Natural Products as Therapeutic Agents for Schistosomiasis
Sanaa Ahmed Ali
Schistosomiasis (known as Bilharziasis) is the disease caused by a blood born fluke (trematode) of the genus Schistosoma. The intermediate hosts of all digenetic trematodes are snails and schistosomes are no exception. Adult schistosome worms live in a mammalian host, Schistosomiasis is the second most prevalent tropical disease in Africa after malaria and is of great public health and socio-economic importance in the developing world. This study is to clarify that Natural product extracts with non-toxic medicinal properties should be explored for possible intervention in schistosomiasis as a disease involving impairment of metabolism of infected subjects. These inspire more hope for reducing the intensity of schistosomal infection by reduction in worm burden, ova count, granuloma size and number leading to improvement in histopathological picture of liver, spleen and kidney as a result of reducing inflammatory and fibrotic reactions of schistosoma.
April 13, 2010; Accepted: May 15, 2010;
Published: July 14, 2010
Schistosomiasis is the second most prevalent tropical disease in Africa after
malaria and is of great public health and socio-economic importance in the developing
world (Engles et al., 2002). Schistosoma mansoni-causative
agent of intestinal bilharzia-originated in Africa but was carried to South
America, with the slave trade; it is transmitted by snails of the genus Biomphalaria
snails (link). Schistosoma haematobium which causes urinary bilharzia
is transmitted by snails of the species Bulinus, which inhabit less permanent
water bodies (Ross et al., 2002). The third major
species of schistosome is S. japonicum, used to be widespread in Japan,
China and the Far East and was the cause of widespread and gross morbidity and
mortality. It affects not only man but also domestic and wild animals. S.
japonicum is transmitted by an amphibious snail (species Oncomelania)
which makes snail control relatively easy. There are two minor species of schistosomiais,
First, S. intercalatum which is confined to West Africa and lives in
the mesenteric vessels of man causing abdominal pain and bloody diarrhea. The
second is S. mekongi, which is another form of intestinal schistosoma
is found predominantly in Southeast Asia. The main reservoir for this species
is dogs (Reich and Fenwick, 2001) as shown in Table
LIFE CYCLE OF SCHISTOSOME
Schistosomiasis is a disease which is caused by various human-pathogenic trematodes
belonging to the genus Schistosoma, more than 200 million people at present
suffer from disease due to this parasitosis At the moment about 500-600 million
people in 74 countries, that is approximately a tenth of the world population,
are living with the risk of infection. Once in the human body, the cercariae
develop further to schistosomula, schistosomes have separate sexes) (Urbani
et al., 1997). Afterwards, the worms migrate upstream to their final
destination within the venules of the bladder, rectum or colon.
|| Illustrate the species of schistosomiasis; intermediate host;
form of the disease and endemic area of each species
|| The Schistosomiasis life cycle
Here, egg production starts (300 to 3000 day-1, depending on the
species) (Bergquist, 2002) as shown in Fig.
Inflammatory responses to the eggs lodged in the liver, bladder, or ureters
rather than the worms themselves that cause the principal pathology associated
with all forms of schistosomiasis (Davis et al.,
1999). The shape and size of the eggs of the three major schistosome species
are useful diagnostic features (Aka et al., 1999).
Eggs reaching the liver are too large to reach the sinusoidal plexus and accumulate
in presinusoidal venules within the portal triads, especially in the left lobe.
There they induce granulomatous inflammation, fibrosis, venous obstruction,
portal hypertension and splenomegaly (Stich et al.,
1999). Liver enlargement initially tends to correspond in size to the intensity
of concurrent or recent infections. Thus, hepatomegaly reflects granulomatous
perioval inflammation rather than consequent fibrosis and occurs early in the
evolution of chronic disease (Olds et al., 1996).
GEOGRAPHICAL DISTRIBUTION AND SPREAD OF THE DISEASE
Schistosomiasis is principally a disease of tropical and subtropical regions
and is found in South and Central America, Africa, Asia and Southeast Asia.
It is considered an endemic in 74 developing countries and more than 80% of
infected people live in Africa (Anonymous, 2004). It
has been estimated that 200 million people a year become infected (Keiser
et al., 2002). A new focus of schistosomiasis infection is appearing
in non-endemic areas as well as in areas where no autochthonous cases were reported
for a long period of time. Examples are finding new foci of S.mansoni
in Djibouti (Koeck et al., 1999) and reappearing
of cases of S. haematobium in Jordan (Arbaji et
al., 1998) present in Egypt, where control operation started many decades
ago, land reclaimed along the Nile River has resulted in the introduction of
There are several factors that govern the outcome of the transmission process
in areas where schistosomiasis is endemic such as the infection rates among
snails and degree of human contact with water, which depends on social and cultural
habits of the populations. Mammalian reservoirs of schistosomiasis In addition
to human infection, Schistosoma species are also found in animals. They
are responsible for transmission of the infection For S. japonicum group,
The main animal reservoirs are cattle, buffalo, pig, dogs and rats. In the Philippines,
animal reservoirs such as cow, water buffalo, dogs and pigs were responsible
for 25% of environmental contamination. Animal infection with S. japonicum
species were also reported from Indonesia and in Japan (WHO,
CONTROL OF SCHISTOSOMIASIS
Control through the intermediate host
Snail control: The control Schistosomiasis is through disrupting its life
cycle. Snails, which are Schistosomiasiss intermediate host, once destroyed,
will prevent miracidiums from changing into cercariae (Yuan,
1989). To achieve this goal, the use of copper sulfate or copper carbonates
material (Abel and Dessein, 1998) or Bromoacetamide
(1c) to kill snails in swimming areas. For control of schistosomiasis, one strategy
is based on the premise that snails resistant to parasitic infection could be
used as biological competitors to replace existing susceptible snails in endemic
areas (Yuan, 1989). This approach, however, requires
a more thorough understanding of the genetics of the complex interrelationship
between parasites and snails as shown Fig. 2. In which show
the species of schistosomiasis and the different methods for controlling the
Environmental control: Schistosomiasis can only be transmitted by water
contacts mostly for domestic and recreational purposes and also occupational
(Aka et al., 1999). Therefore, providing safe
water supply and sanitary facilities safe including safe drinking-water, washing
facilities, cattle watering facilities and bathing, not only reduce the risk
of infection with schistosomiasis, but also reduce the source of infection with
other parasite and bacterial infections (Arene et al.,
||Diagrammatic feature of different methods for control schistosomiasis
in the intermediate host and the main host
Control by using molluscicides: The use of molluscicides for the control
of the disease is also important as, unlike the use of synthetic drugs, it prevents
the reinfection of people after treatment. Metallic salts, such as copper sulfate,
were among the first agents used and were most effective when applied to standing
bodies of water. Copper sulfate was introduced by dragging burlap sacks filled
with large CuSO4 crystals behind slow moving boats. This compound
worked well enough, but it also limited algal growth, that in turn affected
growth patterns of fish that served as primary sources of protein (WHO,
1993). Newer molluscicides, such as nicotinanilide, organotin, dibromo-nitraozo-benzene,
sodium pentachlorophenate, tritylmorpholine, sodium dichloro-bromopheno, niclosamide
and acetamide analogs replaced copper sulfate, as these were deemed safer to
the environment (Zhang et al., 1996).
Niclosamide used be a drug of choice for schistosomiaisis, but too many suffered
from the same side effect of depletion of glycogen stores. This led in some
cases to coma, an unacceptable outcome of treatment. Its use is limited by cost,
as well. Plant-derived molluscicides have proven too variable in their effectiveness
and are difficult to manufacture (Andrews et al.,
Biological control: It was shown that Microsporidium sp. can
interfere with the development of the sporocyst stage of S. mansoni.
More of these kinds of associations most likely exist in nature and discovering
them may result in the development of a useful adjunct to current control strategies
(Dunne et al., 1995). A number of predator/competitor
snail species are receiving more and more attention as potential control agents,
as well. In well-controlled situations, such as small, artificial ponds. In
Grenada, Martinique, Guadelupe, Puerto Rico and St. Lucia showed that Ampullariidae
(Pomacea glauca and Marisa cornuarietis) and Thiaridae (Tarebia
granifera and Melanoides tuberculata) snails out-competed Biomphalaria
sp. for space and resources. Competitor snail species were also used successfully
as a follow up measure after molluscicide use in some rivers of central Venezuela
(Katz, 1998). Temperature can determine whether or not
snails can reproduce. Below 100°C, which occurs usually in early spring
in sub-tropical environments, reproduction is severely inhibited. Both adults
and eggs succumb at temperatures that exceed 300°C (Zhang
et al., 1990).
Control through the main host
Health education: Many countries lack the funds, or do not realize the inherent
need to implement health education programs that inform the populace of ways
to protect themselves from schistosomiasis (Zhen, 1993).
Currently, in countries that have been able to implement such programs, they
tend to emphasize the control of human behavior as they relate to the spread
of schistosomiasis. Earlier versions of these programs stressed the need for
snail control and the attendant reduction of transmission. Educated, informed
people are able to adopt control strategies at the personal level, even if it
requires reducing their contact with contaminated water sources, or making water
safe to drink.
Treatment and prophylaxis
Vaccine development: Vaccine, ultimately, is anticipated to be the most
effective form of Schistosomiasis treatment and control (Kojima,
2004). If proved to be effective and inexpensive enough for worldwide distribution,
it would eliminate the need for snail and reservoir host control. Thus far,
the vaccine based on irradiated cercariae offers almost complete protection
in experimental animals (Doenhoff et al., 1988).
The first generation vaccines were directed against infection and/or worm fecundity.
Currently there is a natural balance, tempering anti-schistosomal responses
by stimuli down-regulating the granulomatous reaction against eggs in the tissue
(Capron et al., 1995). Present study promises
to improve the understanding of cytokine interaction in the development of pathology
and immunity, looking for a way to induce maximum levels of immunity without
enhancing egg-associated reactions (Doenhoff, 1998).
Fasciola and Schistosoma worm antigens mixed with or without saponin as well
as saponin alone succeeded to protect mice against S. mansoni infection
with more potent effect of the separately saponin and Fasciola antigens. This
protection is achieved by reduction in total, male and female worms as well
as the levels of toxins elaborated by them. This proved the role of these antigens
in eliminating the product of oxidative stress and assistance in immune-mediated
destruction of eggs that ameliorate the histopathological picture of the liver
cells and preserve its function (Maghraby et al.,
2010a). Schistosoma mansoni egg granuloma size reduction in liver
section after vaccination with Fassiola or Schistosoma egg, in addition to Fassiola
or Schistosoma egg with saponin antigens (Maghraby et al.,
As recombinant DNA techniques cannot yet be utilized to produce carbohydrate
antigens it is more useful to focus on antigens which are predominantly of protein
nature. In addition, carbohydrate antigens often cross-react with egg antigens
and augment the risk of activating granulomatous reactions. The comparison between
the relatively small granulomas of chronic schistosomiasis and those associated
with early infection (Von Lichtenberg, 1987) and the
fact that most anti-carbohydrate antibodies eventually become down-regulated
(Omer-Ali et al., 1989), also emphasizes the
usefulness of protein antigens. The list of published schistosome antigens,
now numbering in excess of one hundred, comes from various parasite stages with
the schistosomulum surface membrane being the preferential target (McKerrow
et al., 1985).
Chemotherapy: This is the most effective method for reducing the infection
rates of schistosomiasis. Access to very effective drug in the last three decades
has resulted in reducing the prevalence and morbidity of the disease in many
areas of the world and reducing the public health importance of Schistosomisis
in some countries (Doenhoff, 1998). Treatment of infected
cases provides the most effective short-term results in control of schistosomiasis
(Castro et al., 2002). It also reduces morbidity
and rate of the transmission. Treatment of cases as a control method require
proper planning such as defining objectives of treatment, using the most reliable
case finding method, selection of appropriate drug, section of the population
to be treated, correct dosage schedule and having adequate information on the
drug and its side-effects (Cioli et al., 1995).
Because case detection is the first approach for planning chemotherapy and selection
of most effective chemotherapy, diagnostic techniques available will be described
first. Although, several drugs were used for treatment of Schistosomiasis in
the past, now only a few drugs are used. Introduction of praziquantel has transformed
the treatment of schistosomiasis (Colley et al.,
2001). This drug is effective, generally in a single dose, against all species
of the parasite. Other drugs include metrifonate, which is active against S.
haematobium and oxamniquine, which is effective against S. mansoni.
Synthetic antischistosomal drugs
Praziquantel: Praziquantel is a heterocyclic pyrazine-isoquinoline
and is highly active against a wide range of trematodes, including all species
of schistosome pathogenic to humans Praziquantel with a single dose of 40 mg
kg-1 is effective. In the treatment of all forms of schistosomiasis
in both adults and children. The cure rate is usually 60-90% with egg reductions
of 90-95% in those not cured (Andrews, 1981) Praziquantel
although generally well olerated, it may induce abdominal discomfort, bloody
diarrhoea, nausea, headache, dizziness, urticaria and rectal bleeding in patients
with heavy worm loads (Beck et al., 2001).
Resistance to praziquantel in the treatment of schistosomiasis has been reported
from Egypt where the drug has been used aggressively for more that 10 years
(Doenhoff et al., 2000; El-Banhawey
et al., 2007; El-Ansary et al., 2007).
There are some reports of the possibility of resistance of some strains of schistosomiasis
to praziquantel (Fallon et al., 1995; Mandour
et al., 1990) some believe this resistance does not exist (Ismail
et al., 1999).
Metrifonate: Metrifonate is an organophosphorus compound originally
used as an insecticide. It is well tolerated and is very effective in the treatment
of S. haematobium mostly in mass chemotherapy programs (Danso-Appiah
and De-Vlas, 2002). Because of the lower coast of metrifonate and the low
side-effects, this drug is recommended for the mass-treatment of school children.
Even when viable worms remain, egg counts after one year is reduced to less
than 20% of pretreatment levels.
The effective dose in adults and children is 7.5 mg kg-1 on given
three times at intervals of two weeks (Feldmeier and Chitsulo,
1999). Because of the side effect of this drug, metrifonate should not be
used for mass chemotherapy in communities recently exposed to insecticides or
other agricultural chemicals with an anticholinesterase action. After administration,
of metrifonate abdominal pain, nausea, vomiting, diarrhoea, headache and vertigo
Oxamniquine: Oxamniquine, a tetrahydroquinoline derivative is used for
the treatment of schistosomiasis due to S. mansoni both in the acute
stage and in patients with hepatosplenic involvement. The effective dose varies
between 15 and 60 mg kg-1 given over two to three days (Botros
et al., 1989). Since oxamniquine has been known to cause seizures.
Epileptic patients should remain under observation for several hours following
treatment. It is used extensively in control programs in South America. Some
strains of S. mansoni are resistant to this drug. Side effects of oxamniquine
are dizziness, drowsiness, headache and raise of the levels of serum transaminases
in some patients (Fallon and Doenhoff, 1994).
Artemisinin: There is some concern that large-scale use of an artemisinin
derivative against Schistosomiasis might select for resistance in malaria parasites.
Although, this risk appears to be low, mainly because of the very short elimination
half-lives of artemisinins (Genovese et al., 2000;
N'Goran et al., 1997, 2003),
at present, use of these combinations should not be recommended in areas where
both schistosome and malaria parasites coexist (Hastings
et al., 2002; Xiao et al., 2002).
Virulence mechanisms contributing to the disease process: In infection
by S. mansoni, the major pathologic changes are not caused by the adult
worm itself but by eggs which do not reach the intestinal lumen, but instead,
become trapped in other body tissues. At these sites, areas of local inflammation
are produced, cumulating in the formation of granulomas around eggs (Giboda
and Smith, 1994). The eggs of Schistosomoes are lethal to a humans
body system. When the body detects these eggs, an inflammatory reaction is triggered.
Instead of killing the eggs, the eggs gain a protein capsule from the inflammatory
cells, which in turn regulate its ovulation. The encapsulated eggs cause liver
damage. Eggs undetected by the bodys defense system also harm the body.
The embryos in the un-capsulated eggs release a toxin that damages the liver
(Reynolds et al., 2002). The formation of granuloma
around schistosome eggs in the liver and the intestine is the major cause of
pathology in schistosome infections. Granuloma and the subsequent fibrosis in
the liver appear to be primarily responsible for mortality and morbidity by
this highly endemic parasitic disease (El-Banhawey et
al., 2007). Ultrasound is used for detection of complications of infection
in animals resulted in a marked decrease in liver glycogen (Akpinar
and Metin, 1999). Visible to the human eye are the enlargement of the liver
and spleen. Once symptoms have been noticed treatment can occur. In vivo
microscopy revealed in addition to these lesions, dilatation and sacculation
of sinusoids. These lesions were associated with varying degrees of reduction
of blood flow due to schistosomules (El-Banhawy et al., 2007; Aly
and Hamed, 2006). Enlargement of the spleen and especially liver will continue
resulting development of the arteriovenous shunts in the lever. Ascites of the
liver and esophageal varices may proceed. Among sever cases hepatomegaly and
enlargement of the spleen are found in high number of cases (Talaat
and Miller, 1998). Other clinical manifestations of chronic schistosomiasis
include core pulmonale due to egg deposition in the lungs and subsequent development
of pulmonary hypertension. Pulmonary complications of S. mansoni infection
manifest with bronchopulmonary symptoms (Akpinar and Metin,
Total protein was reduced in bilharzail infection. This could be attributed
to cellular damage caused by parasite toxins. The main fraction of total protein
content is albumins and the reduction in total protein may be due to reduction
in albumin fraction level that in turn may be result from decrease anabolism
or increase catabolism; hence, malnutrition and/or malabsorption may contribute
to decrease biosyntheses of albumin (El-Fakahani et
al., 1993; Rizk et al., 2000; El-Ansary
et al., 2007). The significant decrease in total protein is mainly
due to increase in messenger RNA degradation which is the possible cause for
the hypoalbuminemia of murine schistosomiasis (Metwally
et al., 1990). Perioval granulomas in the liver lead to fibrosis.
The enlargement of the spleen may be attributed to the direct deposition of
the eggs in that organ or due to inflammatory and fibrotic reactions in the
splenic host that are the main factors responsible for obstruction to portal
venous flow which its major consequence is splenomegaly, in histopathological
examination, congestion was evident in sinusoids of red pulp and lymphoid follicles
(White pulp) were enlarged. This marked congestion in red pulp showed evidence
of haemorrhages (Aly and Hamed, 2006).
Natural product: The recent approach on the development of new drugs
from natural products for treatment of human diseases especially in developing
countries which still rely on traditional medicinal for their primary health
care based largely from various species of plants (WHO, 2002).
There is still intensive search for effective anti-schistosomal drugs with
minimal side effects (El-Banhawey et al., 2007).
Plants are the basis of traditional medicine systems that have been in existence
for thousands of years and continue into modern times (Jellin
et al., 2000). The antibiotic penicillin being the most well known.
In addition to plants and microbes there has been growing interest in the role
of animals as sources of medicines including products derived from frogs and
from marine snails (Duke, 2002).
Natural products also have considerable value as insecticides, contributing
to human health both through improved agricultural (and hence food) productivity
and in the control of insect-borne diseases. Several other herbs are traditionally
used for treatment of parasites, including male fern (Dryopteris filix
mas) root, tansy (Tanacetum vulgare) leaf, wormwood, sweet annie, black
walnut (Juglans nigra) fruit and cloves (Syzygium aromaticum)
Allium sativum: The antiparasitic nature of Allium sativum
(garlic) is demonstrated in the uses to which it has been applied in folk medicines
around the world. For example, it has been traditionally used to treat parasitic
worms in such diverse cultures as East Asia, India, Italy, North America, Peru,
Saudi Arabia, Tunisia and the West Indies. Traditional practitioners in Greece
have long used garlic extracts to protect against amoebic infections (Mirelman
et al., 1987).
Garlic has been demonstrated to kill parasites, including amoeba (Mirelman
et al., 1987) and hookworm (Bastidas, 1969)
in test tubes and in animals. Older studies in humans support the use of garlic
to treat roundworm, pinworm and hookworm (Koch and Lawson,
1996). However, due to a lack of clinical trials, the amount of garlic needed
to treat intestinal parasites in humans is not known.
Wormseed: Wormseed (Chenopodium ambrosioides) is a traditional
remedy for infections with worms. However, a study in Mexico found that the
powdered herb was not effective at eradicating hookworm, roundworm, or whipworm
Pumpkin seeds: Pumpkin seeds (Cucurbita pepo) have purported
effects against tapeworms. Pumpkins and other squashes are native to North and
Central America, but have since been cultivated around the world (Oliver
et al., 2003). The seeds are primarily used in herbal medicine; the
yellow blossoms of pumpkins are also used as medicine in some native. Active
constituents: Pumpkin seeds contain several major groups of active constituents:
essential fatty acids, amino acids, phytosterols (e.g., beta-sitosterol) minerals
and vitamins. Other major constituents include mucilaginous carbohydrates and
minerals (Sheir et al., 2001). Curcurbitin is
a constituent in pumpkin seeds that has shown anti-parasitic activity. In China,
pumpkin seeds have been shown to effectively treat acute Schistosomiasis, a
severe parasitic disease occurring primarily in Asia and Africa that is transmitted
by snails (Weiss, 1985).
Anise: Anise may have modest antiparasitic actions and has been recommended
by some practitioners as a treatment for mild intestinal parasite infections
74 (Weiss, 1985).
Olive leaf: Olive leaf has been used in traditional medicine to reduce
fever, blood sugar, blood pressure and as a diuretic (Privitera,
1996). In 1854, the Pharmaceutical Journal contained an article outlining
its use to counter cases of fever and malaria (Bruneton, 1999).
Active constituents: Olive leaf has a wide number of constituents, including
oleuropein and several types of flavonoids (e.g., rutin, apigenin, luteolin.
Olive leaf is listed in Duke's Handbook of Medicinal Herbs as antibacterial,
antioxidant and a hypoglycemic, with indications against such diverse conditions
as malaria, lymphtic disorders and Schistosomiasis (Duke, 2002).
Vernonia amygdalina leaf: The curative and prophylactic effects of petroleum
ether and ethanolic leaf extracts of Vernonia amygdalina Del (family
compositae) have potential curative effects on kidney, liver and spleen experimental
Schistosomiasis in mice (Ogboli et al., 2000).
Lapachol: DArco (1996-2003) and its constituents
have demonstrated antiviral properties against various viruses including Herpes
I and II, influenza, poliovirus and vesicular stomatitis virus. Its anti-parasitic
actions against various parasites including malaria, Schistosoma and Trypansoma
have been clinically validated (Gilbert et al., 1970;
Cheever, 1997). Lapachol, a chief constituent of the
wood and bark of the pau d'arco tree, has anti-inflammatory, antimalarial, antibacterial,
antifungal, antiparasitic and immunomodulatory activity (Austin,
1979; Jellin et al., 2000), many of which have
been backed up by results from animal and other laboratory studies (Foster
and Tyler, 1999).
Echinacea: Echinacea is used for a range of benefits, including as an
antiviral, an immune stimulant and to relieve urinary tract infections and yeast-related
disorders. Extracts from Echinacea purpurea add to the body's resistance
to bacterial and viral infection (Jellin et al., 2000;
Bruneton, 1999) and have shown indirect antiviral activity
Peppermint: Curled mint (Mentha crispa) leaf, a close relative
of peppermint, has been shown in a preliminary trial to help relieve the symptoms
of giardia and amoeba infections in children and adults, as well as to eliminate
these parasites in many cases (Santana et al., 1992).
This study used a tincture of curled mint in the amount of 2 mL three times
per day for five days, or 1 mL three times per day for five days for children.
Given their close relationship, peppermint could probably be substituted for
curled mint when curled mint is unavailable.
Myrrh: Myrrh is an oleo-gum resin from the stem of the plant Commiphora
mol. A new trend for treatment of liver disorders as a result of S. mansoni
infection is the use of natural plant extract of Commiphora (Mirazid) (Sheir
et al., 2001). Commiphora extract (Mirazid) has been proved to be
safe antifasciolicidal drug without any side effect (Hassan
et al., 2003). Moreover, it's very effective in treatment of Schistosoma
haematobium (El-Baz et al., 2003). Also,
Massoud et al. (2004) reported that Mirazid caused
disruption of S. mansni worms' tegument and collapse of tubercles causing
eradication in worm burden. Natural Purified Commiphora plants extract caused
significant increase in ATP, TA, Pi, glucose, glycogen, adenosine deaminase
and protein, after reduction caused by infection, this enhancing ability of
the extract may be related to antioxidantive activities (Aly
and Aly, 2006). In various reports concerning S. mansoni, Sheweita
et al. (1998) pointed out that levels of reduced glutathione and
glutathione reductase increased, while the activity of glutathione-S-transferase
decreased in human and mice infected with S. mansoni. In this respect
S. mansoni infection alters and consumes the hepatic levels of glutathione,
superoxide dismutase, catalase and glutathione metabolizing enzymes (antioxidant
system) and these alterations may affect the capacity of the liver to detoxify
or neutralize the effect of toxic endogenous and exogenous compounds (Van
Waarde et al., 1990).
Citrus reticulata: Citrus has been reported to have anti-leukemia
(Mak et al., 1999), inhibited human cancer cell
proliferation (Tian et al., 2001) antibacterial
activity (Jayaprakasha et al., 2000), antioxidants
activity (Tanizawa et al., 1992). Antibiotic properties
(Tkachenko et al., 1999), antimicrobial and antibacterial
activities (Jayaprakasha et al., 2000), respectively.
Thus the significant improvement of Citrus plants on all the previous mentioned
parameters in infected mice may be attributed to citrus fruits contain high
concentrations of several polymethoxylated flavones (Demirci
et al., 2000). The latter group of compounds occurs without glycosidic
classes of phenols, including numerous hydroxycinnamates, flavonoid glycosides
and linkages and has been shown to inhibit the proliferation of number of cancer
and protect protein against six oxidative damage (Manthey
and Guthrie, 2002). The anti-inflammatory activities of citrus flavonoids
a rise from the antioxidant properties of these compounds (Manthey
et al., 2001). Antibiotic, free radical scavenger, anti-leukemia
and antibacterial activities (Akira et al., 2000),
respectively. In addition, the citrus seeds and its flours were rich in oil
and protein and proved to be a good source for minerals K, Ca, P, Na, Fe and
Mg (Sabah et al., 1986). The essential oil of
citrus plants was shown to possess also antimicrobial activities (Demirci
et al., 2000). Eradication of the number of egg count and worm burden
is shown in infected mice treated with Mirazid more than citrus plants extracts
which give an additional support for the curative effects of both extracts (Aly
and Aly, 2006).
Ailanthus altissima: The chloroform extract of Ailanthus altissima
stem bark wide range of biological activities showed a pronounced improving
effect against organs (liver-kidney-spleen) damage caused by parasitic infection
(Aly and Hamed, 2006). A. altissima possesses
antituberculosic activity antiplasmodial activity (Okunade
et al., 2003) and antitumor activity (Tamura
et al., 2003).
Zizyphus spina-christi: The ethanolic extract of Zizyphus
spina-christi root shows antidiabetic activity, antimicrobial activity (Shahat
et al., 2001) and antidiarrheal activity (Adzu
et al., 2003) antischistosomal activity (Aly et
al., 2006; El-Rigal et al., 2006). Caused
reduction in the number of worm burden, ova count granuloma size and count as
well as improvement in the histopathological picture of liver, kidney and spleen
of infected mice (Aly and Hamed, 2006).
Berberine: Berberine is derived from several plants, including barberry,
Oregon grape, goldenseal and goldthread (Coptis chinensis). Preliminary
trials have shown that berberine can be used successfully to treat giardia infections
(Choudhry et al., 1972; Gupte,
1975). In addition, test tube studies show that berberine kills amoebae,
although it is not known whether this effect occurs in humans (Kaneda
et al., 1991; Miyares et al., 1988).
The amount required is approximately 200 mg 3 times per day for an adult-a level
high enough to potentially cause side effects. Therefore, berberine should not
be used without consulting a doctor.
Ipecac: Emetine and other alkaloids in ipecac kill several types of
parasites; including amoeba, pinworms and tapeworms (Oelkers,
1962 ; Wright and Phillipson, 1990). Generally,
the amounts of ipecac needed to produce these effects in people are high and
can lead to severe side effects. Emetine or its somewhat safer form, dihydroemetine,
are reserved for rare cases of people infected with amoebae who are not cured
by using anti-amoeba drugs (Schmeller and Wink, 1998)
because of the danger involved, ipecac and emetine should never be use.
Wormwood: Wormwood general strengthening herb that benefits the whole
body, while stimulating and invigorating the whole digestive process. Helps
the body deal with infections helps kill both the egg and adult stages of over
100 parasites including giardia (affecting more and more people), amoebas, many
worms and liver flukes (Kaneda et al., 1991).
Other traditional applications include regulating menstruation and reducing
fever (Schmeller and Wink, 1998). Duke's handbook of
Medicinal Herbs lists antibacterial and antifungal properties for wormwood (Bastidas,
Rhizoma rhei: Rhizoma rhei effective against Schistosomiasis (parasitic disease from fresh water snails infecting over 200 million people in 74 countries) (Duke, 2002). Mild natural laxative which evacuates parasites, cryptosporidium (protozoa) and toxins.
Sarsaparilla: Sarsaparilla strengthens the bones and muscles. This herb
is used to treat urinary tract infections, rheumatoid arthritis, boils, abscesses
and to neutralize mercury toxicity (Colley et al.,
Rhubarb root-rheum officinale: Rhubarb root purges the body of bile,
parasites and a stagnating food by stimulating the gall duct to expel toxic
waste matter. It has been shown to alleviate chronic liver problems by cleansing
the liver (Wright and Phillipson, 1990).
Thyme: Traditionally it is the thyme leaf and flowering tops that have
been used therapeutically. In folk medicine thyme is used to stimulate the appetite,
suppress coughing and relieve digestive disorders such as chronic gastritis,
diarrhoea in children and flatulence. It is also used to expel parasitic worms
(Miyares et al., 1988; Gupte,
1975; Oelkers, 1962), particularly in children.
Black walnut: Black walnut has been used in folk medicine as an astringent,
laxative and a vermifuge. It is used to expel tapeworms and other internal and
external parasites (Choudhry et al., 1972). The
American Medical Ethnobotany Reference Dictionary claims that the juice from
black walnut hull is effective against ringworm, but some warnings have been
issued regarding the topical use of this herb. Black walnut is traditionally
regarded as being antiparasitic and a vermifuge (kills worms) (Schmeller
and Wink, 1998; Sheir et al., 2001).
Pulicaria crispa: The ethanolic extract of natural medicinal
plant Pulicaria crispa have an immunostimulatory effect against schistosomiasis
before and after S. mansoni infection. Al-Yahya et
al. (1988) added that it has a chemopreventive activity against cancer
diseases. In addition, the plant extract of Pulicaria incisa given orally
to normal rats showed transient hypoglycemic effects only 1 h after administration
(Shabana et al., 1990). Moreover, ethanolic extracts
of pulicaria orientalis and butanol extracts of aerial part of Plucaria
gnaphaloides (PG) showed antibacterial activity against both Gram-positive
and Gram-negative bacteria as well as antifungal activities (Ali
et al., 2001; Mahasneh, 2002). Pulicaria
crispa plants extract give an additional support for the protection role
against schistosomiasis. Mice pre-treated with Pulicaria crispa extract
showed no side effects of most parameters compared to the normal healthy control
group (Hamed et al., 2004).
Eitharexlum quadrangular Jacq.: Ethanolic extract of Citharexylum
quadrangular Jacq receded also immuonmodulatory effect against schistosomiasis
before and after S. mansoni infection (Shalaby and
Bahgat, 2003). The same outers added that, this plant extract showed also
antimicrobial effect against E. coli, C. albicans and Batrytis
alli. It can be applied clinically as a prophylactic treatment against schistosomiasis
together with the ideal anti-schistosomal drug praziquantel. Significant amelioration
was noticed in the levels of liver function enzyme activities in S. mansoni
infected mice as a result of prophylactic treatment with. Citharexylum quadrangular
Jacq with significant reduction of worm burden and ova count. Hence, both
plant extracts can be applied clinically as a prophylactic treatment against
schistosomiasis (Hamed et al., 2004).
Curcuma longa: Curcuma longa extract as a plant with recently
reported many medicinal properties (Olajide, 1999).
It was tested as antibilharzial drug. The obtained data proved that C. longa
extract was efficient in the repletion of the depleted glycogen reserves and
induced a significant elevation of glucose concentration in control and infected
C. longa-treated animals (Rizk et al., 2000).
The potential activity of this plant extract in inducing glycogen and glucose
levels could be easily correlated to the previous reports of El-Ansary
and Farouk (2001). They reported that C. longa extract was effective
in restoring normal Adenylate Energy Charge (AEC), through the activation of
the oxidative phosphorylation pathway. Stimulation of oxidative phosphorylation
as the main ATP-generating pathway could explain the glycogen. Higher glycogen
reserves in C. longa-treated control animals could acertain the mode
of action of this extract (El-Banhawey et al., 2007).
Curcumin, obtained from powdered rhizomes of plant Curcuma longa Linn.,
is commonly used as coloring agent in food, drugs and cosmetics (Chuang
et al., 2000). Curcuma longa extract as a remarkable non-toxic
plant with many medicinal properties should be explored for possible intervention
in schistosomiasis as a disease involves impairment of metabolism of infected
subjects (El-Ansary et al., 2007).
Curcumin inhibits cancer at initiation, promotion and progression stages of
tumor development (Radhakrishna et al., 2004;
Mohanty et al., 2004). Research in Germany and
India shows that curcumin can also help prevent gallbladder disease (Olajide,
1999; Chuang et al., 2000).
Capparis spinosa and Acacia arabica: Molluscicides may
induce various pathological manifestations to the snails which could render
the molluscan hosts less suitable to parasitic infection (El-Ansary
et al., 2001). The powdered activity of Capparis spinosa and
Acacia arabica showed molluscicidal activity against Biomphalaria
alexandrina specific intermediate hosts to Schistosoma mansoni. C.
spinosa has antimicrobial activity against some bacterial and some fungal
species (Mahasneh, 2002). Lyophilized extract of C.
spinosa showed a significant antioxidant effect (Bonina
et al., 2002; Germano et al., 2002) predicted
through measuring some glycoclytic related parameters such as lactate/pyruvate
ratio, glycogen and adenine nucleotides, that glycolysis as an emergency pathway
for generating ATP is of critical importance for trematode-infected, B. alexandrina
(Aly et al., 2004).
Endod: Endod berries, thesource of the molluscicidal saponins. Although,
we now know that preparation and application of the endod berries is a safe
procedure and that the molluscicidal saponins are decomposed to water and carbon
dioxide in the environment, some outstanding questions are still to be solved.
One of the future projects should deal with ecotoxicology in respect of the
biological impact of the Endod berries on the environment. Toxicity testing
of endod, a natural plant extract, as a prerequisite for its safe use as a molluscicide
(Lemma, 1965, 1970). The berries
may be less detrimental to the ecosphere than are the synthetic molluscicides;
however, they still are harmful to life in the water (Lemma
et al., 1983). Also snails that are not host snails for schistosomes
and to fish. The dead snails and fish are not poisonous to their predators or
scavengers, but the lack of prey for some time may influence at least part of
the river system (Amusan et al., 1995).
In conclusion, the author proposed that natural product extracts with non-toxic
medicinal properties should be explored for possible intervention in schistosomiasis
as a disease involving impairment of metabolism of infected subjects. These
inspire more hope for reducing the intensity of schistosomal infection by reduction
in worm burden, ova count, granuloma size and number leading to improvement
in histopathological picture of liver, spleen and kidney as a result of reducing
inflammatory and fibrotic reactions of schistosoma.
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