ArticlePDF Available

Curcumin: Natural Antimicrobial and Anti Inflammatory Agent

Authors:

Abstract and Figures

The pursuance of novel antimicrobial and anti-inflammatory agents has been expanding due to a significant need for more efficient pharmacotherapy of various infections and chronic diseases. During the last decade, pharmacokinetics, pharmacodynamics and pharmacological properties of curcumin have been extensively studied. The aim of the present study was to evaluate the antibacterial activity of curcumin against both Gram-positive and Gram-negative bacteria as well as its antifungal activity by using in vitro agar well diffusion assay. Moreover, the anti-inflammatory activity of curcumin was determined with in vitro assay of inhibition of protein denaturation. Results demonstrated wide antimicrobial activity of curcumin upon all of the test bacteria and fungi. The strongest activity of curcumin was observed at a concentration of 0.50 mg/ml against S. aureus, L. monocytogenes, E. coli, P. aeruginosa and C. albicans, resulting in a maximum zone of inhibition of 14.7 mm, 14.3 mm, 13.7 mm, 10.7 mm and 10.7 mm, respectively. Findings suggested that the Original Research Article antimicrobial activity of curcuminis demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting heat-induced protein denaturation, which activity is also depended upon the concentrations. The present study emphasises the potential application of curcumin as a natural antimicrobial and anti inflammatory agent. However, findings of this study are restricted to consideration should be given to conducting a study involving wider do well as including further research on
Content may be subject to copyright.
_____________________________________________________________________________________________________
*Corresponding author: E-mail: belma.pehlivanovic@ffsa.unsa.ba;
Journal of Pharmaceutical Research International
32(43): 1-8, 2020; Article no.JPRI.64487
ISSN: 2456-9119
(Past name: British Journal of Pharmaceutical Research, Past ISSN: 2231-2919,
NLM ID: 101631759)
Curcumin: Natural Antimicrobial and Anti
Inflammatory Agent
Pehlivanović Belma
1*
, Čaklovica Kenan
2
, Lagumdžija Dina
1
, Omerović Naida
1
,
Žiga Smajić Nermina
1
, Škrbo Selma
1
and Bečić Fahir
1
1
Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sarajevo, Bosnia and
Herzegovina.
2
Department of Food Safety, Veterinary Faculty, University of Sarajevo, Bosnia and Herzegovina.
Authors’ contributions
This work was carried out in collaboration among all authors. Author PB designed the study,
performed the experiment and wrote the first draft of the manuscript. Author ČK manage the analyses
of the study. Authors LD, ON, ŽSN, ŠS and BF manage the literature searches and wrote the first
draft of the manuscript. All authors read and approved the final manuscript.
Article Information
DOI: 10.9734/JPRI/2020/v32i4331060
Editor(s):
(1)
Dr. Rafik Karaman, Al-Quds University, Palestine.
Reviewers:
(1)
M. Sakthi Priya, Tamil Nadu Veterinary and Animal Sciences University, India.
(2)
Nishant Kumar Gupta, India.
Complete Peer review History:
http://www.sdiarticle4.com/review-history/64487
Received 01 November 2020
Accepted 06 January 2021
Published 23 January 2021
ABSTRACT
The pursuance of novel antimicrobial and anti-inflammatory agents has been expanding due to a
significant need for more efficient pharmacotherapy of various infections and chronic diseases.
During the last decade, pharmacokinetics, pharmacodynamics and pharmacological properties of
curcumin have been extensively studied. The aim of the present study was to evaluate the
antibacterial activity of curcumin against both Gram-positive and Gram-negative bacteria as well as
its antifungal activity by using in vitro agar well diffusion assay. Moreover, the anti-inflammatory
activity of curcumin was determined with in vitro assay of inhibition of protein denaturation. Results
demonstrated wide antimicrobial activity of curcumin upon all of the test bacteria and fungi. The
strongest activity of curcumin was observed at a concentration of 0.50 mg/ml against S. aureus, L.
monocytogenes, E. coli, P. aeruginosa and C. albicans, resulting in a maximum zone of inhibition of
14.7 mm, 14.3 mm, 13.7 mm, 10.7 mm and 10.7 mm, respectively. Findings suggested that the
Original Research Article
antimicrobial activity of curcuminis
demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting
heat-
induced protein denaturation, which activity is also depended upon the concentrations. The
pre
sent study emphasises the potential application of curcumin as a natural antimicrobial and anti
inflammatory agent. However, findings of this study are restricted to
consideration should be given to conducting a study involving wider do
well as including further research on
Keywords:
Curcumin; in vitro; antimicrobial agent; anti
1. INTRODUCTION
Rational
phytotherapy implies the use of natural
products,
which therapeutic efficiency and safety
are based on scientific evidence
natural products and phytochemicals have been
investigated for different pharmacological
properties in order to serve as a
potential source
for novel medicines [2]. Lately, due to the
continuing increase of infections and chronic
diseases worldwide, the detection of potential
agents is of crucial importance [3]. The
pursuance of novel antimicrobial and anti
inflammatory age
nts has been expanding due to
a
significant need for more efficient
pharmacotherapy of various infections and
chronic diseases. Numerous
in vitro
studies have shown that phytochemicals possess
a wide range of pharmacological activity
including
antimicrobial and anti
activity [4-
6]. Investigation of phytochemicals with
potential antimicrobial and anti
activity is rapidly growing and therefore leads to
more frequent substitutions of synthetic
medicines due to the developm
ent of resistance
and risk of side effects [7].
Curcumin or diferuloylmethane
(1
(4-hydroxy-3-
methoxyphenyl) hepta
3,5-
dione)] is bioactive phytochemical present in
the rhizomes of plant
Curcuma
Fig. 1. Curcumin
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020
; Article no.JPRI
2
antimicrobial activity of curcuminis
dependent upon the concentrations. Furthermore, results
demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting
induced protein denaturation, which activity is also depended upon the concentrations. The
sent study emphasises the potential application of curcumin as a natural antimicrobial and anti
inflammatory agent. However, findings of this study are restricted to
in vitro
consideration should be given to conducting a study involving wider dose range test substances as
well as including further research on
in vivo models.
Curcumin; in vitro; antimicrobial agent; anti
-inflammatory agent.
phytotherapy implies the use of natural
which therapeutic efficiency and safety
are based on scientific evidence
[1]. Various
natural products and phytochemicals have been
investigated for different pharmacological
potential source
for novel medicines [2]. Lately, due to the
continuing increase of infections and chronic
diseases worldwide, the detection of potential
agents is of crucial importance [3]. The
pursuance of novel antimicrobial and anti
-
nts has been expanding due to
significant need for more efficient
pharmacotherapy of various infections and
in vitro
and in vivo
studies have shown that phytochemicals possess
a wide range of pharmacological activity
antimicrobial and anti
-inflammatory
6]. Investigation of phytochemicals with
potential antimicrobial and anti
-inflammatory
activity is rapidly growing and therefore leads to
more frequent substitutions of synthetic
ent of resistance
(1
E,6E)-1,7-bis
methoxyphenyl) hepta
-1,6-diene-
dione)] is bioactive phytochemical present in
Curcuma
long L.
Zingiberaceae (Fig.
1).Curcumin belongs to a
group of curcuminoids
natural phenols
responsible for yellow colour. It has been used
as a spice and traditional medicine in Ayurvedic
medicine [8,9]. During the last decade,
pharmacokinetics, pharmacodynamics
pharmacological properties of this yellow
polyphenolic compound have been extensively
studied.
Significant antitumor, antioxidant,
antiviral, lipid-
lowering, chemopreventive,
hepatoprotective and neuroprotective properties
of curcumin have been
confirmed [
Recent studies have also confirmed the
pharmacological activity of curcumin as anti
inflammatory and immunomodulatory agent [14].
It is established that mechanism of anti
inflammatory activity of curcumin
occurs through
the inhibition of cyclooxygenase-
2 (COX
lipoxygenases (LOX), and the induction of nitric
oxide synthase (iNOS). Also, it is suggested that
curcumin inhibits the action of inflammatory
cytokines, such as interleukins and chemokines
[1
5,16]. Due to its pronounced anti
activity, curcumin is considered to be a potential
mediator of accelerating the healing process of
acute and chronic wounds and may inhibit the
production of tumor necrosis factor
α) and TNF-α-media
ted cellular signalling
pathway [16]. Antimicrobial potential of curcumin
has been evaluated against a wide range of
microorganism
s, including both Gram
Fig. 1. Curcumin
– structural formula
; Article no.JPRI
.64487
dependent upon the concentrations. Furthermore, results
demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting
induced protein denaturation, which activity is also depended upon the concentrations. The
sent study emphasises the potential application of curcumin as a natural antimicrobial and anti
-
assays and
se range test substances as
1).Curcumin belongs to a
natural phenols
responsible for yellow colour. It has been used
as a spice and traditional medicine in Ayurvedic
medicine [8,9]. During the last decade,
pharmacokinetics, pharmacodynamics
and
pharmacological properties of this yellow
-orange
polyphenolic compound have been extensively
Significant antitumor, antioxidant,
lowering, chemopreventive,
hepatoprotective and neuroprotective properties
confirmed [
10-13].
Recent studies have also confirmed the
pharmacological activity of curcumin as anti
-
inflammatory and immunomodulatory agent [14].
It is established that mechanism of anti
-
occurs through
2 (COX
-2) and
lipoxygenases (LOX), and the induction of nitric
oxide synthase (iNOS). Also, it is suggested that
curcumin inhibits the action of inflammatory
cytokines, such as interleukins and chemokines
5,16]. Due to its pronounced anti
-inflammatory
activity, curcumin is considered to be a potential
mediator of accelerating the healing process of
acute and chronic wounds and may inhibit the
production of tumor necrosis factor
-alpha (TNF-
ted cellular signalling
pathway [16]. Antimicrobial potential of curcumin
has been evaluated against a wide range of
s, including both Gram
-positive
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
3
and Gram-negative bacteria as well as the fungi
[14,17,18]. Curcumin has been described as a
promising antifungal of clinical interest with
stronger antifungal activity than fluconazole [19].
A recent study has suggested a possible
mechanism of antifungal activity of curcumin
through photodynamic technology and oxidative
stress [20]. Still, the mechanisms of antimicrobial
activity of curcumin have not been precisely
determined.Some authors suggested that
antibacterial mechanisms of curcumin are
mediated by inhibition of bacterial cell
proliferation, resulting in blocking Z-ring
formation dynamics [21]. Others implied that its
activity is due to the effects on virulence and
biofilm propagation [22].The mechanisms by
which curcumin exhibits its antimicrobial activity
differ depending on the strain and therefore can
not be generalised [18,23].
The aim of the present study is to evaluate the
antibacterial activity of curcumin against both
Gram-positive and Gram-negative bacteria as
well as its antifungal activity by using in vitro agar
well diffusion assay. Moreover, the present study
estimated anti-inflammatory activity of curcumin
with in vitro assay of inhibition of protein
denaturation.
2. MATERIALS AND METHODS
Curcumin was obtained from Sigma-Aldrich
(CAS No: 458-37-7;St.Louis, MO, USA).Ethanol
(puriss. p.a., 99.8%)was purchased from
Sigma-Aldrich; dimethylsulfoxide (DMSO) (99.5%
Ph.Eur.,M=78.13) from Semikem d.o.o. (BiH);
nutrient agar and antibiotic discs were purchased
from Laboratorios Conda S.A. All other
chemicals used were of the highest analytical
grade available. Spectrometer Lambda 25
UV/VIS, Perkin Elmer, was used for measuring
absorbance and incubator Lab-Line Imperial III,
Barnstead, USA, for incubation of Petri plates.
2.1 In vitro Antimicrobial Activity
Antibacterial activity of curcumin was evaluated
with in vitro agar well diffusion assay, against
both Gram-positive and Gram-negative bacteria,
as well as the antifungal activity. The following
strains were obtained from American Type of
Culture Collection (ATCC): S. aureus
(ATCC6538), L. monocytogenes (ATCC 35152),
P. aeruginosa (ATCC 9027), E. coli (ATCC8739)
and C. albicans (ATCC10231). During the
preparation of inoculums, suspensions of
microorganisms were adjusted on approximately
1.5×10
8
CFU/ml and cultured on nutrient agar. In
every Petri plate 4 wells of 6 mm diameter were
created with sterile borer. Curcumin was
dissolved in DMSO and prepared in form of
solutions at the following concentrations: 0.10,
0.25, 0.35 and 0.50 mg/ml. In each well, a total
volume of 100 µl of test curcumin solutions was
applied. The volume of 100 µl of DMSO was
used as negative control and applied into the
wells. Following standard antibiotics were applied
as positive control: Chloramphenicol (30µg/disc),
Ceftizoxime (30µg/disc), Amikacin (30µg/disc)
and Nystatin (100µg/disc).
After application of test substances, Petri plates
containing bacteria were incubated at 37 °C for
18–24h and plates with fungi at 25ºC for 48h.
After the incubation period, the diameter of zone
of inhibition (mm) was measured and recorded
for each plate. The experiment was performed in
triplicate.
2.2 In vitro Anti-Inflammatory Activity
Anti-inflammatory activity of curcumin was
evaluated with in vitro assay of heat-induced
inhibition of protein denaturation. Curcumin was
dissolved in DMSO and prepared as test
solutions at the final concentrations: 100, 200,
300, 400 and 500 µg/ml acetylsalicylic acid was
used as positive control and prepared at the
same concentrations as the test curcumin
solutions. The reaction mixture contained 2.0 ml
of the test solution, 2.8 ml of phosphate buffer
saline with adjusted pH 6.4 and 0.2 ml of egg
albumin. Control mixture contained 2.0 ml of
distilled water instead of the test solution. The
mixtures were incubated for 15 min at 37 ± 2°C
and then heated for 5 min at 70°C. After cooling
down at the room temperature, absorbance was
measured at 660 nm [24]. Measurements were
performed in triplicate. Anti-inflammatory activity
was expressed as the percentage of inhibition of
protein denaturation and calculated by using the
following formula:
Inhibition (%) = 100 x (1 – Abs
sample
/Abs
control
)
3. RESULTS AND DISCUSSION
3.1 In vitro Antimicrobial Activity
Due to increased development of multidrug-
resistance microorganisms, there is a constant
need for novel antimicrobial agents derived from
different sources [3]. So far, phytochemicals
have remained the leading source for potential
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
4
antimicrobial agents, whether investigated
independently or in a combination with another
substance [2,25]. Recent studies have
demonstrated a wide range of antimicrobial
properties of curcumin mediated by different
mechanisms, such as alteration of gene
expression, inhibition of bacterial DNA replication
and disruption of the bacterial cell membrane
[26-28].Literature data demonstrate the beneficial
and preventive role of curcumin against various
microorganisms [29-31]. Despite various studies
evaluating the antimicrobial activity of curcumin,
further research is required with different
concentrations against different strains of
microorganisms. In this study, an in vitro agar
well diffusion assay was used to assess the
antimicrobial activity of test curcumin solutions at
different concentrations. Antimicrobial activity of
curcumin solutions was determined by the
presence and size of zones of inhibition against
test strains of bacteria and fungi. Results of the
measurement of diameters of zones of inhibition
(mm) of curcumin solutions are given in Table 1.
For negative control, no zones of inhibitions were
observed while positive control, standard
antibiotics, demonstrated the most efficient
inhibition of microbial growth (Table 2).
Test curcumin solutions showed antimicrobial
activity upon all of the test bacteria, both Gram-
positive and Gram-negative, as well as the fungi.
Compared to the positive control, curcumin
solutions were less efficient in suppressing
microbial growth. However, the strongest activity
of curcumin solutions was observed at a
concentration of 0.50 mg/ml against S. aureus,
L. monocytogenes, E. coli, P. aeruginosa and
C. albicans, resulting in a maximum zone of
inhibition of 14.7 mm, 14.3 mm, 13.7 mm,
10.7mm and 10.7 mm, respectively. Our results
demonstrated a stronger antimicrobial activity of
curcumin solutions against Gram-positive than
Gram-negative bacteria. These findings are in
accordance with a recently published study by
Adamczak et al. [27]. Significantly higher
antimicrobial activity of curcumin against Gram-
positive than Gram-negative bacteria was also
reported by other authors [30,31]. This is
explained with the difference in the structure of
bacterial cell walls as the cells of Gram-positive
bacteria are not surrounded by an outer
membrane. The cells of Gram-negative bacteria
are more resistant due to the presence of an
outer membrane that prevents antimicrobial
agents to reach and damage the inner
membrane of the cell wall [31]. Furthermore,
results of this study implied that the application of
higher concentrations of curcumin solutions
results in a larger diameter of zones of inhibition.
Therefore, antimicrobial activity of curcumin, both
antibacterial and antifungal, is dependent upon
the concentrations. These findings consist of a
recently reported study, which emphasises that
an increase in curcumin dose results in
increased antibacterial activity [32]. Results of
the previous study imply that the antifungal
activity of curcumin against C. albicans generally
increases by increasing the dose [33].However,
investigation of antifungal activity is restricted to
only one positive control and it is mandatory to
conduct further research on a wider range of
fungi. A recent study by Narayanan et al. [34]
revealed the variable antifungal activity of
curcumin against planktonic and biofilm phase of
different Candida species and therefore implied
that curcumin could be considered a therapeutic
alternative to conventional antifungals [34].
3.2 Invitro anti-Inflammatory Activity
Previous studies have reported curcumin as a
potential anti-inflammatory agent, which activity
is mediated via different mechanisms [14-16].
The present study was designed to evaluate the
anti-inflammatory activity of curcumin solutions at
different concentrations by applying in vitro assay
of heat-induced inhibition of protein denaturation
[24]. This in vitro assay is applicable for
preliminary screening of potential anti-
inflammatory drugs derived from plant sources
[32]. Results of this study demonstrated the high
effectiveness of test curcumin solutions
compared to standard acetylsalicylic acid in
inhibiting heat-induced protein denaturation
(Fig. 2).
Test curcumin solutions showed mean inhibition
of egg albumin denaturation of 87.51%, 81.36%,
78.56%, 69.87% and 63.14% at the
concentration of 1.00 mg/ml, 0.75 mg/ml, 0.50
mg/ml, 0.25 mg/ml and 0.10 mg/ml, respectively.
Acetylsalicylic acid, which served as positive
control, showed inhibition of egg albumin
dentauration of 96.84%, 91.27%, 87.59%,
85.12% and 85.03% at the concentration of 1.00
mg/ml, 0.75 mg/ml, 0.50 mg/ml, 0.25 mg/ml and
0.10 mg/ml, respectively. Maximum egg
albumin inhibition was detected at the
concentration of 1.00 mg/ml for both curcumin
and acetylsalicylic acid. Therefore, test curcumin
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
5
Table 1. Antimicrobial activity of test curcumin solutions
Test
curcumin
solutions
(mg/ml)
Escherichia
coli
(ATCC8739)
Pseudomonas
aeruginosa
(ATCC9027)
Staphylococcus
aureus
(ATCC6538)
Lysteria
monocytogenes
(ATCC 35152)
Candida
albicans
(ATCC10231)
0.10 10.7 9.7 12.0 12.3 9.0
0.25 11.1 10.0 12.3 12.3 9.3
0.35 12.3 10.3 13.0 14.0 10.7
0.50 13.7 10.7 14.7 14.3 10.7
Table 2. Antimicrobial activity of testpositive and negative controls
Test
controls
The diameter of zone of inhibition (mm)
Escherichia
coli
(ATCC8739)
Pseudomonas
aeruginosa
(ATCC9027)
Staphylococcus
aureus
(ATCC6538)
Lysteria
monocytogenes
(ATCC35152)
Candida
albicans
(ATCC10231)
CHL
(30µg/disc)
14.7 8.0 10.0 18.0 NT
ZOX
(30µg/disc)
10.3 ND 10.3 11.0 NT
AMK
(30µg/disc)
10.3 18.3 20.0 18.7 NT
Nystatin(100
µg/disc)
NT NT NT NT 15.7
DMSO ND ND ND ND ND
*CHL=Chloramphenicol; ZOX=Ceftizoxime; AMK=Amikacin; DMSO=Dymethylsulfoxide; ND=not detected;
NT=not tested
Fig. 2. Anti-inflammatory activity of test curcumin solutions
1=0.10 mg/ml; 2=0.25 mg/ml; 3=0.50 mg/ml; 4=0.75 mg/ml; 5=1.00 mg/ml
solutions demonstrated noticeable anti-
inflammatory activity. Furthermore, our results
indicated that an increase in curcumin
concentration, as well as the concentration of
0
20
40
60
80
100
1 2 3 4 5
Inhibition (%)
Concentration (mg/ml)
Acetylsalicylic
acid
Curcumin
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
6
acetylsalicylic acid, leads to an increase in
percentage of inhibition of protein denaturation.
Therefore, anti-inflammatory activity of
curcumin is dependent upon the concentrations.
Similar findings were reported in previously
published study by Ullah et al. [24].
4. CONCLUSION
Various studies, conducted as in vitro assays,
have revealed different therapeutic applications
of curcumin due to its different molecular
mechanisms. Findings of the present in vitro
study confirmed consideration of curcumin as a
natural antimicrobial and anti-inflammatory
agent. Test curcumin solutions demonstrated
strong antibacterial, antifungal and anti-
inflammatory activity. With an increase of
curcumin concentration antimicrobial and anti-
inflammatory activity increased, which
implied that observed activity is dependent
upon the concentration of curcumin. However,
findings of this study are restricted to in vitro
assays and consideration should be
given to conducting a study involving
wider dose range of test substances, as well as
including further research on in vivo models.
In conclusion, the present study emphasises
the potential application of curcumin as a
natural antimicrobial and anti-inflammatory
agent.
CONSENT
It is not applicable.
ETHICAL APPROVAL
It is not applicable.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
REFERENCES
1. Petrović S, Kukić-Marković J, Pavlović-
Drobac M. Biljni lekoviti proizvodi: uslovi za
bezbednu primenu. Arh. farm. 2012;
62:119-136. Bosnian.
2. Fabricant DS, Fansworth NR. The value of
plants used in traditional medicine for drug
discovery. Environ Health Persp. 2001;
109(1):69-75.
DOI: 10.1289/ehp.01109s169
3. World Health Organization (WHO),
antimicrobial resistance: Global report on
surveillance. World Health Organization;
2014.
4. Mandal P, Babu SSP, Mandal NC.
Antimicrobial activity of saponins from
Acacia auriculiformis. Fitoterapia. 2005;
76(5):462-465.
DOI: 10.1016/j.fitote.2005.03.004
5. Lai HY, Yau YY, Kim KH. Blechnum
orientale Linn - A fern with potential as
antioxidant, anticancer and antibacterial
agent. BMC Complem Altern Med.
2010;10(15).
DOI: 10.1186/1472-6882-10-15.
6. Fawole OA, Amoo SO, Ndhlala AR, Light
ME, Finnie JF, Van Staden J. Anti-
inflammatory, ant cholinesterase,
antioxidant and phytochemical properties
of medicinal plants used for pain-related
ailments in South Africa. J Ethno
pharmacol. 2010;127:235-241.
7. Dos Santos ATB, da Silva AraújoTF, Da
Silva LCN, da Silva CB, de Oliveira AFM,
Araújo JM. Organic extracts from Indi
goferasuffruticosa leaves have antimicro
bial and synergic actions with
Erythromycin against Staphylococcus
aureus. Front Mi crobiol. 2015;6:13.
8. Pehlivanović B, Bečić F. curcumin:
phytochemical therapy in the treatment of
hyperlipidemia. Bulletin of the Chemists
and Technologists of Bosnia and
Herzegovina. 2019;52,11-16.
9. Pulido-Moran M, Moreno-Fernandez J,
Ramirez-Tortosa C, Ramirez-Tortosa M.
Curcumin and Health. Molecules.
2016;21(3):264.
DOI:https://doi.org/10.3390/molecules2103
0264
10. Aggarwal BB, Harikumar KB. Potentional
therapeutic effects of curcumin, the anti-
inflamatori agent, against neurodege
nerative, cardiovascular, pulmonary,
metabolic, autoimmune and neoplastic
diseases. Int J Biochem Cell Biol. 2009;
41(1):40-59.
11. Aggarwal BB, Sundaram C, Malani N,
Ichikawa H. Curcumin: the Indian solid
gold. Adv Exp Med Biol. 2007;595:1-75.
12. Aggarwal BB, Sung B. Pharmacological
basis for the role of curcumin in chronic
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
7
diseases: An age-old spice with modern
targets. Trends Pharmacol Sci. 2009;
30(2):85-94.
13. Beevers CS, Huang S. Pharmacological
and clinical properties of curcumin.
Botanics: Targets and Therapy. 2011;1:5-
18.
14. Menon VP, Sudheer AR. Antioxidant
and anti-inflammatory properties of
curcumin. Adv Exp Med Biol. 2007;
595:105-125.
15. He Y, Yue Y, Zheng X, Zhang K, Chen SI
Du Z. Curcumin, inflammation and chronic
diseases: how are They Linked.
Molecules. 2015;20(5):9183-9213.
16. Betts WJ, Wareham DW. In Vitro activity of
curcumin in combination with epigallocate
chingallate (EGCG) versus multidrug-
resistant Acinetobacter baumanni. BMC
Microbiol. 2014;14:172.
DOI: 10.1186/1471-2180-14-172
17. Moghadamtousi SZ, Kadir HA,
Hassandarvish P, Tajik H, Abubakar
S,Keivan Z. A review on antibacterial,
antiviraland antifungal activity of curcumin.
Bio Med Research International. 2014;
2014:186864.
DOI: 10.1155/2014/186864
18. Martins CVB, da Silva DL, Neres T,
Magalhães TFF, Watanabe GA, Modolo
LV et al. Curcumin as a promising
antifungal of clinical interest. Journal of
Antimicrobial Chemotherapy. 2009;
63(2):337-339.
19. Song L, Zhang F, Yu J, Wei C, Han Q,
Meng X. Antifungal effect and possible
mechanism of curcumin mediated
photodynamic technology against Penicilliu
mexpansum. Postharvest Biology and
Technology. 2020;167:111234.
20. Rai D, Singh JK, Roy N, Panda D.
Curcumin inhibits FtsZ assembly: An
attractive mechanism for its antibacterial
activity. Biochem J. 2008;410(1):147-155.
21. Karaman M, Fırıncı F, Ayyıldız A, Bahar
IH. Effects of Imipenem, Tobramycin and
Curcumin on biofilm formation of
Pseudomonas aeruginosa strains. Mikro
biyolojiBulteni.2013;47(1):192-194.
22. Tyagi P, Singh M, Kumari H, Kumari A,
Mukhopadhyay K. Bactericidal Activity of
Curcumin I Is Associated with Damaging of
Bacterial Membrane. PLoS ONE. 2015;
10(3):e0121313.
DOI: 10.1371/journal.pone.0121313
23. Ullah AHM, Zaman S, Juhara F, Akter L,
Tareq MS, Masum EH et al. Evaluation of
antinociceptive, in-vivo & in-vitro anti-
inflammatory activity of ethanolic extract of
Curcuma zedoaria rhizome. Comple
mentary and Alternative Medicine.
2014;14:346.
24. CheesmanM ,Ilanko A , Blonk B , Cock
I . Developing new antimicrobial therapies:
are synergistic combinations of plant
extracts/compounds with conventional
antibiotics the solution? Pharmacogn Rev.
2017;11(22):57-72.
25. Praditya D, Kirchhoff L, Brüning J,
Rachmawati H, Steinmann J, Steinmann,
E. Anti-infective properties of the golden
spice curcumin. Front Microbiol. 2019;10:
912.
26. Adamczak A, Ożarowski M, Karpiński TM.
Curcumin, a Natural Antimicrobial Agent
with Strain-Specific Activity. Pharma
ceuticals (Basel). 2020;13(7):153.
DOI:10.3390/ph13070153
27. Tyagi P, Singh M, Kumari H, Kumari A,
Mukhopadhyay K. Bactericidal activity of
curcumin I is associated with damaging of
bacterial membrane. PLoS One. 2015;
10(3):e0121313.
DOI: 10.1371/journal.pone.0121313.
28. Murugesh J, Annigeri RG, Mangala GK,
Mythily PH, Chandrakala J. Evaluation of
the antifungal efficacy of different
concentrations of Curcuma longa on
Candida albicans: An in vitro study. J Oral
Maxillofac Pathol. 2019;23(2):305.
29. Polaquini CR, Morão LG, Nazaré
AC,Torrezan GS, Dilarri G, Cavalca LB et
al. Antibacterial activity of 3,30-dihy
droxycurcumin (DHC) is associated with
membrane perturbation. Bioorg. Chem.
2019;90:103031.
30. Breijyeh Z, Jubeh B, Karaman R.
Resistance of Gram-negative bacteria to
current antibacterial agents and appro
aches to resolve it. Molecules. 2020;
25(6):1340.
31. Sandikci Altunatmaz S, Yilmaz Aksu FG,
Basaran K, Altiner D, Buyukunal
SK.Antimicrobial effects of curcumin
against L. monocytogenes, S. aureus, S.
typhimurium and E. coli O157:H7
pathogens in minced meat. Veterinarni
Medicina. 2016;(5):256-262.
32. Babaii N, Zamaninejad S. Inhibitory Effect
of Curcumin on Candida-albicans compare
Pehlivanović et al.; JPRI, 32(43): 1-8, 2020; Article no.JPRI.64487
8
dwith Nystatin: An in-vitro Study. JDMT.
2016;5(4):196-201.
33. Narayanan VS, Muddaiah S, Shashidara
R, Sudheendra US, Deepthi NC,
Samaranayake L. Variable antifungal
activity of curcumin against planktonic and
biofilm phase of different candida species.
Indian J Dent Res. 2020;31(1):145-148.
© 2020 Pehlivanović et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution
License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Peer-review history:
The peer review history for this paper can be accessed here:
http://www.sdiarticle4.com/review-history/64487
... Alippilakkote and Sreejith (2018) tested a curcumin loaded poly (lactic acid) nanocapsule and reported a MIC of 468 µg/mL for S. aureus and 937 µg/mL for E. coli. When investigating the antimicrobial activity of curcumin using inhibition zone measurements, Belma et al. (2021) reported the strongest activity of curcumin solutions at a concentration of 500 µg/mL, resulting in an inhibition zone of 14.7 mm against S. aureus and 13.7 mm against E. coli. According to Holetz (2002), the antimicrobial activity of natural compounds was classified into the following groups regarding to the MIC values: i) high antimicrobial activity: MIC < 100 µg/mL; ii) moderate activity: MIC: 100 -500 µg/mL; ...
... Despite the variation in biological activity found in the studies above, according to Holetz (2002), all presented a moderate antimicrobial activity of curcumin against S. aureus, while for E. coli, it demonstrated a low active or inactive activity. These findings agree with the literature available that indicated the more effective antimicrobial activity of curcumin on Gram-positive than on Gram-negative bacteria, which could be explained by the difference in the structure of bacterial cell walls (Belma et al., 2021;Bhawana et al., 2011). ...
Article
Full-text available
Foodborne diseases and microbiological control represent the major challenge for the food industry. New technologies using natural agents have attracted increasing interest. Therefore, this study aimed to evaluate the in vitro susceptibility of Staphylococcus aureus and Escherichia coli to water-soluble curcumin (WSC) combined with acidic pH and blue LED light. The minimum inhibitory concentration (MIC) and bacterial photoinactivation were conducted using different photosensitizer concentrations. For S. aureus, the combination of WSC with lactic acid and 2.5 min illumination time reduced MIC from 500 µg/mL to 15.62 µg/mL, and WSC with citric acid reduced MIC from 125 µg/mL to 7.81 µg/mL after 5 min of light exposure. WSC without illumination did not inhibit E. coli growth (MIC >1,000 µg/mL), however, when applied with photodynamic therapy (5 min blue LED illumination), WSC at 62.5 µg/mL with lactic acid and WSC at 7.81 µg/mL with citric acid eliminated E. coli cells. The results obtained suggest that water-soluble curcumin with organic acids when combined with a blue LED light was effective against foodborne pathogens.
... Therefore, results indicated that the antimicrobial activity of a tested combination of curcumin and rosuvastatin is dependent upon the concentration. These findings are consistent with those previously published for curcumin and rosuvastatin separately [16,21]. However, there are no available data on the antimicrobial activity of a combination of curcumin and rosuvastatin. ...
... Furthermore, our results revealed that an increase in the concentrations leads to an increase in protein denaturation inhibition, therefore indicating that anti-inflammatory activity of a combination of curcumin and rosuvastatin is dependent upon the concentration. Findings from this study are in accordance with our results for individually examined substances curcumin and rosuvastatin [16,21]. ...
Chapter
Full-text available
Due to the increased rate of infectious diseases, an insufficient number of therapeutics and antibiotic resistance, the detection of potential sources of novel therapeutic agents is of crucial importance. As the current medicines are simply not sufficient, further studies have been based on a combinational approach that evaluates the synergistic pharmacological activity of plantderived compounds and other medicines. Curcumin, a natural polyphenol extracted from plant Curcuma longa L., and rosuvastatin, synthetic lipid-lowering medicine, pose a wide range of pharmacological properties. So far, the combined activity of curcumin and rosuvastatin has not been investigated. The aim of this study was to examine the potential synergistic antimicrobial, antioxidant and anti-inflammatory in vitro activity of a combination of curcumin and rosuvastatin. In vitro agar well diffusion method was used to determine antibacterial activity against Gram-positive and Gram-negative bacteria as well as the antifungal activity. Antioxidant activity was evaluated by a commonly used in vitro assay for scavenging free radicals. In vitro assay of inhibition of protein denaturation was applied for the determination of anti-inflammatory activity. Results have demonstrated that a combination of curcumin and rosuvastatin suppressed the growth of all tested strains of microorganisms, therefore implying significant antimicrobial activity. Results have also suggested that a combination of curcumin and rosuvastatin shows a dose-dependent activity in scavenging free radicals and inhibiting protein denaturation. Therefore, the present in vitro study emphasizes the potential application of a combination of curcumin and rosuvastatin as antimicrobial, antioxidant and anti-inflammatory agents. However, current findings are limited to in vitro assays and further research should be conducted involving in vivo models.
Article
Full-text available
Curcumin, a principal bioactive substance of turmeric (Curcuma longa L.), is reported as a strong antioxidant, anti-inflammatory, antibacterial, antifungal, and antiviral agent. However, its antimicrobial properties require further detailed investigations into clinical and multidrug-resistant (MDR) isolates. In this work, we tested curcumin’s efficacy against over 100 strains of pathogens belonging to 19 species. This activity was determined by the broth microdilution method and by calculating the minimum inhibitory concentration (MIC). Our findings confirmed a much greater sensitivity of Gram-positive than Gram-negative bacteria. This study exhibited a significantly larger variation in the curcumin activity than previous works and suggested that numerous clinical strains of widespread pathogens have a poor sensitivity to curcumin. Similarly, the MICs of the MDR types of Staphylococcus aureus, S. haemolyticus, Escherichia coli, and Proteus mirabilis were high (≥2000 µg/mL). However, curcumin was effective against some species and strains: Streptococcus pyogenes (median MIC = 31.25 µg/mL), methicillin-sensitive S. aureus (250 µg/mL), Acinetobacter lwoffii (250 µg/mL), and individual strains of Enterococcus faecalis and Pseudomonas aeruginosa (62.5 µg/mL). The sensitivity of species was not associated with its affiliation to the genus, and it could differ a lot (e.g., S. pyogenes, S. agalactiae and A. lwoffii, A. baumannii). Hence, curcumin can be considered as a promising antibacterial agent, but with a very selective activity.
Article
Full-text available
Antimicrobial resistance represents an enormous global health crisis and one of the most serious threats humans face today. Some bacterial strains have acquired resistance to nearly all antibiotics. Therefore, new antibacterial agents are crucially needed to overcome resistant bacteria. In 2017, the World Health Organization (WHO) has published a list of antibiotic-resistant priority pathogens, pathogens which present a great threat to humans and to which new antibiotics are urgently needed the list is categorized according to the urgency of need for new antibiotics as critical, high, and medium priority, in order to guide and promote research and development of new antibiotics. The majority of the WHO list is Gram-negative bacterial pathogens. Due to their distinctive structure, Gram-negative bacteria are more resistant than Gram-positive bacteria, and cause significant morbidity and mortality worldwide. Several strategies have been reported to fight and control resistant Gram-negative bacteria, like the development of antimicrobial auxiliary agents, structural modification of existing antibiotics, and research into and the study of chemical structures with new mechanisms of action and novel targets that resistant bacteria are sensitive to. Research efforts have been made to meet the urgent need for new treatments; some have succeeded to yield activity against resistant Gram-negative bacteria by deactivating the mechanism of resistance, like the action of the β-lactamase Inhibitor antibiotic adjuvants. Another promising trend was by referring to nature to develop naturally derived agents with antibacterial activity on novel targets, agents such as bacteriophages, DCAP(2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2(hydroxymethyl)propane1,3-diol, Odilorhabdins (ODLs), peptidic benzimidazoles, quorum sensing (QS) inhibitors, and metal-based antibacterial agents.
Article
Full-text available
Background: Candidal infections have increased significantly in denture wearers, especially in immunocompromised patients. The increase in resistance to existing antifungal drugs and number of patients at risk, in conjunction with the restricted number of commercially available antifungal drugs that still present many side effects, are the cause for this problem. These limitations emphasize the need to develop new and more effective antifungal agents with lesser side effects. Materials and methods: The present study was undertaken to investigate the possible antifungal action of the alcoholic extract of different concentrations of Curcuma longa on four dilutions of Candida albicans (1:10, 1:20, 1:40 and 1:80) and to determine its minimum inhibitory concentration (MIC) and minimum fungicidal concentration using Sabouraud's agar medium. Results: There was complete inhibition of the growth of all four dilutions of Candida at a concentration of 800 μl which is considered as the MIC of alcoholic extract of turmeric on C. albicans, and the minimum fungicidal concentration was at 1600 μl. Conclusion: This study indicates a potent antifungal action of C. longa against C. albicans.
Article
Full-text available
The search for novel anti-infectives is one of the most important challenges in natural product research, as diseases caused by bacteria, viruses, and fungi are influencing the human society all over the world. Natural compounds are a continuing source of novel anti-infectives. Accordingly, curcumin, has been used for centuries in Asian traditional medicine to treat various disorders. Numerous studies have shown that curcumin possesses a wide spectrum of biological and pharmacological properties, acting, for example, as anti-inflammatory, anti-angiogenic and anti-neoplastic, while no toxicity is associated with the compound. Recently, curcumin’s antiviral and antibacterial activity was investigated, and it was shown to act against various important human pathogens like the influenza virus, hepatitis C virus, HIV and strains of Staphylococcus, Streptococcus, and Pseudomonas. Despite the potency, curcumin has not yet been approved as a therapeutic antiviral agent. This review summarizes the current knowledge and future perspectives of the antiviral, antibacterial, and antifungal effects of curcumin.
Article
Full-text available
The aim of this study was to determine the antimicrobial efficacy of curcumin, one of the active components of the Curcuma longa (turmeric) plant, against food pathogens in a minced meat medium. Salmonella Typhimurium ATCC 14028, Listeria monocytogenes ATCC 7644, Escherichia coli O157:H7 ATCC 33150 and S. aureus ATCC 25923 strains were used as food pathogens. Minimum inhibitory concentrations (MICs) were determined using the macrodilution method. MIC values for curcumin were found to be 125 μg/ml for L. monocytogenes and S. aureus, and 250 μg/ml for S. Typhimurium and E. coli O157:H7. Food pathogens were added to the minced meat at 10⁴ CFU/g (including the control group) and curcumin at doses of 0.5%, 1% and 2% (except the control). The curcumin-supplemented minced meat and control were analysed 0-7 days later. At the end of seven days, it was seen that the 2% dose of curcumin had lowered L. monocytogenes and S. aureus counts by approximately 3 log CFU/g, and E. coli O157:H7 and S. Typhimurium counts by approximately 2 log CFU/g; the 1% dose had lowered L. monocytogenes, S. aureus, E. coli O157:H7 and S. Typhimurium counts by approximately 2 log CFU/g; and that the 0.5% curcumin dose had lowered L. monocytogenes and S. aureus count by approximately 2 log CFU/g, and E. coli O157:H7 and S. Typhimurium count by approximately 1 log CFU/g. Changes in bacterial counts were found to be statistically significant (P ≤ 0.05). It was observed that antibacterial effect increased in direct proportion to dose, while sensory approval decreased. In this study, 0.5% and 1% curcumin doses were determined to be sensorily acceptable. It was concluded that, in view of the scientific benefits and antimicrobial efficacy of curcumin, it may be used instead of, or in smaller doses together with preservative additives in foods where colour change is not important.
Article
Full-text available
It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.
Article
Full-text available
Curcumin, an important constituent of turmeric, is known for various biological activities, primarily due to its antioxidant mechanism. The present study focused on the antibacterial activity of curcumin I, a significant component of commercial curcumin, against four genera of bacteria, including those that are Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). These represent prominent human pathogens, particularly in hospital settings. Our study shows the strong antibacterial potential of curcumin I against all the tested bacteria from Gram-positive as well as Gram-negative groups. The integrity of the bacterial membrane was checked using two differential permeabilization indicating fluorescent probes, namely, propidium io-dide and calcein. Both the membrane permeabilization assays confirmed membrane leakage in Gram-negative and Gram-positive bacteria on exposure to curcumin I. In addition, scanning electron microscopy and fluorescence microscopy were employed to confirm the membrane damages in bacterial cells on exposure to curcumin I. The present study confirms the broad-spectrum antibacterial nature of curcumin I, and its membrane damaging property. Findings from this study could provide impetus for further research on curcumin I regarding its antibiotic potential against rapidly emerging bacterial pathogens.
Article
Contamination of Penicillium expansum has dramatic impacts on the development of the fruit and vegetable industry. In this study, the antifungal effect and its mechanism of curcumin mediated photodynamic technology (PDT) against P. expansum spores was investigated. Results indicated that PDT inactivated 99.7 % spores and inhibited spore germination, mycelial growth and disease severity of the blue mold rot on apple fruit. PDT induced the generation of reactive oxygen species (ROS), which caused oxidative damage of spores and further disrupted cellular structure. In addition, excessive ROS triggered the antioxidant defense systems of spores. Moreover, ultimate result of cell death induced by PDT was apoptosis for short time illumination, and necrosis for long time. These results can be an asset to exploit PDT for further application in controlling harvest diseases of the fruit and vegetable.
Article
Objective: To evaluate the in vitro antifungal activity of curcumin against 2 strains of Candida albicans (ATCC 90028 and a clinical isolate - JY strain) and 1 isolate each of 3 nonalbicans - Candida species [Candida parapsilosis (ATCC 22019), C. glabrata (ATCC 90030), and C. dublieniensis (MYA 646)]. Materials and methods: Planktonic MIC of the 4 Candida species was determined using micro broth dilution assay according to CLSI M27-A3 criteria. The biofilm development and sensitivity assay were performed with the 2 C. albicans strains. Results: Curcumin at high concentrations (0.1-2 mg/mL) was effective in inhibiting planktonic organisms of all the 5 tested Candida strains. The planktonic phase and the biofilm phase of C. albicans ATCC 90028 exhibited similar MIC values for curcumin (0.5 mg/mL). Both curcumin and fluconazole were ineffective against the mature biofilms of JY strain. Conclusion: Our results reported here for the first time, in particular for the biofilm state of C. albicans, imply that curcumin a natural product could be used as a therapeutic alternative to conventional antifungals although further investigations are required to evaluate its potential.