Research Paper Medical Sciences Volume : 1 | Issue : 2 | Dec 2015

EXPLORATION
&
WONDERS
OF
MEDICINAL
PLANT

“ASAFOETIDA”(HEENG)
CONSTITUENT
GALBANIC
ACID

AS
ANTICANCEROUS
AND
ANTIMUTAGENIC
AGENT

1,2 1 1 1
* Syeda Sarah Abbas | Safila Naveed | Fatima Qamar | Saba Javed Hussain |
2
Syed Hameez Jawed
1
Faculty of Pharmacy, Jinnah University for Women. Karachi, Pakistan.
* Corresponding Author, Email Id : syedasarahabbas@yahoo.com
2
Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Pakistan.

ABSTRACT
Asafetida is a oleo-gum resin, it is a dried latex obtained from roots and rhizomes by incision. Asafetida is not only used as a culinary spice but
also traditionally used to treat various diseases, including asthma, gastrointestinal disorders and intestinal parasites. This oleo-gum-resin pos-
sess antifungal, anti-diabetic, anti-inflammatory, anti-mutagenic and antiviral, antispasmodic, antioxidant, ant diabetic, antimicrobial,
antiulcer ,anti hemolytic, chemo preventive. There are various chemical compounds comprises of sugars and polysulfide. Asafetida chiefly sub-
sumes resin (40-65%), gum (20-25%), and volatile oil (4-20%). The asafetida comprises a number of sesquiterpenes of which assaresinotannol is
the chief sesquiterpene. Asafetida is also used as a flavoring agent and used as a constituent of many spice mixtures. It is used to flavor, curries,
meatballs, daal and pickles. Asafetida is also used as a flavoring agent and used as a constituent of many spice mixtures. Galbanic acid (GBA) is
the active constituent present in the asafetida having anti cancerous activity, it provide inhibitory effects on HIF-1 activation during hypoxia
and normoxia. The investigation of galbanic acid (GBA) has done by fluorescence quenching, absorption spectroscopy, FT-IR, molecular dock-
ing and molecular dynamics (MD) simulation procedures.

Key word: oleo-gum resin, anti-mutagenic, antispasmodic, Galbanic acid(GBA), normoxia, fluorescence quenching, spectroscopy.

OBJECT:
The main assessment of this review article is to emphasize the most
latest and recent researches on anti cancerous effect of
ASAFEOTIDA (heeng), having different principle constituents
responsible in treating the lethal diseases.
INTRODUCTION:
Ferula asafetida belonging to family umbelliferae its plant is a tall
perennial which grows up to 2 m and needs a dry moist soil. The dried
latex and by making deep incision on the roots and rhizomes, an oleo-
gum-resin, known as asafetida is obtained.[1]. Asafoetida is not only
used as a culinary spice but also traditionally used to treat various dis-
eases, including asthma, gastrointestinal disorders, intestinal para-
sites, etc. This oleo-gum-resin possess antifungal, anti-diabetic, anti-
inflammatory, anti-mutagenic and antiviral actions .There are vari-
ous chemical compounds are found including sugars and
polysulfides.[2] . Asafoetida chiefly subsume resin (40-65%), gum (20-
25%), and volatile oil (4-20%).[2]
from different Ferula species, and were tested for their MDR reversal
properties. when combined with very non-toxic concentrations of the
sesquiterpene coumarins (50 μM) including umbelliprenin,
farnesiferol B, farnesiferol C and lehmferin, proved significant MDR
reversal activity of these coumarins.sesquiterpene coumarins
reverses the P-glycoprotein-mediated multidrug resistance in MCF-
7/Adr cancer cells[17].
ROLE OF GALLBANIC ACID:
Galbanic acid (GA) is a biologically active sesquiterpene coumarin is
obtaines from ferula species. This compound demonstrates various
biological properties including anticancer, cancer chemopreventive,
anticoagulant, antiviral, and antileishmanial activities. GA can
inhibit the growth of prostate cancer cells via decreasing androgen
receptor abundance.[18].Two new sesquiterpene coumarins isolated
from the plant Ferula narthex Boiss fnarthexone and fnarthexol,
with three coumarin derivatives, conferol , conferone and
umbelliferone[19].

The asafoetida comprises a number of sesquiterpenes of which
assaresinotannol is the chief sesquiterpene present in either free
form or in combined form with ferulic acid or galbanic acid,
[3]..Different studies have resonate that asafoetida exhibits numer-
ous pharmacological activities and act as therapeutically such as
antispasmodic[4,5], antifungal[6],antioxidant[7,8], antidiabetic[9],
antimicrobial[10], antiulcer[11], antihemolytic[8], chemoprev-
entive[12,13]antiviral[14]. Asafoetida is also used as a flavoring
agent and used as a constituent of many spice mixtures. It is used to
flavor, curries, meatballs, daal and pickles. Whereas the whole plant
is used as a fresh vegetable. This herb is also used as an antidote for
opium. Asafoetida has a reeking smell and a nauseating taste; charac-
teristics that also encumbrance with the name devil's dung. In Persia
asafoetida was used as a condiment and called the “food of the gods”.
This herb is the major component in the Ayurvedic system.[15].
Ferula gummosa Boiss. also has medicinal applications in treating a
cancer. seed and gum extracts possess a antiproliferative activities.
F. gummosa also having a effect on the induction of apoptosis and cell
cycle arrest. F. gummosa ethanol extract also used as a
chemotherapeutic agent.[16].The present study also demonstrate
that the fifteen sesquiterpene coumarins were isolated and purified
Galbanic acid (GBA) provide inhibitory effects on HIF-1 activation
during hypoxia and normoxia and whereas Hypoxia Inducible Fac-
tor-1(HIF-1)involved to shows the transcriptional role in the adapta-
tion of hypoxic solid tumors to low oxygen environment. GBA down-
regulates both HIF-1α and HIF-1β mRNA expression in both hypoxia
and normoxia. Our latest researches demonstrate that GBA may not
only inhibit HIF-1 activation through down-regulation of its subunit
expression in hypoxia, and it also increasing EGFR by degradation in
normoxia.[20]
MECHANISM TO TREAT CANCER:
Tumour reducing activity of eight commonly used spices in India was
studied in mice transplanted intraperitoneally with Ehrlich ascites
tumour. Oral administration of extracts of, asafoetida could increase
the percentage of life span in these mice by 64.7%, 52.9%, 47% and
41.1%.[21]. Latest studies reflects that prolong apoptotic effect of
GBA-SLNs (GBA-loaded solid lipid nanoparticles) compared with
GBA may be due to the accumulation of GBA-SLNs in the tumor site
because of deviant tumor pathology [22]. Recent research also shows
that the human breast cancer mostly spread by The 4T1 cells tumor
growth and metastatic pattern in BALB/c in mice. Traditional folk
medicine have been the most important source having a

International Educational Scientific Research Journal [IESRJ] 15

Research Paper
anticancerous activity.[23]. The anti-proliferative activity was ana-
lyzed by BrdU assay.[24]BrdU can be incorporated into the newly syn-
thesized DNA of replicating cells (during the S phase of the cell cycle)
and substituting for thymidine during DNA replication. Antibodies
specific for BrdU can then be used to detect the incorporated chemical
and indicating cells that were actively replicating their DNA. Binding
of the antibody requires denaturation of the DNA, usually by expos-
ing the cells to acid or heat.Because it is neither radioactive nor
myelotoxic at labeling concentrations, it is widely preferred for in vivo
studies of cancer cell proliferation.[25] The resulting DNA-bound
bromouracil moiety was subsequently detected by commercial anti-
BrdU mAb without the need for a denaturation step[26].
The exact mechanism of action of(GBA) still unclear but the present
study revealed that the apoptotic mechanism of GBA was investi-
gated mainly in H460 non-small cell lung carcinoma (NSCLC) cells
because H460 cells were most susceptible to GBA than A549, PC-9
and HCC827 NSCLC cells. Galbanic acid showed cytotoxicity in wild
EGFR type H460 and A549 cells better than other mutant type PC-9
and HCC827 NSCLC cells. Also, GBA significantly increased the num-
ber of Terminal deoxynucleotidyl transferase dUTP nick end labeling
(TUNEL) positive cells and sub G1 population in H460 cells. Western
blotting revealed that GBA cleaved poly (ADP-ribose) polymerase
(PARP), activated Bax and caspase 9, attenuated the expression of
Bcl-2, Bcl-xL, and Myeloid cell leukemia 1 (Mcl-1) in H460 cells. How-
ever, interestingly, overexpression of Mcl-1 blocked the ability of GBA
to exert cytotoxicity, activate caspase9 and Bax, cleave PARP, and
increase sub G1 accumulation in H460 cells. These findings suggest
that GBA induces apoptosis in H460 cells via caspase activation and
Mcl-1 inhibition in H460 cells as a potent anticancer agent for NSCLC
treatment.[27]
MOLECULAR MECHANISM OF GALLBANIC ACID:
The molecular mechanism of galbanic acid (GBA) binding to matrix
metalloproteinase 9 (MMP9) was investigated by fluorescence
quenching, absorption spectroscopy, FT-IR, molecular docking and
molecular dynamics (MD) simulation procedures. The fluorescence
emission of MMP9 was quenched by GBA. The titration of MMP9 by
various amount of GBA was also followed by UV–Vis absorption spec-
troscopy. The results also demonstrate that GBA, having a biologi-
cally active sesquiterpene coumarin derivative, has a strong ability
to bind strongly to MMP9.Molecular docking results indicated that
the main active binding site for GBA has been located in a hydropho-
bic cavity in the vicinity of Zn atom. Moreover, MD simulation proce-
dure suggested that GBA as a sesquiterpene coumarin derivative
can interact with MMP9, without producing any effect on secondary
structure of MMP9.[28].
Some researches also shows that Ferula assa-foetida's resin has an
inhibitory effect on angiogenesis in chick chorioalantoic membrane. It
seems that compounds of Ferula assa-foetida's resin can be used to
inhibitangiogenesis in cancer tissues[29].
CONCLUSION:
In this review article we prominence the presence of Gallbanic acid
that is responsible to treat life threatning and lethal disease that usu-
ally caused the death of most of the individuals thorough out the
world.
16
Volume : 1 | Issue : 2 | Dec 2015
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