TIPS 1282 No.
of Pages 3
Forum
Curcumin as an
Adjunct Drug for
Infectious Diseases
Govindarajan Padmanaban1,*
and Pundi N Rangarajan1
Curcumin, by virtue of its ability to
function as an immunomodulator,
has the potential to serve as an
adjunct drug to treat infectious dis-
eases and provide long-term pro-
tection. The current need is to
establish clinical trials with curcu-
min as an adjunct drug against
specific infectious diseases.
Millions of those living in poverty are dis-
proportionately afflicted by infectious dis-
eases, with prolonged illness, life-long
disability, and mortality accounting for
almost nine million deaths annually. In
addition to HIV, TB, and malaria,
neglected tropical diseases (NTDs), com-
prising 17 bacterial[1_TD$IF], protozoan, and viral
infections (e.g., leishmaniasis, African try-
panosomiasis, Chagas, cysticercosis,
dengue, rabies, etc.) account for around
40% of the global disease burden [1,2].
While strategies are debated in terms of
public health measures to prevent and
contain infectious diseases, major issues
at the therapeutic level are the exorbitant
treatment costs of current treatments, the
increasing challenges posed by drug and/
or antibiotic resistance, and the conse-
quent need to discover new, more afford-
able, drugs. It is in this context that the use
of dietary curcumin, an affordable, non-
toxic, adjunct drug with no history of drug
resistance, to treat infectious diseases
needs to be seriously investigated.
Curcumin as an Antimicrobial
Agent
Curcumin, which is extracted from tur- What is the Best Way Forward?
meric, is a well-known enigmatic molecule We suggest that the best approach to has been demonstrated can be used to
with potential health benefits in a large investigating the drug potential of study its efficacy in human clinical trials.
Cytokines Transcripon
factors
Enzymes Adhesion
Cancers
Parasic
Hepac molecules
and
biliary
Bacterial Inflammatory
Micro Cell cycle
Curcumin
RNAs proteins
Neuro
Viral degenerave
Cardio
Renal
Protein vascular Growth
Metabolic factors
kinases
Apoptoc Receptors
machinery
Figure 1. Snapshot of Diseases that Could be Treated with Curcumin (Blue Circles) and its
Molecular Targets (Black Circles).
number of diseases [3], with an equally
curcumin would be to undertake clinical
large number of identified molecular tar-
trials with select infectious diseases in
gets (Figure 1) [4]. It has also been
which it would be possible to use curcu-
reported to be effective against pathogens
min as an adjunct drug to standard ther-
causing infectious diseases [5]. Most of
apy and for which the treatment duration
the clinical trials (more than 100, either
is short. With the development of resis-
completed or ongoing) focus on cancers
tance to antibiotics in general, curcumin
and systemic disorders, and have trended
may hold promise to ameliorate drug
toward a general positive outcome; how-
resistance, since it tends to decrease
ever, these results need to be confirmed
the toxicity and dose of the primary drug
with well-planned, randomized designs.
[3]. While most anti-infectives kill the path-
By contrast, there are few examples of
ogen by inhibiting fundamental molecular
clinical trials investigating curcumin as
processes relating to its growth and sur-
a treatment for infectious diseases,
vival, curcumin may offer protection
although many preclinical studies have
through immunomodulation of the host
indicated significant beneficial effects
response rather than by a direct killing
(see below). effect on the pathogen. Thus, specific
infectious diseases of major concern
where the potential for the use of curcumin
Trends in Pharmacological Sciences, Month Year, Vol. xx, No. yy 1
 TIPS 1282 No. of Pages 3
Potential Diseases for Curcumin
Adjunct Therapy
Helicobacter[2_TD$IF] pylori[3_TD$IF] is a common human
pathogen that infects half of the popula-
tion of the world, and, in some cases, is
responsible for inflammation of the gastric
mucosa that leads to gastric cancer. Its
incidence is higher in the developing
world than elsewhere due to socioeco-
nomic factors. Development of antibiotic
resistance is also an issue. In a recent
study in the mouse model of H. pylori
infection, curcumin was shown to coun-
teract all the inflammatory parameters
based on cytokine, chemokine, and
Toll-like receptor (TLR) PCR assays,
and the C13 urea-breath test [6]. An
encouraging development was the orga-
nization of a human clinical trial with 150
patients to study the impact of the addi-
tion of curcumin to a 10-day standard
triple therapy (proton-pump inhibitor,
clarithromycin, and amoxicillin) [7]. This
is on the basis that curcumin may show
synergistic effects, when used in combi-
nation therapy.
Methicillin-resistant Staphylococcus aureus
(MRSA) has been associated with consid-
erable morbidity and mortality and is a major
public health issue worldwide. The rapid
spread of antibiotic resistance is posing a
serious challenge to its treatment. MRSA
has established itself as a common noso-
comial pathogen and is being increasingly
implicated in both healthcare- and commu-
nity-associated infections [8]. Curcumin has
been shown to significantly decrease the
minimal inhibitory concentration of the anti-
biotics oxacillin, ampicillin, ciprofloxacin,
and norfloxacin, which are currently used
against MRSA. Curcumin–oxacillin treat-
ment was shown to reduce bacterial counts
below detectable limits within 24 h [9]. How-
ever, further studies are needed to deter-
mine the efficacy of this combination
therapy in vivo.
The combination of curcumin with the
antimalarial drug arteether is effective in
killing the murine malaria parasite, Plas-
modium berghei. It is also effective in
2 Trends in Pharmacological Sciences, Month Year, Vol. xx, No. yy
preventing parasite recrudescence by Thus, curcumin as an adjunct drug would
inhibiting the inflammatory T helper type provide long-term benefits through immu-
1 (Th1) response and promoting the anti- nomodulation, and this is especially rele-
inflammatory Th2 response [10]. It is able vant in cases where a vaccine is not
to prevent sequestration of parasite- available. As a start, specific examples
infected red blood cells in the brain and where proof of principle exists for the effi-
the onset of neurological symptoms in cacy of curcumin in vivo can be taken up
experimental cerebral malaria (ECM). In for evaluation in the presence and
particular, curcumin shows synergism absence of the primary drug in use. It is
with arteether in curing ECM after the proposed that philanthropic organiza-
onset of symptoms [11]. Mortality in cere- tions, such as the Bill & Melinda Gates
bral malaria is as high as 15–25%, despite Foundation, could promote preclinical
the use of primary treatment with artemi- and efficacy trials for assessing the bene-
sinin derivatives. fits of curcumin and formulations that can
enhance bioavailability, if considered nec-
Chagas disease, which is caused by infec- essary, as an adjunct drug in the exam-
tion with Trypanosoma cruzi, infects six– ples discussed, where a substantial
seven million people worldwide, mostly in population in the developing countries is
Latin America, although the disease is at risk. Since the treatments are for a
now spreading to other continents. It relatively shorter period for infectious dis-
can lead to cardiac and gastrointestinal ease (relative to cancer, for example) and
complications, resulting in mortality and the end points are clearly quantifiable, this
physical disabilities. The disease is curable would help to establish curcumin as a
with benznidazole and nifurtimox, when viable, affordable adjunct drug to treat
treated soon after infection, with efficacy specific infectious diseases. An advan-
decreasing the longer the infection lasts. tage to the study of infectious diseases
Curcumin treatment has been shown to is that the beneficial effects can be
cause a significant reduction in macro- assessed in clear terms, unlike cancers,
phage infiltration and inflammation in both where more often the patient benefits can
the heart and liver. Curcumin-treated remain blurred by the long duration of
infected mice displayed a 100% survival treatment required and the complex
rate in contrast to the 60% survival rate nature of the disease. Such an approach
commonly observed in untreated infected would establish the use of curcumin
mice [12]. Therefore, it would be useful to backed by hard-core scientific and clinical
test the efficacy of combination therapy evidence that may pave the way for its
with curcumin. wider use. It might be that the use of
curcumin as an adjunct drug rather than
Concluding Remarks as a primary anticancer drug would elicit a
It would appear that curcumin may have credible beneficial response.
beneficial effects in treating infectious dis-
eases, despite issues with poor bioavail- Acknowledgments
ability and rapid metabolism. It might be The research on the use of curcumin to treat experi-
that curcumin modulates immune mem- mental malaria in the authors’ laboratory was carried
ory in the presence of either the pathogen out in a Centre of Excellence project supported by the
Department of Biotechnology, Government of India.
or antigen(s) from the pathogen generated
G.P. is a senior scientist of the Indian National Science
by the direct killing effect of the primary
Academy.
drug. In certain instances, it is able to aid
the immune response and prevent fresh 1Department of Biochemistry, Indian Institute of Science,
infection as well as to offer protection and Bangalore 560012, India
cure long after the primary drug has dis- *Correspondence: geepee@biochem.iisc.ernet.in
appeared from the system, as shown in (G. Padmanaban).
the case of experimental malaria [10,11]. http://dx.doi.org/10.1016/j.tips.2015.09.007
 TIPS 1282 No. of Pages 3
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