROS). Curcumin is an effective scavenger of ROS and reactive nitrogen species[1011] and in other finding, the antioxidant activity was established by inhibition of controlled initiation of styrene oxidation.[12]

The effective anticancer property of curcumin is attributed to its antioxidant effect that control DNA damage and free radical–mediated lipid peroxidation.[13]

Curcumin also have an important in the health management through its anti-inflammatory effects. However, the exact mechanism by which curcumin shows its anti-inflammatory effects are not entirely understood. But, it is believe that curcumin shows role as anti-inflammatory via inhibition of enzymes such as cyclooxygenase-2 (COX-2) and 5-lipooxygenase. It was confirmed that its role in the management of diseases via inhibition of pathogenesis of diseases.

Role of Curcumin in the Diseases Management Described as Following

Anti-oxidant activity

Antioxidant activity of herbs shows function in health management via its role in neutralization of free radical species. Finding based on in vitro showed that curcumin is an effective scavenger of ROS and reactive nitrogen species[1011] and in other finding, the antioxidant activity was established by inhibition of controlled initiation of styrene oxidation.[12] The effective anticancer property of curcumin is attributed to its antioxidant effect that control DNA damage and free radical–mediated lipid peroxidation.[13]

It also exerts powerful inhibitory effect against hydrogen peroxide-induced damage in human keratinocytes and fibroblasts.[14] In addition, curcumin, chief constituents of turmeric shows role in the improvement of the activities of detoxifying enzymes such as glutathione-S-transferase (GST).[15] Earlier study reported that curcumin efficiently inhibits intracellular amyloid toxicity at low dosages based on rats through its free radical scavenging activity.[16]

Experiment based on rat model confirmed that oral administration of curcumin showed noteworthy reversal in lipid peroxidation, brain lipids as well as produced enhancement of glutathione.[17]

Anti-diabetic activity

Study was performed to check the effects of curcumin and it was found that administration of curcumin enhanced the activities of all antioxidant enzymes.[18] Furthermore, curcumin treated rats has shown noteworthy increase in gene expression such as insulin-like growth factor-1, B-cell lymphoma 2, superoxide dismutase and GST as compared groups such as nondiabetic and diabetic untreated rats.[18] Another study based on rat showed that insulin secretion, heme oxygenase (HO)-1 gene expression and HO activity were significantly increased after isolated islets of Langerhans treated in curcumin.[19] Recent study summarized the role of curcumin in the prevention or delaying of diabetic retinopathy via modulation of various biological activities[20] and oral administration of curcumin with dose 0.05% w/w in diets for 9 weeks showed role in the inhibition of diabetes-induced increase in acetylated histones in the retinas.[21]

Anti–inflammatory activity

Nonsteroidal anti-inflammatory drugs are most commonly used drugs worldwide in the treatment of inflammation and are approved for orthopedic conditions and wound. However, such drugs show an adverse side effect and causes gastric ulcer. Curcumin have shown a vital effect in the prevention of inflammatory process via modulation or inhibition of various molecular pathways [Figure 1 and Table 1]. A study based on animal model, curcumin, a chief ingredient of turmeric inhibited arachidonic acid metabolism and inflammation in skin epidermis through downregulation of the pathways of cyclooxygenase and lipoxygenase and other study reported that curcumin possesses anti-inflammatory activity.[2223]

Figure 1

Curcumin shows role as anti-inflammatory via inhibition of various genetic pathways

Table 1

Pharmalogical activities

Previous studies has shown that its effect in the reduction of neutrophil infiltration in inflammatory conditions.[242526] Other results showed that curcumin inhibited arthritis at a dose of 40 mg/kg, and acute toxicity was not noticed at doses up to 2 g/kg body weight.[23] Earlier finding has shown that curcumin exerts its anti-inflammatory effects in murine colitis models via inhibition of COX-2-and pro-inflammatory cytokine expression[272829] and suppression of nuclear factor kappa B (NF-κB) activation.[3031] Curcumin, chief constituents of turmeric shows a role in the suppression of both acute and chronic inflammation as it block the formation of enzymes such as COX-2 involved in inflammation.[57] Curcumin supplementation is linked with lowered plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-6, and monocyte chemoattractant protein-1 in diabetic rats and in high glucose treated monocytes.[32]

Anti-microbial activity

The frequency of drug resistance against microorganism is rapidly growing worldwide and resistance against antimicrobial agents is one of the main culprits of the treatment disintegrate. A safe and effective natural source is needed to overcome such types of problem. Curcumin, a chief ingredient of turmeric has been confirmed to have antibacterial, antiviral, and antifungal activities.[8] A study finding revealed that curcumin exhibited inhibitory activity on methicillin-resistant Staphylococcus aureus strains with minimum inhibitory concentration value of 125–250 μg/Ml.[58] Curcumin, chief ingredients of turmeric showed role in the inhibition of growth of all Helicobacter pylori strains in vitro that were isolated from infected patients suffering from gastrointestinal disorders.[33] Curcumin possesses antibacterial property against a number of Gram-positive and Gram-negative bacteria[59] and study finding revealed that curcumin and its new derivatives such as gallium-curcumin and Cu-curcumin have remarkable antiviral effects on HSV-1 in cell culture.[7] Moreover, other investigators have also reported that anti-bacterial activity of curcumin.[606162]

Gastro-protective effect

Curcumin show gastroprotective effect and also reduced peptic ulcer and its associated complications [Figure 2 and Table 1]. Earlier investigation has shown that curcumin increases mucin secretion and may hence act as a gastroprotectant against irritants.[63] Administration of acetylsalicylic acid on an empty stomach has shown severe gastric lesions and serious damage to the internal lining of the gastric mucosa, whereas administered with curcumin in the fasting condition did not show reddish lesions or swelling of the gastric mucosa.[64] Another vital study demonstrated that antiulcer activity of curcumin in indomethacin-induced gastric ulceration and its association with down-regulation of matrix metalloproteinase (MMP)-9 activity and up-regulation of MMP-2 activity[34] and oral dose of curcumin (60 mg/kg) blocks 85% of gastric damage.[34] Study reported that curcumin and omeprazole showed role in the prevention of gastric lesions development in the gastric wall during the acute phase of gastric ulcer diseases.[35]

Figure 2

Pharmalogical activities of curcumin

Hepato-protective effect

Liver is one of the important human organs, which play a major role in detoxification of xenobiotics. Various factors are responsible for the hepatic complications such as parasitic and viral infections, autoimmune diseases and intoxication with various xenobiotics including chlorinated solvents, alcohol, drugs, fungal toxins, industrial pollutants, and radioactive isotopes.[65] In this vista, curcumin-based therapeutics for a liver disorder has been in use in different part of the world for a long time.

Study based on rat model demonstrated that oral administration of curcumin with a dose of 200 mg/kg not only protected against dimethylnitrosamine-induced hepatic injury but also showed more than 3-fold induction of HO-1 protein expression and activity in rat liver.[36]

An experiment based on mice model via carbon tetrachloride 4 (CCl4) induced liver toxicity has proved that pretreatment with picroliv, curcumin, and ellagic acid normalized serum aminotransferase activities, decreased levels of malondialdehyde, improved the antioxidant status and also normalized the hepatic histo-architecture.[66] Other study reported that administration of C. longa was found to provide noteworthy protection in CCl4 induced increases in the level of serum glutamic oxaloacetic transaminase and serum glutamate pyruvate transaminase and serum bilirubin[67] and curcumin treatment protected the liver from the arsenic-induced deterioration of antioxidant levels.[68]

Cardio-preventive effect

Cardiovascular diseases are a major global health problem and one of the major causes of death worldwide. Previous investigation based on two different heart failure model in vivo-hypertensive salt-sensitive rats and surgically induced rat model of myocardial infarction has shown that curcumin inhibit p300-HAT and that finally prevent the development of heart failure.[37] Another study based on male rat reported that curcumin possesses a potential cardioprotective effect against sodium fluoride intoxication.[69] A study finding reported that curcumin, chief constituent of turmeric pre- and co-treatment decreased the severity of pathological changes and therefore, could have a protective effect against the damage caused by myocardial infarction (MI).[70] A recent study reported that curcumin prevented ISO-induced cardiac hypertrophy, oxidative stress, inflammatory events, necrosis, and neutrophil infiltration and protected cardiomyocytes from cellular injury.[71]

Photo-protection activity

Medicinal plants are rich source of antioxidant and antioxidant activity of plants shows importance in the neutralization of adverse effect of ultraviolet (UV) light. Curcumin plays an important role in control of various types of pathogenesis and also shows a role in skin protector due to antioxidant activity. The previous study based on flow cytometric analysis revealed that increase in intracellular oxidative stress caused by UV irradiation could be abolished by curcumin.[72] Earlier study data clearly showed that topical application of curcumin inhibits UVB-induced carcinogenesis and also decreases various UVB-induced biomarkers.[73]

Neuro-protective effect

Turmeric and its chief constituents such as curcumin show a role as neuro-protector [Figure 2 and Table 1], but the exact mechanism of action is not fully understood. It is considered that due to the phenolic compound present in turmeric shows neuroprotective effect. In vitro based study has confirmed that curcumin improves survival of cortical neurons induced by oxygen-glucose deprivation (OGD)/reoxygenation and reduced OGD-induced cell injury.[38] Furthermore, results also revealed that curcumin decreases infarct volume and inhibits oxidative stress after focal cerebral ischemia/reperfusion injury in middle cerebral artery occlusion rats.[38]

Another study based in vitro showed that levels of the active oxygen decreased in chronic ischemic PC12 cells when treated with curcumin, and expression of uncoupling protein 2 notably increased after treated with curcumin.[74] A study result suggests that curcumin, the chief component of turmeric significantly modulates arsenic-induced cholinergic dysfunctions in the brain and also demonstrated neuroprotective efficacy of curcumin[75] and curcumin modulates the levels of norepinephrine, dopamine, and serotonin in the brain.[7677]

Anti-obesity effect

Obesity is a major health problem worldwide, and it is also causes various types of pathogenesis. A study results demonstrated that curcumin improves insulin signaling, glucose disposal, as well as blocks obesity during high-fat diet consumption.[78] Curcumin therapy ameliorates the inflammatory consequences of obesity in murine obesity models as compared to control obese animals. In addition, curcumin treated obese animals also showed decreased NF-κB activity in liver tissue.[79] Oral curcumin supplementation was shown to prevent the development of obesity-associated inflammation, insulin resistance, and diabetes.[79] Curcumin at cellular and whole organism levels shows potential health benefits for prevention of obesity and associated metabolic disorders through suppressing angiogenesis in adipose tissue, up-regulating adipocyte energy metabolism.[39]

Effect on hypertension

Hypertension and associated complication is a one of the culprits in the pathogenesis of diseases. In this concerned, curcumin has proven an important role in the prevention of hypertension [Figure 2]. Earlier finding concluded that increase of blood pressure due to N-nitro-L-arginine-methylester can be partially prevented by piperine or curcumin, the result of combination of curcumin and piperine being less significant[80] and other finding showed that hypertension reducing the effect of curcumin.[40]

Anti-tumor activity

Numerous natural products or products based on plant seed, flower, leaves, and stem have confirmed their role in tumor prevention. Curcumin, chief constituent of turmeric has been shown to inhibit the activity of the drug-metabolizing enzymes (cytochrome p450 and p450 reductase).[81] Numerous studies based on animals model found that dietary curcumin increased the activity of Phase II enzymes, such as GSTs[414243] and downregulated vascular endothelial growth factor through inhibition of peroxisome proliferator-activated receptor δ in colon cancer cells.[44] A study results noticed that noteworthy reduction in cell viability in curcumin-treated cells, which was consistent with induction of apoptosis and associated with down-regulation of Notch-1 and NF-κB.[82] A study finding reported that curcumin is able to induce apoptosis and inhibit the proliferation of melanoma cells.[83]

Effect on respiratory disorder

Respiratory disorder such as asthma, bronchitis, and cold coughs rapidly increasing worldwide due to the continuous increasing of environmental pollutants. Currently used drugs in this prospective are not a permanent solution and also causes other adverse complications. Curcumin shows a valuable role in the control of respiratory related complications [Figure 2 and Table 1].

A study results demonstrated that curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior.[84] Oral administration of curcumin has inhibited bleomycin-induced pulmonary fibrosis in rats[45] and cigarette smoke-induced lung inflammation and emphysema in mice.[85] Study finding suggested that curcumin is a potent anti-inflammatory agent that prevents the release of TNF-α and protects against the pulmonary and cardiovascular effects of diesel exhaust particle.[46]

Immunomodulatory effect

Immunomodulatory process plays an important role in the modulations of immune system either by enhance the immune response or suppressing the immune response. Curcumin, active compound of turmeric shows pivotal role in the modulation of immune system. A study was performed to check the effect of curcumin on T, B cells and macrophages and results showed that curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating cytotoxic T-lymphocyte antigen 4 (CTLA-4).[47] Other study confirmed that curcumin inhibited the proliferation induced by concanavalin A, phytohemagglutinin (PHA), and phorbol-12-myristate-13-acetate of lymphocytes derived from fresh human spleen.[8687] Experiment results noticed that curcumin, chief ingredients of curcumin inhibits PHA-induced T-cell proliferation, interleukin-2 production, NO generation, and lipopolysachharide-induced NF-κB and augments NK cell cytotoxicity.[88] Numerous previous results have shown that curcumin role as immunomodulatory that shows an important effect in the modulation of activation of T cells, B cells, macrophages, dendritic cells, cell cycle protein, cell-mediated and humoral mediated immunity.[484950]

Anti-malarial activity

Malaria is infectious diseases caused by blood parasites and a major health problem in the terms of morbidity and mortality. Plants such as carica papaya show an important role in the prevention of malaria[89] and it is affordable and also shows fewer side effects. The experiment was performed on mice, and results confirmed that oral administration of curcumin to mice infected with malaria parasite showed role in the reduction of blood parasitemia by 80%–90% and enhance their survival significantly.[51] Other study results concluded that curcumin, chief ingredient of spice turmeric showed a cytotoxic effect in Giardia lamblia inhibiting the parasite growth and adherent capacity, induced morphological alterations and provoked apoptosis-like changes.[52]

Nephro-protective effect

Effect of curcumin on renal function and oxidative stress in streptozotacin-induced diabetic rats was examined, and study results showed that treatment with curcumin for 2 weeks significantly attenuated both renal dysfunction and oxidative stress in diabetic rats.[53] Previous studies confirmed that curcumin showed protective effects against nephrotoxicity.[5455]

Reduction in sperm motility

The study was made to investigate the sperm-immobilizing effects of curcumin, and it was found that incubation of normal human sperm with curcumin resulted in a dose-and time-dependent loss of sperm motility.[56] Another study was performed based on in male albino rats to examine the contraceptive effect of the crude extracts of C. longa and results of the study showed a reduction in sperm motility and density was observed in both the treated groups.[90]

Radiosensitizer effect

Prostate cancer cell line PC3 based study confirmed that curcumin, is a major chemical component of turmeric confer radiosensitizing effects in prostate cancer cell line through inhibiting the growth of human prostate PC-3 cancer cells[91] and other studies based on cancer cells confirmed curcumin role as a promising radiosensitizer.[85]

Conclusion

The health-promoting effects of curcumin are well recognized and are in practice in traditional medicine since ancient time. Ayurveda and Unani based preparation of curcumin are popular in the diseases management due to its nontoxic and fewer side effect properties. A considerable number of in vitro, in vivo and clinical trials based studies revealed that turmeric and its ingredients are effective modulator of biological process. Curcumin shows a pivotal role in diseases cure through the modulation of various genes and enzymes involve in the pathogenesis. Further details studies based on animal models and clinical trials are required to improve the efficacy, safety, and mode of action of curcumin in diseases prevention and management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.