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Abstract

This short review addresses the knowledge on curcumin use against parasite infections from traditional to modern medicine. Curcumin is the active ingredient of turmeric (Curcuma longa). The extract of the rhizome of turmeric has been traditionally used against various diseases including parasitic infections. Recently, the crude extract of turmeric and its active ingredient curcumin have been explored with respect to the biological and molecular activity against many pathogens. The antioxidant, antitumor, and anti-inflammatory properties of curcumin make it a promising natural drug to be used against bacterial, fungal, and viral agents. Antiparasitic effects of curcumin have attracted considerable attention over the last decades. Curcumin has been found to display activity against various parasites both in vitro and in vivo. However, the effects of curcumin become obvious in most cases at relatively high dose levels. The bio-molecular and cellular processes involved in curcumin effects on parasites are not sufficiently understood at present and more research in this area is inevitable to define the actual applicability of curcumin in parasite control measures and therapy. We here review the available information on the therapeutic potential of curcumin against parasites obtained from in vitro studies, animal models, and clinical trials.
Chapter 6
Curcumin: A Natural Herb Extract
with Antiparasitic Properties
Md. Shahiduzzaman and Arwid Daugschies
Abstract This short review addresses the knowledge on curcumin use against
parasite infections from traditional to modern medicine. Curcumin is the active
ingredient of turmeric (Curcuma longa). The extract of the rhizome of turmeric has
been traditionally used against various diseases including parasitic infections.
Recently, the crude extract of turmeric and its active ingredient curcumin have
been explored with respect to the biological and molecular activity against many
pathogens. The antioxidant, antitumor, and anti-inflammatory properties of curcu-
min make it a promising natural drug to be used against bacterial, fungal, and viral
agents. Antiparasitic effects of curcumin have attracted considerable attention over
the last decades. Curcumin has been found to display activity against various
parasites both in vitro and in vivo. However, the effects of curcumin become
obvious in most cases at relatively high dose levels. The bio-molecular and cellular
processes involved in curcumin effects on parasites are not sufficiently understood
at present and more research in this area is inevitable to define the actual applica-
bility of curcumin in parasite control measures and therapy. We here review the
available information on the therapeutic potential of curcumin against parasites
obtained from in vitro studies, animal models, and clinical trials.
6.1 Introduction
The plant turmeric, Curcuma longa L. (Zingiberaceae family), has a long history of
therapeutic use in Indian and Chinese medicines for the treatment of flatulence,
dyspepsia, liver disorder, jaundice, urinary tract diseases, wound, inflammation, and
Md. Shahiduzzaman
Department of Parasitology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
e-mail: szamanpara@yahoo.com
A. Daugschies (*)
Institute of Parasitology, University of Leipzig, An den Tierkliniken 35, 04103 Leipzig, Germany
e-mail: daugschies@vetmed.uni-leipzig.de
H. Mehlhorn (ed.), Nature Helps..., Parasitology Research Monographs 1,
DOI 10.1007/978-3-642-19382-8_6, #Springer-Verlag Berlin Heidelberg 2011
141
other diseases. It has also been used in the treatment of intestinal parasites and of
parasitic skin infection. The scientific backgrounds for the curcumin effects have
been discovered gradually. A crude extract of turmeric contains curcumin and
curcuminoids (Rasmussen et al. 2000) where curcumin is the major constituent.
Curcumin is a polyphenolic orange–yellow compound and the main coloring prin-
ciple of curcumin is 1,7-bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-3,5-
dione (diferuloylmethane). Curcumin has attracted considerable attention in recent
years due to its remarkable pharmacological activities, including antioxidant, anti-
tumor, and anti-inflammatory activities (Surh 2002; Aggarwal et al. 2003; Choi
et al. 2006; Shen and Ji 2007; Goel et al. 2008). It exerts influence on a variety of
biological and cellular processes. Curcumin has been suggested to be useful in
antidiabetic (Srinivasan and Menon 2003), anti-HIV (Jordan and Drew 1996;
Barthelemy et al. 1998), antibacterial (Negi et al. 1999; Mahady et al. 2002), and
antifungal treatment (Kim et al. 2003). In addition to inhibiting the growth of a
variety of pathogens, curcumin has been shown to have anthelmintic and antipro-
tozoal activities (Nose et al. 1998; Araujo et al. 1998, 1999; Koide et al. 2002). The
current experience regarding curcumin effects in various scenarios rewards more
research into the drug targets that might be suitable for therapeutic invention. The
purpose of this review is to provide a brief summary of the current published
knowledge of curcumin as a potential antiparasitic drug.
6.2 Curcumin Effects on Parasites
6.2.1 Helminths
Juice of turmeric traditionally has long been used to cure worm infections in south
and south-east Asia (Nadkarni 1976). Recently, it has been reported that the extract of
C. longa is active against Schistosoma mansoni (El-Ansary et al. 2007; El-Banhawey
et al. 2007) and Caenorhabditis elegans (Atjanasuppat et al. 2009). Curcumin
treatment modulates cellular and humoral immune responses of infected mice
and leads to a significant reduction of parasite burden and liver pathology in acute
murine schistosomiasis. It also possesses in vitro activity against adult S. mansoni
worms (Magalhaes et al. 2009) and is suspected to have therapeutic potential in the
treatment and prevention of schistosomiasis (Allam 2009). Antifibrogenic and anti-
inflammatory properties of curcumin may reduce Opisthorchis viverrini-induced
fibrosis and prevent cholangiocarcinoma development that may be associated with
opisthorchiasis (Boonjaraspinyo et al. 2009; Pinlaor et al. 2010). Thus, curcumin may
be useful as a chemopreventive drug by reducing the severity of O. viverrini-
associated disease and the risk of cholangiocarcinoma. It has been suggested that
this property of curcumin can be explained by reduction of the oxidative and nitro-
genic DNA damage that may be due to suppression of oxidant-generating genes and
enhancement of antioxidant genes in the nucleus of bile duct epithelial and inflamma-
tory cells (Pinlaor et al. 2009). Although particularly trematode infections have been
142 Md. Shahiduzzaman and A. Daugschies
studied, curcumin seems also to have a positive effect in nematode infections such
as Toxocara canis in dogs (Kiuchi et al. 1993). T. canis is a zoonotic parasite and,
like other ascarid infections, is very prevalent worldwide and particularly in
many developing countries. It would be of considerable benefit if curcumin effects
would also be seen in human infections with Ascaris lumbricoides or A. suum in
swine, however, no scientific data has been published in this respect so far.
6.2.2 Protozoa
Antiprotozoal activities of curcumin have been reported extensively over the last
decade. The spice rhizome of turmeric (1% crude extract), as well as its main
medicinal component, curcumin (0.05%), appear effective in reducing upper- and
mid-small-intestinal infections caused by Eimeria acervulina and Eimeria maxima
but they do not act beneficially in Eimeria tenella infections (Allen et al. 1998).
However, in vitro incubation of E. tenella sporozoites with curcumin showed
considerable effects on sporozoite morphology and viability and resulted in
decreased invasion of MDBK cells (Khalafalla et al. 2010). Curcumin, as an
alcoholic extract, was found to have antiprotozoal activity against Entamoeba
histolytica (Dhar et al. 1968). Antiprotozoal activities of curcumin were also
described for Plasmodium (Reddy et al. 2005; Cui et al. 2007), Leishmania (Araujo
et al. 1998; Rasmussen et al. 2000; Koide et al. 2002; Saleheen et al. 2002; Das et al.
2008), Trypanosoma (Nose et al. 1998), and Giardia lamblia (Pe
´rez-Arriaga et al.
2006), both in vitro and in vivo. Curcumin was able to reduce parasitemia by
80–90% in Plasmodium berghei-infected mice (Reddy et al. 2005). Recently,
curcumin was found to be effective against Cryptosporidium parvum in cell culture.
C. parvum appears to be more sensitive to curcumin than Plasmodium,Giardia, and
Leishmania (Shahiduzzaman et al. 2009). Synergistic antiprotozoal effects were
shown when curcumin was applied in combination with other drugs. For instance,
the combination of artemisinin and curcumin shows additive activity in killing
Plasmodium falciparum in culture and enabled experimentally P. berghei-infected
mice to survive (Nandakumar et al. 2006). Drug resistance of Plasmodium strains is
a major threat to malaria control. However, chloroquine-resistant P. falciparum
(Reddy et al. 2005) and artemisinin-resistant Plasmodium chabaudi (Martinelli
et al. 2008) were found to be sensitive to curcumin in culture and in mice,
respectively. These are promising data that may open alternative options for
malaria control, particularly where drug resistance has become a relevant issue.
6.3 Mode of Action and Perspectives
It appears that curcumin acts against parasites through unique biomolecular
mechanisms which would explain its activity on both drug-sensitive and drug-
resistant parasite strains. Various studies have shown that curcumin has antioxidant
6 Curcumin: A Natural Herb Extract with Antiparasitic Properties 143
and anti-inflammatory properties and that it modulates numerous targets and cell
signaling pathways. These include growth factors, growth factor receptors, tran-
scription factors, cytokines, enzymes, and genes regulating apoptosis.
The discovery of the antioxidant properties of curcumin explains many of its
wide-ranging pharmacological activities. Curcumin is an effective antioxidant and
scavenges superoxide radicals, hydrogen peroxide, and nitric oxide (NO) from
activated macrophages (Joe and Lokesh 1994). Curcumin is associated with the
maintenance of reactive oxygen species (ROS) and activity of NO in a dose-
depending manner. High doses (20–50 mM) of curcumin induce formation of
ROS (Balasubramanyam et al. 2003) by elevation of cytosolic calcium through
the release of calcium ions from intracellular stores. Moreover, influx of extracel-
lular calcium leads to depolarization of mitochondrial membrane potential, release
of cytochrome c into the cytosol and concomitant nuclear alterations. For instance,
deoxynucleotidyltransferase-mediated dUTP end labeling and DNA fragmentation
in P. falciparum (Cui et al. 2007) and Giardia (Pe
´rez-Arriaga et al. 2006) were
observed and promising antileishmanial activity (Das et al. 2008) was supposed to
be related to this molecular mechanism. In leishmaniasis inducible nitric oxide
synthase (iNOS) is correlated with increasing doses of curcumin leading to intra-
cellular killing of Leishmania major (Liew et al. 1990, 1991; Green et al. 1990).
Leitch and Qing (1999) reported that both reactive nitrogen species (RNS) and ROS
play protective roles in experimental cryptosporidiosis in mice. Cryptosporidium
has a poor capacity to scavenge ROS (Entrala et al. 1997), making it potentially
more susceptible to killing by such oxygenic compounds. Certain ROS, especially
hydroxyl radicals and hydrogen peroxide, produced as a result of parasite exposure
to ultraviolet irradiation, resulted in inactivation (photo-toxicity) of C. parvum
oocysts (Gerrity et al. 2008; Ryu et al. 2008). Conversely, low doses (1–15 mM)
of curcumin activate peroxisome proliferator-activated receptor gamma, deactivate
type 1 response, inhibit iNOS, and interferes with adaptive immunity thus exacer-
bating the pathogenic effects of Leishmania donovani infection (Adapala and Chan
2008). Curcumin in low doses also is capable of blocking the action of both NO and
NO congeners on intracellular Leishmania or scavenges ROS produced as a result
of activation of macrophages in leishmaniasis infection. This contributes to protec-
tion of promastigotes and amastigotes of the visceral species, L. donovani, and
promastigotes of the cutaneous species, L. major (Chan et al. 2005) from host attack
after phagocytosis by for example macrophages. Despite the wide evidence that NO
can be regarded as a natural antiprotozoal weapon, little efforts have been made to
develop and test NO-based drugs. This is mainly due to the difficulty in designing
suitable chemical carriers that are able to release the right amount of NO, in the
right place and at the right time, to avoid toxic effects against nontarget host cells.
The curcumin diphasic effect against parasites that depends on applied dose and
exposure time may be advantageous for development of such an antiparasitic drug.
Antiparasitic activities of curcumin are achieved through effects on transcription
of genes. Recent studies find that histone acetylation plays an important role in
eukaryotic gene transcription, carcinogenesis, and the therapy of cancer. Generally,
histone acetylation contributes to the formation of a transcriptionally competent
144 Md. Shahiduzzaman and A. Daugschies
environment by “opening” chromatin and permits access of transcription factors to
DNA (Fry and Peterson 2002; Lehrmann et al. 2002) whereas histone deacetylation
contributes to a “closed” chromatin state and transcriptional repression. The histone
acetylation–deacetylation balance is accurately maintained through a balance of
histone acetyltransferase (HAT) and histone deacetylase. Curcumin induces histone
hypoacetylation in vivo mainly through inhibition of HAT and concomitant genera-
tion of ROS by curcumin effects also contribute to inhibition of HAT activity (Kang
et al. 2005). Histone deacetylase is a novel therapeutic target for fungal-derived
antiprotozoal agents (like acipidin). Such drugs may alter proliferation of apicom-
plexan parasites (Darkin-Rattray et al. 1996). In vitro, curcumin effects on recom-
binant P. falciparum have been attributed to inhibition of histone deacetylation (Cui
et al. 2007) and inhibition of HAT activity (Balasubramanyam et al. 2004). A new
member of the apicomlexan histone deacetylase family has been recently described
in C. parvum (Rider and Zhu 2009), and it seems to be possible that a respective
mechanism is involved in inhibition of growth of Cryptosporidium by curcumin.
Curcumin induces hypoacetylation of histone H3 at K9 and K14, but not of H4 at
K5, K8, K12, and K16. The specific inhibition of the PfGCN5 HAT and generation
of ROS have been supposed to be responsible for curcumin-related cytotoxicity for
malaria parasites (Cui et al. 2007). Curcumin inhibits the intracellular adhesion
molecules that contribute to sequestration and establishment of Toxoplasma
(Barragan et al. 2005) and Plasmodium (Chakravorty and Craig 2005). The ortho-
logue of mammalian sarcoplasmic–endoplasmic reticulum Ca
2+
–ATPase in
P. falciparum, PfATP6, is the molecular target of artemisinins, which are the most
potent antimalarials available (Eckstein-Ludwig et al. 2003). It has been demon-
strated by docking simulation that curcumin can efficiently inhibit PfATP6, which
provides some deeper insights into the antimalarial mechanism of curcumin (Ji and
Shen 2009).
Curcumin is found to significantly increase adhesion but remarkably reduce
viability of Giardia trophozoites (Pe
´rez-Arriaga et al. 2006). It has been found
that biomolecular discharge from apical organelles of C. parvum and Toxoplasma
gondii is essential for host cell invasion and this depends on parasite intracellular
calcium levels (Chen et al. 2004; Lovett et al. 2002; Lovett and Sibley 2003).
Reduced intracellular calcium levels in free sporozoites decrease secretion from the
apical complex, thus reducing invasion and infection by the zoites. Curcumin
mechanistically interferes with protein kinase C (PKC) and calcium regulation
through increased ROS generation (Balasubramanyam et al. 2003). PKC-like
enzymes play a critical role in attachment and in internalization of Leishmania
mexicana (Varez-Rueda et al. 2009). Hypocalcimic action and inhibition of PKC by
curcumin therefore should be taken into account to develop suitable and novel
drugs for control of infection of parasite into host cells.
A significant inhibition of C. parvum sporozoite invasion of HCT cells by curcu-
min was reported in vitro (Shahiduzzaman et al. 2009). Infectivity of sporozoites is
mediated by interaction of molecules secreted from sporozoites with matching recep-
tors present on both parasite and host cell (Nesterenko et al. 1999). Phospholipase A2
(PLA2), a secretory mammalian host cell enzyme involved in arachidonic acid
6 Curcumin: A Natural Herb Extract with Antiparasitic Properties 145
metabolism, has been supposed to be associated with infectivity of Toxoplasma
(Saffer et al. 1989; Saffer and Schwartzman 1991) and Cryptosporidium (Pollok
et al. 2003). Curcumin was found to inhibit mammalian phospholipase (Huang et al.
1991; Rao et al. 1995) and it appears possible that similar effects on parasite PLA2
may reduce infectivity of sporozoites. However, other enzymes are also thought to
play a pivotal role in apicomplexan host cell invasion. Inhibition of C. parvum serine
protease (Forne et al. 1996) and arginine aminopeptidase (Okhuysen et al. 1994, 1996)
was reported to reduce the ability of sporozoites to infect host cells. Blocking of T.
gondii serineprotease (Conseil et al. 1999) significantly reduced the level of infection.
Curcumin is able to suppress both serine protease and aminopetidase activity in a
variety of tissues and cells (Shim et al. 2003; Ukil et al. 2003) and thus it may well be
that curcumin acts as an inhibitor of host cell invasion by impairing the function of
respectively relevant parasite enzymes. Curcumin has been proposed as a HIV-1 or
HIV-2 protease inhibitor (Sui et al. 1993). Parasite infections like cryptosporidiosis
and toxoplasmosis are known to be opportunistic pathogens that cause severe disease
in immunocompromised individuals. Thus, a protease inhibitor such as curcumin
could be of double benefit by directly acting on HIV and on opportunistic protozoa.
A glutathione transferase (PfGST) isolated from P. falciparum has been asso-
ciated with chloroquine resistance. Curcumin is a potent inhibitor of PfGST which
may open alternative perspectives for management of drug resistance in malaria
(Mangoyi et al. 2010).
Curcumin inhibits metalloproteinase activity including classical matrix metallo-
proteinase inhibitors such as EDTA, EGTA, phenantroline, and also tetracycline in
Trypanosoma brucei infection (de Sousa et al. 2010). It is suspected to inhibit the
matrix metalloproteinase-9-like molecules in Trypanosoma cruzi (Nogueira de Melo
et al. 2010) and Theileria annulata-infected bovine leukocytes (Baylis et al. 1995).
Metalloproteinases mediate the metastatic phenotype of T. annulata-transformed
cells (Adamson and Hall 1996). This property of curcumin has not been extensively
studied in terms of antiparasitic potential but deserves further research.
The apoptotic response of infected intestinal epithelial cells is actively sup-
pressed by C. parvum via up regulation of survivin, favoring parasite replication
(Liu et al. 2008). Curcumin-mediated down regulation of survivin induces apoptosis
in tumor cells and similarly may enhance apoptosis of C. parvum-infected cells.
Caspase-dependent apoptosis during infection with C. parvum raises the possibility
that therapeutic interference with host cell death could alter the course of the
pathology in vivo (Ojcius et al. 1999). In T. gondii-infected cells, the termination
of NF-
kappa
B(
k
B) signaling is associated with reduced phosphorylation of p65/RelA,
an event involved in the ability of NF-
k
B to translocate to the nucleus and to bind to
DNA. The phosphorylation of p65/RelA represents an event downstream of IaB
degradation that may be targeted by pathogens to subvert NF-
k
B signaling (Shapira
et al. 2005). Curcumin can effectively down-regulate NF-
k
B, thus inhibiting Ikap-
paBalpha kinase and reducing IkappaBalpha phosphorylation, leading to cell cycle
arrest, apoptosis, and suppression of proliferation (Shishodia et al. 2005) of parasite-
infected cells. Thioredoxin reductases (TrxRs) are essential for cell growth and
survival and they appear good targets for antitumor therapy. The parasitic nematode
146 Md. Shahiduzzaman and A. Daugschies
Haemonchus contortus contains two TrxRs, a cytoplasmic enzyme HcTrxR1 with a
selenocysteine in the active site (Gly–Cys–SeCys–Gly), similar to the mammalian
TrxR, and a mitochondrial enzyme HcTrxR2 with a Gly–Cyc–Cys–Gly active site
which is unique to nematodes. Curcumin inhibition of TrxRs (Hudson et al. 2010)
may reduce parasite proliferation which is attractive for control strategies. It has
been shown that curcuminoids strongly bind to P. falciparum thioredoxin (PfTrxR)
and glutathione (PfGR) reductases which has allowed the development of automated
high-throughput screening to rapidly determine the binding affinity of respective
enzyme ligands (Mulabagal and Calderon 2010).
6.4 Curcumin Analogs
Synthetic curcumin analogs exhibit more potent antiparasitic effects than curcumin
extracted from turmeric. The natural curcuminoids (curcumin, demethoxycurcumin,
bisdemethoxycurcumin) exhibit low antitrypanosomal and antileishmanial activity. In
contrast, curcumin derivatives (methylcurcumin) with des-O-methylcentrolobine are
very active against the extracellular form (promastigotes) and intracellular form (amas-
tigotes) of Leishmania amazonensis (Araujo et al. 1999). Curcuminoids synthesized by
the condensation of 2,4-pentanedione with differently substituted benzaldehydes and
the compound 1,7-bis-(2-hydroxy-4-methoxyphenyl)-1,6-heptadiene-3,5-dione are
highly effective in vitro against L. amazonensis promastigotes (Gomes et al. 2002b).
Chemically modified curcumin for example 1,7-bis-(4-propargyl-3-methoxyphenyl)-
1,6-heptadiene-3,5-dione, is about ten times more efficient against L. amazonensis
promastigotes than the original curcumin (Gomes et al. 2002a). The highly active
analog 1,7-bis(4-hydroxy-3-methoxyphenyl) hept-4-en-3-one (40) is particularly active
against kinetoplastid parasites. The diminazene-resistant strain of Trypanosoma brucei
brucei (TbAT1-KO) B48 is susceptible to curcuminoids carrying a conjugated keto
(enone) motif. The enone motif 40 was found to exert particularly high trypanocidal
activity against all Trypanosoma species and strains tested (Changtam et al. 2010).
6.5 Conclusions
In recent years, the molecular basis for curcumin efficacy has been extensively
investigated. Understanding of curcumin effects on the biomolecular or cellular
level will hopefully help to identify and develop new therapeutic options. Curcumin
is nontoxic to mammals at even high doses which makes it attractive as a potential
antiparasitic drug, however, synthetic analogs of curcumin are superior in effi-
ciency as compared to natural curcumin. In any case, curcumin extracted from
turmeric represents an accessible and low-cost alternative for control of parasites in
populations living in risk areas and thus further research into the potential of this
natural plant product appears very rewarding.
6 Curcumin: A Natural Herb Extract with Antiparasitic Properties 147
References
Adamson RE, Hall FR (1996) Matrix metalloproteinases mediate the metastatic phenotype of
Theileria annulata-transformed cells. Parasitology 113:449–455
Adapala N, Chan MM (2008) Long-term use of an antiinflammatory, curcumin, suppressed type 1
immunity and exacerbated visceral leishmaniasis in a chronic experimental model. Lab Invest
88:1329–1339
Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and
clinical studies. Anticancer Re 23:363–398
Allam G (2009) Immunomodulatory effects of curcumin treatment on murine schistosomiasis
mansoni. Immunobiology 214:712–727
Allen PC, Danforth HD, Augustine PC (1998) Dietary modulation of avian coccidiosis. Int J
Parasitol 28:1131–1140
Araujo CAC, Alegrio LV, Castro D, Lima MEF, Leon LL (1998) Leishmania amazonensis: in vivo
experiments with diarylhetanoids from Leguminosae and Zingiberaceae plants. Mem Inst
Oswaldo Cruz 93:306–310
Araujo CA, Alegrio LV, Gomes DC, Lima ME, Gomes-Cardoso L, Leon LL (1999) Studies on the
effectiveness of diarylheptanoids derivatives against Leishmania amazonensis. Mem Inst
Oswaldo Cruz 94:791–794
Atjanasuppat K, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, Whitfield PJ
(2009) In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants
from Thailand. J Ethnopharmacol 123:475–482
Balasubramanyam M, Koteswari AA, Kumar RS, Monickaraj SF, Maheswari JU, Mohan V (2003)
Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic
implications. J Biosci 28:715–721
Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK
(2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase,
represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-depen-
dent chromatin transcription. J Biol Chem 279:51163–51171
Barragan A, Brossier F, Sibley LD (2005) Transepithelial migration of Toxoplasma gondii
involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite
adhesin MIC2. Cell Microbiol 7:561–568
Barthelemy S, Vergnes L, Moynier M, Guyot D, Labidalle S, Bahraoui E (1998) Curcumin and
curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency
virus long terminal repeat. Res Virol 149:43–52
Baylis HA, Megson A, Hall R (1995) Infection with Theileria annulata induces expression of
matrix metalloproteinase 9 and transcription factor AP-1 in bovine leucocytes. Mol Biochem
Parasitol 69:211–222
Boonjaraspinyo S, Boonmars T, Aromdee C, Srisawangwong T, Kaewsamut B, Pinlaor S,
Yongvanit P, Puapairoj A (2009) Turmeric reduces inflammatory cells in hamster opisthorch-
iasis. Parasitol Res 105:1459–1463
Chakravorty SJ, Craig A (2005) The role of ICAM-1 in Plasmodium falciparum cytoadherence.
Eur J Cell Biol 84:15–27
Chan MM, Adapala NS, Fong D (2005) Curcumin overcomes the inhibitory effect of nitric oxide
on Leishmania. Parasitol Res 96:49–56
Changtam C, de Koning HP, Ibrahim H, Sajid MS, Gould MK, Suksamrarn A (2010) Curcuminoid
analogs with potent activity against Trypanosoma and Leishmania species. Eur J Med Chem
45:941–956
Chen XM, O’Hara SP, Huang BQ, Nelson JB, Lin JJ, Zhu G, Ward HD, LaRusso NF (2004)
Apical organelle discharge by Cryptosporidium parvum is temperature, cytoskeleton, and
intracellular calcium dependent and required for host cell invasion. Infect Immun
72:6806–6816
148 Md. Shahiduzzaman and A. Daugschies
Choi H, Chun YS, Kim SW, Kim MS, Park JW (2006) Curcumin inhibits hypoxia-inducible
factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor
growth inhibition. Mol Pharmacol 70:1664–1671. doi: 10.1124/mol.106.025817
Conseil V, Soete M, Dubremetz JF (1999) Serine protease inhibitors block invasion of host cells
by Toxoplasma gondii. Antimicrob Agents Chemother 43:1358–1361
Cui L, Miao J, Cui L (2007) Cytotoxic effect of curcumin on malaria parasite Plasmodium
falciparum: inhibition of histone acetylation and generation of reactive oxygen species. Anti-
microb Agents Chemother 51:488–494
Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, Cannova C,
Meinke PT, Colletti SL, Bednarek MA, Singh SB, Goetz MA, Dombrowski AW, Polishook
JD, Schmatz DM (1996) Apicidin: a novel antiprotozoal agent that inhibits parasite histone
deacetylase. Proc Natl Acad Sci USA 93:13143–13147
Das R, Roy A, Dutta N, Majumder HK (2008) Reactive oxygen species and imbalance of calcium
homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani.
Apoptosis 13:867–882
de Sousa KP, Atouguia J, Silva MS (2010) Partial biochemical characterization of a metallopro-
teinase from the bloodstream forms of Trypanosoma brucei brucei parasites. Protein J
29:283–289
Dhar ML, Dhar MM, Dhawan BN, Mehrotra BN, Ray C (1968) Screening of Indian plants for
biological activity: I. Indian J Exp Biol 6:232–247
Eckstein-Ludwig U, Webb RJ, Van G, East JM, Lee AG, Kimura M, O’Neill PM, Bray PG, Ward
SA, Krishna S (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature
424:957–961
El-Ansary AK, Ahmed SA, Aly SA (2007) Antischistosomal and liver protective effects of
Curcuma longa extract in Schistosoma mansoni infected mice. Indian J Exp Biol 45
(9):791–801
El-Banhawey MA, Ashry MA, El-Ansary AK, Aly SA (2007) Effect of Curcuma longa or
praziquantel on Schistosoma mansoni infected mice liver: histological and histochemical
study. Indian J Exp Biol 45(10):877–889
Entrala E, Mascaro C, Barrett J (1997) Anti-oxidant enzymes in Cryptosporidium parvum oocysts.
Parasitology 114(Pt 1):13–17
Forne JR, Yang S, Du C, Healey MC (1996) Efficacy of serine protease inhibitors against
Cryptosporidium parvum infection in a bovine fallopian tube epithelial cell culture system.
J Parasitol 82:638–640
Fry CJ, Peterson CL (2002) Unlocking the gates to gene expression. Science 295:1847–1848
Gerrity D, Ryu H, Crittenden J, Abbaszadegan M (2008) Photocatalytic inactivation of viruses
using titanium dioxide nanoparticles and low-pressure UV light. J Environ Sci Health A
Toxicol Hazard Subst Environ Eng 43:1261–1270
Goel A, Kunnumakkara AB, Aggarwal BB (2008) Curcumin as “Curecumin”: from kitchen to
clinic. Biochemical Pharmacology 75:787–809
Gomes DC, Alegrio LV, de Lima ME, Leon LL, Araujo CA (2002a) Synthetic derivatives of
curcumin and their activity against Leishmania amazonensis. Arzneimittelforschung
52:120–124
Gomes DC, Alegrio LV, Leon LL, de Lima ME (2002b) Total synthesis and anti-leishmanial
activity of some curcumin analogues. Arzneimittelforschung 52:695–698
Green SJ, Crawford RM, Hockmeyer JT, Meltzer MS, Nacy CA (1990) Leishmania major
amastigotes initiate the L-arginine dependent killing mechanism in IFN-c-stimulated macro-
phages by induction of tumor necrosis factor-a. J Immunol 145:4290–4297
Huang MT, Lysz T, Ferraro T, Abidi TF, Laskin JD, Conney AH (1991) Inhibitory effects of
curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer
Res 51:813–819
Hudson AL, Sotirchos IM, Davey MW (2010) Substrate specificity of the mitochondrial thior-
edoxin reductase of the parasitic nematode Haemonchus contortus. Parasitol Res 107:487–493
6 Curcumin: A Natural Herb Extract with Antiparasitic Properties 149
Ji HF, Shen L (2009) Interactions of curcumin with the PfATP6 model and the implications for its
antimalarial mechanism. Bioorg Med Chem Lett 19:2453–2455
Joe B, Lokesh BR (1994) Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the
generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta
1224:255–263
Jordan WC, Drew CR (1996) Curcumin – a natural herb with anti-HIV activity. J Natl Med Assoc
88:333
Kang J, Chen J, Shi Y, Jia J, Zhang Y (2005) Curcumin-induced histone hypoacetylation: the role
of reactive oxygen species. Biochem Pharmacol 69:1205–1213
Khalafalla RE, M
uller U, Shahiduzzaman M, Dyachenko V, Desouky AY, Alber G, Daugschies A
(2010) Effects of curcumin (diferuloylmethane) on Eimeria tenella sporozoites in vitro. Para-
sitol Res. doi:10.1007/s00436-010-2129-y
Kim GM, Choi KJ, Lee HS (2003) Fungicidal property of Curcuma longa L. rhizome-derived
curcumin against phytopathogenic fungi in a greenhouse. J Agric Food Chem 51:1578–1581
Kiuchi F, Goto Y, Sugimoto N, Akao N, Kondo K, Tsuda Y (1993) Nematocidal activity of
turmeric: synergistic action of curcuminoids. Chem Pharm Bull 41:1640–1643
Koide T, Nose M, Ogihara Y, Yabu Y, Ohta N (2002) Leishmanicidal effect of curcumin in vitro.
Biol Pharm Bull 25:131–133
Lehrmann H, Pritchard LL, Harel-Bellan A (2002) Histone acetyltransferasesand deacetylases in
the control of cell proliferation and differentiation. Adv Cancer Res 86:41–65
Leitch GJ, Qing HE (1999) Reactive nitrogen and oxygen species ameliorate experimental
cryptosporidiosis in the neonatal BALB/ c mouse model. Infect Immun 67:5885–5891
Liew FY, Millott S, Parkinson C, Palmer RM, Moncada S (1990) Macrophage killing of Leish-
mania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol 144:4794–4797
Liew FY, Li Y, Moss D, Parkinson C, Rogers MV, Moncada S (1991) Resistance to Leishmania
major infection correlates with the induction of nitric oxide synthase in murine macrophages.
Eur J Immunol 21:3009–3014
Liu J, Enomoto S, Lancto CA, Abrahamsen MS, Rutherford MS (2008) Inhibition of apoptosis in
Cryptosporidium parvum-infected intestinal epithelial cells is dependent on survivin. Infect
Immun 76(8):3784–3792
Lovett JL, Sibley LD (2003) Intracellular calcium stores in Toxoplasma gondii govern invasion of
host cells. J Cell Sci 116:3009–3016
Lovett JL, Marchesini N, Moreno SN, Sibley LD (2002) Toxoplasma gondii microneme secretion
involves intracellular Ca(2+) release from inositol 1, 4, 5-triphosphate (IP(3))/ryanodine-
sensitive stores. J Biol Chem 277:25870–25876
Magalhaes LG, Machado CB, Morais ER, Moreira EB, Soares CS, da Silva SH, Da Silva Filho
AA, Rodrigues V (2009) In vitro schistosomicidal activity of curcumin against Schistosoma
mansoni adult worms. Parasitol Res 104:1197–1201
Mahady GB, Pendland SL, Yun G, Lu ZZ (2002) Turmeric (Curcuma longa) and curcumin inhibit
the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 22:4179–4181
Mangoyi R, Hayeshi R, Ngadjui B, Ngandeu F, Bezabih M, Abegaz B, Razafimahefa S, Rasoa-
naivo P, Mukanganyama S (2010) Glutathione transferase from Plasmodium falciparum –
Interaction with malagashanine and selected plant natural products. J Enzyme Inhib Med Chem
25:854–862
Martinelli A, Rodrigues LA, Cravo P (2008) Plasmodium chabaudi: efficacy of artemisinin +
curcumin combination treatment on a clone selected for artemisinin resistance in mice. Exp
Parasitol 119:304–307
Mulabagal V, Calderon AI (2010) Development of binding assays to screen ligands for Plasmo-
dium falciparum thioredoxin and glutathione reductases by ultrafiltration and liquid chroma-
tography/mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:987–993
Nadkarni KM (1976) Indian Materia Medica. Popular Prakashan, Bombay, p 1074
Nandakumar DN, Nagaraj VA, Vathsala PG, Rangarajan P, Padmanaban G (2006) Curcumin-
artemisinin combination therapy for malaria. Antimicrob Agents Chemother 50:1859–1860
150 Md. Shahiduzzaman and A. Daugschies
Negi PS, Jayaprakasha GK, Jagan L, Rao M, Sakariah KK (1999) Antibacterial activity of turmeric
oil: a byproduct from curcumin manufacture. J Agric Food Chem 47:4297–4300
Nesterenko MV, Woods K, Upton SJ (1999) Receptor/ligand interactions between Cryptosporid-
ium parvum and the surface of the host cell. Biochim Biophys Acta 1454:165–173
Nogueira de Melo AC, de Souza EP, Elias CG, dos Santos AL, Branquinha MH, vila-Levy CM,
dos Reis FC, Costa TF, Lima AP, de Souza Pereira MC, Meirelles MN, Vermelho AB (2010)
Detection of matrix metallopeptidase-9-like proteins in Trypanosoma cruzi. Exp Parasitol
125:256–263
Nose M, Koide T, Ogihara Y, Yabu Y, Ohta N (1998) Trypanocidal effects of curcumin in vitro.
Biol Pharm Bull 21:643–645
Ojcius DM, Perfettini JL, Bonnin A, Laurent F (1999) Caspase-dependent apoptosis during
infection with Cryptosporidium parvum. Microbes Infect 1(14):1163–1168
Okhuysen PC, DuPont HL, Sterling CR, Chappell CL (1994) Arginine aminopeptidase, an integral
membrane protein of the Cryptosporidium parvum sporozoite. Infect Immun 62:4667–4670
Okhuysen PC, Chappell CL, Kettner C, Sterling CR (1996) Cryptosporidium parvum metalloa-
minopeptidase inhibitors prevent in vitro excystation. Antimicrob Agents Chemother
40:2781–2784
Pe
´rez-Arriaga L, Mendoza-Magan
˜a ML, Corte
´s-Za
´rate R, Corona-Rivera A, Bobadilla-Morales L,
Troyo-Sanroma
´n R, Ramı
´rez-Herrera MA (2006) Cytotoxic effect of curcumin on Giardia
lamblia trophozoites. Acta Trop 98(2):152–161
Pinlaor S, Yongvanit P, Prakobwong S, Kaewsamut B, Khoontawad J, Pinlaor P, Hiraku Y (2009)
Curcumin reduces oxidative and nitrative DNA damage through balancing of oxidant–antiox-
idant status in hamsters infected with Opisthorchis viverrini. Mol Nutr Food Res
53:1316–1328
Pinlaor S, Prakobwong S, Hiraku Y, Pinlaor P, Laothong U, Yongvanit P (2010) Reduction of
periductal fibrosis in liver fluke-infected hamsters after long-term curcumin treatment. Eur J
Pharmacol 638:134–141
Pollok RC, McDonald V, Kelly P, Farthing MJ (2003) The role of Cryptosporidium parvum-
derived phospholipase in intestinal epithelial cell invasion. Parasitol Res 90:181–186
Rao CV, Rivenson A, Simi B, Reddy BS (1995) Chemoprevention of colon carcinogenesis by
dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 55:259–266
Rasmussen HB, Christensen SB, Kuist LP, Karazmi AA (2000) Simple and effective separation of
the curcumins, the antiprotozoal constituents of Curcuma longa. Planta Med 66:396–398
Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN (2005) Curcumin for
malaria therapy. Biochem Biophys Res Commun 326:472–474
Rider SD Jr, Zhu G (2009) An apicomplexan ankyrin-repeat histone deacetylase with relatives in
photosynthetic eukaryotes. Int J Parasitol 39:747–754
Ryu H, Gerrity D, Crittenden JC, Abbaszadegan M (2008) Photocatalytic inactivation of Crypto-
sporidium parvum with TiO(2) and low-pressure ultraviolet irradiation. Water Res
42:1523–1530
Saffer LD, Schwartzman JD (1991) A soluble phospholipase of Toxoplasma gondii associated
with host cell penetration. J Protozool 38:454–460
Saffer LD, Long Krug SA, Schwartzman JD (1989) The role of phospholipase in host cell
penetration by Toxoplasma gondii. Am J Trop Med Hyg 40:145–149
Saleheen D, Ali SA, Ashfaq K, Siddiqui AA, Agha A, Yasinzai MM (2002) Latent activity of
curcumin against leishmaniasis in vitro. Biol Pharm Bull 25:386–389
Shahiduzzaman M, Dyachenko V, Khalafalla RE, Desouky AY, Daugschies A (2009) Effects of
curcumin on Cryptosporidium parvum in vitro. Parasitol Res 105:1155–1161
Shapira S, Harb OS, Margarit J, Matrajt M, Han J, Hoffmann A, Freedman B, May MJ, Roos DS,
Hunter CA (2005) Initiation and termination of NF-kappaB signaling by the intracellular
protozoan parasite Toxoplasma gondii. J Cell Sci 118:3501–3508
Shen L, Ji HF (2007) Theoretical study on physicochemical properties of curcumin. Spectrochim
Acta A Mol Biomol Spec- trosc 67: 619–623
6 Curcumin: A Natural Herb Extract with Antiparasitic Properties 151
Shim JS, Kim JH, Cho HY, Yum YN, Kim SH, Park HJ, Shim BS, Choi SH, Kwon HJ (2003)
Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin.
Chem Biol 10:695–704
Shishodia S, Amin HM, Lai R et al (2005) Curcumin (diferuloylmethane) inhibits constitutive
NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis
in mantle cell lymphoma. Biochem Pharmacol 70:700–713
Srinivasan A, Menon VP (2003) Protection of pancreatic b-cell by the potential antioxidant
bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes.
J Pharm Pharm Sci 6:327–333
Sui Z,Salto R, Li J, Craik C,Ortiz de Montellano PR (1993) Inhibition of the HIV-1 and HIV-2 proteases
by curcumin and curcumin boron complexes. Bioorg Med Chem 1:415–422
Surh YJ (2002) Anti-tumor promoting potential of selected spice ingredients with antioxidative
and anti-inflammatory activities: a short review. Food Chem Toxicol 40:1091–1097
Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK (2003) Curcumin, the major
component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-
induced colitis. Br J Pharmacol 139:209–218
Varez-Rueda N, Biron M, Le PP (2009) Infectivity of Leishmania mexicana is associated with
differential expression of protein kinase C-like triggered during a cell-cell contact. PLoS
One 4:7581
152 Md. Shahiduzzaman and A. Daugschies
... The antiparasitic effect of curcumin, which is one of the active compounds in Curcuma longa has been observed to be dose-dependent, with higher concentrations of the compounds exhibiting the greatest effects. However, the exact mechanism of its action is still poorly understood and need to be studied in more detail [4]. Curcumin extract has been found to be effective against Shistosoma mansoni and earthworm muscle cells in a dose-dependent manner [5,6]. ...
... Curcumin is a natural polyphenol that is responsible for antiproliferative activity on dividing cells; this activity may have caused the muscle growth suppression in earthworm. Although the antiparasitic effect of curcumin is more obvious at a higher concentration, the exact mechanism of action is not yet fully understood and may vary depending on the helminth parasite [4]. ...
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... It is also known for its anti-infl ammatory effects as it selectively inhibits the expression of cyclooxygenase-2 (COX-2) enzyme mRNA (Goel et al., 2001). Additional targets of curcumin include growth factors and their receptors, enzymes, cytokines and cell signaling pathways (Shahiduzzaman and Daugschies, 2011). Moreover, curcumin targets factors that promote angiogenesis such as vascular endothelial growth fatcor (VEGF), fi broblast growth factor (FGF) and matrix metalloproteinases (MMPs) (Wang and Chen, 2019). ...
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... 107 Curcumin inhibits intracellular adhesion molecules that lead to Toxoplasma sequestration and development and is correlated to the P. falciparum glutathione transferase [PfGST] chloroquine resistance. 108 Therefore, curcumin is a powerful PfGST inhibitor that can open up alternative prospects for drug resistance management in malaria. Thus, thioredoxin reductase inhibition by curcumin can reduce parasite proliferation, which is beneficial for control strategies. ...
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Turmeric (Curcuma longa L.) is a spice utilized widely in India, China, and Southeast Asia as an aromatic stimulant, a food preservative, and coloring material. The commonly used names of turmeric are castor saffron, turmeric, and saffron root. Turmeric is a yellow–orange polyphenolic natural substance derived from C. longa rhizomes. It has been used to treat common inflammatory diseases, tumors, biliary diseases, anorexia, cough, topical wounds, diabetic injuries, liver disorders, rheumatism, and sinusitis. Extensive studies on the biological properties and pharmacological consequences of turmeric extracts have been conducted in recent years. Curcumin, the primary yellow biocomponent of turmeric, has anti-inflammatory, antioxidant, anticarcinogenic, antidiabetic, antibacterial, antiprotozoal, antiviral, antifibrotic, immunomodulatory, and antifungal properties. Defense assessment tests showed that curcumin is well tolerated at high doses, without adverse effects. Thus, curcumin is a highly active biological material with the potential to treat different diseases in modern medicine. This current review article focuses on curcumin's biological characteristics. Additionally, the most popular methods for curcumin encapsulation are discussed. Several effective techniques and approaches have been proposed for curcuminoid capsulation, including nanocomplexing, gelation, complex coacervation, electrospraying, and solvent-free pH-driven encapsulation. This review also highlights curcumin's chemical properties, allowing the readers to expand their perspective on its use in the development of functional products with health-promoting properties. This article is protected by copyright. All rights reserved.
... As a natural product of a tropical plant, curcumin also has a great potential as a drug against infections and tropical diseases [8,9]. It was tested against various protozoal parasites and it showed activity against Leishmania, Plasmodia and Toxoplasma species [10,11]. Curcumin and certain metal complexes of it displayed activity against Leishmania major [12]. ...
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... are not completely understood, more investigations are needed to clarify its actual therapeutic effects (Shahiduzzaman et al., 2009;Shahiduzzaman and Daugschies, 2011). Previous studies have confirmed that Cryptosporidium is sensitive to curcumin even more than other protozoan parasites such as Giardia and Plasmodium (Shahiduzzaman et al., 2009). ...
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... Kurkumin merupakan senyawa polifenolik hidrofobik yang salah satunya terdapat pada rhizoma tanaman Curcuma longa Linn. Senyawa ini memiliki aktivitas farmakologi yang luas seperti antiinflamasi,anti mutagenik, anti oksidan, anti kanker (Maheswari dkk., 2006), anti mikroba (De dkk., 2009), dan anti parasit (Shahiduzzaman dan Daugschies, 2011). Senyawa ini terbukti memiliki aktivitas antiinflamasi (Majeed dkk.,1995) dan bersifat selektif menghambat COX-2 (Zhang dkk., 1999).Oleh karena itu, kurkumin merupakan senyawa potensial sebagai agen antiinflamasi yang lebih aman dibandingkan Obat Antiinflamasi Non Steroid (OAINS)yang bersifat non selektif, seperti ibuprofen dan piroksikam, yang memiliki efek samping gastrointestinal seperti perforasi, perdarahan lambung dan duodenal, dispepsia, serta nyeri abdomen (Vane dan Botting, 1996). ...
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Curcumin (Cur), a well-known dietary pigment derived from Curcuma longa, is a promising anticancer drug, but its in vivo target molecules remain to be clarified. Here we report that exposure of human hepatoma cells to Cur led to a significant decrease of histone acetylation. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the enzymes controlling the state of histone acetylation in vivo. Cur treatment resulted in a comparable inhibition of histone acetylation in the absence or presence of trichostatin A (the specific HDAC inhibitor), and showed no effect on the in vitro activity of HDAC. In contrast, the domain negative of p300 (a most potent HAT protein) could block the inhibition of Cur on histone acetylation; and the Cur treatment significantly inhibited the HAT activity both in vivo and in vitro. Thus, it is HAT, but not HDAC that is involved in Cur-induced histone hypoacetylation. At the same time, exposure of cells to low or high concentrations of Cur diminished or enhanced the ROS generation, respectively. And the promotion of ROS was obviously involved in Cur-induced histone hypoacetylation, since Cur-caused histone acetylation and HAT activity decrease could be markedly diminished by the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) or their combination, but not by their heat-inactivated forms. The data presented here prove that HAT is one of the in vivo target molecules of Cur; through inhibiting its activity, Cur induces histone hypoacetylation in vivo, where the ROS generation plays an important role. Considering the critical roles of histone acetylation in eukaryotic gene transcription and the involvement of histone hypoacetylation in the lose of cell viability caused by high concentrations of Cur, these results open a new door for us to further understand the molecular mechanism involved in the in vivo function of Cur.
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Toxoplasma gondii crosses non-permissive biological barriers such as the intestine, the blood-brain barrier and the placenta thereby gaining access to tissues where it most commonly causes severe pathology. Herein we show that in the process of migration Toxoplasma initially concentrates around intercellular junctions and probably uses a paracellular pathway to transmigrate across biological barriers. Parasite transmigration required viable and actively motile parasites. Interestingly, the integrity of host cell barriers was not altered during parasite transmigration. As intercellular adhesion molecule 1 (ICAM-1) is upregulated on cellular barriers during Toxoplasma infection, we investigated the role of this receptor in parasite transmigration. Soluble human ICAM-1 and ICAM-1 antibodies inhibited transmigration of parasites across cellular barriers implicating this receptor in the process of transmigration. Furthermore, human ICAM-1 immunoprecipitated the mature form of the parasite adhesin MIC2 present on the parasite surface, indicating that this interaction may contribute to cellular migration. These findings reveal that Toxoplasma exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues.
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Curcumin (1) an important yellow dye isolated from Curcuma longa rhizomes, exhibits a variety of pharmacological effects such as anti-inflammatory antioxidant and antiviral activity. Ten curcuminoids (2-11) were synthesized by the condensation of 2,4-pentanedione with differently substituted benzaldehydes, using the boron complex approach, which avoided Knoevenagel condensation at C-3 of the diketone. The curcuminoids were assayed in vitro against Leishmania amazonensis promastigotes using pentamidine isethionate (CAS 140-64-7) as the reference drug. Compound (5) 1,7-bis-(2-hydroxy-4-methoxyphenyl)-1,6- heptadiene-3,5-dione) was the most effective.
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PURPOSE. To evaluate the antioxidant defense by bis-o-hydroxycinnamoylmethane, analogue of the naturally occurring curcuminoid bis-demethoxycurcumin in streptozotocin induced diabetes in male Wistar rats and its possible protection of pancreatic cell against gradual loss under diabetic condition. METHODS. Male wistar rats were divided into five groups. Group1 served as control rats. Group2 was control rats treated intragastrically with bis-o-hydroxycinnamoyl methane at a dose of 15mg/kg body weight for 45 days. Group3, 4 and 5 rats were injected with 40mg/kg body weight of streptozotocin to induce diabetes. Group4 rats were treated with the drug similar to group2 and group5 rats treated with the reference drug glibenclamide intragastrically for a similar period. After 45 days, the levels of plasma glucose, glycated hemoglobin, enzymic antioxidants ( SOD, CAT) and non-enzymic antioxidants Vit C, Vit E was determined. Histopathological sections of the pancreas were examined. RESULTS. The levels of plasma glucose and glycated hemoglobin which were elevated in group3 diabetic rats were reduced after treatment with the drug. The antioxidant levels showed an increase in the case of treated diabetic rats as compared to group3 diabetic rats. The islets were shrunken in group3 diabetic rats in comparison to normal rats. In the treated diabetic rats there was expansion of islets. CONCLUSIONS. The experimental drug bis-o-hydroxycinnamoylmethane enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects the pancreatic beta-cell against loss and exhibits antidiabetic property.
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A new curcuminoid, cyclocurcumin (IV), was isolated from the nematocidally active fraction of turmeric, the rhizome of Curcuma longa, together with three known curcuminoids, curcumin (I), demethoxycurcumin (II) and bisdemethoxycurcumin (III). The structure of IV was elucidated on the basis of spectral data and confirmed by the partial synthesis from curcumin (I). Although the above curcuminoids were ineffective when they were applied independently, the nematocidal activity increased remarkably when they were mixed, suggesting a synergistic action between them.
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The in vitro schistosomicidal activity of curcumin (doses ranging from 5 to 100μM) was carried out against Schistosoma mansoni adult worms. Curcumin (at 50 and 100μM) caused death of all worms. When tested at the doses of 5 and 20μM, it decreased the worm viability in comparison with negative (Roswell Memorial Park Institute (RPMI) 1640 medium alone or RPMI 1640 medium with 10% dimethyl sulfoxide) and positive (heat-killed worms at 56°C or praziquantel 10μM) control groups. All pairs of coupled adult worms were separated into individual male and female by the action of curcumin at the doses of 20 to 100μM. When tested at 5 and 10μM, curcumin reduced egg production by 50% in comparison with the positive control group. It is the first time that the schistosomicidal activity has been reported for curcumin.