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An update review on Commiphora molmol and related species

Authors:

Abstract

The origins of myrrh and frankincense are traced to the Arabian Peninsula. According to Herodotus (5th century BC): "Arabia is the only country which produces frankincense, myrrh, cassia, and cinnamon.., the trees bearing the frankincense are guarded by winged serpents of small size and various colors." Diodorus Siculus wrote, in the second half of the first century BC, that "all of Arabia exudes a most delicate fragrance; even the seamen passing by Arabia can smell the strong fragrance that gives health and vigor." He also mentioned gold mines so pure that no smelting was necessary. The Magi, carrying myrrh, frankincense, and gold, came from the East: Arabia. The frankincense trade route, with transport by donkeys and later by camel caravans, reached Jerusalem and Egypt from the Dhofar region of what is today Oman, through Yemen, turning north to follow the Red Sea coast. It is likely that the same or similar species of the resin-bearing plants grew across the Red Sea in the area that is now Somalia and Ethiopia, while the collection of the gum resins was initiated in Arabia. Myrrh contributed much in the human welfare. Schistosomiasis was known in ancient Egypt since remote times. Haematuria with urinary bladder disturbances was mentioned in four Papyrus papers dated back to 1950-1900 BC, and Schistosoma ova was detected in a cirrhotic liver of a mummy from 1200 BC (Ruffer, 1910). Also, Fasciola eggs were detected in a mummy (Looss, 1896). Fascioliasis infected over 17 million people worldwide causing marked morbidity and mortality (Haseeb et al., 2002). Schistosomiasis affected over 200 million people in 74 countries and territories worldwide (WHO, 1999) causing several chronic complications. Both were incriminated to predispose or accompanied human hepatitis and predisposed to HCV (Wahib et al., 2006). Most zoonotic helminthes induced immune response (Nutman, 2001) characterized by producing of type 2 cytokines, Ig G1, IgG2, IgE antibodies and eosinophil and mast cell activation (Hoffman et al., 2002). Treatment of fascioliasis required high or drug multiple doses with side effect (Farid et al., 1990). In schistosomiasis, praziquantel (PZQ) in use for > 20 years was faced with low efficacy (Leishout et al., 1998), or with increased resistance (Coles et al., 1986; Watt et al., 1988; Herrera et al., 1994; Ismail et al., 1994; 1999; Tonelli et al., 1995; Stelma et al., 1995; Fallon et al., 1997; Bennett et al., 1997; Boisier et al., 1998; Periera et al., 1998; Kusel and Hagan, 1999; Liang et al., 2000; King et al., 2000; N'Goran et al., 2003; Raso et al., 2004), potentiality of carcinogenicity, genotoxicity (Rosenkranz et al., 1995), mutagenicity (Montero et al., 1993), big dose lethality and enhanced clastogenicity of environmental pollutants (Anwar, 1994). On the other hand, Nomicos (2007) in USA reported that since antiquity, the genus Commiphora is composed of more than 200 species, and exploited as a natural drug to treat pain, skin infections, inflammatory conditions, diarrhea, and periodontal diseases. He added that in more recent history, products derived from C. myrrha and various other species of Commiphora are becoming recognized to possess significant antiseptic, anesthetic, and antitumor properties. Traditional practice and evidence-based research have supported that these properties are directly attributable to terpenoids (especially furanoses-quiterpenes), the active compounds present in myrrh essential oil. Very recently, current studies have focused on applying clinical trial methodologies to validate its use as an antineoplastic, an antiparasitic agent, and as an adjunct in healing wounds. Weeks and Simpson (2007) in USA presented the molecular phylogeny of Commiphora, a predominantly tropical African, arid-adapted tree genus to test the monophyly of its taxonomic sections and to identify clades to help direct future study of this species-rich and geographically widespread taxon. The multiple fossil calibrations of Commiphora phylogeny proved that it is sister to Vietnamese Bursera tonkinensis and that its crown group radiation corresponds with the onset of the Miocene. Auffray (2007) in France studied the impact of two types of antioxidant on sebum squalene peroxidation by UV irradiation. The first type was free radical scavenger (Butyl hydroxyl toluene and an olive extract rich in hydroxytyrosol). The second type was the essential oil of C. myrrha, a singlet oxygen quencher. These properties were confirmed using the 2,2-diphenyl-1-picrylhydrazyl test for anti-radical capacity and 1,3-diphenylisobenzofuran test for the capacity to quench singlet oxygen. Also, the author extended an ex vivo method to classify the efficacy of cosmetics to protect squalene by collecting sebum in vivo and irradiating it in a controlled way. The squalene monohydroperoxide formation was monitored by high performance liquid chromatography. This method compared the efficiency of 3 antioxidants at 0.6% in a cosmetic formulation to protect squalene from photo oxidation. The data showed that essential oil of C. myrrha gave the best protection against squalene peroxidation, and that squalene peroxidation during solar exposure was mainly because of singlet oxygen and not due to free radical attack, and that sun care cosmetics should make use not only of free radical scavengers but also of singlet oxygen quenchers. This study aimed to review more than 70 out of hundreds papers (Pub-med-indexed for Medline) on the medical importance and safety of Commiphora molmol and other Commiphora species.
763
Journal of the Egyptian Society of Parasitology, Vol. 38, No. 3, December 2008
J. Egypt. Soc. Parasitol., 38 (3), 2008: 763 - 796
AN UPDATE REVIEW ON COMMIPHORA MOLMOL
AND RELATED SPECIES
By
ABDULKADER M.D. TONKAL AND TOSSON A. MORSY
Department of Medical Parasitology, Faculty of Medicine
King Abdul Aziz University, Jeddah, Saudi Arabia, and Department of
Parasitology, Faculty of Medicine, Ain Shams University, Cairo
11566, Egypt
Abstract
The origins of myrrh and frankincense are traced to the Arabian
Peninsula. According to Herodotus (5th century BC): "Arabia is the
only country which produces frankincense, myrrh, cassia, and cinna-
mon.., the trees bearing the frankincense are guarded by winged ser-
pents of small size and various colors." Diodorus Siculus wrote, in the
second half of the first century BC, that "all of Arabia exudes a most
delicate fragrance; even the seamen passing by Arabia can smell the
strong fragrance that gives health and vigor." He also mentioned gold
mines so pure that no smelting was necessary. The Magi, carrying
myrrh, frankincense, and gold, came from the East: Arabia. The fran-
kincense trade route, with transport by donkeys and later by camel
caravans, reached Jerusalem and Egypt from the Dhofar region of
what is today Oman, through Yemen, turning north to follow the Red
Sea coast. It is likely that the same or similar species of the resin-bea-
ring plants grew across the Red Sea in the area that is now Somalia
and Ethiopia, while the collection of the gum resins was initiated in
Arabia. Myrrh contributed much in the human welfare.
Schistosomiasis was known in ancient Egypt since remote times.
Haematuria with urinary bladder disturbances was mentioned in four
Papyrus papers dated back to 1950-1900 BC, and Schistosoma ova
was detected in a cirrhotic liver of a mummy from 1200 BC (Ruffer,
1910). Also, Fasciola eggs were detected in a mummy (Looss, 1896).
Fascioliasis infected over 17 million people worldwide causing mark-
ed morbidity and mortality (Haseeb et al., 2002). Schistosomiasis aff-
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764
ected over 200 million people in 74 countries and territories world-
wide (WHO, 1999) causing several chronic complications. Both were
incriminated to predispose or accompanied human hepatitis and pred-
isposed to HCV (Wahib et al., 2006). Most zoonotic helminthes indu-
ced immune response (Nutman, 2001) characterized by producing of
type 2 cytokines, Ig G1, IgG2, IgE antibodies and eosinophil and ma-
st cell activation (Hoffman et al., 2002). Treatment of fascioliasis req-
uired high or drug multiple doses with side effect (Farid et al., 1990).
In schistosomiasis, praziquantel (PZQ) in use for >20 years was faced
with low efficacy (Leishout et al., 1998), or with increased resistance
(Coles et al., 1986; Watt et al., 1988; Herrera et al., 1994; Ismail et
al., 1994; 1999; Tonelli et al., 1995; Stelma et al., 1995; Fallon et al.,
1997; Bennett et al., 1997; Boisier et al., 1998; Periera et al., 1998;
Kusel and Hagan, 1999; Liang et al., 2000; King et al., 2000; N'Gor-
an et al., 2003; Raso et al., 2004), potentiality of carcinogenicity, ge-
notoxicity (Rosenkranz et al., 1995), mutagenicity (Montero et al.,
1993), big dose lethality and enhanced clastogenicity of environment-
al pollutants (Anwar, 1994)..
On the other hand, Nomicos (2007) in USA reported that since
antiquity, the genus Commiphora is composed of more than 200 spe-
cies, and exploited as a natural drug to treat pain, skin infections, infl-
ammatory conditions, diarrhea, and periodontal diseases. He added
that in more recent history, products derived from C. myrrha and va-
rious other species of Commiphora are becoming recognized to poss-
ess significant antiseptic, anesthetic, and antitumor properties. Tradi-
tional practice and evidence-based research have supported that these
properties are directly attributable to terpenoids (especially furanoses-
quiterpenes), the active compounds present in myrrh essential oil. Ve-
ry recently, current studies have focused on applying clinical trial me-
thodologies to validate its use as an antineoplastic, an antiparasitic ag-
ent, and as an adjunct in healing wounds. Weeks and Simpson (2007)
in USA presented the molecular phylogeny of Commiphora, a pre-
dominantly tropical African, arid-adapted tree genus to test the mono-
phyly of its taxonomic sections and to identify clades to help direct
future study of this species-rich and geographically widespread taxon.
The multiple fossil calibrations of Commiphora phylogeny proved
that it is sister to Vietnamese Bursera tonkinensis and that its crown
group radiation corresponds with the onset of the Miocene. Auffray
PDF Created with deskPDF PDF Writer - Trial :: http://www.docudesk.com
765
(2007) in France studied the impact of two types of antioxidant on se-
bum squalene peroxidation by UV irradiation. The first type was free
radical scavenger (Butyl hydroxyl toluene and an olive extract rich in
hydroxytyrosol). The second type was the essential oil of C. myrrha,
a singlet oxygen quencher. These properties were confirmed using the
2,2-diphenyl-1-picrylhydrazyl test for anti-radical capacity and 1,3-
diphenylisobenzofuran test for the capacity to quench singlet oxygen.
Also, the author extended an ex vivo method to classify the efficacy
of cosmetics to protect squalene by collecting sebum in vivo and irra-
diating it in a controlled way. The squalene monohydroperoxide for-
mation was monitored by high performance liquid chromatography.
This method compared the efficiency of 3 antioxidants at 0.6% in a
cosmetic formulation to protect squalene from photo oxidation. The
data showed that essential oil of C. myrrha gave the best protection
against squalene peroxidation, and that squalene peroxidation during
solar exposure was mainly because of singlet oxygen and not due to
free radical attack, and that sun care cosmetics should make use not
only of free radical scavengers but also of singlet oxygen quenchers.
This study aimed to review more than 70 out of hundreds papers
(Pub-med-indexed for Medline) on the medical importance and safety
of Commiphora molmol and other Commiphora species.
Review on Commiphora molmol and other species
Commiphora molmol (family: Burseraceae) common name Myrrh,
Gum-Myrrh/Myrrha or Mur Makkah or El Murrah (Armoush and El-
Omary, 2003). Commiphora molmol was approved by U.S. Food and
Drug Admi-nistration for food use (21 code of Federal Registration-
CFR 172.510) and was given generally recognized as safe (GRAS) st-
atus as a flavor ingredient (No. 2765) by the Flavor Extract Manufact-
turer’s Association (FEMA) (Hall and Oser, 1965; Ford et al., 1992).
The council of Europe (1981) included myrrh in the list of plants and
parts thereof that was acceptable for use in foods. Myrrh is one of the
oldest known medical plants and was widely used by Ancient Egypt-
ians for medical purposes as well as in mummification. It was one of
the three gifts believed to have been offered to infant Jesus by Magi
(Chevalier, 1996).
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766
Tariq et al. (1986) in Saudi Arabia found that petroleum ether ext-
ract of the oleo-gum resin of Commiphora molmol, at a dose of 500
mg/kg body weight, produced significant inhibition of carrageenan
induced inflammation and cotton pellet granuloma. The extract also
gave significant anti-pyretic activity in mice. They added that studies
on the fractionation of phytoconstituents and their mechanism of act-
ion were in progress.
Al-Awadi and Gumaa (1987) and Al-Awadi et al. (1991) in Kuw-
ait reported that among five plants used by Kuwaiti diabetics, extracts
of myrrh and aloe increased glucose tolerance in rats. Nigella sativa
seeds (Roman coriander), gum olibanum (Frankincense) and gum as-
safoetida did not affect blood glucose.
Michie and Cooper (1991) successfully used and recommended
Frankincense and myrrh as safe and effective remedies in children.
Qureshi et al. (1993) in Saudi Arabia studied the genotoxic, cytot-
oxic and anti-tumor properties of Commiphora molmol (oleo gum res-
in) in normal and Ehrlich ascites carcinoma cell-bearing mice. In nor-
mal mice, the genotoxic and cytotoxic activity was evaluated on the
bases of the frequency of micronuclei and the ratio of polychromatic
to normochromatic cells in bone marrow, which was substantiated by
the biochemical changes in hepatic cells. The anti-tumor activity was
evaluated from the total count and viability of Ehrlich ascites carcino-
ma cells and their nucleic acid, protein, mal-ondialdehyde, and eleme-
ntal concentrations in addition to observations on survival and the
trend of changes in body weight. The tumors at the site of injection
were evaluated for histopathological changes. Treatment with C. mol-
mol (125-500 mg/kg) showed no clastogenicity but was highly cytot-
oxic in normal mice. The results achieved in Ehrlich ascites carcino-
ma cell-bearing mice revealed the cytotoxic and antitumor activity of
C. molmol which was equivalent to those of the standard cytotoxic
drug cyclophosphamide. They added that on the basis of the non-mut-
agenic, anti-oxidative, and cytotoxic potential of C. molmol, its use in
cancer therapy was appropriate but, needed more investigation.
Al-Harbi et al. (1994) in Saudi Arabia studied the anti-clastogenic
and biochemical potentials of C. molmol in Swiss albino mice treated
with cyclophosphamide (CP). C. molmol treatment (125-500 mg/kg)
was not mutagenic. It caused a highly significant dose-dependent mi-
to-depressant effect in the femoral cells and reduction of RNA levels
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767
in hepatic cells as com-pared with control. CP treatment gave increa-
se in the frequency of micronuclei, cytotoxicity and reduction in the
contents of nucleic acids and proteins. Pretreatment with C. molmol
could neither alter the biochemical and cytological effects of CP nor
gave any additive effect of both treatments.
Al-Harbi et al. (1994a,b) in Saudi Arabia studied the anti-carcin-
ogenic potential of C. molmol (oleo-resin) in Ehrlich-solid-tumor-bea-
ring mice. The antitumor activity of C. molmol was evaluated from
the tot-al count and viability of Ehrlich solid tumor cells and nucleic
acid, protein, malondialdehyde and glutathione levels at the end of 25
& 50 days of treatment. Observations of animal survival rate and me-
asurements of tumor and body weight were made. The Ehrlich solid
tumors were also evaluated for histopathological changes. Treatment
with C
.
molmol (250 & 500 mg/kg/day) was found to be cytotoxic in
Ehrlich solid tumors cells. The antitumor potential of C. molmol was
comparable to the standard cytotoxic drug cyclophosphamide. The
effect of C. molmol was less pronounced after 50 days treatment that
confirmed cytotoxic & anticarcinogenic potential of C. molmol. More
study was warranted to explore its mode of action and safety for use
in cancer treatment.
Massoud et al. (1996) studied efficacy of myrrh on volunteers, and
schistomiasis mansoni patients with hepatosplenomagaly. Two mont-
hs follow-up post-treatment, they found none significant side effects
in all volunteers. In patients elevated liver and kidney function tests
became normal but SGOT was still significantly high than normal.
Excreted eggs were 181/gm feces dropped to 3-4 dead. Also, distal
polypi and colonic ulcer cases dropped significantly.
Blay et al. (1996) in Spain obtained Ketobutenolide 3, from santo-
nin (1) and were transformed into two natural furanoeudesmanes 4 &
5, isolated from C. molmol and Tubipora musica, respectively. Trans-
and cisdecalin systems were obtained by stereo-selective reduction of
the C(4)-C(5) double bond in 3 in the following way: hydrogenation
of 3 over Pd/C followed by acidic treatment gave the cis-isomer 10 as
the major product; selective hydrogenation of the C(1)-C(2) double
bond with the Wilkinson's catalyst followed by reduction with NaTeH
yielded mainly the trans isomer 9. Compounds 9 & 10 were transfor-
med into 4 & 5 in parallel sequences. Optical rotation and CD measu-
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768
rements of the synthetic products revealed that the stereo-chemistry
of both natural products should be revised to their enantiomeric form.
Anderson et al. (1997) reported that minor components with smo-
oth muscles relaxing properties from scented myrrh C. guidotti, a spe-
cies allied to C. molmol.
Al-Harbi et al. (1997) screened the aqueous suspension of C. mol-
mol (oleo-resin) for gum its potential to protect gastric mucosa again-
st ulcers caused by 80% ethanol, 25% NaCl, 0.2 NaOH, indomethacin
and combined indomethacin-ethanol treatment. Pretreatment at doses
of 250, 500 & 1000 mg/kg provided dose-dependent protection agai-
nst the ulcerogenic effects of different necrotizing agents used. The
effects caused by ethanol were further investigated. Treatment of rats
with 1 ml of 80% ethanol caused depletion of stomach wall mucus,
reduction in the concentration of protein-nucleic acids and NP-SH
groups in stomach wall. Ethanol treatment caused histopathologic le-
sions including necrosis, erosion, congestion and haemorrhage of sto-
mach wall. Pretreatment offered a dose-dependent protection against
all these effects. In the same manner it affected the malondialdehyde
concentration altered by ethanol treatment. C
.
molmol offered protect-
ion against mucosal damage caused by indomethacin and combina-
tion with ethanol. The protective effect of C. molmol was attributed to
its effect on mucus production, increase in nucleic acid and non-prot-
ein sulfhydryl concentration, was mediated through its free radical-
scavenging, thyroid-stimulating & prostaglandin-inducing properties.
Massoud et al. (1997) reported the therapeutic efficacy, toxicity
and side effects of a special formulation of myrrh in human volunt-
eers and human infected with S. mansoni complicated with hepato-
splenomegaly. No significant side effects were observed, liver and re-
nal function tests were normal in all treated controls at 1, 2, 4 & 8 we-
eks post-treatment. In S. mansoni patients elevated SGOT & alkaline
phosphatase, elevated blood urea and serum creatinines were normali-
zed after treatment. SGPT showed significant drop after treatment,
but still higher than normal. Infected patients excreted, on average,
181 eggs/gm feces, which dropped to 4e.pg. 8 weeks after treat-ment
and all were dead. Percentage of distal polypi and colonic ulcer cases
dropped significantly after treatment. A significant drop in the perce-
ntage of cases had significant antibody titre after treatment.
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769
Atta and Alkofahi (1998) in Jordan studied the anti-nociceptive
effect of ethanolic extract of 11 traditionally Jordanian plants by the
acetic acid-induced writhing and hot-plate test in mice. Anti-inflamm-
atory effect was determined by xylene-induced ear oedema in mice
and cotton pellet granuloma test in rats. Mentha piperita, Cinnamom-
um zeylanicum, Apium graveolens, Eucalyptus camaldulentis and Ru-
ta graveolens possessed an anti-nociceptive effect against acetic acid-
induced writhing and hot plate-induced thermal stimulation. M
.
Pipe-
rita, Jasminum officinale, C. molmol and Beta vulgaris possessed an
anti-inflammatory effect against acute (xylene-induced ear oedema)
and chronic (cotton-pellet granuloma) inflammation. The anti-nocice-
ptive and anti-inflammatory effects were dose dependent, proving use
of some plants for painful and inflammatory conditions.
El-Gohary et al. (1999) in Egypt treated 17 parasitologic, serologic
and clinically proved active fascioliasis with myrrh and reported that
cure rate of 94%.
Olajide (1999) in Nigeria evaluated six medicinal plants indigeno-
us to Africa (Azadiractha indica, Bridelia ferruginea, C. molmol, Ga-
rcinia kola and Curcuma long) for activity on experimental thrombo-
sis in mice. The extract of C. molmol exhibited the strongest anti-thr-
ombotic activity, but Ageratum conyzoides did not show activity.
Massoud (1999a) studied the schistosomicidal activity and therap-
eutic efficacy of combined action of resin and volatile oil derived
from myrrh (from C. molmol stem) on human active haematobiasis,
as well as its tolerability, side effects, hepatotoxicity and nephrotoxi-
city in six groups (3 normal & 3 patients). He found that the drug
(15mg/Kg for 3 consecutive days) caused radical clinic-parasitologic
cure, and with neither hepato-toxic nor nephrotoxic side effects.
Massoud (1999b) studied the schistosomicidal activity and therap-
eutic efficacy of combined action of resin and volatile oil derived
from myrrh on human active mansoniasis, as well as its tolerability,
side effects, hepatotoxicity and nephro-toxicity in six groups of patie-
nts. The drug caused radical clinic-parasitologic cure, and was well
tolerated with neither hepatotoxic nor nephrotoxic side effects.
Massoud et al. (2000) used purified oil and oleo-resin of the Ara-
bian or Somali gum C. molmol as molluscicides against Biomphalaria
alexandrina, Bulinus truncatus and Lymnaea natalensis. The results
showed that the oil extract had a higher molluscicidal potency than
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770
the oleo-resin LC50 against L. natalensis was lower than that utilized
for B. alexandrina or B. truncatus. It was 5, 4 & 3 for exposure peri-
ods of 24, 48 & 96 hours respectively. But, the oleo-resin extract sho-
wed more pronounced cercarial potency than the oil, their deaths was
remarked within 15 minutes of exposure to 10, 5 & 2.5 ppm.
Massoud and Labib (2000) in Egypt proved that Myrrh (oleo-gum-
resin) have insecticidal activity against mosquito larvae. Oil extract of
Myrrh possessed median lethal activity against 2nd, 3rd & 4th instar la-
rvae of Culex pipiens at 0.016x 10(2), 0.17x10(2) & 1.6x 10(2) g/l re-
spectively. The LC50 against 3rd instar larvae of Aedes caspius was
0.2x10 (2) g/l. Oleo-resin extract showed toxicity against 2nd, 3rd, 4th
instar larvae of C
.
pipiens recording LC50 values of 0.06x10(2), 0.09x
10(2) & 0.5x10(2) g/l respectively. LC50 against 3rd stage larvae of A.
caspius was 0.08x 10)2 ( g/l. The extract had no toxic effect against the
water bug Sphaerodema urinator (Dufor) and water beetle Hydaticus
leander (Rossi). Histologically, Myrrh treated mosquito larvae show-
ed great pathological effect on fat, muscles, gut and nervous tissues.
Shonouda et al. (2000) in Egypt studied the effects of the extract
C. molmol, and sublethal treatments of profenofos/chlorofluazuron,
fenvalerate and pyriproxyfen on larvae of S. littoralis. Myrrh induced
the highest activity after 7 days with 10000 ppm conc. and mortality
reached 44.4%. Profenofos/chlorofluazuron gave a mortality of 54%
after one day with 100 ppm. Different treatments showed adverse eff-
ects on pupation, emerging adults and larval duration. The myrrh hig-
hest conc. (10000 ppm) induced 35% pupation. No pupa resulted with
profenofos/chlorofluazuron, but fenvalerate and pyriproxyfen gave
13.3% at 50 ppm. At 10000 ppm of myrrh, 25% adult was emerged;
also fenvalerate and pyriproxyfen decreased emergency to 13.3% at
50 ppm. No larval mortality was in controls at 7 days and pupation
and adult emergence were 90%. Bioassay of mixtures indicated anta-
gonistic effects on Spodoptera larval mortality. Myrrh with profeno-
fos/chlorofluazuron showed additive effect. They recommended my-
rrh alone or in combination with sublethal doses of the insecticide.
Massoud et al. (2000) studied the haematological parameters as
well as liver and kidney functions in male albino mice after oral ad-
ministration of mirazid at 3 different dose levels of 50, 100 & 200 mg
/kg/body weight daily for 8 weeks. Blood samples were collected aft-
er 1, 2, 4 & 8 weeks. Mirazid action on chromosomal cytology was
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771
studied, and on prenatal fetal skeleton in pregnant female mice from
6th to 15th day of pregnancy. The results showed no statistical signi-
ficant changes in haematological parameters and liver and kidney
functions, except in cholesterol conc. with a decrease ranged from 16-
35%, and no chromosomal aberrations. Drug given to pregnant rats
did not cause any abnormalities in the fetal skeleton.
Rao et al. (2001) in Saudi Arabia studied the acute (24-h) and
chronic (90-days) oral toxicity of C. molmol in mice. Dosages in acu-
te study were 0.5, 1.0 and 3 g/kg, while in chronic was 100 mg/kg per
day. All the external morphological, biochemical and haematological
changes, in addition to body and vital organ weights were recorded.
There was no significant difference in mortality in the acute or chron-
ic treatment as compared to controls. At the end of treatment, weight
gain in the treated as well as control groups was significant. There
was a significant increase in weight of testes, caudae epididymides
and seminal vesicles in treated group. Biochemical data revealed no
differences in C. molmol treated animals, but haematologic data reve-
aled a significant increase in RBC & Hb levels compared to control.
C. molmol did not show any spermato-toxic effects.
Motawea et al. (2001) in Egypt tested the efficacy and safety of
Mirazid® (combination from oleo-resin extract from Myrrh) in treat-
ment of human fascioliasis. A total of 292 patients participated in the
trial. Mirazid was given in a dose of 10 mg/kg/day for 6 consecutive
days an hour before breakfast. Adults received capsule form and
children received suppository form after defecation. All were subject-
ed to history taking and clinical and ultrasonographic examinations
were done before treatment and 4 weeks post-treatment. Kato-thick
smear was repeated weekly for four weeks follow-up. There was an
overt clinical, ultrasonographic and laboratory improvement with mi-
nimal or negligible side effects. Parasitologic cure rate was 98.6% at
4 weeks follow-up. This rate was higher in patients with mixed infec-
tion. The untreated 1.4% cases by a single course showed marked
reduction of egg count which was of utmost public health significance
as it decreased disease transmission in the community.
Massoud et al. (2001) in Egypt studied the mosquitocidal plant
extracts of Myrrh, C. molmol namely; oil and oleo-resin had larvicidal
activity against Culex pipiens larvae. Oleo-resin induced significant
higher toxic action than oil. Solvent (cremophore EL) did not perform
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772
any toxic activity. The Impact of oleo-resin and oil extracts on the
protein profile of the larvae was evaluated in to explain their mode of
action. Electrophoretic analysis of total proteins, lipoproteins and gly-
coproteins revealed inhibitory action of the extracts on protein conte-
nts. Larvicidal activity was related to loss of certain enzymes inhibit-
ed by the extracts that affected the metabolic processes.
Gaballah et al. (2001) assessed the effectiveness of Mirazid (com-
bination of resin and oil extract of Myrrh; C. molmol), a herbal drug
for treatment of S. mansoni in field situations in Kafr El-Hessa villa-
ge. Mirazid was given to 364 diagnosed cases in a dose of 10mg/kg/
body weight for three consecutive days on empty stomach an hour be-
fore breakfast. Clinical features and symptoms were recorded before
and after treatment. They were followed up by Kato-thick smear anal-
ysis and hatching at 2, 4, 6, 8 & 12 week post-treatment. Rectal and
colonic snips were taken 3 months post-treatment to assess cure.
There was significant symptoms improvement. Side effects were min-
imal. The cure rates, 3 months after a single course of treatment were
91.8% by Kato, 95.9% by hatching and 96.7% by colonic and rectal
snip. No ova were detected in all snips. Cases not responding to a
single course of treatment showed marked reduction of egg intensity.
Massoud et al. (2001) in Egypt treated seven patients passing Fa-
sciola eggs in their stools with myrrh. The drug (8 parts of resin & 3.5
parts of volatile oils, all extracted from myrrh) was given in a dose of
12 mg/kg per day for 6 consecutive days in the morning on an empty
stomach. The patients were followed for 3 months. The drug proved
effective, and with pronounced improvement of the general condit-
ion, with the amelioration of all symptoms and signs. A dramatic drop
in the egg count was detected at the end of treatment. Eggs were no
longer detectable in the feces 3 weeks after treatment and after a foll-
ow-up period of 3 months. Eosinophilic counts, elevated liver enzy-
mes, and Fasciola antibody returned to nearly normal level. Neither
signs of toxicity nor adverse effect occurred. They concluded that the
myrrh was safe, well tolerated and effective for treating fascioliasis.
Allam et al. (2001) in Egypt studied the molluscicidal properties
of the oil extract of C. molmol (Myrrh) against Egyptian snails: Biom-
phalaria alexandrina, Bulinus truncatus and Lymnaea cailliaudi. The
impact of the extract on the egg cluches of B. alexandrina and L. cai-
lliaudi was also evaluated. Snails and their eggs were exposed for 24
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773
& 48 hr at 22-26oC to various extract concentrations. The results gave
different susceptibilities B. alexandrina showed higher LD50 & LD90
(155, 195 ppm) than B. truncatus (50, 95 ppm) and L
.
cailliaudi (50,
85 ppm) after 24 hr exposure. 100% mortality was obtained for egg of
B. alexandrina and L. cailliaudi at concentrations of 100 ppm and 75
ppm respectively. Lower concentrations were needed to obtain the
same results after 48 hr. The authors stated that myrrh had a mollusci-
cidal effect on snails, and their eggs, and recommended field studies.
Badria et al. (2001) in Egypt used the alcoholic extract of the oleo-
gum resin from C. molmol in treating schistosomiasis in experimental
mice. Oral administration of the combination resulted in a significant
reduction in the worm burden of mice, induced separation of females
from males, and shifted the females from their normal habitat in the
liver. This caused marked reduction in number of immature eggs laid.
They added that an increase in percent-age of mature stage from
14.9+1.7 in controls to 93+7.5 & 93.4+8.2 in mice treated with Mira-
zid in dose of 250 & 500 mg/Kg respectively.
Massoud et al. (2001) in Egypt carried out a field study for effica-
cy and safety of Mirazid (oleo-resin extract of Myrrh, C. molmol) in
cestodes treatment. The cases were 51 Hymenolepis nana, (9 with mi-
xed infestation), two H. diminuta of which one with Taenia saginata.
Mirazid was given in a dose of 10 mg/kg/d. for 3 consecutive days an
hour before breakfast for those with H. nana & H. diminuta and for
13 consecutive days for T. saginata. Parasitologic cure rate was 98%
for H. nana (single or mixed) a week post-treatment and 100% 2, 3 &
4 weeks follow-up. The cure rate was 100% for H. diminuta a week
follow-up. T. saginata was recovered by treatment.
Massoud et al. (2001) in Egypt carried out a field study for effica-
cy and safety of Mirazid in nematodes treatment.. The patients were
176 cases of Ascaris lumbricoides, 71 cases of Enterobius vermicu-
laris, 20 of Trichocepalus trichuris & 205 cases of Trichostrongylus
colibriformis. Mirazid was given in a dose of 10 mg/kg/day for 9
consecutive days an hour before breakfast for all cases except for tho-
se with E. vermicularis that were given for 3 consecutive days (cap-
sule form for adults and suppository form for children). All were sub-
jected to history taking and clinical examined before treatment and 4
weeks follow-up. Kato-thick smear was repeated weekly for four
weeks follow-up. There was overt clinical improvement with ne-
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774
gligible side effects. Parasitologic cure rate was 99.4 % for A. lumb-
ricoides, 100% for E. vermicularis, T. trichuris and T. colibriformis at
4 weeks post-treatment. Cases still positive after single course show-
ed marked reduction of egg count that was of utmost public health
significance as decreased the transmission.
Sheir et al. (2001) reported that since resistance to praziquantel
was demonstrated, alternative drugs must be considered. Myrrh from
the stem of the plant C. molmol was used to treat 204 patients with
schistosomiasis. The drug was given at a dose of 10 mg/kg of body
wt/day for three days, and induced a cure rate of 91.7%. Re-treatment
of cases who did not respond with a dose of 10 mg/kg of body wei-
ght/day for six days gave a cure rate of 76.5%, increasing the overall
cure rate to 98.09%. They concluded that the drug was well tolerated,
and side effects were mild and transient. 20 cases provided biopsy
samples six months after treatment and none showed any living ova.
Massoud et al. (2002) studied the effect of mirazid on bile flow
and male fertility, and concluded that it could be given for a long
period at high dose levels as a well tolerated remedy, with high safety
margin for male reproduction and bile flow.
Tipton et al. (2003) in USA determined myrrh oil (MO) cytotoxic-
ity to human gingival fibroblasts and epithelial cells and its effect,
measured by ELISA, on interleukin (IL)-1beta-stimulated IL-6 & IL-
8 production. Cell viability and cytotoxicity were determined by met-
abolic reduction of a tetrazolium salt to a formazan dye (MTT assay)
and by release of lactate dehydrogenase (LDH) from membrane dam-
aged (LDH release assay) cells, respectively. Based on MTT assay,
24-hr & 48-hr exposures to </=0.001% MO had little effect on fibro-
blast & epithelial cell (24-hr only) viability. At 48-hr (0.001-0.0005
%) MO decreased epithelial cell viability 30-50%. After 24- & 48-hr
MO, at >/= 0.005%, maximally decreased viability of all cell lines. In
LDH release assay, exposure to </=0.0001% MO caused <10% cytot-
oxicity to all cells. At 24 hr, >/=0.0025% MO caused maximal cytot-
toxicity; </=0.001% MO caused 10-70% cytotoxicity. At longer exp-
osure times, epithelial cells were more susceptible to cytotoxic effects
of MO. There was little or no detectable IL-1beta-stimulated produc-
tion of IL-6 or IL-8 by cells exposed to >/=0.0025% MO, probably
reflective viability loss. At sub-toxic MO levels (0.001-0.00001%),
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775
there was a significant reduction of IL-1beta-stimulated IL-6 & IL-8
production by the fibroblasts, but not by epithelial cells.
El Baz et al. (2003) in Egypt evaluated the efficacy of Mirazid (C.
molmol) in the treatment of parasitological, clinical and ultrasono-
graphy confirmed schistosomiasis haematobium cases. A 70 of 885
individuals of both sexes (>15 to 60 years old) positive for S
.
haemat-
obium were selected. They had light infection (1-10 eggs/10ml), mod-
erate infection (10-100 eggs/10ml.) and heavy infection (>100/10ml).
They were subjected to urine and stool analysis, renal function tests,
clinical examination & abdominal-pelvic ultrasound, and treated with
Mirazid as 10 mg/Kg. Eight patients were unable to swallow the drug.
Of 62 patients, 57 (91.9%) were cured after 2 months and cure rate
reached 59 (95.2%) on 3rd month post-treatment. Cure was evaluated
clinically, parasitologically and by ultrasonography. Mirazid in a dose
of 2 capsules on an empty stomach before breakfast for 6 successive
days proved very effective and safe for schistosomiasis haematobium.
Haridy et al. (2003) in Egypt studied the efficacy of Mirazid (C.
molmol or Myrrh) in sheep naturally infected with fasciolialsis. A to-
tal dose of one or two capsules (300 mg each) was given for one, two
or three successive days on an empty stomach an hour before break-
fast. A total dose of 600 mg gave a cure rate of 83.3%, while a total
dose of 900 to 1200 mg gave a complete cure rate (100%), without
clinical side effect. The cure rate was achieved by stool examination
and/or macroscopically on slaughtering the sheep. Mirazid proved to
be safe and very effective in sheep fascioliasis.
Massoud et al. (2003) treated two human patients with dicrocoeli-
asis dendriticum one with Praziquantel (25mg/kg, 3 times daily after
meals, for four successive days) and second patient with Mirazid (2
capsules of 300 mg. daily an hour before breakfast, for six successive
days). They were diagnosed and followed-up clinically and parasitol-
ogically. Besides, one imported sheep and two locally bred goats nat-
urally infected with D. dendriticum were successfully treated with Ol-
eo-resin solution (dose of 6 ml of 10gm% equal to 2 Mirazid capsules
before breakfast) per os once daily for four successive days. The ani-
mals were slaughtered on 5th day. Mirazid (capsule or solution) was
effective against dicrocoeliasis in man and animal respectively.
Hassan et al. (2003) in Egypt measured Mirazid ability for contra-
cting the worm muscle and its effect on the worm surface by ultra-str-
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776
ucture to monitor the in vitro effect of drug. Three groups of white al-
bino mice (5 mice in each group) were infected by 100 S. mansoni ce-
rcariae per mouse. The 3rd group served as a control. Seven weeks po-
st-infection the mice were sacrificed perfuse and worms were collec-
ted. Muscle tension of the worms collected from the first group of mi-
ce, was assayed in response to Mirazid in rising concentrations of
100, 200, 300 & 400 nM. The in vitro effect of Mirazid on muscle te-
nsion of single S. mansoni worm was determined using a special de-
vice to determine percentage of change in worm length (shorting).
The drug elicited somatic muscle contraction and reached the highest
response with 400 nM Mirazid. The maximal increase in the muscle
tension (shorting 48%) was induced by the highest concentration
(400nM) of the drug. The worms collected from the second group of
mice were scanned by EM. The worms were exposed each to 10 ul of
Mirazid in concentration of (6-10) and collected after 10, 20 & 30 min-
utes of exposure. Ten minutes exposure caused disruption of the tegu-
ment and collapse of tubercles. After 20 minutes the tegument appea-
red edematous with more disruption and more shrinkage of tubercles.
After 30 minutes, the tegument appeared markedly edematous with
extensive disruption of the inter-papillary areas and sensory bulbs.
The spines covering the tubercles were lost.
Hegab and Hassan (2003) examined 68 individuals, 30 of whom
were presented with Fasciola infection, 20 were infected with other
parasites but not Fasciola (infected control group) and 18 individuals
were parasite-free (normal control group). For all groups, the circula-
ting Fasciola antigens (CFAgs) and anti- Fasciola IgG4 isotype were
estimated by ELISA technique. Complete blood count, liver functions
tests and abdominal ultra-sonography were performed for all Fascio-
la-infected patients. Patients with fascioliasis were received a myrrh-
derived drug (mirazid) in a dose of 10 mg/kg one hour before break-
fast for six consecutive days. Re-measuring of the above parameters
was performed one and three months after therapy. Detection of
CFAgs was found to be a useful marker for assessment of core. No
cross reaction was observed between Fasciola and other parasites by
using CFAg (100% specificity). The level of these antigens correlated
positively with signs of cure either clinically or ultrasonographically.
Detection of IgG4 isotype was a more sensitive and accurate immune-
dignostic tool for fascioliosis, but it was not a useful marker for cure
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777
assessment. They concluded that Mirazid possessed high therapeutic
efficacy on fascioliasis without any remarkable side effects.
Massoud and Habib (2003) in Egypt reported that Myrrh had mol-
luscicidal effect on infected Bulinus truncatus and Biomphalaria ale-
xandrina at low concentrations (10 & 20 ppm respectively) after 24
hours exposure. The number of dead-snails increased with prolonga-
tion of exposure time. All Schistosoma free cercariae were killed by
2.5 ppm within 15 minutes. One day-old egg masses were more sus-
ceptible to the ovicidal effect of Myrrh than the five-day old ones.
Both type of eggs were more resistant to the effect of Myrrh than the
adult snails, embryogenesis began to stop at 20 ppm and eggs were all
killed at 60 & 80 ppm. Shedding of cercariae of S. mansoni from infe-
cted B. alexandrina stopped at 1 ppm and was suppressed at 0.8 ppm.
Snail fecundity decreased at 1 ppm.
Hassan et al. (2004) used modified Kato thick stool smear method to
detect Fasciola eggs and other parasites in human patients. The abdo-
minal pain was the major presenting symptom (87.7%) followed by
pallor (83.3%) and fever (16.7%). Anaemia and hepatomegaly were re-
corded in 77.7% of patients compared to 27.7% with splenomegaly.
Abdominal ultrasonography revealed hepatomegaly and common bile
duct dilatation in 77.7% of patients. Moreover, 5 patients showed dia-
gnostic Olympic game rings. All patients had positive IgG4 levels, 55
patients were positive for specific total IgG & IgG1, whereas, only 24
patients had positive IgG2 levels (26.6%). All negative control group
showed no cross reactions. On the other hand, ELISA detecting IgG4
showed the highest specificity (95%), followed by IgG2 (85%) and the
least specific test was obtained with detection of IgG (70%) and IgG1
(65%). One month after treatment, 91.1% of patients (82/90) were com-
pletely cured and even after another two months follow-up. In the com-
pletely cured patients none of anti-Fasciola isotypes was significantly
changed. So, detection of anti-Fasciola isotypes especially IgG4 is very
specific for the accurate diagnosis of human fascioliasis.
Massoud et al. (2004) in Egypt studied the efficacy of purified ol-
eo-resin extract of myrrh derived from C. molmol as a new natural an-
tischistosomal drug. The effect of myrrh on the ultrastructural profile
of the non infected normal mice liver was also studied. Sixty male
mice were divided into 3 main groups (20 each): GI, non infected co-
ntrols, GII, infected animals and GIII, infected animals treated with
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778
myrrh extract 8 weeks post infection (500 mg/kg body weight). Drug
was given orally on an empty stomach after overnight fasting for five
successive days. All animals were sacrificed after 12 weeks from the
beginning of the experiment and small pieces of the liver were exci-
sed and prepared for ultrastructural study. Liver of non infected anim-
als which received myrrh extract showed a more or less normal ultra-
structural profile. Infected groups showed alterations of the ultrastru-
cture of most of the hepatocytes with extensive intercellular fibrosis
with abundant granulomas in the portal tract. In treated group, most
of the hepatocytes showed normal organelles with numerous micro-
villi extending into patent spaces. The marked reduction of granulo-
mas in the portal areas and the amelioration of intercellular fibrosis
were noticed.
Massoud et al. (2004) in Egypt planned to evaluate in vitro produ-
ction of IL-1 beta and IL-4 by peripheral blood mono-nuclear cells
(PBMCs) and total IgE in patients with fascioliasis before and 3 mon-
ths after treatment with purified extract of myrrh from C. molmol to
determine the role of these variables in immuno-pathogenesis of the
disease in relation to this new drug. A total of 35 patients with chro-
nic fascioliasis with age ranged from 9-45 years in addition to 10 hea-
lthy subjects with matched age and sex served as controls were stud-
ied. Serum and in vitro IL-1 & IL-4 were estimated by enzyme immu-
no-assay (ELISA) before and 3 months after therapy. Results revealed
significant increase in IL-1 beta in patients before treatment than con-
trol (p<0.001) but it decreased significantly after therapy (p<0.001) to
reach the control level (p=0.16). In contrast, IL-4 was significantly
lower than control before therapy (p=0.04) and increased significantly
after treatment (p<0.001) to reach normal levels as control (p=0.59).
Total IgE was significantly elevated in patients before treatment
(p<0.001) and it did decrease significantly with treatment (p<0.001),
although it remained significantly higher than the control level. They
concluded that Mirazid was an effective fasciolicidal drug. Also, the
IL-1 might be involved in disease immuno-pathogenesis and the depr-
essed IL-4 might be a phenomenon of the parasite immune supperssi-
on. The complete decline of total IgE was not an early criterion of
cure.
Abo-Madyan et al. (2004a) in Egypt among 1019 individuals para-
sitologically examined, the prevalence of S. haematobium and S. ma-
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779
nsoni were 4.2% & 2.4% respectively and the geometric mean egg
count (GMEC) were 33.2 eggs/10 ml urine and 113.3 eggs/gm stool.
Most of the patients with haematobiasis and mansoniasis were >15 ye-
ars (56.4% & 53.8%), males (56.4% & 53.8%) & illitterates (46.2%
& 46.2%). All cases were treated by Myrrh (Mirazid) as two capsules
(600 mg) on an empty stomach an hour before the breakfast for six
consecutive days and were followed up clinically and parasitologica-
lly by urine analysis by the sedimentation and nucleopore techniques
and by hatching test and by stool analysis by sedimentation and Kato-
Katz techniques and by hatching test. The parasitological cure rate
after three months was 97.4 % & 96.2% for S. haematobium and S
.
mansoni cases with the marvelous clinical cure without any side-effe-
cts. Patients not completely responded to a single course of treatment
showed marked reduction of egg intensity. They concluded that Mira-
zid proved to be safe and very effective in treatment of S. haema-
tobium and S. mansoni infections under field conditions.
Al-Mathal and Fouad (2004) in Saudi Arabia reported that Myrrh
extract of C. molmol (Mirazid) successfully and safely treated clinica-
lly and parasitologically proven 18 dicrocoeliasis dendriticum patien-
ts. The dose was 2 capsules ( 300 mg each) given on an empty stoma-
ch an hour before the breakfast for six successive days. The cure
(100%) was achieved clinically and by stool analysis for two months
follow up. 15 sheep naturally infected with D. dendriticum as proven
parasitologically were successfully and safely treated with 2 capsules
(300 mg each) on an empty stomach an hour before breakfast for four
successive days. The 100% cure was achieved in sheep by stool anal-
ysis for 7 days and macroscopically for detection of any adult worm
after slaughtering. The total dose required to treat infected sheep
(2400 mg) less than that required for human treatment (3600 mg).
Haridy et al. (2004) in Egypt evaluated C. molmol or Myrrh (Mira-
zid) in treating sheep naturally infected with Moniezia expansa. Total
doses of one, two or three capsules (300 mg each) were given for one,
two, three, four, five, six, seven & eight successive days on an empty
stomach an hour before offering their breakfast. Every day the stools
were examined microscopically and macroscopically for eggs and/or
gravid segments. When the stool was negative, the treatment was sto-
pped. That sheep group was examined macroscopically after slaught-
ering for adult worms in intestine. A total dose of 3600 mg given as 3
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780
capsules per days for four days gave a cure rate of 100.0% with no
clinical side effects. A dose of 4800 mg given as two capsules per day
for eight days gave a cure rate of 100.0% with no clinical side effects.
A total dose of 2400 given as one capsule per day for eight days gave
a cure rate 40.0%. They concluded that Myrrh extract of C. molmol
proved to be safe and very effective in sheep monieziasis expansa.
Abo-Madyan et al. (2004b) in Egypt reported 1.7% fascioliasis
among 1019 individuals examined for parasitosis, and the geometric
mean egg count (GMEC) was 33.2 eggs/gram stools. A total of 23.5%
of fascioliasis patients were asymptomatic. The most frequent symp-
toms were abdominal distension and flatulence (76.5%), right hypo-
chondrial pain (17.6%) and epi-gastric pain (17.6%). The most preva-
lent signs were pallor (52.9%), tender right hypochondrium (23.5%)
and tinge of jaundice 17.6( %). All patients were treated by Mirazid as
two capsules (600 mg) on an empty stomach an hour before the brea-
kfast for six consecutive days and followed up clinically and parasite-
logically. The parasitological cure rate, two and three months after
treatment was 88.2% and 94.1% with an overt clinical cure without
any side-effects. But, patients whom were not completely responded
to a single course of treatment showed a marked reduction of the egg
intensity.
Soliman et al. (2004) in Egypt treated 21 children with fascioclia-
sis (8 males & 13 females) with mean age of 10.4 years, and 8 child-
ren with schistosomiasis mansoni (6 males & 2 females) with mean
age of 11.37 years were treated with Myrrh (Mirazid) an oleo-gum re-
sin from stem of C. molmol tree. Ten healthy cross matched children
were utilized as controls. Diagnosis was based on detection of F. hep-
atica or S. mansoni eggs in stool by Kato-Katz technique. Mirazid
was given as 10 mg/kg/d one hour before the breakfast for 3 consecu-
tive days in schistosomiasis and for 6 days in fascioliasis. Clinical ev-
aluation and stool analysis were done initially and at 2, 4 & 12 weeks
post treatment to evaluate cure. Rectal snip was done for responding
schistosomiasis cases to confirm the recovery. Automated complete
blood count with the manual assessment of eosinophils, sera total IgE
and in vitro cytokines assay (IL-1 beta, IL-4, IL-5) by ELISA were
performed before treatment and repeated 12 weeks only for patients
after therapy. Parasitologic cure was 90.9 % in fascioliasis and 100%
in schistosomiasis at 4 weeks post treatment. After a second dose
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781
Fasciola patients who remained positive were cured. Total IgE was
significantly higher in Fasciola and Schistosoma patients before treat-
ment compared to control (p<0.001; 0.005 respectively) and decrea-
sed significantly with treatment (p=0.001; 0.036). IL-1beta was high-
er in both patient groups than control (p< 0.001; 0.003) and decreased
significantly after 12 weeks to control level (p<0.001; 0.017IL-5) was
high before treatment in both groups (p= 0.041; 0.027) and decreased
significantly after 12 weeks after therapy (p=0.005; 0.012). IL-4 did
not differ from control before therapy (p= 0.58; 0.79) but increased
significantly after treatment in both patient groups (p= 0.04; 0.02).
They concluded that Mirazid proved an effective fasciolicidal and
schistosomicidal drug. IL-1beta and IL5 were high in fascioliasis and
schistosomiasis, but decreased with therapy denoting immuno-patho-
genesis. The depressed IL-4 was a parasite immune evasion or host
regulatory mechanism and cytokine levels may be criteria of cure.
Al Faraj (2005) in Saudi Arabia reported that Commiphora mol-
mol antagonism the anticoagulant effect of warfarin.
Omar et al. (2005) in Egypt evaluated and compared hepato-toxic,
genotoxic and carcinogenic effects of Praziquantel (PZQ) and Mira-
zid (MZ) on adult male albino rats by assessment of serum levels of
ALT, AST & bilirubin, histopathological study of the liver and cytog-
enetic study of bone marrow cells. 100 rats were divided into 4 grou-
ps: I- negative control, II- control rats received distilled water, III- re-
ceived weekly single oral dose of PZQ (1500 mg/kg) for 6 weeks, and
IV- received daily oral dose of MZ (500 mg/kg) for 6 weeks. At the
end of the study 10 rats of each group were examined for the levels of
AST, ALT, & Bilirubin. After scarification, liver sections were exam-
ined by light microscopy. Another 10 rats of each group were submit-
ted to the cytogenetic examination. PZQ induced a significant incre-
ase in the mean values of AST, ALT & bilirubin with areas of hyaline
degeneration, fatty changes, dysplasia & necrosis in liver sections. It
induced a significant increase in incidence of chromosomal aberrat-
ions as polyploidy, fragment, deletion & ring chromosome as compa-
red with control group. MZ induced a non significant increase in
mean values of AST, ALT & bilirubin, with a normal hepatic tissue,
and a non significant increase in the incidence of chromosomal aber-
rations, as compared with control. On comparison of both drugs, PZQ
induced a significant hepatotoxic, genotoxic and carcinogenic effects.
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782
They concluded that praziquantel was considered to be a hepatotoxic,
genotoxic and carcinogenic drug. But, Mirazid® was a safe and prom-
ising anti-parasitic drug, without any hepatotoxic, genotoxic and car-
cinogenic effects.
Massoud et al. (2005) in Egypt studied the effect of 5 concentrat-
ions of purified extract of Myrrh from C. molmol tree on the fowl tick
Argas persicus under normal laboratory conditions. This showed that
Myrrh had dependant dose toxic effect on A. persicus female. Toxici-
ty increased gradually daily post treatment. The LC50 was 1.28%,
0.88%, 0.84%, 0.50% & 0.42% at1st, 2nd, 3rd, 6th & 12th days respect-
ively. At 12th day, the mortality rates were 63, 67, 76, 87 & 94% for
concentrations, 0.625, 1.25, 2.5, 5 & 10%, respectively against 5% in
control. Histo-pathological and TEM examinations showed the lysing
of epithelial gut cells in treated groups. The lysed epithelial gut cells
showed irregularly distributed nucleus, commonly at low concentra-
tions and rarely in high concentrations of Myrrh. The lysed epithelial
gut cells, without nucleus or with aggregated one beside the basal la-
mina, were common at high concentrations and rare in low Myrrh co-
ncentrations. They concluded that Myrrh rapidly penetrated cuticle to
body cavity and destroyed epithelial gut cells and caused ticks’ death.
Massoud et al. (2005) in Egypt studied the efficacy of purified
oleo-resin extract of myrrh derived from C. molmol tree (Mirazid) ag-
ainst an Egyptian strain of Schistosoma mansoni in seventy adult ma-
le mice. They were divided into 4 groups: G.I: control non-infected
non-treated mice. G.II: non-infected treated mice and was subdivided
into two subgroups, II-A: included mice received Myrrh extract dis-
solved in cremophore EL & II-B: included mice which were treated
with cremophore EL. G.III: consisted of infected non-treated animals
and G.IV: included infected mice treated with myrrh extract. The dr-
ug was given 8 weeks post infection in a dose of 500 mg/kg body
weight/day for 5 successive days. All animals were sacrificed after 12
weeks from beginning of the experiment. Liver paraffin sections were
prepared and stained with H&E, Masson's Trichrome stain, PAS stain
and Wilder's technique. A morphometric study was performed for the
mean number and perimeter of the granulomas. Area percentage of
the total collagen content around central veins and in portal areas was
also estimated. The animals' livers in G.II showed a more or less nor-
mal histologic profile when com-pared to G.I. G.IV showed complete
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783
preservation of the hepatic architecture. Most of the hepatocytes were
almost normal. The reticular net-work in the central part of the gran-
ulomas as well as in the portal tracts appeared rarefied. The hepatic
reticular network was preserved. A significant decrease in number &
size of granulomas with significant reduction in collagen content dep-
osition in portal tracts and around central veins was detected as com-
pared to G.III. The data proved the efficacy of myrrh as an anti-schis-
tosomal drug.
Fathy et al. (2005) in Egypt tried C. molmol (Mirazid=MZ) against
heterophyids (Pygidiopsis genata), using praziquantel as a therapeut-
ic control. Results showed that MZ in emulsion form was a promising
drug for treatment of heterophyidiasis, as proved by significant reduc-
tion of worm count, overt surface tegumental changes like deformity
and erosion of tegumental spines seen by SEM. The effective dose
was 500 mg/kg/d for 3 successive days, gave 100% reduction in wo-
rm load. The proved efficacy of Mirazid favors its use as a natural
new alternative for treating heterophyidiasis.
Abo-Zinadah (2005) in Saudi Arabia successful treatment of two
imported sheep infected with fascioliasis with Macca mur.
Hamed and Hetta (2006) in Egypt investigated the effect of Schi-
stosoma mansoni infection on mice livers after treatment with the eth-
anolic extract of Citrus reticulata root or the oleo-resin extract from
Myrrh of C. molmol tree (Mirazid), as a new anti-schistosomal drug.
Marker enzymes for different cell organelles were measured; succin-
ate dehydrogenase (SDH); lactate dehydrogenase (LDH) and its iso-
enzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP)
and 5'-nucleotidase. Liver function enzymes; aspartate aminotransfer-
ase (AST); alanine aminotransferase (ALT) and alkaline phosphatase
(ALP) were estimated. Parasitological studies through ova count and
worm burden was taken into consideration. The results showed a mar-
ked reduction in SDH, LDH, AST, and ALT enzyme activities and a
significant increase in G-6-Pase, AP, 5'-nucleotidase, and ALP after
S. mansoni infection. An alteration in LDH subunits was seen. They
concluded that C. reticulata or Mirazid improved all the enzyme acti-
vities with a noticeable reduction in ova count and worm burden.
Haridy et al. (2006) in Egypt examined 213 farm animals found
that cattle were infected with Fasciola sp. and Paramphistomum sp.,
buffaloes were infected with Fasciola sp. and Paramphistomum sp.,
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784
while sheep were infected with Fasciola sp., Dicrocoeleum dendri-
ticum and Paramphistomum sp. The three animal species were treated
for paramphistomiasis with a total dose of 1800, 6000 , and 7500 mg
of oleo-resin solution of C. molmol (6 ml of 10g% =2 Mirazid). Cure
was 100% in sheep, 80% in cattle and 44.4 % in buffaloes. High dose
for cattle and buffaloes to reach 100% cure was not tried.
Al-Mathal and Fouad (2006) in Saudi Arabia found that C. molmol
(Myrrh) had molluscicidal effect on Biomphalaria arabica at low co-
ncentration (40 ppm) after 48 hrs exposure. The number of dead-sna-
ils increased with increasing the exposure time. One day-old egg ma-
sses were more susceptible (death 100% with 80ppm) to ovicidal ef-
fect of C. molmol than the 5-day old ones (death 95% with 80 ppm).
The eggs were more resistant to C. molmol effect than adults, embry-
ogenesis began to stop at 20 ppm and eggs were all killed at 60 & 80
ppm. B. arabica fecundity decreased at 1 ppm. They recommended C.
molmol as a safe molluscidide.
Shoukry (2006) in Egypt studied the effect of Myrrh on B. connoll-
yi, the snail-vector of the trematod-parasite Opisthorchis sp. found
that C. molmol had molluscicidal effect on B. connollyi at a concen-
tration of 80 ppm after 72 hr. exposure. The mortality rate increased
by increasing the exposure time (death 100% at 72 hr. with 80 ppm &
death 100% at 96 hr. with 40 ppm). She added that C. molmol was re-
commended as a cheap herbal molluscicide.
Massoud et al. (2006) in Egypt studied C. molmol extract (Miraz-
id) on 24 patients having Strongyloides larvae in their stools. Each st-
ool sample was examined by direct saline smear, formalin-ether sedi-
mentation technique and agar plate culture. Patients were treated with
Mirazid® double course for a month was followed up by stool exami-
nation by traditional method and agar plate culture for three consecu-
tive months. Five cases out of 24 were asymptomatic (20.8%). The
symptoms included the abdominal manifestations as nausea and vo-
miting (16.7%), epi-gastric pain and nausea (12.5%), generalized abd-
ominal pain (12.5%), chronic diarrhoea (16.7%), irregular bowel hab-
it (8.3%), and urticaria with abdominal pain (4.2%). Agar plate cultu-
re gave 100% positivity, even in negative cases by coprological meth-
ods either direct smear and/or sedimentation method. All cases were
cured by Mirazid given for one month except three cases. But, only
one case responded to repeated course of Mirazid, while the other two
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785
had larvae in stool. On combined therapy of Mirazid and Meben-
dazole larvae were eliminated as approved by agar culture.
Ahmed et al. (2006) in India found that phytochemical examinat-
ion of C. myrrha (Nees) Engl. afforded six compounds identified as
cadina-3-en-15-ol (myrracadinol A) (1), 7, 8-seco-2, 5-dihydroxy-12-
acetoxycalam-8-ene (myrracalamene A) (2), 7, 8-seco-2, 3, 5-hydrox-
y-12-acetoxycalame-8-ene (myrracalamene B) (3), 7, 8-seco-cad-in-3,
8-dien-2beta, 12-diol (myrracadinol B) (4), 7, 8-seco-12-hydro-xycal-
am-8-ene (myrracalamene C) (5), 7, 8-seco-cadin-3,7(12)-dien-5alp-
ha, 10 alphadiol (myrracadinol C) (6) along with a tria-cont-1-ene (5).
Massoud et al. (2007a) studied the efficacy and safety of Mirazid
in treatment of human hymenolepiosis was carried out in a rural villa-
ge in Talkha Center (Dakahlia G.). Kato thick smear stool examinat-
ion showed 51 cases of Hymenolepis nana (9 of them had concomita-
nt parasitosis), two cases of H. diminuta. Mirazid was given in a dose
of 10 mg/kg/d for nine consecutive days an hour before breakfast for
hymenolepiosis cases, as capsule for adults and suppository for child-
ren. All cases were subjected to history taking before treatment and
six weeks post-treatment and stool examination was repeated weekly
for six weeks post-treatment. There was overt clinical improvement
with negligible side effects. Parasitologic cure was 40/41 or 95.2%
for H. nana and 100% for H. diminuta one week post-treatment, up to
six weeks follow-up for all patients. The two H. nana patients were
cured by another Mirazid course.
Massoud et al. (2007b) examined a total of 3278 patients attended
Mansoura University Hospitals' Clinics with gastro-intestinal troubles
suggesting parasitosis by direct smear and by Kato-Katz methods for
parasites especially Heterophyes heterophyes. Fifty clinically and par-
asitologically proved pure heterophyiasis patients were given Mira-
zid® as two capsules for 9 successive days on an empty stomach an
hour before breakfast. All the cases were subjected to history taking
and clinical examination before treatment and were followed-up for
four weeks post-treatment. There was an overt clinical and parasite-
logical improvement. A total of 47 out of 50 (94%) were cured. Ano-
ther course was given to the three patients who were still positive, but
only two of them were cured (66.7%). The overall cure rate was 49/
50 (98%) and none had any side effect. The history and treatment of
this zoonotic parasite was critically discussed.
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786
Massoud et al. (2007c) experimentally proved that the two extracts
from the herbal plant, Commiphora molmol showed a high mollusci-
cidal effect against Lymnaea natalensis. The oil extract was more pot-
ent than the oleo-resin. A concentration of 10 ppm of the oil extract
killed 100% of L. natalensis after 5th day, but the oleo-resin extract
killed 100% of them at a concentration 20 ppm after 5th day.
Abbass et al. (2007) in Saudi Arabia identified the major chemical
constituents of aerial part of C. opobalsamum L. to evaluate its extra-
cts and isolated compounds in preliminary in vitro assays for antimic-
robial, antimalarial, antitumor, anti-inflammatory (COX-2 inhibiti-
on), antioxidant and estrogenic activity. Six compounds were isolat-
ed; triterpenes friedelin, canophyllal, and oleanonic acid; the flavon-
ols mearnsetin and quercetin; and syringic acid. The ethyl acetate ext-
ract was moderately active against Staphylococcus aureus, Pseudom-
onas aeruginosa, and Plasmodium falciparum; while petroleum ether
and chloroform extracts inhibited COX-2 at 5 and 10 microg ml (-1),
respectively. Syringic acid showed moderate antimalarial, anticandi-
dal, and antimycobacterial activity; while mearnsetin and querce-tin
exhibited antioxidant activity comparable to ascorbic acid and trolox.
Paraskeva et al. (2008) in South Africa analyzed ten Commiphora
species for the anti-oxidant, antimicrobial, anti-inflammatory, antica-
ncer properties, and cytotoxic effects. The best anti-oxidant activity
was for stem extracts of C. tenuipetiolata, C. neglecta & C. mollis.
Extracts generally exhibited poor anti-oxidant activity, except with C.
schimperi (stem), C. neglecta (stem), C. tenuipetiolata (stem & leaf),
and C. edulis (stem). Stem extracts exhibited moderate to good inhibi-
tory activity with C. pyracanthoides. A greater selectivity was exhi-
bited by extracts against Gram-positive bacteria and yeasts than
against Gram-negative ones. C. marlothii (stem) killed Staphyloco-
ccus aureus over 24hours, a concentration-dependent anti-bacterial
activity began after ca. 30 min. All concentrations exhibited antibac-
terial activity, with complete bactericidal effect achieved by 24th hr.
The most active Commiphora species against SRB anticancer assay
were C. glandulosa (leaf & stem) and C. marlothii (leaf). The MCF-7
cells exhibited the highest sensitivity to indigenous species, with C.
edulis (leaf & stem), C. glandulosa (leaf & stem), C. marlothii (leaf),
C. pyracanthoides (leaf & stem), C. schimperi (stem), and C. viminea
(stem) with inhibition activity >80%. C. glandulosa (leaf & stem) and
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787
C. pyracanthoides (leaf & stem) were the most active species against
SF-268 cells. Majority of Commiphora extracts were non-cytotoxic
against Graham human kidney epithelial cells.
Massoud et al. (2008) divided sixty cryptosporidiosis patients in
Mansoura University Hospitals, 36 males and 24 females, with age
from few months to ten years (mean age 6.1) into three cross-matched
groups of 20 patients each. All patients received the glutamine-based
oral rehydration solution with 111 mmol/l glutamine, 20 mg zinc ace-
tate once a day and vitamin A supplementation (200,000 IU) once a
day for 2 weeks. For treatment, G1 received Mirazid® (10mg /kg for 2
weeks), G2 received Paromomycin® (500 mg qid for 2 weeks), and
G3 received a combination of Mirazid (10mg/kg) and Paromomycin
(500 mg) for two weeks. The result was assessed according to scales:
0= no improvement, 1= symptoms began improvement (reduction of
diarrhea frequency and stool volume, less abdominal pain, less nausea
& vomiting), 2= diarrhea eradication, 3= weight gain, 4= oocyst cou-
nts reduction, 5= reduction in diarrhea and oocyst counts, 6= eradi-
cation of diarrhea and oocysts. G3 showed significantly higher differ-
ence than G1 & G2 in the 1st week (p=.036, 0.025 respectively), no
significant difference in 2nd week, a significantly higher difference
than in G1 (0.003), & G2 (0.006) in 3rd week, and a significantly
higher difference than G1 (0.014), & G2 (0.01) in 4th week, but with-
out significant differences in oocyst shedding in the 3 groups.
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... According to the current study, the mean tensile strength var- acidic or neutral pH levels [12]. ...
... The stool samples were examined microscopically for S. mansoni eggs by direct thin smears and by Kato-thick smear (Katz et al, 1972). Patients were given a prescription order of appropriate anti-parasitic drugs in the form of Mirazid ® , an extract from Commiphora molmol (Family: Burseraceae) common name Myrrh, Gum-Myrrh/ Myrrha or Mur Makkah or El-Murrah (Al-Mathal, 2007;Tonkal and Morsy, 2008). C. molmol was successfully used to control B. arabica under laboratory conditions (Al-Mathal and Fouad, 2006) and to treat human infected with Bertiella studeri; Cestode: Anoplocephalidae (Al-Mathal et al, 2010) Statistical analysis: Data were computerized and analyzed using SPSS windows version 11.5. ...
... Erko et al. (2012) found relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia. Tonkal and Morsy (2008) gave a review on Commiphora molmol and related species as an antihelminthic herbal drug. Basyoni and El-Sabaa (2013) reported that Myrrh was effective and could be a promising drug against the Egyptian strains of T. spiralis (tissue helminthic infection) with results nearly comparable to the ivermectin. ...
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