Sunteți pe pagina 1din 13

EXCLI Journal 2013;12:943-955 – ISSN 1611-2156

Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Original article:

BENEFICIAL THERAPEUTIC EFFECTS OF NIGELLA SATIVA


AND/OR ZINGIBER OFFICINALE IN HCV PATIENTS IN EGYPT
Adel Abdel-Moneim1, Basant M Morsy2, Ayman M Mahmoud1*, Mohamed A Abo-Seif3,
Mohamed I Zanaty2
1
Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University,
Egypt
2
Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University,
Egypt.
3
Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Egypt

* Corresponding author: Ayman M Mahmoud; Physiology Division, Zoology Department,


Faculty of Science, Beni-Suef University, Salah Salim St., 62511, Beni-Suef, Egypt.
E-mail: ayman.mahmoud@science.bsu.edu.eg; aymano911@yahoo.com
Tel.: +201144168280

ABSTRACT
Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis
C virus (HCV) worldwide. The current study was designed to evaluate the beneficial thera-
peutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in
Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched
healthy subjects were included in this study. Exclusion criteria included patients on interferon
alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced
cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities
and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time
and concentration, international normalized ratio, alpha fetoprotein and viral load were all as-
sessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingi-
ber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg
of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug
reactions were assessed initially, periodically, and at the end of the study. Both extracts as
well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver
function parameters; with more potent effect for the combined therapy. In conclusion, admin-
istration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhib-
ited potential therapeutic benefits via decreasing viral load and alleviating the altered liver
function, with more potent effect offered by the mixture.

Keywords: Hepatitis C, Nigella sativa, Zingiber officinale, viral load

INTRODUCTION hepatocellular carcinoma (HCC) (Alter,


2007; Lavanchy, 2011). It has been shown
Hepatitis C virus (HCV) infection often
that there is an alarming increase in the in-
is conducive to chronic hepatitis due to the
cidence of HCC in HCV patients in Egypt
low viral clearance rate, leading to liver cir-
(Anwar et al., 2008). According to the
rhosis (LC) and subsequent progression to

943
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

World Health Organization (WHO) there ti-cancer, anticlotting, anti-inflammatory,


are 130-170 million people infected with and analgesic activities (Chrubasik et al.,
the hepatitis C virus, corresponding to 2- 2005; Ali et al., 2008).
2.5 % of the world’s total population Nigella sativa (N. sativa) is used as a
(WHO, 2013). Egypt has the highest preva- food condiment in the Middle East, and its
lence of HCV worldwide (15 %) and the seeds/oil have been shown to possess anti-
highest prevalence of HCV-4 (67 %) with a inflammatory, antiviral and antineoplastic
predominance of subtype 4a (55 %) (Ngu- activity in various in vitro and in vivo stud-
yen and Keeffe, 2005; Elkady et al., 2009; ies (Zaher et al., 2008). There are many re-
Khattab et al., 2011, WHO, 2013). ports of its biological activities including:
The standard therapy, which is based on immunopotentiation, antitumor, anti-
a combination of pegylated interferon alpha inflammatory, analgesic, antihypertensive,
(IFN-α) and ribavirin (McHutchison et al., antidiabetic, respiratory stimulation, anti-
1998), results in highly variable outcomes, bacterial, antifungal, anticestode and
is very expensive and has severe side ef- antinematode effects (Ali and Blunden,
fects that are difficult to endure for the pa- 2003; Al-Naggar et al., 2003).
tients (Di Bisceglie and Hoofnagle, 2002; To date, studies addressed the use of
Calland et al., 2012). Therefore, the estab- ethanolic extracts of Z. officinale, N. sativa
lishment of a new treatment modality with- and their mixture in HCV patients are
out serious adverse effects is desirable scanty. Hence, we sought to evaluate the
(Vermehren and Sarrazin, 2011). efficacy, safety, and tolerability of Z. offici-
Medicinal plants have been found to nale and N. sativa extracts, individually and
play a major role in managing human dis- in combination, as an alternative therapy in
eases. Historically, numerous important the management of HCV patients.
modern drugs have been developed from
molecules originally isolated from natural MATERIALS AND METHODS
sources (Lee, 2000; Balunas and Kinghorn, This was a prospective, single-armed,
2005). The search for new bioactive mole- self-controlled pilot study, conducted at the
cules in plants in key therapeutic areas such Hepatology Unit, Gastroentrology Depart-
as immunosuppression, infectious diseases, ment, Beni-Suef University Hospital, Beni-
cancer and metabolic disorders is still an Suef University, Egypt.
active part of pharmaceutical research
(Newman and Cragg, 2012). About 40 new
Patients
drugs launched on the market between 2000 Sixty volunteer patients with proven
and 2010, originate from terrestrial plants, chronic HCV who were selected from ad-
terrestrial microorganisms, marine organ- mitted patients at the Hepatology Unit, Be-
isms, and terrestrial vertebrates and inver- ni-Suef University Hospital, with fifteen
tebrates (Brahmachari, 2011). age-matched healthy controls were included
Ginger (Zingiber officinale) is a well- in this study.
known and widely used herb, which con- Inclusion criteria included all patients
tains several interesting bioactive constitu- diagnosed with HCV and negative for
ents and possesses health-promoting prop- HBV. Exclusion criteria included patients
erties (Ajayi et al., 2013). From its origin in on IFN-α therapy; infection with HBV or
Southeast Asia and its spread to Europe, it hepatitis immunodeficiency virus; drug-
has a long history of use as herbal medicine induced liver diseases; advanced cirrhosis;
to treat a variety of ailments including vom- HCC or other malignancies; blood picture
iting, pain, indigestion, and cold induced abnormalities such as anemia (hemoglobin
syndromes (White, 2007). More recently, it concentration of 10 g/dl or less), leucopenia
was reported that ginger also possessed an- (white blood cells 1.500/µl or less) and

944
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

thrombocytopenia (platelets count 80.000/µl Clinical and laboratory assessment


or less); major severe illness such as renal All eligible patients and controls were
failure, congestive heart failure, respiratory subjected to the following at enrollment and
failure or autoimmune disease; or non- after 1 month therapy: (1) Full clinical as-
compliance to treatment. Informed consent sessment with an emphasis on hepato-
was obtained from all patients, and the in- and/or splenomegaly, jaundice, palmar ery-
stitutional ethical committee approved the thema, flapping tremors, spider naevi, low-
study protocol, which conformed with the er-limb edema, and ascites; (2) Laboratory
ethical guidelines of the 1975 Declaration investigation of liver functions including
of Helsinki. aspartate aminotransferase (AST) and ala-
nine aminotransferase (ALT) were assayed
Extract preparation according to the method of Schumann and
N. sativa seeds and Z. officinale rhi- Klauke (2003) using reagent kit purchased
zomes were purchased from the local herb- from Noble Diagnostic (Egypt); lactate de-
alist in Egypt. The seeds and rhizomes were hydrogenase (LDH) was determined ac-
authenticated by a specialist of Plant Tax- cording to the method of Teitz (1986) using
onomy in Botany Department, Faculty of reagent kit purchased from Human (Ger-
Science, Beni-Suef University, Egypt. Both many); alkaline phosphatase (ALP) was
were cleaned, dried, mechanically pow- assayed according to the International Fed-
dered, extracted with 96 % ethanol and eration of Clinical Chemistry (IFCC, 1980)
evaporated with rotary evaporator to render using BioSystem (Spain) commercial kit,
the extract alcohol free. The extracts were gamma glutamyl transferase (γGT) assay
made into soft gelatin capsules, each con- was performed according to Persijn and van
taining 500 mg of N. sativa and/or Z. offici- der Slik (1976) using kits from Reactivos
nale extracts. The above procedures were GPL (Spain); albumin was assayed accord-
undertaken in the Arab Company for Phar- ing to the method of Webster (1974) using
maceuticals & Medicinal Plants (Mepaco- kits of Diamond Diagnostic (Egypt); total
Medifood), Enshas EL Raml, Sharkeiya bilirubin, was determined using reagent kit
Factory, Sharkeiya, Egypt. purchased from Diamond Diagnostic
(Egypt), according to the method of Kaplan
Treatment protocol (1984) and prothrombin time (PT), pro-
Included patients and controls were thrombin concentration (PC) and interna-
classified into five groups each comprising tional normalized ratio (INR) were deter-
fifteen patients as follows; Group 1 served mined according to the method of Wanger
as healthy subjects; Group 2 (HCV) served and Dati (1998) using kits supplied by Sie-
as HCV control; Group 3 (HCV+N) re- mens Healthcare Diagnostic (USA) and (3)
ceived a capsule containing 500 mg N. sati- Serum α-fetoprotein (AFP) was assayed
va extract twice daily; Group 4 (HCV+G) according to Forest and Pugeat (1987) us-
received a capsule containing 500 mg Z. ing kits purchased from VIDAS bio
officinale extract twice daily and Group 5 Merieux (France) and quantitative real time
(HCV+NG) received a capsule containing polymerase chain reaction (qRT-PCR) for
500 mg of each extract twice daily. Patients HCV using Roche Amplicor HCV monitor
were followed up weekly throughout the version 2.0 (Roche Diagnostics, Branch-
study period for assessing treatment adher- burg, NJ), with lower detection limit < 50
ence, tolerability and incidence of adverse IU/ml.
reactions.
Statistical analysis
The data were statistically analyzed us-
ing SPSS v.16. Results were expressed as

945
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Mean ± Standard error (SE) and all statisti- mixture seemed to be more effective in re-
cal comparisons were made by means of ducing serum AFP levels.
one-way ANOVA test followed by Dun-
can’s multiple range test post hoc analysis.
A P value less than 0.05 was considered
significant.

RESULTS
The effects of N. sativa, Z. officinale
and their mixture on viral load of control
and treated patients were depicted in Figure
1. After one month treatment with N. sativa
and/or Z. officinale ethanolic extracts, pa- Figure 2: Serum AFP in healthy, HCV control
tients exhibited a significant (P<0.001) de- and treated patients. Data are expressed as
crease in viral load as compared to HCV mean ± SE, means which share the same su-
control group. The recorded data were perscript symbol(s) are not significantly differ-
145.13 ± 26.93, 152.13 ± 29.73 and 102.93 ent, P<0.001.
± 12.89 for HCV+N, HCV+G and
HCV+NG groups, respectively. Treatment The activities of serum liver marker en-
with the mixture of both extracts seemed to zymes, AST, ALT, γGT, LDH and ALP,
be the most effective in reducing viral load were represented in Figure 3a-e. The HCV
and there were five cases who showed a control group exhibited significantly
non-detectable viremia. (P<0.001) elevated serum activities of all
assayed enzymes when compared to the
corresponding healthy subjects. Admin-
istration of N. sativa, Z. officinale and their
mixture significantly (P<0.001) ameliorated
the elevated liver marker enzymes. Al-
though there were non-significant differ-
ences between the administered treatments
on liver marker enzymes, mixture of both
extracts offered more potent effect on de-
clining the elevated enzyme activities.
Serum albumin of the HCV control
Figure 1: Viral load in control and treated pa- group exhibited a significant (P<0.001) de-
tients. Data are expressed as mean ± SE, crease in comparison to healthy control
means which share the same superscript sym- group. On the other hand, serum total bili-
bol(s) are not significantly different, P<0.001. rubin showed an opposite pattern, where it
was significantly (P<0.001) elevated in
HCV control patients as compared to their
The serum concentrations of AFP were corresponding healthy subjects (Table 1).
significantly (P<0.001) elevated in HCV Similarly, PT and INR were significantly
control patients as compared to the corre- (P<0.01) elevated in HCV control group,
sponding healthy subjects (Figure 2). On while PC was significantly (P<0.05) de-
the other hand, all treatments were very ef- clined. All previously mentioned parame-
fective in alleviating the elevated AFP lev- ters were potentially improved following
els. However, while all used treatments treatment with N. sativa and/or Z. offici-
have more or less similar effects, the used nale.

946
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Figure 3: Serum liver enzymes of healthy, HCV control and HCV treated patients; (a) ALT, (b) AST,
(c) γGT, (d) LDH and (e) ALP. Data are expressed as mean ± SE, means which share the same su-
perscript symbol(s) are not significantly different, P<0.001.

DISCUSSION drug-resistant viruses have urged a growing


Chronic hepatitis C is a major global need for developing new, more effective
health burden with an estimated 160 million chemotherapeutic agents with less side ef-
infected individuals worldwide. This long- fects for successful HCV treatment (Sheir
term disease evolves slowly, often leading et al., 2013). In the current study, admin-
to chronicity and potentially to liver failure istration of N. sativa, Z. officinale and their
(Calland et al., 2012). The lack of vaccine mixture resulted in a significant decrease in
for HCV infections, the high cost of the viral load and AFP, with a more potent ef-
drugs specially in low-income countries fect offered by the mixture. We hypothe-
with a high prevalence of HCV, ineffective sized that efficacy of the mixture might be
attributed to the synergistic effect of the
therapy and the rapid emergence of new
included active compounds.

947
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Table 1: Albumin, total bilirubin, PT, PC and INR in healthy, HCV and HCV treated patients
Albumin Total Bilirubin PT PC INR
(g/dl) (mg/dl) (Sec) ( %)

Healthy 4.57 ± 0.09a 0.21 ± 0.03c 12.86 ± 0.06b 95.68 ± 0.65c 1.05 ± 0.01b

HCV Control 3.69 ± 0.09b 0.83 ± 0.08a 13.69 ± 0.19a 88.61 ± 1.47d 1.13 ± 0.02a

HCV + N 4.32 ± 0.11a 0.37 ± 0.07bc 11.93 ± 0.24d 105.94 ± 2.89a 0.95 ± 0.02d
HCV + G 4.29 ± 0.11a 0.46 ± 0.05b 12.49 ± 0.24cb 99.75 ± 2.35cb 1.01 ± 0.03bc

HCV + NG 4.47 ± 0.08a 0.42 ± 0.06b 12.17 ± 0.14cd 102.68 ± 1.55ab 0.98 ± 0.02cd

F-Prob. P<0.001 P<0.001 P<0.001 P<0.001 P<0.001

Data are expressed as mean ± SE, means which share the same superscript symbol(s) are not signifi-
cantly different.

Barakat et al. (2013) revealed that N. been identified so far. One of these involves
sativa administration resulted in a signifi- marked induction of reactive oxygen spe-
cant decrease in viral load, with 16.67 % of cies (ROS) in infected cells leading to oxi-
patients becoming seronegative, and 50 % dative stress (Ivanov et al., 2013). In addi-
showing a significant decrease in the quan- tion, HCV-related fibrosis, cirrhosis and
titative viral count. Among these, 66.7 % liver failure have been found to be the re-
had cirrhosis and 33.3 % had chronic liver sult of an adaptive immune response to
disease, implying antiviral activity. Also, HCV-infected cells (Nelson, 2001), which
the anti-inflammatory, antiviral and is mediated by induction of endoplasmic
antineoplastic activities of N. sativa have reticulum and oxidative stress, and down-
been previously documented in various in regulation of the antiapoptotic proteins, nu-
vitro and in vivo studies (Zaher et al., clear factor-κB and Bcl-xl, in infected
2008). To our best knowledge no studies hepatocytes (Joyce and Tyrrell, 2010).
have explored the therapeutic effects of Z. Thymoquinone, the main constituent of
officinale extract in HCV patients. Hence, N. sativa seeds, protects organs against oxi-
we assumed that the observed beneficial dative damage induced by a variety of free
therapeutic effects of the used extract might radical generating pathologies (Tekeoglu et
be attributed to its rich content of the anti- al., 2007; Kanter, 2008; Radad et al., 2009).
oxidant and anti-inflammatory compounds. In addition, many studies have addressed
It is relevant here to mention the in- the hepatoprotective effects of thymoqui-
volvement of oxidative stress in the patho- none (Nagi and Mansour, 2000; Meral et
genesis of hepatic dysfunction in human al., 2001; El-Dakhakhny et al., 2002;
which has been investigated for many years Mahmoud et al., 2002). Furthermore, a
(Spirli et al., 2001; Alpini et al., 2002; Ce- study by Salem and Hossain (2000) record-
saratto et al., 2004; Jabłonowska et al., ed a striking reduction of murine cytomeg-
2005). HCV infection often leads to liver alovirus titer in both spleen and liver of
fibrosis and cirrhosis, various metabolic mice treated with N. sativa compared with
alterations including steatosis, insulin and control mice.
interferon resistance, and development of Regarding antioxidant content, Z. offici-
hepatocellular carcinoma or non-Hodgkin nale is the third amongst 1000 food items
lymphoma. Multiple molecular mechanisms analysed by Halvorsen et al. (2006). [6]-
that trigger the emergence and development Dehydroshogaol, [6]-shogaol and 1-
of each of these pathogenic processes have dehydro-[6]-gingerdione were shown to be

948
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

potent inhibitors of nitric oxide (NO) syn- zymes are considered the most sensitive
thesis in activated macrophages as reported markers of liver injury as they are found in
by Li et al. (2011). The antioxidant activity the cytoplasm of liver cells, thus damage of
of [6]-gingerol against linoleic acid autoxi- these cells lead to their rapid leakage into
dation and phospholipids peroxidation has the blood circulation (Ramaiah, 2007). The
been demonstrated earlier (Ippoushi et al., present investigation showed a significant
2003). In addition, it has been found to pro- increase in serum ALT, AST, LDH, γGT
tect against cellular damages induced by and ALP activities and total bilirubin levels
peroxynitrite (Ippoushi et al., 2003). It pro- of untreated HCV patient as compared to
tected DNA from lipopolysaccharide- healthy subjects. The significantly elevated
induced oxidation damage in rats (Ippoushi liver enzymes could be attributed to viral-
et al., 2007). In the study conducted by Du- induced hepatocellular damage. On the oth-
gasani et al. (2010), [6]-shogaol has exhib- er hand, administration of N. sativa, Z. of-
ited the most potent antioxidant properties, ficinale and their mixture greatly improved
compared to [6]-gingerol, [8]-gingerol and the altered serum liver enzymes and this
[10]-gingerol. The recorded antioxidant ef- may be mediated through their hepatopro-
ficacy of [6]-shogaol can be attributed to tective effects.
the presence of α,β-unsaturated ketone moi- In consistent with our results, a recent
ety (Dugasani et al., 2010). Moreover, the study by Barakat et al. (2013) showed that
contained phenolic compounds of ginger, N. sativa seed oil potentially alleviated se-
such as gingerol and shogoal, possess anti- rum liver marker enzymes in Egyptian
oxidant (Jeyakumar et al., 1999), anti- HCV patients. They also revealed that N.
cancer (Shukla and Singh, 2007), anti- sativa oil administration was tolerable, safe,
inflammatory (Hudson et al., 2006; Habib decreased viral load, and improved oxida-
et al., 2008), anti-angiogenesis (Huang et tive stress and clinical condition. Mallikar-
al., 2000) and anti-artherosclerotic proper- juna et al. (2008) demonstrated that oral
ties (Coppola and Novo, 2007). Further- administration of 200 mg/kg ginger etha-
more, the phagocytic activity of blood leu- nolic extract along with country-made liq-
kocytes was increased in rainbow trout fed uor significantly alleviated the elevated se-
with plant extracts containing food, espe- rum AST, ALT and ALP activities as well
cially 1 % ginger (Dügenci et al., 2003). as tissue lipid peroxide levels in experi-
Zhou et al. (2006) demonstrated that the mental animals. Moreover, Lebda et al.
volatile oil of ginger influences both cell- (2012) reported that rabbits fed with basal
mediated immune response and non- diet supplemented with 2 % ginger powder
specific proliferation of T lymphocyte, and and ginger extract; hot and cold for 30 days
may exert beneficial effects in a number of showed significant decrease of serum AST,
clinical conditions, such as chronic inflam- ALT, ALP and γGT activities as compared
mation and autoimmune diseases. Hence, with control group. Furthermore, many
the observed antiviral potential of N. sativa studies had addressed the potent hepatopro-
and/or Z. officinale was mediated through tective effect of ginger extract in induced
their antioxidant, immunomodulatory and hepatotoxicity (Mallikarjuna et al., 2008;
anti-inflammatory efficacies. El-Sharaky et al., 2009; Motawi et al.,
The role of liver enzymes in the as- 2011).
sessment of chronic hepatitis C remains Serum albumin is the most abundant
important due to the fact that the majority plasma protein (Don and Kaysen, 2004) and
of clinical indexes estimating the degree of is essential for maintaining oncotic pressure
liver fibrosis are based on liver transami- of the vascular system (Quinlan et al.,
nases (Giannini and Testa, 2003; Forns et 2005). Serum albumin and prothrombin
al., 2004; Lackner et al., 2005). These en- time can be considered useful tools, alone

949
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

or combined in clinical scores, for evaluat- REFERENCES


ing liver function (Botta et al., 2003). Ajayi OB, Akomolafe SF, Akinyemi FT.
Chronic HCV patients may suffer a de- Food value of two varieties of Ginger (Zin-
crease in serum albumin level (Mason et al., giber officinale) commonly consumed in
1999), and improvement in hypoalbu- Nigeria. ISRN Nutr 2013;2013:359727.
minemia has been shown to improve prog-
nosis (Nagao and Sata, 2010) and quality of Al-Gaby AM. Amino acid composition and
life (Kotoh et al., 2005). In addition, a re- biological effects of supplementing broad
cent study by Shin and Moon (2010) re- bean and corn proteins with Nigella sativa
ported that in chronic liver diseases, the se- (black cumin) cake protein. Nahrung 1998;
rum albumin level is reduced due to protein 42:290-4.
synthesis disruption in the liver. In the cur-
rent study, administration of ginger and N. Ali BH, Blunden G. Pharmacological and
sativa as well as their mixture significantly toxicological properties of Nigella sativa.
increased serum albumin levels, indicating Phytother Res 2003;17:299-305.
an improvement in clinical condition. Prior
studies have shown similar effects of N. sa- Ali BH, Blunden G, Tanira MO, Nemmar
tiva administration to animals (Al-Gaby, A. Some phytochemical, pharmacological
1998; Tollba and Hassan, 2003; Shewita and toxicological properties of ginger (Zin-
and Taha, 2011) and to HCV patients giber officinale Roscoe): a review of recent
(Barakat et al., 2013). Similarly, Motawi et research. Food Chem Toxicol 2008;46:
al. (2011) revealed the potency of Z. offici- 409–20.
nale in alleviating serum total protein and
bilirubin levels in carbon tetrachloride- Al-Naggar TB, Gómez-Serranillos MP,
induced liver fibrosis in rats. Carretero ME, Villar AM. Neuropharmaco-
Therefore, the potent therapeutic effects logical activity of Nigella sativa L. extracts.
offered by the mixture of N. sativa and Z. J Ethnopharmacol 2003;88:63-8.
officinale in this study may be attributed to
the synergism between their active constit- Alpini G, McGill J, Larusso N. The patho-
uents. Guimarães et al. (2011) reported that biology of biliary epithelia. Hepatology
the most potent antioxidant activity was 2002;35:1256-68.
found in combinations of different herbs,
suggesting synergistic effects. So the syn- Alter MJ. Epidemiology of hepatitis C virus
ergistic effect of using mixture of herbs are infection. World J Gastroenterol 2007;13:
designed to work together to produce a gen- 2436-41.
tle, balanced and greater effect to correct
underlying imbalances than temporary re- Anwar WA, Khaled HM, Amra HA, El-
lief (Liu and Du, 2012; Sarg et al., 2012; Nezami H, Loffredo CA. Changing pattern
Rajput and Mandal, 2012). of hepatocellular carcinoma (HCC) and its
In conclusion, our findings suggest that risk factors in Egypt: possibilities for pre-
administration of both N. sativa and/or Z. vention. Mutat Res 2008;659:176-84.
officinale ethanolic extracts to HCV pa-
tients was safe, tolerable, decreased viral Balunas MJ, Kinghorn AD. Drug discovery
load, and improved clinical condition. In from medicinal plants. Life Sci 2005;78:
addition, the current study recommends the 431–41.
use of mixtures of herbal therapy to in-
crease their synergetic effects against HCV
and decrease their side effects.

950
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Barakat EMF, El Wakeel LM, Hagag RS. Dugasani S, Pichika MR, Nadarajah VD,
Effects of Nigella sativa on outcome of Balijepalli MK, Tandra S, Korlakunta JN.
hepatitis C in Egypt. World J Gastroenterol Comparative antioxidant and anti-inflam-
2013;19:2529-36. matory effects of [6]-gingerol, [8]-gingerol,
[10]-gingerol and [6]-shogaol. J Ethno-
Botta F, Giannini E, Romagnoli P, Fasoli pharmacol 2010;127:515-20.
A, Malfatti F, Chiarbonello B et al. MELD
scoring system is useful for predicting Dügenci SK, Arda N, Candan A. Some me-
prognosis in patients with liver cirrhosis dicinal plants as immunostimulant for fish.
and is correlated with residual liver func- J Ethnopharmacol 2003;88:99-106.
tion: a European study. Gut 2003;52:134-9.
El-Dakhakhny M, Mady N, Lembert N,
Brahmachari G. Natural products in drug Ammon HP. The hypoglycemic effect of
discovery: impacts and opportunities - an Nigella sativa oil is mediated by extrapan-
assessment. In: Brahmachari G (ed.): Bio- creatic actions. Planta Med 2002;68:465-6.
active natural products (pp 1-199). Singa-
pore: World Scientific Publishing Co., Elkady A, Tanaka Y, Kurbanov F, Sugau-
2011. chi F, Sugiyama M, Khan A et al. Genetic
variability of hepatitis C virus in South
Calland N, Dubuisson J, Rouillé Y, Séron Egypt and its possible clinical implication. J
K. Hepatitis C virus and natural com- Med Virol 2009;81:1015-23.
pounds: a new antiviral approach? Viruses
2012;4:2197-217. El-Sharaky AS, Newairy AA, Newairy AA,
Kamel MA, Eweda SM. Protective effect of
Cesaratto L, Vascotto C, Calligaris S, Tell ginger extract against bromobenzene-
G. The importance of redox state in liver induced hepatotoxicity in male rats. Food
damage. Ann Hepatol 2004;3:86-92. Chem Toxicol 2009;47:1584-90.

Chrubasik S, Pittler MH, Roufogalis BD. Forest MG, Pugeat M (eds.). Binding pro-
Zingiberis rhizoma: a comprehensive re- teins of steroid hormones (pp 53-86). Col-
view on the ginger effect and efficacy pro- loque INSERM. Montrouge: Libbey, 1987.
files. Phytomedicine 2005;12:684–701.
Forns X, Ampurdanès S, Llovet JM, Apon-
Coppola G, Novo S. Statins and peripheral te J, Quintó L, Martínez-Bauer E et al.
arterial disease: effects on claudication, dis- Identification of chronic hepatitis C patients
ease progression, and prevention of cardio- without hepatic fibrosis by a simple predic-
vascular events. Arch Med Res 2007;38: tive model. Hepatology 2004;39:862-3.
479-88.
Giannini E, Testa R. Noninvasive diagnosis
Di Bisceglie AM, Hoofnagle JH. Optimal of fibrosis: The truth is rarely pure and nev-
therapy of hepatitis C. Hepatology 2002; er simple. Hepatology 2003;38:1312-3.
36:S121–7.
Guimarães R, Barros L, Carvalho AM, Fer-
Don BR, Kaysen G. Serum albumin: rela- reira IC. Infusions and decoctions of mixed
tionship to inflammation and nutrition. herbs used in Folk Medicine synergism in
Semin Dial 2004;17:432-7. antioxidant potential. Phytother Res 2011;
25:1209-14.

951
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Habib SH, Makpol S, Abdul Hamid NA, Jabłonowska E, Tchórzewski H, Lewko-


Das S, Ngah WZ, Yusof YA. Ginger ex- wicz P, Kuydowicz J. Reactive oxygen in-
tract (Zingiber officinale) has anti-cancer termediates and serum antioxidative system
and anti-inflammatory effects on ethionine- in patients with chronic C hepatitis treated
induced hepatoma rats. Clinics (Sao Paulo) with IFN-alpha and thymus factor X. Arch
2008;63:807-13. Immunol Ther Exp (Warszaw) 2005;53:
529–33.
Halvorsen BL, Carlsen MH, Phillips KM,
Bøhn SK, Holte K, Jacobs DR Jr et al. Con- Jeyakumar SM, Nalini N, Menon VP. Anti-
tent of redox-active compounds (ie, antiox- oxidant activity of ginger (Zingiber offici-
idants) in foods consumed in the United nale) in rats fed a high fat diet. Med Sci Res
States. Am J Clin Nutr 2006;84:95-135. 1999;27: 341-4.

Huang S, DeGuzman A, Bucana CD, Fidler Joyce MA, Tyrrell DL. The cell biology of
IJ. Nuclear factor-kappa B activity corre- hepatitis C virus. Microbes Infect 2010;12:
lates with growth, angiogenesis, and metas- 263-71.
tasis of human melanoma cells in nude
mice. Clin Cancer Res 2000;6:2573-81. Kanter M. Effects of Nigella sativa and its
major constituent, thymoquinone on sciatic
Hudson EA, Fox LH, Luckett JCA, Manson nerves in experimental diabetic neuropathy.
MM. Ex vivo cancer chemoprevention re- Neurochem Res 2008;33:87-96.
search possibilities. Environ Toxicol Phar-
macol 2006;21:204-14. Kaplan LA. Glucose. In: Kaplan LA, Pesce
AJ: Clinical chemistry: theory, analysis,
IFCC. Methods for the measurement of cat- and correlation (pp 1032-6). St. Louis, MO:
alytic concentration of enzymes. J Clin Mosby, 1984.
Chem Clin Biochem 1980;18:521-34.
Khattab MA, Ferenci P, Hadziyannis SJ,
Ippoushi K, Azuma K, Ito H, Horie H, Hi- Colombo M, Manns MP, Almasio PL et al.
gashio H. [6]-Gingerol inhibits nitric oxide Management of hepatitis C virus genotype
synthesis in activated J774.1 mouse macro- 4: recommendations of an international ex-
phages and prevents peroxynitrite-induced pert panel. J Hepatol 2011;54:1250-62.
oxidation and nitration reactions. Life Sci
2003;73:3427-37. Kotoh K, Nakamuta M, Fukushima M,
Matsuzaki C, Enjoji M, Sakai H et al. High
Ippoushi K, Takeuchi A, Ito H, Horie H, relative fat-free mass is important for main-
Azuma K. Antioxidative effects of daikon taining serum albumin levels in patients
sprout (Raphanus sativus L.) and ginger with compensated liver cirrhosis. World J
(Zingiber officinale Roscoe) in rats. Food Gastroenterol 2005;11:1356-60.
Chem 2007;102:237-42.
Lackner C, Struber G, Liegl B, Leibl S, Of-
Ivanov AV, Bartosch B, Smirnova OA, ner P, Bankuti C et al. Comparison and val-
Isaguliants MG, Kochetkov SN. HCV and idation of simple noninvasive tests for pre-
oxidative stress in the liver. Viruses 2013; diction of fibrosis in chronic hepatitis.
5:439-69. Hepatology 2005;41:1376-82.

Lavanchy D. Evolving epidemiology of


hepatitis C virus. Clin Microbiol Infect
2011;17:107-15.

952
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Lebda MA, Taha NM, Korshom MA, Man- Meral I, Yener Z, Kahraman T, Mert N. Ef-
dour AEA, El-Morshedy AM. Biochemical fect of Nigella sativa on glucose concentra-
effect of ginger on some blood and liver tion, lipid peroxidation, anti-oxidant de-
parameters in male New Zealand rabbits. fence system and liver damage in experi-
Online J Anim Feed Res 2012;2(2):197- mentally-induced diabetic rabbits. J Vet
202. Med A Physiol Pathol Clin Med 2001;48:
593-9.
Lee KH. Research and future trends in the
pharmaceutical development of medicinal Motawi TK, Hamed MA, Shabana MH,
herbs from Chinese medicine. Public Hashem RM, Aboul Naser AF. Zingiber
Health Nutr 2000;3:515–22. officinale acts as a nutraceutical agent
against liver fibrosis. Nutr Metab (London)
Li F, Wang Y, Parkin KL, Nitteranon V, 2011;8:40.
Liang J, Yang W et al. Isolation of quinone
reductase (QR) inducing agents from ginger Nagao Y, Sata M. Serum albumin and mor-
rhizome and their in vitro anti-inflam- tality risk in a hyperendemic area of HCV
matory activity. Food Res Int 2011;44: infection in Japan. Virol J 2010;7:375.
1597-603.
Nagi MN, Mansour MA. Protective effect
Liu A-L, Du G-H. Antiviral properties of of thymoquinone against doxorubicin-
phytochemicals. In: Patra AK (ed.): Dietary induced cardiotoxicity in rats: a possible
phytochemicals and microbes (pp 93-126). mechanism of protection. Pharmacol Res
Dordrecht: Springer Sciene+Business Me- 2000;41:283–9.
dia, 2012.
Nelson DR. The immunopathogenesis of
Mahmoud MR, El-Abhar HS, Saleh S. The hepatitis C virus infection. Clin Liver Dis
effect of Nigella sativa oil against the liver 2001;5:931-53.
damage induced by Schistosoma mansoni
infection in mice. J Ethnopharmacol 2002; Newman DJ, Cragg GM. Natural products
79:1–11. as sources of new drugs over the 30 years
from 1981 to 2010. J Nat Prod 2012:75;
Mallikarjuna K, Sahitya Chetan P, Sath- 311–35.
yavelu Reddy K, Rajendra W. Ethanol tox-
icity: rehabilitation of hepatic antioxidant Nguyen MH, Keeffe EB. Prevalence and
defense system with dietary ginger. Fito- treatment of hepatitis C virus genotypes 4,
terapia 2008;79:174-8. 5, and 6. Clin Gastroenterol Hepatol 2005;
3:S97-S101.
Mason AL, Lau JY, Hoang N, Qian K, Al-
exander GJ, Xu L et al. Association of dia- Persijn JP, van der Slik W. A new method
betes mellitus and chronic hepatitis C virus for the determination of gamma-glutamyl-
infection. Hepatology 1999;29:328-33. transferase in serum. J Clin Chem Clin Bio-
chem 1976;14:421-7.
McHutchison JG, Gordon SC, Schiff ER,
Shiffman ML, Lee WM, Rustgi VK et al. Quinlan GJ, Martin GS, Evans TW. Albu-
Interferon alfa-2b alone or in combination min: biochemical properties and therapeutic
with ribavirin as initial treatment for chron- potential. Hepatology 2005;41:1211-9.
ic hepatitis C. Hepatitis Interventional
Therapy Group. N Engl J Med 1998;339:
1485–92.

953
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

Radad K, Moldzio R, Taha M, Rausch WD. Shin M-O, Moon J-O. Effect of dietary
Thymoquinone protects dopaminergic neu- supplementation of grape skin and seeds on
rons against MPP+ and rotenone. Phytother liver fibrosis induced by dimethyl-nitro-
Res 2009;23:696-700. samine in rats. Nutr Res Pract 2010;4:369–
74.
Rajput S, Mandal M. Antitumor promoting
potential of selected phytochemicals de- Shukla Y, Singh M. Cancer preventive
rived from spices: a review. Eur J Cancer properties of ginger: A brief review. Food
Prev 2012;21:205-15. Chem Toxicol 2007;45:683-90.

Ramaiah S. A toxicologist guide to the di- Spirli C, Nathanson M, Fiorotto R, Duner


agnostic interpretation of hepatic biochemi- E, Denson L, Sanz J. Proinflammatory cy-
cal parameters. Food Chem Toxicol 2007; tokines inhibit secretion in rat bile duct epi-
45:1551–7. thelium. Gastroenterology 2001;121:156-
69.
Salem ML, Hossain MS. In vivo acute de-
pletion of CD8(+) T cells before murine Teitz N. Fundamentals of clinical chemis-
cytomegalovirus infection upregulated in- try. Philadelphia, PA: Saunders, 1986.
nate antiviral activity of natural killer cells.
Int J Immunopharmacol 2000;22:707-18. Tekeoglu I, Dogan A, Ediz L, Budan-
camanak M, Demirel A. Effects of thymo-
Sarg T, Abdel-Ghani A, Zayed R, El-Sayed quinone (volatile oil of black cumin) on
M. Bioactive compounds from Phyllanthus rheumatoid arthritis in rat models. Phytoth-
atropurpureus. J Nat Prod 2012;5:10-20. er Res 2007;21:895-7.

Schumann G, Klauke R. New IFCC refer- Tollba AAH, Hassan MSH. Using some
ence procedures for the determination of natural additives to improve physiological
catalytic activity concentrations of five en- and productive performance of broiler
zymes in serum: preliminary upper refer- chicks under high temperature conditions 2-
ence limits obtained in hospitalized sub- black cumin (Nigella Sativa) or garlic (Alli-
jects. Clin Chem Acta 2003;327:69-79. um sativum). Egypt Poul Sci 2003;23:327-
40.
Sheir Z, Badra G, Salama O, Gomaa AI,
Saber W. Effect of combination of some Vermehren J, Sarrazin C. New hepatitis C
natural products and chloroquine on HCV therapies in clinical development. Eur J
infection in Egyptian patients: Pilot study. J Med Res 2011;16:303-14.
Liver 2013;2:116.
Wanger C, Dati F. Prothrombin time (PT)
Shewita RS, Taha AE. Effect of dietary test. In: Thomas L (ed): Cilinical laboratory
supplementation of different levels of black diagnostics (pp 599-601). Frankfurt: TH-
seed (Nigella Sativa L.) on growth perfor- books Verlagsges., 1998.
mance, immunological, hematological and
carcass parameters of broiler chicks. World Webster D. A study of the interaction of
Academy of Science, Engineering and bromcresol green with isolated serum glob-
Technology (WASET) 2011;53:788-94. ulin fractions. Clin Chim Acta 1974;53:
109-15.

White B. Ginger: an overview. Am Family


Phys 2007;75:1689–91.

954
EXCLI Journal 2013;12:943-955 – ISSN 1611-2156
Received: July 31, 2013, accepted: October 28, 2013, published: November 11, 2013

World Health Oranization. Hepatitis C. Up-


dated July.
http://www.who.int/mediacentre/factsheets/
fs164/en/index.html.

Zaher KS, Ahmed WM, Zerizer SN. Obser-


vations on the biological effects of black
cumin seed (Nigella sativa) and green tea
(Camellia sinensis). Global Veterinaria
2008;2:198-204.

Zhou H, Deng Y, Xie Q. The modulatory


effects of the volatile oil of ginger on the
cellular immune response in vitro and in
vivo in mice. J Ethnopharmacol 2006;105:
301-5.

955

S-ar putea să vă placă și