Research Paper
Medical Science
E-ISSN : 2455-295X | Volume : 1 | Issue : 2 | Dec 2015
EXPLORATION & WONDERS OF MEDICINAL PLANT “ASAFOETIDA”(HEENG) CONSTITUENT GALBANIC ACID AS ANTICANCEROUS AND ANTIMUTAGENIC AGENT * Syeda Sarah Abbas
1,2
Syed Hameez Jawed 1
1
1
1
| Safila Naveed | Fatima Qamar | Saba Javed Hussain |
2
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 possess 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 subsumes 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 docking 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 oleogum-resin, known as asafetida is obtained.[1]. Asafoetida is not only used as a culinary spice but also traditionally used to treat various diseases, including asthma, gastrointestinal disorders, intestinal parasites, etc. This oleo-gum-resin possess antifungal, anti-diabetic, antiinflammatory, anti-mutagenic and antiviral actions .There are various chemical compounds are found including sugars and polysulfides.[2] . Asafoetida chiefly subsume resin (40-65%), gum (2025%), and volatile oil (4-20%).[2] 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 numerous pharmacological activities and act as therapeutically such as antispasmodic[4,5], antifungal[6],antioxidant[7,8], antidiabetic[9], antimicrobial[10], antiulcer[11], antihemolytic[8], chemopreventive[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; characteristics 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
International Educational Scientific Research Journal [IESRJ]
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 MCF7/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]. Galbanic acid (GBA) provide inhibitory effects on HIF-1 activation during hypoxia and normoxia and whereas Hypoxia Inducible Factor-1(HIF-1)involved to shows the transcriptional role in the adaptation of hypoxic solid tumors to low oxygen environment. GBA downregulates 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
15
Research Paper anticancerous activity.[23]. The anti-proliferative activity was analyzed by BrdU assay.[24]BrdU can be incorporated into the newly synthesized 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 exposing 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 antiBrdU 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 investigated 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 number 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. However, 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]
E-ISSN : 2455-295X | Volume : 1 | Issue : 2 | Dec 2015 REFERENCES: 1) Shah B, Seth A. 1st ed. New York: Elsevier; 2010. Textbook of Pharmacognosy and Phytochemistry; pp. 319–21. 2) Milad Iranshahy,Mehrdad Iranshahi, Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assafoetida oleo-gum-resin)—A review, Journal of Ethnopharmacology,Volume 134, Issue 1, 8 March 2011, Pages 1–10 3) Wallis TE. 5th ed. New York: CBS Publisher; 2004. Textbook of Pharmacognosy; pp. 503–5. 4) Mohammad F, Freshteh F, Hassanabad ZF. Antispasmodic and hypotensive activity of Ferula asafoetidagum extract. J Ethnopharmacol. 2004;91:321–4. 5) Gholamnezhad Z, Byrami G, Boskabady MH. Possible mechanism of the relaxant effect of asafoetida.Avicenna J Phytomed. 2012;2:10–6. 6) Houghton PJ, Apendino G, Maxia L. A meroterpenoid NF- β inhibitor and drimane sesquiterpenoids from asafoetida. J Nat Prod. 2006;69:1101–4. [PubMed] 7). Dehpour AA, Ebrahimzadeh MA, Fazel NS. Antioxidant activity of methanolic extract of Ferula assafoetida and its essential oil composition. Grasas Y Aceites. 2009;60:405–12. 8). Nabavi SM, Ebrahimzadeh MA, Nabavi SE. Antioxidant and antihaemolytic activity of Ferula foetida regel. Eur Rev Med Pharmacol Sci. 2011;15:157–64. [PubMed] 9). Abu Zaiton AS. Antidiabetic activity of Ferula assafoetida extract in normal and alloxan-induced diabetic rats. Pak J Biol Sci. 2010;13:97–100. [PubMed] 10). Mishra N, Behal KK. Antimicrobial activity of some spices against selected microbes. Int J Pharm Pharm Sci. 2010;2:187–96. 11). Alqasoumi S, Al-Dosari M, Al-Howiriny T. Gastric antiulcer activity of a pungent spice Ferula assafoetida in rats. Farmacia. 2011;59:750–9. 12). Mohammad S, Alam A, Sultana S. Asafoetida inhibits early events of carcinogenesis: A chemopreventive study. Life Sci. 2001;68:1913–21. [PubMed] 13). Mishra N, Behal KK. Chemopreventive activity of some spices against selected cell line. Der Pharm Sin.2011;2:31–5. 14). Lee CL, Chiang CL, Cheng HL. Influenza A (H1N1) and cytotoxic agents from Ferula assafoetida. J Nat Prod. 2009;30:1–5.
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 spectroscopy. The results also demonstrate that GBA, having a biologically 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 hydrophobic cavity in the vicinity of Zn atom. Moreover, MD simulation procedure 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 usually caused the death of most of the individuals thorough out the world.
16
15). Poonam Mahendra and Shradha Bisht, Ferula asafoetida: Traditional uses and pharmacological activity, Pharmacognosy Reviews, 2012 Jul-Dec; 6(12): 141–146 16). Jamal Kasaian, Milad Iranshahy & Mehrdad Iranshahi, Synthesis, biosynthesis and biological activities of galbanic acid – A review, Pharmaceutical Biology,Volume 52, Issue 4, 2014 17). Shumaila Bashir, Mahboob Alam, Achyut Adhikari, New antileishmanial sesquiterpene coumarins from Ferula narthex Boiss, Phytochemistry Letters,Volume 9, September 2014, Pages 46–50 18). Hoda Gudarzi, Mona Salimi, Saeed Irian,Amir Amanzadeh, Ethanolic extract of Ferula gummosa is cytotoxic against cancer cells by inducing apoptosis and cell cycle arrest, Natural Product Research: Formerly Natural Product Letters,Volume 29, Issue 6, 2015 19). Jamal Kasaian,Fatemeh Mosaffa, Javad Behravan, Reversal of P-glycoprotein-mediated multidrug resistance in MCF-7/Adr cancer cells by sesquiterpene coumarins, Fitoterapia,Volume 103, June 2015, Pages 149–154 20). M.C. Unnikrishnan,R. Kuttan, Tumour reducing and anticarcinogenic activity of selected spices, cancer letter,May 15, 1990Volume 51, Issue 1, Pages 85–89 21). Morteza Eskandani, Jaleh Barar, Jafar Ezzati Nazhad, Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles, Pharmaceutical Biology,Volume 53, Issue 10, 2015
International Educational Scientific Research Journal [IESRJ]
Research Paper
E-ISSN : 2455-295X | Volume : 1 | Issue : 2 | Dec 2015
22). Amir Hossein Mansourabadi; Ali Shams,Reza Mansourin, Effects of fennel, asafetida and ginseng ethanolic extracts on growth and proliferation of mouse breast cancer 4T1 cell lines, Advanced herbal medicine, Article 5, Volume 1, Issue 2, Spring 2015, Page 34-39 23). Lehner B, Sandner B, Marschallinger J, Lehner C, Furtner T, Couillard-Despres S, et al. The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival. Cell Tissue Res. 2011; 345(3): 313-28. 24). Fujimaki T, Matsutani M, Nakamura O, Asai A, Funada N, Koike M, et al. Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults. Cancer. 1991; 67(6): 1629-34. 25). Cappella P, Gasparri F, Pulici M, Moll J. A novel method based on click chemistry, which overcomes limitations of cell cycle analysis by classical determination of BrdU incorporation, allowing multiplex antibody staining. Cytometry A. 2008; 73(7): 626-36. 26). Morteza Eskandani, Jalal Abdolalizadeh, Hamed Hamishehkar, Galbanic acid inhibits HIF-1α expression via EGFR/HIF-1α pathway in cancer cells, Fitoterapia, Volume 101, March 2015, Pages 1–11 27). Bum-Seok Oh,, Eun Ah Shin, Ji Hoon Jung, Apoptotic Effect of Galbanic Acid via Activation of Caspases and Inhibition of Mcl-1 in H460 Non-Small Lung Carcinoma Cells, Phytotherapy Research, Volume 29,Issue 6,pages 844–849, June 2015 28). Amir Kiani, Khadijeh Almasi, Yalda Shokoohinia, Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9, International Journal of Biological Macromolecules, Volume 81, November 2015, Pages 308–315 29). Seyed Damoon Sadoughi, Saide Zafar-Balanezhad, Javad Baharara, Investigating the effect of ethanolic extract of Ferula assa-foetida's resin on angiogenesis in chick chorioalantoic membrane, RJMS 2015, 22(131): 80-87
International Educational Scientific Research Journal [IESRJ]
17