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Review

    Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease
    Angélica M. González Sánchez – University of Puerto Rico at Cayey
    __________________________________________________________________

    Abstract
            Inflammatory bowel disease (IBD) is one of the most serious diseases of the
    gastrointestinal tract. Although its causes are not well known, it has been linked to a deregulation
    on the molecules that control stress response in the intestinal tissue. These uncontrolled
    molecules cause severe inflammation in the intestine as an immune response to stress. Curcumin
    is a natural herb-derived compound commonly used for cooking and as an organic remedy for
    common illnesses. Recent researches have shown a relationship between curcumin and IBD. It
    has been concluded that curcumin has a direct effect on regulating the molecules that are
    decontrolled in IBD intestinal tissue. The reasons why curcumin does this are not thoroughly
    understood by the scientific community, but they have been linked to its antioxidant properties,
    as well as to its capacity to bind to several proteins and enzymes. More research needs to be done
    in order to fully comprehend curcumin’s behavior, to establish its safe dosage, to increase its
    bioavailability and to prove it as a viable therapeutic alternative for IBD.
    ____________________________________________________________________________
    Keywords: Inflammatory Bowel Disease (IBD) / curcumin / stress-response pathways / NF-κB
    / cytokines / chemokines / white blood cells / p38 MAPK / MPO / antioxidant / bioavailability.

     Introduction
        Inflammatory bowel disease (IBD) is an           causes a stress response and leads to IBD, it is
acute syndrome on which the gastrointestinal             thought that it arises from uncontrolled
wall suffers severe inflammation. Its causes             pathways of molecules related to the immune
remain unknown, although recent investigations           system (Salh et al., 2003).
have linked it to genetic, environmental and                     Intestinal mucosa has several functions,
immunological factors, which are the most                mostly on absorbing nutrients and on protecting
prominent ones (Pithadia and Jain, 2011). Even           the organism from infections. When swollen,
though it is a rare condition statistically (Jian et     this mucosal doesn’t work as it’s supposed to,
al., 2005), its implications on people’s quality of      leading to mayor complications. Some of these
life make it a huge and relevant field for               complications can be reflected as severe
investigations.                                          symptoms such as abdominal pain, ulcers,
        Despite origins of IBD are uncertain, its        bleeding diarrhea, weight loss due to the
main source is the inflammation of the intestinal        diarrhea, anemia, between others. Other
mucosa. Because inflammation is almost always            conditions have also been associated to side
linked to an immune response, analysis of IBD            effects of IBD, such as osteoporosis, arthritis,
has focused on stress-response causes. Since             skin rashes, liver disease and colon cancer. IBD
there haven’t been found any pathogen that               rarely causes death on its own, but some of its



    November 2011
Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease



complications, such as extreme diarrhea and              the herb Curcuma longa. It can take many
anemia can cause weakness of the organism,               chemical structures, called curcuminoids
which can make it susceptible to other illnesses.        (Anand et al., 2008), but its main constituents
        IBD can be divided into two main types:          always are several hydroxyl radicals (HO),
Ulcerative colitis and Crohn’s disease. Both of          hydroxide ions (OH-), oxides (O2), methyl
these share the characteristic inflammation of           (CH3) and methoxides (CH3O-) groups which
the intestinal mucosa but they differ on the             join together forming rings which make the
specific areas of the intestinal tract that they         compound a hydrophobic polyphenol. It has
affect. While Ulcerative colitis affects only the        been traditionally used in foods as a component
colon, Crohn’s disease can affect any area from          of the spice turmeric and as an herbal remedy
the gastrointestinal tract, especially the lowest        for several illnesses because polyphenols are
part of the small intestine, called the ileum.           known to be natural antioxidants (Rajasekaran,
        Actual treatments for IBD focus on               2011). Since its first documented use as a
lessening and delaying the symptoms of the               medical treatment in 1937 (Srivastava et al.,
condition, but not necessarily on effectively            2011), curcumin has revealed antioxidant, anti-
transposing the causes of the inflammation,              inflammatory,       antimicrobial     and      anti-
which will be described further on. Most of              carcinogenic activities (Anand et al., 2008).
them consist on anti-inflammatory medicines              Exactly how curcumin accomplishes these
and       immune-suppressors,          such       as     duties is not well known. However, it has been
aminosalicylates,      monoclonal        antibodies,     linked to its ability to bind to several proteins
corticosteroids, antibiotics, between others.            and regulatory enzymes and to inhibit oxidation
These treatments have been improving in the              chain reactions which can cause damage or
last decades by the development of targeted              death to the cell by activating multiple
biologic therapies, the optimization of older            intracellular signaling pathways (Srivastava et
therapies, and a better understanding of the             al., 2011). That way, curcumin regulates the
mucosal immune system involved in the                    presence of several molecules, which in turn
pathogenesis of IBD (Pithadia and Jain, 2011).           control a great number of cellular processes
However, these therapies are still very                  especially stress response. The regulation of
unspecific, meaning that they would treat some           these molecules, which are mostly transcription
of the symptoms but others might remain                  factors, enzymes and proteins, is directly related
untreated. They also cause lots of side effects, as      to immunity and inflammation. That’s why
for example steroid dependence, anaphylaxis              curcumin has been linked to the treatment of
and pancreatitis. These treatments are vastly            immune and inflammatory diseases, such as
expensive too. That’s why new, more accessible           IBD.
and natural therapies for IBD are needed                         This paper is intended to present the
currently.                                               relationship between curcumin and IBD and
        A new therapeutic approach for IBD that          why it is considered a potential treatment for
has been studied since decades ago is the use of         this condition. It will do so by presenting studies
curcumin. This compound, also called                     that have proved its benefits and its limitations
diferuloylmethane, is obtained from the roots of         as a therapeutic alternative.




November 2011                                                                                              2
Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease



Macroscopic effects of curcumin on IBD                 inflammation and eventual elimination of
        As shown by several studies of rat             disease-causing agents. They are mostly present
models with induced IBD, curcumin effectively          in T helper cells, which are a type of white
counteracts many of the effects of IBD in many         blood cell. When well regulated, cytokines and
ways. On the rat colitis models, it showed             chemokines contribute to the health of the
tangible effects out of the intestine were an          organism and help to maintain a balance on
increase in the rate of survival and weight gain       inflammation. As for example, for cytokines
were noticeable (Jian et al., 2005) (Salh et al.,      there are both inflammatory and anti-
2003). Curcumin also caused a decrease in the          inflammatory ones. The inflammatory ones,
inflammation of the intestinal tissues. The            such as interleukin-1 beta (IL-1β), activate at
studies concluded that all of these macroscopic        any threatening signal, but when the attack is
effects are directly related to microscopic            counteracted, the anti-inflammatory ones, such
processes of the cell (see Figure 2).                  as interleukin-10 (IL-10), activate and make the
                                                       tissue go back to normal. Chemokines are
Deregulated molecules in IBD                           responsible for sending signals to alert on the
        There are several proteins and                 presence of foreign agents, therefore inducing
transcription factors that are responsible of          the production of leucocytes (white blood cells),
regulating immunity in the intestines and,             especially macrophages to engulf them. After
therefore, they are in charge of protecting it         the pathogen is eliminated, the signaling stops.
from external damaging agents or pathogens.                    On IBD, NF-κB binding activity is
When appropriately regulated, these proteins           increased, which leads to a rise in the immune
and transcription factors help on the well-            and      inflammatory     response      by     the
functioning of the intestinal tract and normal         overproduction of cytokines and chemokines.
protection given by the intestinal mucosa.             Therefore, in inflammatory bowel disease
However, when deregulated they can cause an            chemokines are up-regulated and provide a
uncontrollable inflammation in the tissue with         continuous signal for the production of white
no apparent cause. This happens because the            blood cells, which results on inflammation (Jian
overproduction or underproduction of these             et al., 2005).       Equally, pro-inflammatory
agents alters normal cell pathways, as those           cytokines are highly expressed in IBD, while
related to immunity, which are stress-response         anti-inflammatory cytokines are at low rates
pathways. This occurs on IBD (see Figure 1).           (Salh et al., 2003).
        One of the transcription factors whose                 There are other deregulated proteins in
presence is not normal in the intestinal tissue        IBD that alter pathways related to intrusion, also
and mucosa of IBD patients is the nuclear factor       called stress-responsive signaling pathways.
kappa-light-chain-enhancer of activated B cells        One of them is the mitogen-activated protein
(NF-κB). This factor binds to the DNA to               kinase 38 (p38 MAPK) which, under stress,
produce proteins such as cytokines and                 helps to produce lymphocytes (a type of white
chemokines. These proteins are responsible of          blood cell), cyclooxygenases and lipoxygenases.
detecting foreign cells and pathogens, creating        These lasts ones are enzymes responsible of
an immune response which can result in                 modulating inflammation by the production of a




November 2011                                                                                          3
Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease



  hormone called prostaglandin. This p38 MAPK            Microscopic effects of curcumin on IBD
  also secretes chemokines, as does NF-κB. In the
  case of IBD, p38 MAPK is over-activated,
  which leads to an overproduction of
  lymphocytes, chemokines, cyclooxygenases and
  lipoxygenases (Srivastava et al., 2011),
  consequently causing extreme inflammation.
          Because of the huge presence of white
  blood cells in the intestinal tissues of IBD
  patients, there’s also an over-expression of
  myeloperoxidase (MPO) in IBD (Salh et al.,
  2003). MPO is a peroxidase enzyme present in
  neutrophil granulocytes, a type of white blood
  cells. This enzyme produces hypoclorous acid
  radical and the amino acid tyrosyl radical upon
  oxidation. In other words, the oxidation of MPO                                           Figure 2: Summary
  causes the formation of highly reactive                                                   of the macroscopic
  molecules with negative charge which are used                                             and microscopic
  by the neutrophils to kill bacteria and other                                             effects of curcumin
  pathogens when they are well-regulated. When                                              on IBD.
  they are not well-regulated, they can run free in
  the body and cause many reactions that might
  lead to aging, degenerative diseases, and cancer.              Most of the recent researches on
                                                         curcumin have concluded that it displays
Figure 1: Summary of
                                                         immunomodulatory         activity   upon      the
the deregulated
                                                         deregulation of molecules on IBD (Srivastava et
molecules responsible for
                                                         al., 2011). It has shown to regulate the NF-κB
inflammation on IBD.
                                                         pathway and to suppress its binding activity.
                                                         Therefore, it has functioned to reduce IL-1β
                                                         expression and to increase IL-10 expression
                                                         (Rajasekaran, 2011). As a consequence it
                                                         inhibits the proliferation of macrophages and
                                                         other types of white blood cells. Curcumin is
                                                         also useful on diminishing the activation of p38
                                                         MAPK, therefore controlling the production of
                                                         lymphocytes,         cyclooxygenases         and
                                                         lipoxygenases. The ways by which curcumin
                                                         achieves all these activities are still not well
                                                         known, but there are being studies conducted
                                                         about it (Srivastava et al., 2011). It has been




  November 2011                                                                                         4
Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease



preliminarily linked to curcumin’s ability on           suitable     environment      for     curcumin’s
binding to several proteins and enzymes.                transference. By adding itself to curcumin it can
        Finally, curcumin has presented an effect       therefore promote its absorbance because of its
on the offsetting of myeloperoxidase activity           lipophilic-hydrophobic inside and hydrophilic
because of its antioxidant properties (Salh et al.,     outside (Yadav et al., 2009). Other
2003). As an antioxidant, curcumin functions to         investigations have proposed to block
inhibit the oxidation of MPO by oxidizing itself,       curcumin’s metabolic pathways, to improve its
therefore preventing free radicals from running         effective transportation through the body with
freely in the body and reducing the oxidation           the use of new nanoparticle systems and to
chain reactions.                                        encapsulate the compound (Rajasekaran, 2011).
                                                        More development still has to be done to reach
Curcumin’s usage and limitations                        curcumin’s enhancement.
        Actual reviews on curcumin’s effective          Figure 3:
concentration dose reveal some ambiguity.               Curcumin’s
While ones say that it has shown to be safe at          limitations
very high doses (Anand et al., 2008), other             as a
studies imply that it’s effective and safe dosages      therapeutic
can vary upon the type of cell treated. For some        alternative
cells it might be toxic at high concentrations,         for IBD.
and for others not (Srivastava et al., 2011).
Further investigations need to be done to define
at which concentration curcumin’s functionality
increases and is secure enough for human
consumption. That might be one of the reasons
why curcumin isn’t commonly used for
therapeutic purposes.                                   Conclusion
        Another limitation of curcumin has been                 Although not so many researches have
proved to be its low oral bioavailability due to        been accomplished on relating curcumin to IBD,
its poor solubility and rapid metabolism                most of them have shown similar conclusions
(Rajasekaran, 2011). Bioavailability is the             on its proactivity on this disease. Not all of them
amount of substance that is really absorbed and         have concluded curcumin’s effects in all the
used by an organism when the substance, mostly          same molecules and pathways, but all of them
a drug, is introduced into the body. Recent             have related its outcomes on its regulatory
research has shown that curcumin’s low                  properties. Moreover, it can be concluded that
bioavailability is compensable by making                curcumin is a good modulator of the appropriate
certain modifications to the compound. One of           quantities of molecules needed for stress
those modifications can be making an inclusion          response. Since IBD has been linked to a
complex between curcumin and a soluble                  deregulation on the stress response pathways,
compound, such as cyclodextrin (CD). This               curcumin’s therapeutic effects on IBD have
complex is very soluble and can create a                been observable. However, we can determine



November 2011                                                                                            5
Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease



that there are still many aspects about curcumin         Pithadia A, Jain S. 2011. Treatment of inflammatory
that aren’t well comprehended (see Figure 3).            bowel disease (IBD). Pharmacological Reports.
We conclude that additional research is                  63(1):629-642.
necessary. Eventually, as more research on this          Rajasekaran S. 2011. Therapeutic potential of
                                                           curcumin in gastrointestinal diseases. World
topic is promoted, curcumin’s use would be
                                                           Journal of Gastrointestinal Pathophysiology. 2(1):
better understood and it will probably be able to
                                                           1-14.
function as an alternative treatment for IBD.
                                                         Salh B, Assi K, Templeman V, Parhar K, Owen D,
                                                           Gómez A, Jacobson K. 2003. Curcumin attenuates
References                                                 DNB-induced murine colitis. American Journal of
Anand P, Thomas S, Kunnumakkara A, Sundaram                Physiology Gastrointestinal and Liver Physiology.
 C, Harikumar K, Sung B, Tharakan S, Misra K,              285:G235-G243.
 Priyadarsini I, Rajasekharan K, Aggarwal B. 2008.
 Biological activities of curcumin and its analogues     Srivastava R, Singh S, Dubey S, Misra K, Khar A.
 (Congeners) made by man and Mother Nature.                2011. Immunomodulatory and therapeutic activity
 Biochemical Pharmacology Journal. 76(1):1590-             of curcumin. International Immunopharmacology
 1611.                                                     Journal. 11(1):331-341.

Jian Y, Mai G, Wang J, Zhang Y, Luo R, Fang Y.           Yadav V, Suresh S, Devi K, Seema Y. 2009. Effect
  2005. Preventive and therapeutic effects of NF-         of Cyclodextrin Complexation of Curcumin on its
  kappaB inhibitor curcumin in rats colitis induced       Solubility and Antiangiogenic and Anti-
  by trinitrobenzene sulfonic acid. World Journal of      inflammatory Activity in Rat Colitis Model.
  Gastroenterology. 11(12):1747-1752.                     AAPS PharmSciTech. 10(3):752-762.




November 2011                                                                                              6

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Review paper angelica

  • 1. Review Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease Angélica M. González Sánchez – University of Puerto Rico at Cayey __________________________________________________________________ Abstract Inflammatory bowel disease (IBD) is one of the most serious diseases of the gastrointestinal tract. Although its causes are not well known, it has been linked to a deregulation on the molecules that control stress response in the intestinal tissue. These uncontrolled molecules cause severe inflammation in the intestine as an immune response to stress. Curcumin is a natural herb-derived compound commonly used for cooking and as an organic remedy for common illnesses. Recent researches have shown a relationship between curcumin and IBD. It has been concluded that curcumin has a direct effect on regulating the molecules that are decontrolled in IBD intestinal tissue. The reasons why curcumin does this are not thoroughly understood by the scientific community, but they have been linked to its antioxidant properties, as well as to its capacity to bind to several proteins and enzymes. More research needs to be done in order to fully comprehend curcumin’s behavior, to establish its safe dosage, to increase its bioavailability and to prove it as a viable therapeutic alternative for IBD. ____________________________________________________________________________ Keywords: Inflammatory Bowel Disease (IBD) / curcumin / stress-response pathways / NF-κB / cytokines / chemokines / white blood cells / p38 MAPK / MPO / antioxidant / bioavailability. Introduction Inflammatory bowel disease (IBD) is an causes a stress response and leads to IBD, it is acute syndrome on which the gastrointestinal thought that it arises from uncontrolled wall suffers severe inflammation. Its causes pathways of molecules related to the immune remain unknown, although recent investigations system (Salh et al., 2003). have linked it to genetic, environmental and Intestinal mucosa has several functions, immunological factors, which are the most mostly on absorbing nutrients and on protecting prominent ones (Pithadia and Jain, 2011). Even the organism from infections. When swollen, though it is a rare condition statistically (Jian et this mucosal doesn’t work as it’s supposed to, al., 2005), its implications on people’s quality of leading to mayor complications. Some of these life make it a huge and relevant field for complications can be reflected as severe investigations. symptoms such as abdominal pain, ulcers, Despite origins of IBD are uncertain, its bleeding diarrhea, weight loss due to the main source is the inflammation of the intestinal diarrhea, anemia, between others. Other mucosa. Because inflammation is almost always conditions have also been associated to side linked to an immune response, analysis of IBD effects of IBD, such as osteoporosis, arthritis, has focused on stress-response causes. Since skin rashes, liver disease and colon cancer. IBD there haven’t been found any pathogen that rarely causes death on its own, but some of its November 2011
  • 2. Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease complications, such as extreme diarrhea and the herb Curcuma longa. It can take many anemia can cause weakness of the organism, chemical structures, called curcuminoids which can make it susceptible to other illnesses. (Anand et al., 2008), but its main constituents IBD can be divided into two main types: always are several hydroxyl radicals (HO), Ulcerative colitis and Crohn’s disease. Both of hydroxide ions (OH-), oxides (O2), methyl these share the characteristic inflammation of (CH3) and methoxides (CH3O-) groups which the intestinal mucosa but they differ on the join together forming rings which make the specific areas of the intestinal tract that they compound a hydrophobic polyphenol. It has affect. While Ulcerative colitis affects only the been traditionally used in foods as a component colon, Crohn’s disease can affect any area from of the spice turmeric and as an herbal remedy the gastrointestinal tract, especially the lowest for several illnesses because polyphenols are part of the small intestine, called the ileum. known to be natural antioxidants (Rajasekaran, Actual treatments for IBD focus on 2011). Since its first documented use as a lessening and delaying the symptoms of the medical treatment in 1937 (Srivastava et al., condition, but not necessarily on effectively 2011), curcumin has revealed antioxidant, anti- transposing the causes of the inflammation, inflammatory, antimicrobial and anti- which will be described further on. Most of carcinogenic activities (Anand et al., 2008). them consist on anti-inflammatory medicines Exactly how curcumin accomplishes these and immune-suppressors, such as duties is not well known. However, it has been aminosalicylates, monoclonal antibodies, linked to its ability to bind to several proteins corticosteroids, antibiotics, between others. and regulatory enzymes and to inhibit oxidation These treatments have been improving in the chain reactions which can cause damage or last decades by the development of targeted death to the cell by activating multiple biologic therapies, the optimization of older intracellular signaling pathways (Srivastava et therapies, and a better understanding of the al., 2011). That way, curcumin regulates the mucosal immune system involved in the presence of several molecules, which in turn pathogenesis of IBD (Pithadia and Jain, 2011). control a great number of cellular processes However, these therapies are still very especially stress response. The regulation of unspecific, meaning that they would treat some these molecules, which are mostly transcription of the symptoms but others might remain factors, enzymes and proteins, is directly related untreated. They also cause lots of side effects, as to immunity and inflammation. That’s why for example steroid dependence, anaphylaxis curcumin has been linked to the treatment of and pancreatitis. These treatments are vastly immune and inflammatory diseases, such as expensive too. That’s why new, more accessible IBD. and natural therapies for IBD are needed This paper is intended to present the currently. relationship between curcumin and IBD and A new therapeutic approach for IBD that why it is considered a potential treatment for has been studied since decades ago is the use of this condition. It will do so by presenting studies curcumin. This compound, also called that have proved its benefits and its limitations diferuloylmethane, is obtained from the roots of as a therapeutic alternative. November 2011 2
  • 3. Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease Macroscopic effects of curcumin on IBD inflammation and eventual elimination of As shown by several studies of rat disease-causing agents. They are mostly present models with induced IBD, curcumin effectively in T helper cells, which are a type of white counteracts many of the effects of IBD in many blood cell. When well regulated, cytokines and ways. On the rat colitis models, it showed chemokines contribute to the health of the tangible effects out of the intestine were an organism and help to maintain a balance on increase in the rate of survival and weight gain inflammation. As for example, for cytokines were noticeable (Jian et al., 2005) (Salh et al., there are both inflammatory and anti- 2003). Curcumin also caused a decrease in the inflammatory ones. The inflammatory ones, inflammation of the intestinal tissues. The such as interleukin-1 beta (IL-1β), activate at studies concluded that all of these macroscopic any threatening signal, but when the attack is effects are directly related to microscopic counteracted, the anti-inflammatory ones, such processes of the cell (see Figure 2). as interleukin-10 (IL-10), activate and make the tissue go back to normal. Chemokines are Deregulated molecules in IBD responsible for sending signals to alert on the There are several proteins and presence of foreign agents, therefore inducing transcription factors that are responsible of the production of leucocytes (white blood cells), regulating immunity in the intestines and, especially macrophages to engulf them. After therefore, they are in charge of protecting it the pathogen is eliminated, the signaling stops. from external damaging agents or pathogens. On IBD, NF-κB binding activity is When appropriately regulated, these proteins increased, which leads to a rise in the immune and transcription factors help on the well- and inflammatory response by the functioning of the intestinal tract and normal overproduction of cytokines and chemokines. protection given by the intestinal mucosa. Therefore, in inflammatory bowel disease However, when deregulated they can cause an chemokines are up-regulated and provide a uncontrollable inflammation in the tissue with continuous signal for the production of white no apparent cause. This happens because the blood cells, which results on inflammation (Jian overproduction or underproduction of these et al., 2005). Equally, pro-inflammatory agents alters normal cell pathways, as those cytokines are highly expressed in IBD, while related to immunity, which are stress-response anti-inflammatory cytokines are at low rates pathways. This occurs on IBD (see Figure 1). (Salh et al., 2003). One of the transcription factors whose There are other deregulated proteins in presence is not normal in the intestinal tissue IBD that alter pathways related to intrusion, also and mucosa of IBD patients is the nuclear factor called stress-responsive signaling pathways. kappa-light-chain-enhancer of activated B cells One of them is the mitogen-activated protein (NF-κB). This factor binds to the DNA to kinase 38 (p38 MAPK) which, under stress, produce proteins such as cytokines and helps to produce lymphocytes (a type of white chemokines. These proteins are responsible of blood cell), cyclooxygenases and lipoxygenases. detecting foreign cells and pathogens, creating These lasts ones are enzymes responsible of an immune response which can result in modulating inflammation by the production of a November 2011 3
  • 4. Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease hormone called prostaglandin. This p38 MAPK Microscopic effects of curcumin on IBD also secretes chemokines, as does NF-κB. In the case of IBD, p38 MAPK is over-activated, which leads to an overproduction of lymphocytes, chemokines, cyclooxygenases and lipoxygenases (Srivastava et al., 2011), consequently causing extreme inflammation. Because of the huge presence of white blood cells in the intestinal tissues of IBD patients, there’s also an over-expression of myeloperoxidase (MPO) in IBD (Salh et al., 2003). MPO is a peroxidase enzyme present in neutrophil granulocytes, a type of white blood cells. This enzyme produces hypoclorous acid radical and the amino acid tyrosyl radical upon oxidation. In other words, the oxidation of MPO Figure 2: Summary causes the formation of highly reactive of the macroscopic molecules with negative charge which are used and microscopic by the neutrophils to kill bacteria and other effects of curcumin pathogens when they are well-regulated. When on IBD. they are not well-regulated, they can run free in the body and cause many reactions that might lead to aging, degenerative diseases, and cancer. Most of the recent researches on curcumin have concluded that it displays Figure 1: Summary of immunomodulatory activity upon the the deregulated deregulation of molecules on IBD (Srivastava et molecules responsible for al., 2011). It has shown to regulate the NF-κB inflammation on IBD. pathway and to suppress its binding activity. Therefore, it has functioned to reduce IL-1β expression and to increase IL-10 expression (Rajasekaran, 2011). As a consequence it inhibits the proliferation of macrophages and other types of white blood cells. Curcumin is also useful on diminishing the activation of p38 MAPK, therefore controlling the production of lymphocytes, cyclooxygenases and lipoxygenases. The ways by which curcumin achieves all these activities are still not well known, but there are being studies conducted about it (Srivastava et al., 2011). It has been November 2011 4
  • 5. Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease preliminarily linked to curcumin’s ability on suitable environment for curcumin’s binding to several proteins and enzymes. transference. By adding itself to curcumin it can Finally, curcumin has presented an effect therefore promote its absorbance because of its on the offsetting of myeloperoxidase activity lipophilic-hydrophobic inside and hydrophilic because of its antioxidant properties (Salh et al., outside (Yadav et al., 2009). Other 2003). As an antioxidant, curcumin functions to investigations have proposed to block inhibit the oxidation of MPO by oxidizing itself, curcumin’s metabolic pathways, to improve its therefore preventing free radicals from running effective transportation through the body with freely in the body and reducing the oxidation the use of new nanoparticle systems and to chain reactions. encapsulate the compound (Rajasekaran, 2011). More development still has to be done to reach Curcumin’s usage and limitations curcumin’s enhancement. Actual reviews on curcumin’s effective Figure 3: concentration dose reveal some ambiguity. Curcumin’s While ones say that it has shown to be safe at limitations very high doses (Anand et al., 2008), other as a studies imply that it’s effective and safe dosages therapeutic can vary upon the type of cell treated. For some alternative cells it might be toxic at high concentrations, for IBD. and for others not (Srivastava et al., 2011). Further investigations need to be done to define at which concentration curcumin’s functionality increases and is secure enough for human consumption. That might be one of the reasons why curcumin isn’t commonly used for therapeutic purposes. Conclusion Another limitation of curcumin has been Although not so many researches have proved to be its low oral bioavailability due to been accomplished on relating curcumin to IBD, its poor solubility and rapid metabolism most of them have shown similar conclusions (Rajasekaran, 2011). Bioavailability is the on its proactivity on this disease. Not all of them amount of substance that is really absorbed and have concluded curcumin’s effects in all the used by an organism when the substance, mostly same molecules and pathways, but all of them a drug, is introduced into the body. Recent have related its outcomes on its regulatory research has shown that curcumin’s low properties. Moreover, it can be concluded that bioavailability is compensable by making curcumin is a good modulator of the appropriate certain modifications to the compound. One of quantities of molecules needed for stress those modifications can be making an inclusion response. Since IBD has been linked to a complex between curcumin and a soluble deregulation on the stress response pathways, compound, such as cyclodextrin (CD). This curcumin’s therapeutic effects on IBD have complex is very soluble and can create a been observable. However, we can determine November 2011 5
  • 6. Curcumin’s Therapeutic Effects on Inflammatory Bowel Disease that there are still many aspects about curcumin Pithadia A, Jain S. 2011. Treatment of inflammatory that aren’t well comprehended (see Figure 3). bowel disease (IBD). Pharmacological Reports. We conclude that additional research is 63(1):629-642. necessary. Eventually, as more research on this Rajasekaran S. 2011. Therapeutic potential of curcumin in gastrointestinal diseases. World topic is promoted, curcumin’s use would be Journal of Gastrointestinal Pathophysiology. 2(1): better understood and it will probably be able to 1-14. function as an alternative treatment for IBD. Salh B, Assi K, Templeman V, Parhar K, Owen D, Gómez A, Jacobson K. 2003. Curcumin attenuates References DNB-induced murine colitis. American Journal of Anand P, Thomas S, Kunnumakkara A, Sundaram Physiology Gastrointestinal and Liver Physiology. C, Harikumar K, Sung B, Tharakan S, Misra K, 285:G235-G243. Priyadarsini I, Rajasekharan K, Aggarwal B. 2008. Biological activities of curcumin and its analogues Srivastava R, Singh S, Dubey S, Misra K, Khar A. (Congeners) made by man and Mother Nature. 2011. Immunomodulatory and therapeutic activity Biochemical Pharmacology Journal. 76(1):1590- of curcumin. International Immunopharmacology 1611. Journal. 11(1):331-341. Jian Y, Mai G, Wang J, Zhang Y, Luo R, Fang Y. Yadav V, Suresh S, Devi K, Seema Y. 2009. Effect 2005. Preventive and therapeutic effects of NF- of Cyclodextrin Complexation of Curcumin on its kappaB inhibitor curcumin in rats colitis induced Solubility and Antiangiogenic and Anti- by trinitrobenzene sulfonic acid. World Journal of inflammatory Activity in Rat Colitis Model. Gastroenterology. 11(12):1747-1752. AAPS PharmSciTech. 10(3):752-762. November 2011 6