Download Nigella sativa

PRESENTED BY
DR.OSAMA MOUSTAFA EL-FAYOUMI
Consultant Clinical Pathology
Sub-speciality of Haematology
Chief Of All Labs SGH Group
Madinah Munawarah – KSA
Black seed is a gift to medicine!!
INTRODUCTION
While the main principle of success in using the medical
description of (Prophetic Medicine) is to believe in it but also
we have to go for the scientific explanation for the disease
and its pathogenecity as well. The medicine described, its
mechanism of action and how it will treat? what is the dose?,
what are the drug interactions? and what could cause
synergism for its action?
In that topic our disease is Hep C virus infection and its
complications. Our recommended medicine is Nigella sativa
(Black seed).
Nigella sativa (N. sativa) is used as a food
condiment in the Middle East, and its seeds/oil
have been shown to possess antiinflammatory,
antiviral and antineoplastic activity in various in
vitro and in vivo studies (Zaher et al., 2008).
So we start the discussion hepatitis C Virus
pathogenesis.
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Pathogenesis
A molecular mechanisms that trigger the emergence and
development of each of the pathogenic processes have
been identified as marked induction of a “Reactive
Oxygen Species” (ROS) in infected cells leading to
oxidative stress. To date, markers of oxidative stress were
observed both in chronic hepatitis C patients and in
various in vitro systems, including replicons or stable cell
lines expressing viral proteins.
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Direct measurements in liver tissue from CHC patients
revealed
An increase of ROS ( Reactive Oxygen Species)
concentrations by 2 - 5 orders of magnitude.

A significant increase was also described in lymphocytes of
patients with chronic and occult HCV infection.


These data are backed up by a number of papers reporting :1- Elevated level of total pro-oxidant activity.
2- CHC patients also display decreased levels of
antioxidant defence enzymes.
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HCV has been shown to activate several different
pathways that lead to ROS ( Reactive Oxygen Species)
production, both in hepatocytes and blood cells,
which reside in liver.

Most researchers were focused on revealing ROS
sources inside hepatocytes.

Induction of oxidative stress in these cells has been
assigned to almost all HCV proteins

So, ROS ( Reactive Oxygen Species) is the corner stone
for pathogenesis.
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Schematic representation of mechanisms of oxidative stress
induction in the HCV-infected cells.
 Activation of mitochondrial Ca2+.
Enhanced passive leakage of the ions from the Endoplasmic
Reticulum(ER) and suppressed SERCA pump, responsible
for Ca2+ import into the ER.
 Hepatitis C virus (HCV) proteins induces NADPH oxidases
(Nox) 1 & 4 which contribute to production of H2O2 & O2
 Finally, the ROS (reactive oxygen species) can be generated
through ER (endoplasmic reticulum) cytochrome P450, 2E1
and induced ER (endoplasmic reticulum) stress.

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Oxidative Stress and HCV-Associated
Diseases
HCV infection is associated with various hepatic and
extrahepatic disorders, and oxidative stress leads to liver
injury.
For example, ROS levels, measured in liver using Electron
Paramagnetic Resonance Imaging, correlate with histological
disease
activity
although
not
with
levels
of
serum
transaminases.
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Also Hepatocellular Carcinoma

Oxidative stress is considered as one of the mechanisms, by
which HCV promotes proliferation of hepatocytes and
triggers HCC.

Increased risk on HCC is associated with a polymorphism in
the gene, which encodes an antioxidant defense enzyme. So,
oxidation is increased *oxidative stress*
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Oxidative stress leads to
• DNA damage
• Accumulation of mutations.
Second, formation of HC Carcinoma was shown to depend on
peroxisome proliferator-activated receptor alpha (PPARα)
transcription factor,
e.g., Liver Fibrosis
They include accumulation of DNA damage in response
to ROS ( Reactive Oxygen Species) augmented by
suppressed reparation processes.
 Liver fibrosis is another hepatic dysregulation induced
by oxidative stress in the HCV-infected liver.
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Beneficial Therapeutic Effects of Nigella sativa and/or
Zingiber officinale In HCV Patients in Egypt

Ethanolic extracts of Nigella sativa and Zingiber officinale were
prepared and formulated into gelatinous capsules

Each containing 500mg 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
1- Significantly ameliorated the altered viral load ,alpha fetoproein
2- Liver function parameters ( with more potent effect for the
combined therapy).
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In that study,
Patients: Sixty volunteer patients with proven chronic HCV
who were selected
Inclusion Criteria: Inclusion criteria included all patients
diagnosed with HCV and negative for HBV.
Exclusion Criteria: Exclusion criteria included patients:• On on IFN-α therapy
• Infection with HBV
• Hepatitis immunodeficiency virus
• Drug induced liver diseases
• Advanced cirrhosis
• HCC or other malignancies
• Major severe illness such as renal failure, congestive heart
failure, respiratory failure or
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Extract Preparation: The extracts were made into
soft gelatin capsules, each containing 500 mg of
Nigella sativa and/or Z. officinale extracts.
Treatment protocol: Its classified into five groups:-
Group 1 served as healthy subjects
Group 2 (HCV) served as HCV control
Group 3 (HCV+N) received a capsule containing 500
mg N. sativa extract twice daily
Group 4 (HCV+G) received a capsule containing 500
mg Z. officinale extract twice daily
Group 5 (HCV+NG) received a capsule containing
500 mg of each extract twice daily.
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Clinical & Laboratory Assessment:
• Full clinical assessment with an emphasis on hepatoand/
or splenomegaly, jaundice, palmar erythema..........
• Laboratory investigations of AST, ALT, LDH, ALP, γGT,
albumin, total bilirubin, PT, PC, INR
• Serum α-fetoprotein (AFP) was assayed
• Quantitative real time polymerase chain reaction (qRT-
PCR) for HCV
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Results:
Treatment with the mixture of both extracts (N.S +
Zing) seemed to be the most effective in reducing
viral load and
there were five cases
who showed
a non detectable viremia
complete cure.
19
Reference:
In that study
Figure 1:
Viral load in control and treated patients. Data are expressed
as mean ± SE, means which share the same superscript symbol( s) are not
significantly different, P<0.001.
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The used mixture seemed to be more effective in reducing
serum AFP levels.
Figure 2: Serum AFP in healthy, HCV control and treated patients. Data
are expressed as mean ± SE, means which share the same superscript
symbol(s) are not significantly different, P<0.001.
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
The activities of serum liver marker enzymes, AST, ALT,
γGT, LDH and ALP were potentially improved following
treatment with N. sativa and/or Z. officinale.

Serum albumin of the HCV control group exhibited a
significant (P<0.001) decrease in comparison to healthy
control group.
The efficacy of the mixture might be attributed to the
synergistic effect of the included active compounds of
Nigella sativa + Zingabele.
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Figure 3: Serum liver enzyme s 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 superscript
symbol(s) are not significantly different, P<0.001.
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N.B:-
Thymine, the main constituent of N. sativa seeds, protects
organs against oxidative damage induced by a variety of free
radical generating pathologies
So, the administration of both N. sativa and/or Z. officinale
ethanolic extracts to HCV patients was safe, tolerable,
decreased viral load, and improved clinical condition. In
addition, the current study recommends the use of mixtures of
herbal therapy to increase their synergetic effects against HCV
and decrease their side effects.
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General Anti-viral effect:

In vivo treatment with N. sativa oil induced a striking
anti-viral
effect
against
MCMV
(Murine
CMV)
infection, indicating a promising therapeutic potential of
N. sativa oil as an anti-viral remedy.

Antiviral effect of the N. sativa oil is associated with
enhancing
response
of
CD4
and
CD8
cells,
augmenting their ability of IFN-g production that is
known to render mice more resistant to MCMV
infection.
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
NK cells and specific cells including CD4 and CD8 T
cells plays a central anti-viral role at a certain time
point post infection and this is helped by Nigela sativa

Eventually, the anti-oxidant effect of the N. sativa oil
may represent another mechanism that contributes to
its anti-viral activity.
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Effect of Nigella sativa against
complications of HCV
e.g, Hepatocellular carcinoma
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HCC as complication of HCV
Role of Nigela sativa to supress ROS
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Fig:- N. sativa shows a vital effect in the prevention of cancer through upregulation of tumor suppressor gene and inhibition of VEGF,
Akt/PI3K pathways .
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Complications of HCV even HC Carcinoma
Protective effect of Nigella sativia seeds against
dimethyl/aminoazo/benzene (DAB) which can induce HCC

The effect of
Nigella sativa has been evaluated in
animal studies. There are many reports on its biological
activities including

anti-tumor, Immunopotentiation,

antiinflammatory, analgesic, antihypertensive, anti-
diabetic, respiratory stimulation,

anti-bacterial, antifungal, anticestode and
antinematode effects.
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In that study (HCC),
Animals were divided into 4 groups each
containing 35 rats.
 The first is the untreated control group.
 The second is the carcinogen treated group with
0.05% DAB mixed with diet.
 The third group is the N. sativa control group
treated only with 5.0 % grinded seeds of N.
sativa mixed with diet.
 The fourth group is the treated with 5.0 % N.
sativa plus 0.05% of DAB mixed with diet.

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Table 1. The levels of the ALT, AST, total protein, albumin, and ALP
recorded in the different experimental groups.
From these two figures, its shown that N.S inhibit the carcinogenic effect
of DAB in induc ing HCC I.e, complication of HCV
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In histomorphology Analysis,

In the control untreated group---- Strictly normal architecture

DAB treated group showed---- Dysplasia of liver cells.
----cholangiocarcinoma. 57.1%

Regarding the N. sativa treated group---- Absolutely
normal
architecture (like control group)

DAB plus N. sativa treated group,
•28.6% of them showed RESISTANT bile duct proliferation
•71.4%
NO cirrhosis, NO bile duct proliferation, dysplasia
or carcinoma
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DAB is affecting the liver negatively by increasing the
level of perioxidation and meanwhile decreasing the
level of antioxidant protecting enzymes.
And its proved that Nigella sativa prevent its action.
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N. sativa combined with DAB treatment can effectively
maintain the protective enzymatic balance.
The prominent antioxidant activity of N. sativa was extensively
documented in different experimental situations, including
hepatocarcinogenesis
In many studies, these results give clear evidence that Nigella
sativa lonely induce no harmful effects on the liver.
It exerts hepatoprotective
carcinogens.
effect
against
hepatobiliary
Antioxidant property is mediated its actions.
Investigating other underlying mechanisms merits further
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studies.
Conclusion
Nigella sativa has its multifactorial effect on the HCV
infection, illness course, outcome and prevention of
complications. As it has its antiviral goal effect to
prevent viral infection. the anti-oxidant effect of
Nigella sativa oil may represent another mechanism
that contributes to its anti-viral activity.
Anti-inflammatory,
antiviral
and
antineoplastic
activities of Nigella sativa have been previously
documented in various in vitro and in vivo studies
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Administration of Nigella sativa and/or Zingiber
officinale ethanolic extracts to HCV patients
exhibited potential therapeutic benefit
Even with HCV Complication (Hepatocellular
Carcinoma) it has its general antineoplastic role.
It
exerts
hepatoprotective
effect
against
hepatobiliary carcinogens. Antioxidant property
is mediating its actions. Investigating other
underlying mechanisms merits further studies
until reaching to be FDA approved documented
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