a review on therapeutic applications of curcumin

www.wjpr.net Vol 9, Issue 12, 2020.

Shashanka et al. World Journal of Pharmaceutical Research

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A REVIEW ON THERAPEUTIC APPLICATIONS OF CURCUMIN

Shashanka K. N.*, Mamatha G. T., Parthiban S. and Senthil Kumar G. P.

Department of Pharmaceutics, Bharathi College of Pharmacy, Bharathi Nagar, Maddur

Taluq, Mandya Dist, Karnataka, India.

ABSTRACT

Turmeric (Curcuma longa) is extensively used as a spice, food

preservative and colouring material in India, China and South East

Asia. It has been used in traditional medicine as a household remedy

for various diseases, including biliary disorders, anorexia, cough,

diabetic wounds, hepatic disorders, rheumatism and sinusitis. The

purpose of writing this review was to study the various applications of

curcumin in the treatment of various diseases and its activities like

anti- inflammatory activity, anti- carcinogenic activity, anti -oxidant

activity and anti -diabetic activity, wound healing activity, hepato

protective activity, Anti-arthritis activity, Anti-alzheimer activity,

Anti-parkinson activity, Anti-angiogenesis activity, Anti-bacterial

activity, Anti-fungal activity, Anti-viral activity and Anti-fibrotic

activity. Curcumin plays an important role for the treatment of above-mentioned category of

diseases.

KEYWORDS: Turmeric, Curcumin longa, Curcuminoids, Curcumin.

INTRODUCTION

Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a

member of the ginger family (Zingiberaceae). The other two curcuminoids are

desmethoxycurcumin and bis desmethoxycurcumin. The curcuminoids are polyphenols and

are responsible for the yellow colour of turmeric. Curcumin can exist in at least two

tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase

and in solution. Curcumin can be used for boron quantification in the so -called curcumin

method. It reacts with boric acid forming a red coloured compound, known as rosocyanine.

Curcumin is brightly yellow coloured and may be used as a food colouring.[1]

World Journal of Pharmaceutical Research SJIF Impact Factor 8.084

Volume 9, Issue 12, 686-702. Review Article ISSN 2277– 7105

Article Received on

12 August 2020,

Revised on 02 Sept. 2020,

Accepted on 23 Sept. 2020,

DOI: 10.20959/wjpr202012-18848

*Corresponding Author

Shashanka K. N.

Department of

Pharmaceutics, Bharathi

College of Pharmacy,

Bharathi Nagar, Maddur

Taluq, Mandya Dist,

Karnataka, India.



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Curcumin has antioxidant, anti-inflammatory, antiviral and antifungal actions. Studies have

shown that curcumin is not toxic to humans. Curcumin exerts anti-inflammatory activity by

inhibition of a number of different molecules that play an important role in inflammation.

Turmeric is effective in reducing post -surgical inflammation. Turmeric helps to prevent

atherosclerosis by reducing the formation of blood clumps. Curcumin inhibits the growth of

helicobacter pylori, which causes gastric ulcers and has been linked with gastric cancers.

Curcumin can bind with heavy metals such as cadmium and lead, thereby reducing the

toxicity of these heavy metals. This property of curcumin explains its protective action to the

brain. Curcumin acts as an inhibitor for cyclooxygenase, 5-lipoxygenase and glutathione S-

transferase. It is a common spice, known mostly for its use in Indian dishes as a common

ingredient in curries and other ethnic meals. Turmeric is also been used for centuries in

ayurvedic medicine, which integrates the medicinal properties of herbs with food. This

extraordinary herb has found its way into the spotlight in the west because of its wide range

of medicinal benefits. Turmeric is a potent antioxidant.[1]

Curcumin, its main active constituent, is as powerful and antioxidant as vitamin C, E and

Beta-Carotene, making turmeric usage a consumer choice for cancer prevention, liver

protection and premature aging. Several published studies also show that turmeric inhibits the

growth of several different types of cancer cells. In addition, turmeric is a powerful anti-

inflammatory, easing conditions such as bursitis, arthritis and back pain. Turmeric’s anti-

inflammatory action is likely due to a combination of three different properties.[1]

First, turmeric lowers the production of inflammation inducing histamine. Secondly, it

increases and prolongs the action of the body’s natural anti-inflammatory adrenal hormone,

cortisol and finally, turmeric improves circulation, thereby flushing toxins out of small joints

where cellular wastes and inflammatory compounds are frequently trapped. Research has also

confirmed the digestive benefits of turmeric. Turmeric acts as a cholagogue, stimulating bile

production, thus, increasing the bodies ability to digest fats, improving digestion and

eliminating toxins from the liver.[1]

Chemistry of curcumin

Turmeric is an Indian rhizomatous herbal plant (Curcuma longa) of the ginger family

(Zingiberaceae) of well-known medical benefits. The medicinal benefits of turmeric could be

attributed to the presence of active principles called curcuminoids. One of the most

interesting components of curcuminoid is curcumin, which is a small molecular weight



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polyphenolic compound and lipophillic in nature, hence insoluble in water and also in ether

but soluble in ethanol, dimethylsulfoxide, and other organic solvents. Curcumin is stable at

the acidic pH of the stomach. The other constituents present are volatile oils including

tumerone, atlantone and zingiberone and sugars, proteins and resins. The active constituent of

turmeric- curcumin is isolated from curcuma longa and it provides colour to turmeric. It is a

tautomeric compound existing in enolic form in organic solvents and as a keto form in

water.[9]

Curcumin, C21H20O6, m. p. 183℃ was isolated as early as 1815. The structure and synthesis

of curcumin as diferuloylmethane was confirmed by the work of Lampe et al. and also by

Majeed et al. The main pigments in the rhizomes are curcumin [1, 7-bis-(4-hydroxy-3-

methoxy prenyl)-1, 6-heptadiene-3, 5-dione] and two related demethoxy compounds,

demethoxycurcumin and bisdemethoxycurcumin, which belong to the group of

diarylheptanoids. Besides these three forms of curcuminoids, three minor constituents which

are supposed to be geometrical isomers of curcumin have also been isolated. One of these is

assumed to be a cis-trans geometrical isomer of curcumin based on its UV spectrum, lower

m.p. and lower stability when compared to curcumin which has a trans trans configuration.

Heller (1914) had isolated an isomer of curcumin, with a diketone structure. Cyclocurcumin

having the same molecular formula as that of curcumin with cyclic structure was isolated

from the nematocidally active fraction of turmeric.[2]

Extraction and detection of curcumin[2]

Depending on its origin and the soil conditions where it is grown, turmeric contains 2.5–6.0

% curcuminoids. The word ＂curcuminoids” indicates a group of compounds such as

curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin. Out of these,

curcumin is the major component and cyclocurcumin is the minor component. Although

chlorinated solvents extract curcumin very efficiently from turmeric, they are not commonly

employed due to their non-acceptability in the food industry. Soxhlet extraction, ultrasonic

extraction, microwave, zone-refining and dipping methods have been tried, and among these

the soxhlet, ultrasonic and microwave extractions are the most commonly employed methods.

Another commercially viable and efficient extraction method is by supercritical carbon

dioxide. Being free from organic solvents, pilot plants based on supercritical carbon dioxide

have been established in several countries for the extraction of curcumin from turmeric.

There are also a few reports on enzyme-assisted extraction, where pre -treatment of turmeric



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with enzymes like α-amylase and glucoamylase yielded significant increase in curcumin

yield. However due to higher cost of extraction, this method is not commercially viable.

Curcumin can be separated from curcuminoids by column chromatography by adsorbing the

mixture on silica gel using mixtures of solvents like dichloromethane/acetic acid or

methanol/chloroform to yield three different fractions. The curcumin fraction is further

purified on silica gel using chloroform/dichloromethane and ethanol/methanol mixtures as

eluents.

High-efficient column chromatographic extraction (CCE) procedures were developed for the

extraction of curcumin from turmeric. Turmeric powder was loaded into a column with 2-fold

80% ethanol. The column was eluted with 80% ethanol at room temperature. For quantitative

analysis with a non-cyclic CCE, 8-fold eluent was collected as extraction solution. For large

preparation with a cyclic CCE, only the first 2-fold of eluent was collected as extraction and

other eluent was sequentially circulated to the next columns. More than 99% extraction rates

were obtained through both CCE procedures, compared to a 59% extraction rate by the

ultrasonic-assisted maceration extraction with 10-fold 80% ethanol. The CCE procedures are

high-efficient for the extraction of curcumin from turmeric with minimum use of solvent and

high concentration of extraction solution.

Several HPLC methods are available for detecting/ quantifying curcuminoids. Liquid

chromatography-coupled mass spectrometry has been another versatile tool for detecting

curcumin. Of all these the most sensitive method for detection of curcumin (up to 1 ng/mL) is

by fluorescence, by exciting in the 400 to 450 nm region. Li et al. studied stability of three

curcuminoids and simultaneous determination of curcuminoids in turmeric by HPLC using

ternary gradient system.



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APPLICATIONS OF CURCUMIN[3]

Figure (1): Diagrams of Curcuma longa plant, Turmeric rhizomes and Powdered

turmeric.

Figure (2): Chemical Structure of Curcumin, Demethoxycurcumin and Bis-

demethoxycurcumin.

Turmeric has been used as a food- additives in curries to improve palatability and storage

stability. Curcuminoids a natural coloring agent is recognized as a rich source of phenolic

compounds, consisting of three different compounds such as curcumin, de methoxy curcumin

and bis de methoxy curcumin. It also has potential as a pharmaceutical excipient, since it

possess antioxidant, anti-inflammatory, antimutagenic properties and can reduce blood

glucose. Various biological and medicinal uses of curcumin are listed below,



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Figure (3): Medicinal Uses of Curcumin.

1) Cancer preventing activity of curcumin[4]

Turmeric extract and curcumin were also found to be cancer preventing compounds in

different tumour models. Recently, curcumin has been considered as a potentially important

chemo preventive agent against cancer. Animal studies have demonstrated that curcumin

inhibits carcinogenesis in various sites, including skin, colorecum, mouth, forestomach and

breasts. The genetic changes in carcinogenesis in these organs involve different genes, but

curcumin is effective in preventing carcinogenesis in several organs. Since angiogenesis

(blood vessel formation) is essential for tumour growth and metastasis, it has been suggested

that curcumin can inhibit several cancers through its potential role as anti-angiogenic agent.

There are different active sites within the chemical structure of curcumin. This could be a

good reason why curcumin has been used for multiple purposes. Moreover, through its

unique chemical structure, these multi-purposed actions of curcumin can also act

simultaneously and sequentially.

2) Curcumin in cardiovascular disease[5]

Many studies indicate that curcumin has preventive effects against various cardiovascular

diseases, including atherosclerosis and myocardial infarction. The compounds effect on the

proliferation of peripheral blood mononuclear cells and vascular smooth muscle cells was



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investigated by the evaluation of fetal calf serum-stimulated [3H]-thymidine uptake.

Curcumin (1-100 mM) concentration dependently inhibited the serum-stimulated [3H]-

thymidine incorporation into both A7r5 cells and vascular smooth muscle cells from rabbits.

Curcumin also induced apoptosis in vascular smooth muscle cells and extensively reduced

the membranous protein tyrosine kinase activity, c-Myc mRNA and Bcl-2 mRNA. Several

studies suggest that curcumin inhibits LDL oxidation in atherosclerosis, a disease

characterized by oxidative damage, which affects lipoproteins and the walls of the blood

vessels. Curcumin effectively inhibited LDL oxidation (40-85%), as indicated by inhibition

of the formation of thiobarbituric acid reactive substances after copper ion induced lipid

peroxidation. In addition, curcumin was found to correct cystic fibrosis through opening of

the cystic fibrosis transmembrane conductance regulator channels. Curcumin has a protective

role in myocardial infarction, which is caused by closure of the coronary artery that supplies

blood to the heart muscle. In addition, it was found to prevent cardiac hypertrophy and

myocardial infarction through the inhibition of histone acetyl transferase p300. Curcumin

also blocked aorta banding induced inflammation and fibrosis by disrupting histone acetyl

transferase p300-dependent signaling pathways. This indicates that curcumin may soon

provide a novel therapeutic strategy for cardiovascular diseases.

3) Antioxidant effect of Curcumin[6]

The antioxidant activity of curcumin was reported as early as 1975. It acts as a scavenger of

oxygen free radicals. It can protect haemoglobin from oxidation. In vitro, curcumin can

significantly inhibit the generation of reactive oxygen species (ROS) like superoxide anions,

H2O2 and nitrite radical generation by activated macrophages, which play an important role

in inflammation. Curcumin also lowers the production of ROS in vivo. Its derivatives,

dimethoxy curcumin and bis-de methoxy curcumin also have antioxidant effect. Curcumin

exerts powerful inhibitory effect against H2O2-induced damage in human keratinocytes and

fibroblasts and in NG 108-15 cells. Curcumin reduces oxidized proteins in amyloid pathology

in Alzheimer transgenic mice. It also decreases lipid peroxidation in rat liver microsomes,

erythrocyte membranes and brain homogenates. This is brought about by maintaining the

activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione

peroxidase. Recently, we have observed that curcumin prevents oxidative damage during

indomethacin induced gastric lesion not only by blocking inactivation of gastric peroxidase,

but also by direct scavenging of H2O2 and ·OH. Since ROS have been implicated in the



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development of various pathological conditions, curcumin has the potential to control these

diseases through its potent antioxidant activity.

Contradictory to the above-mentioned antioxidant effect, curcumin has pro oxidant activity.

Kelly et al. reported that curcumin not only failed to prevent single-strand DNA breaks by

H2O2, but also caused DNA damage. As this damage was prevented by antioxidant a-

tocopherol, the pro-oxidant role of curcumin has been proved. Curcumin also causes

oxidative damage of rat hepatocytes by oxidizing glutathione and of human erythrocyte by

oxidizing oxyhaemoglobin, thereby causing haemolysis. The prooxidant activity appears to

be mediated through generation of phenoxyl radical of curcumin by peroxidase–H2O2 system,

which cooxidizes cellular glutathione or NADH, accompanied by O2 uptake to form ROS.

The antioxidant mechanism of curcumin is attributed to its unique conjugated structure,

which includes two methoxylated phenols and an enol form of b-diketone; the structure

shows typical radical-trapping ability as a chain-breaking antioxidant.

4) Wound healing activity of curcumin[7]

Tissue repair and wound healing are complex processes that involve inflammation,

granulation and remolding of the tissue. Sidhu et al (1998) observed that the localization of

transforming growth factor beta and fibronectin, which are important criteria in wound

healing, showed increase in curcumin treated wounds as compared to untreated wounds. Phan

et al (2001) investigated the effects of curcumin on hydrogen peroxide and hypoxanthine-

xanthine oxidase induced damage to cultured human keratinocytes and fibroblasts in an effort

to elucidate the mechanism of wound healing action of curcumin. It was observed that

exposure of human keratinocytes to curcumin (10µg/ml) offered significant protection

against hydrogen peroxide. However, no protective effects were observed against

hypoxanthine-xanthine oxidase injury. The authors concluded that curcumin is a powerful

inhibitor of damage to human keratinocytes and fibroblasts. Thangapazham et al (2007)

showed the beneficial effect of curcumin as proangiogenic agent in wound healing by

inducing transforming growth factor-beta, which induces both angiogenesis and accumulation

of extracellular matrix and continues through the remodeling phase of wound repair.

Panchatcharam et al (2006) found that curcumin treated wound heal much as indicated by

improved rates of epithelialisation, wound contraction and increased tensile strength

confirmed by histopathological examinations.



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5) Hepatoprotective effect of curcumin[8]

Several researchers (Deshpande et al, 1998; Park et al, 2000; Kiso et al, 1983; Donatus et al,

1990; Soni et al, 1992) reported hepatoprotective effects of curcumin against various toxic

compounds such as carbon tetrachloride (CCl4), galactosamine, acetaminophen

(paracetamol), and Aspergillus aflatoxin. The researchers attributed this hepatoprotective

mechanism to its antioxidant behaviour and its potential to decrease the formation of

proinflammatory cytokines. The quantitative change in the bile constituents induced by

sodium curcuminate was evaluated (Ramprasad & Sirsi, 1957). They noted choleretic effects

of sodium curcuminate, a salt of curcumin and postulated that this salt increased biliary

excretion of bile salts, cholesterol, and bilirubin as well as increased bile solubility, which

prevented cholelithiasis. Curcumin possessed choleretic ability which increases bile output

and solubility indicating its beneficial therapeutic application in the treatment of gallstones.

6) Antidiabetic activity of curcumin[9]

Curcumin was reported to possess anti-diabetic activity. The effect of antidiabetic activity

could be attributed to the antioxidant property of curcumin. In their study, researchers

demonstrated curcumin positive effect through the improvement of diabetes-induced

endothelial dysfunction by decreasing superoxide production and vascular protein kinase C

inhibition. Interestingly, recent studies demonstrated the ability of curcumin to have the

capacity to directly quench reactive oxygen species (ROS) that can contribute to oxidative

damage.

This property is known to contribute to the overall protective effects of curcumin. Curcumin

can attenuate cell death caused by oxidative stress, indirectly through induction and/or

activation of antioxidant/ cytoprotective enzymes, such as heme oxygenase-1 (HO-1

). The

protective mechanisms of HO-1

in diabetes could present some emerging therapeutic options

for HO-1

expression in treating diabetic diseases.

Curcumin was evaluated for the prevention of type 2 diabetes in pre-diabetic human

population. The subjects received curcumin capsules for 9month period versus placebo

capsule group. The curcumin-treated group showed a better overall function of β-cells, with

higher HOMA-β and lower C-peptide. The curcumin treated group showed a lower level of

HOMA-IR and higher adiponectin, when compared with the placebo group. The results

indicated that curcumin intervention may have positive effect to a prediabetic population.



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7) Anti -arthritis activity of curcumin[9]

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by

hyperplasia of the synovial fibroblasts. Curcumin is known to possess potent anti-

inflammatory and anti-arthritic properties. Curcumin treatment was carried out on patients

with active rheumatoid arthritis and compared with diclofenac sodium reference group.

Interestingly, the curcumin group showed the highest percentage of improvement in overall

rheumatoid arthritis scores and these scores were significantly better than the patients in the

diclofenac sodium group. More importantly, curcumin group was found to be safe and did not

relate with any adverse events compared to diclofenac sodium group.

It is believed that curcumin antioxidant antiproliferative, anti-inflammatory and immune

suppressive activities shared in the improvement of symptoms to patients suffering from

rheumatoid arthritis. One of the important consequences of RA could be the decreased

apoptosis. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and

the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-

V-based assay. These results show that curcumin might help against hyperplasia of the

synovial fibroblasts in RA.

8) Anti- Alzheimer activity of curcumin[9]

Alzheimer disease (AD) is by far the most common cause of dementia globally. This

neurodegenerative disorder of the brain is chronic and progressive, characterized clinically by

the deterioration in the key symptoms of behavioural and cognitive abilities. Researchers

reported the advantages of curcuminoids as anti- Alzheimer agents.

Curcumin action was demonstrated through the inhibition of the accumulation of amyloid β-

peptide (Aβ) and the formation of β-amyloid fibrils (fAβ) from Aβ, as well as the

destabilization of preformed fAβ in the central nervous system. Consequently, curcumin

would be an attractive therapeutic target for the treatment of Alzheimer's disease.

9) Anti -Parkinson activity of curcumin[9]

Oxidative stress has been implicated in the degeneration of dopaminergic neurons in the

substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature

of pre symptomatic PD is a significant depletion of the thiol antioxidant glutathione (GSH) in

these neurons resulting in oxidative stress, mitochondrial dysfunction, and ultimately cell

death. Curcumin restores depletion of GSH levels, protects against protein oxidation, and



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preserves mitochondrial complex I activity which normally is impaired due to GSH loss.

Thus, it helps in treatment of PD.

Overexpression and abnormal accumulation of aggregated α-synuclein (αS) have been linked

to Parkinson's disease (PD) and other synucleinopathies. αS can misfold and adopt a variety

of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species.

Curcumin can alleviate αS-induced toxicity, reduce intracellular reactive oxygen species ROS

levels and protect cells against apoptosis. Thus, curcumin could be used as anti -Parkinson.

10) Anti -inflammatory activity of curcumin[9]

Curcumin possesses significant anti-inflammatory activity in acute as well as in chronic

models of inflammation. It is as potent as phenylbutazone in the carrageenan oedema test but

only half as potent in chronic tests. Curcumin has been demonstrated to be safe in six human

trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory

activity by inhibition of a number of different molecules that play a role in inflammation.

Curcumin has been shown to regulate numerous transcription factors, cytokines, protein

kinases, adhesion molecules, redox status and enzymes that have been linked to

inflammation.

11) Anti-angiogenesis activity of curcumin[9]

Curcumin was tested for its ability to inhibit the proliferation of primary endothelial cells in

the presence and absence of basic fibroblast growth factor (bFGF), as well as its ability to

inhibit proliferation of an immortalized endothelial cell line. Curcumin was tested for its

ability to inhibit phorbol ester-stimulated vascular endothelial growth factor (VEGF) mRNA

production. Curcumin effectively inhibited endothelial cell proliferation in a dose-dependent

manner. Curcumin demonstrated significant inhibition of bFGF-mediated corneal

neovascularization in the mouse. Curcumin had no effect on phorbol ester-stimulated VEGF

production. These results indicate that curcumin has direct antiangiogenic activity in-vitro

and in-vivo.

12) Antibacterial activity of curcumin[9]

The antibacterial study of curcumin shows the ability to inhibit growth of a variety of

periodontopathic bacteria and Porphyromonas gingivitis Arg- and Lys-specific proteinase

(RGP and KGP, respectively) activities. In addition, curcumin suppressed P. gingivitis

homotypic and Streptococcus gordonii biofilm formations in a dose dependent manner.



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Bacterial growth was suppressed almost completely at very low concentrations of curcumin.

A concentration of 20 µg/mL of curcumin inhibited these P. gingivitis biofilm formations by

more than 80%. On the other hand, 100 µg/mL of curcumin did not suppress the growth of

Aggregatibacter actinomycetemcomitans. Furthermore, at relatively high concentrations,

curcumin targets bacterial membranes (Escherichia coli).

Additionally, many features of a bacterial apoptosis-like response were observed after

treatment with curcumin at the MIC, including membrane depolarization, Ca 2+ influx, PS

exposure and DNA fragmentation. A bacterial apoptosis-like response, induced by curcumin,

by causing reactive oxygen species generation and DNA damage. The study on E. coli and B.

subtilis demonstrated that curcumin by the inhibitory effect against FtsZ polymerization

could suppress the FtsZ assembly leading to disruption of prokaryotic cell division.

On another hands, Curcumin - Polymyxin B used clinically for topical therapy to treat or

prevent traumatic wound infections of the skin. It would not only increase the spectrum of

activity to include Gram-positive bacteria but also combat those isolated resistant. The use of

the combination may also reduce the emergence of resistant isolates during treatments, due to

the multiple antimicrobial targets of duel drug therapy and ease the selective pressure

produced by broad-spectrum antibiotics.

Additionally, curcumin loaded in zein (zein-CUR) fibers showed good antibacterial activity

towards S. aureus and E. coli and the inhibition efficiency increased with the increase of

curcumin contents. Due to the different cell membrane constituent and structure, the

antibacterial activity towards S. aureus was better than that towards E. coli. The study

displayed that the zein-CUR fibers might have potential as a promising material for

antimicrobial applications to inhibit bacterial growth and propagation in food packaging 68.

Also, antibacterial activity of curcumin-chitosan film against Staphylococcus aureus and

Rhizoctonia solani was studied by the zone inhibition method. A better antibacterial activity

was certified compared to PCH film, which is an important consideration in food packaging.

The natural blend films of curcumin and chitosan could be as a promising antimicrobial

packaging for food and agriculture products.

Novel fibrous materials from cellulose acetate (CA) and polyvinylpyrrolidone (PVP) contain

curcumin. The incorporation of PVP resulted in increased hydrophilicity of the fibers and in

faster curcumin release. Likewise, curcumin was found in the amorphous state in the



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curcumin containing fibers and these mats exhibited antibacterial activity against

Staphylococcus aureus (S. aureus). The Curc/CA+Curc/PVP mat prepared by dualspinneret

electrospinning killed all the bacteria at the 4 h. Curcumin fibrous materials are potential

antibacterial for wound dressing applications.

In addition, Surface charge as well as the small size of curcumin nanoparticles plays a key

role in enhancing cell-antimicrobial interaction and antimicrobial efficacy. The fabricated

curcumin nanoparticles showed the best antimicrobial activity against Listeria

monocytogenes. A size reduction to nano-scale is a recently developed strategy used to

improve drug/food delivery and matching the public demand for effective and safe

antimicrobial formulations for control of food borne pathogen.

In-vivo study of antibacterial effect of curcumin on H. pylori compared to OAM

(Omeprazole, Amoxicillin and Metronidazole) treatment revealed poor activity for

eradication of H. pylori (5.9% versus 78.9% for OAM treatment). The reduction in

inflammatory cytokine production was not reported from pylori-infected patients treated with

curcumin. The in-vivo study of 1-week nonantibiotic therapy comprised of curcumin,

pantoprazole, N-acetylcysteine, and lactoferrin against H. pylori infection was not effective

for the eradication of H. pylori. However, the decrease in immunological criteria of gastric

inflammation and dyspeptic symptoms was reported after 2 months of treatment schedule.

Nevertheless, the curcumin administration to the rats with H. pylori-induced gastric

inflammation revealed a significant reduction in macromolecular leakage and NF activation

75. In an in-vivo study of H. pylori-infected C57BL/6 mice administered with curcumin

exhibited immense therapeutic potential and pronounced eradication effect against H. pylori

infection associated with restoration of gastric damage.

13) Anti -fungal activity of curcumin[9]

Substances and extracts isolated from different natural resources especially plants have

always been a rich arsenal for controlling the fungal infections and spoilage. Due to extensive

traditional use of curcumin in food products, various researches have been done in order to

study curcumin with the aspect of controlling fungal related spoilage and fungal pathogens.

The study of addition the curcumin powder in plant tissue culture showed that curcumin at

the 0.8 and 1.0 g/L had appreciable inhibitory activity against fungal contaminations. The

possible mechanism underlying the mentioned antifungal effect was found to be



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downregulation of desaturase (ERG3) leading to significant reduction in ergosterol of fungal

cell. Reduction in production of ergosterol results in accumulations of biosynthetic precursors

of ergosterol which leads to cell death via generation of ROS 138. Reduction in proteinase

secretion and alteration of membrane-associated properties of ATPase activity are other

possible critical factors for antifungal activity of curcumin. Finding new anti-candida

substances seems to be crucial due to development of resistant strain against existing

antifungal drug. The study of curcumin, against 14 strains of Candida, showed that curcumin

is a potent fungicide compound against Candida species with MIC values range from 250 to

2000 μg/ml.

In another study, anti-candida activity of curcumin was demonstrated against 38 different

strains of Candida including some fluconazole resistant strains and clinical isolates of C.

albicans, C. glabrata, C. tropicalis, C. guilliermondii, and C. krusei. The MIC90 values for

sensitive and resistant strains were 250-650 and 250-500 μg/mL, respectively. Intracellular

acidification via inhibition of H+-extrusion was identified as possible mechanism for cell

death of Candida species. The development of hyphae was proved to be inhibited by

curcumin through targeting the global suppressor thymidine uptake 1 (TUP1). Curcumin

exhibited potent antifungal effect via mechanisms associated with disruption of plasma

membrane in Candida albicans.

Curcumin also showed inhibitory effect on Cryptococcus neoformans and C. dubliniensis

with MIC value of 32 mg/L 79. One of the major complications during therapies against

chronic asthma is oropharyngeal candidiasis. Curcumin as a potential candidate for the

treatment of candidiasis with anti-inflammatory activity was studied in a murine model of

asthma. Oral administrator of curcumin is more effective than dexamethasone in reducing

fungal burden in BALB/c mice. It also significantly decreased pathological changes in

asthma. Adhesion of Candida species isolated from AIDS patients to buccal epithelial cells is

also markedly inhibited by curcumin and it was found to be more effective compared to

fluconazole.

The investigation of curcumin mediation for photodynamic therapy can reduce the biofilm

biomass of C. albicans, C. glabrata and C. tropicalis. The results demonstrated that

association of four LED influences for light excitation with 40 μM concentration of curcumin

at 18 J/cm2 inhibited up to 85% metabolic activity of the tested Candida species. The use of

curcumin with light proved to be an effective method for noteworthy improvement in the



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antifungal activity against planktonic form of the yeasts. Photodynamic effect considerably

decreased C. albicans viability in either planktonic or biofilm cultures probably through

increasing the uptake of curcumin by cells. However, to a lesser extent, photodynamic

therapy was found to be phototoxic to the macrophages.

The strong antifungal activity of C. longa rhizome and its low side effect were the main

reasons to investigate its probable synergistic effect with existing fungicides. The synergistic

activity of curcumin with five azole and two polyene drugs including voriconazole,

itraconazole, ketoconazole, miconazole, fluconazole, amphotericin B and nystatin showed

10-35-fold reduction in the MIC values of the fungicides against 21 clinical isolates of C.

albicans. The synergistic activity of curcumin with amphotericin B and fluconazole could be

associated with the accumulation of ROS which will be suppressed by adding an antioxidant.

14) Anti -viral activity of curcumin.[9]

Lack of effective therapeutics for the most of viral diseases, emergence of antiviral drug

resistance and high cost of some antiviral therapies necessitate finding new effective antiviral

compounds. Additionally, the existing antiviral therapies are not always well-tolerated or

quite effective and satisfactory. Hence, the increasing requirement for antiviral substances

will be more highlighted. Plants as a rich source of phytochemicals with different biological

activities including antiviral activities are in interest of scientists.

It has been demonstrated that curcumin as a plant derivative has a wide range of antiviral

activity against different viruses: papillomavirus virus (HPV), influenza virus, Hepatitis B

virus (HBV), Hepatitis C virus (HCV), adenovirus, coxsackie virus, Human norovirus

(HuNoV), Respiratory syncytial virus (RSV) and Herpes simplex 1 (HSV-1). Curcumin

functionalized graphene oxide shown synergistic antiviral effect against respiratory syncytial

virus infection. Respiratory syncytial virus (RSV), which is considered as the major viral

pathogen of the lower respiratory tract of infants, has been implicated in severe lung disease.

Developing a β-cyclodextrin (CD) functionalized graphene oxide (GO) composite, which

displayed excellent antiviral activity and curcumin loading efficiently, showed that the

composite could prevent RSV from infecting the host cells by directly inactivating virus and

inhibiting the viral attachment, which possessed the prophylactic and therapeutic effects

towards virus. The antiviral effect of curcumin was a dose-dependent manner. Curcumin

inhibit activity of inosine-mono phosphate dehydrogenase (IMPDH) enzyme in either non -

competitive or competitive manner. By inhibition of IMPDH this led to reduce the level of



701

intracellular guanine nucleotides which required for adequate RNA and DNA synthesis.

Curcumin mechanism involve in viral entry or other life cycle stages rather than the

replication of viral RNA 91. Therefore, by inhibition of IMPDH Curcumin have potential anti

proliferative, antiviral and antiparasitic effects.

15) Anti- fibrotic activity of curcumin[9]

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown etiology that can

result in respiratory failure. The resulting fibrotic changes in lung architecture lead to

decreased gas exchange and pulmonary compliance. Notably, curcumin effectively reduces

profibrotic effects in fibroblasts in-vitro via the inhibition of key steps in the signaling

pathway of transforming growth factor beta (TGF-b) a multifunctional cytokine belonging to

the transforming growth factor.

It was reported that the activation of peroxisome proliferator-activated receptor gamma

(PPAR-g) by curcumin blocked platelet derived growth factor (PDGF) signaling pathway in

hepatic satellites cells. However, the relationship of PPAR- g and PDGF signaling pathway is

unclear in TGF-b induced differentiation of lung fibroblasts to myofibroblasts. Curcumin

inhibits TGF-β2 driven differentiation of mouse lung fibroblasts to myofibroblasts. Curcumin

and PPAR-γ could potentially be used for effective treatment of IPF.

CONCLUSION

The wisdom and scientific knowledge of curcumin, which were used for its therapeutic

effects in many countries as traditional medicine. For that the pharmacological properties and

applications of curcumin is a rapidly growing, progressing and expanding enterprise.

Curcumin is enriched with many useful phytoconstituents, which are responsible for its

efficacy proven by experimentally and clinically. It has been established beneficial in treating

anti-inflammatory, anti-allergic, anti-bacterial, anti-cancer, anti-microbial, anti-fungal

properties. Because of curcumin facility to affect a good safety profile, was established to be

a potential medicine for the treatment of a number of diseases.

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a review on therapeutic applications of curcumin

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