Antitumor and Phytochemical Properties of Ferula assa-foetida L. Oleo-Gum-Resin against HT-29 Colorectal Cancer Cells In Vitro and in a Xenograft Mouse Model.

Colorectal cancer (CRC) is one of the most frequently occurring tumors. Ferula assa-foetida oleo-gum-resin (OGR) extract is a traditional cooking spice known for its broad spectrum of biological activities such as antifungal, antiparasitic, and anti-inflammatory activities. This study evaluated the antitumor effect of OGR extract against HT-29 colorectal cancer cells. The OGR chemical composition was analyzed using LC-ESI-MS/MS; MTT, clonogenic assays, and a xenograft model were used to measure cytotoxicity, while apoptotic proteins were detected using Western blotting. Phytochemical analysis revealed that the extract was a rich source of isoflavones, xanthones, and other derivatives. In a dose-dependent manner, the OGR extract significantly inhibited colony formation ability and HT-29 cell growth (IC50 was 3.60 ± 0.02 and 10.5 ± 0.1 mg/mL, respectively). On the other hand, the OGR extract significantly induced apoptosis and increased the expression of some pro-death proteins involved in cellular apoptosis including PUMA, BIM, BIK, and BAK. Moreover, in a subcutaneous HT-29 xenograft model, the tumor volume and burden decreased after treatment with the OGR extract (550 ± 32 mm3 and 16.3 ± 3.6, respectively) This study demonstrated that Ferula assa-foetida OGR ethanolic extract has potential antitumor effects against HT-29 CRC cell lines by reducing cell viability and the function of apoptosis. More studies are needed to reveal the underlying mechanisms related to cytotoxicity and apoptosis induction.

"Ferula assa-foetida L" or "Foeniculum vulgare"? Which one is more effective in the management of polycystic ovarian syndrome? A randomized, placebo controlled, triple-blinded.

Objective: There are few evaluation about the effects of Fennel and Ferula on human polycystic ovary syndrome (PCOS). The goals of this study were to evaluate and compare the effectiveness of two medicinal plants of the Apiaceae family (Fennel and Ferula) in management of PCOS. Materials and Methods: The sample size was 47 participants with PCOS who were randomly divided into 3 groups. The Ferula assa-foetida L group received 100 mg of Ferula (n=14), the Foeniculum vulgare group received 46 mg of Fennel (n=15), and the placebo group received placebo twice daily for 3 months (n=14). Results: Before the intervention, there were no significant differences between groups in terms of clinical parameters, endometrial thickness, or ovarian volume. After the interventions, the number of ovarian follicles was decreased in the Ferula and Fennel groups as compared to the placebo group (p<0.05). The number of ovarian follicles in both ovaries in the Ferula and Fennel group decreased and this decrease was significant in the right side as compared to placebo group. Our findings showed significant changes in dehydroepiandrosterone sulfate (DEHAS) and thyroid-stimulating hormone (TSH) levels after the intervention (p<0.03) between the Ferula and Placebo groups. Conclusion: Since use of Ferula could make significant changes in TSH and DEHAS levels and decrease the number of right and left ovarian follicles compared to Fennel and placebo, it can be concluded that this herbal medicine is more effective than Fennel in managing PCOS.

Safety and efficacy of a feed additive consisting of an essential oil from the gum resin of Ferula assa-foetida L. (asafoetida oil) for use in dogs and cats (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from gum resin of Ferula assa-foetida L. (asafoetida oil), when used as a sensory additive (flavouring) in feed for dogs and cats. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of asafoetida oil is safe at the proposed conditions of use of 1.5 mg/kg complete feed for dogs and 0.2 mg/kg complete feed for cats. The additive under assessment should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. Since F. assa-foetida and its preparations are recognised to flavour food, and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Ferula assa-foetida oleo gum resin ethanolic extract alleviated the pancreatic changes and antioxidant status in streptozotocin-induced diabetic rats: A biochemical, histopathological, and ultrastructural study.

The current research examines the effects of administration of 150 and 250 mg/kg body weight/day of ethanolic Ferula assa-foetida L. oleo gum resin extract (FAE) for 42 days in streptozotocin-induced diabetes in rats. On day 42, all rats were euthanized; HOMA-ß, HOMA-IR, and QUICKI levels in pancreas were examined histopathologically and ultrastructurally . Low-dose FAE (150 mg/kg) treatment resulted in significant improvement in serum glucose, insulin and superoxide dismutase, glutathione, and catalase levels (p < .05). It also improved ß-cell function, restored pancreatic ß-cells, and reduced insulin resistance compared to the diabetic control rats. Necrotic and degenerative alterations in the islets, pyknotic ß-cell nuclei, ß-cell degranulation, reduced islet cellular density, and significant vacuolation were found in the islets of STZ-diabetic control group ratsby the histomorphological and ultrastructural examination. The pancreatic histomorphology of low dose of FAE-treated diabetic rats showed remarkable improvements in the islets, such as the ß-cell number and the area of the pancreatic islets. PRACTICAL APPLICATIONS: The experiment revealed that Ferula assa-foetida L. may exert antihyperglycemic activity in STZ diabetes via ß-cell regeneration and its high antioxidant capacity. This work elucidates the role of Ferula assa-foetida L. in diabetes management. Ferula assa-foetida L. gum extract improved the morphological changes of the diabetic pancreas and stimulated the regeneration of the ß cells. The findings demonstrated positive results for the long-term cure of diabetes. Additionally, this study showed the potential of isolating nutraceuticals for the development of medications.

Chemical composition and biological effects of three different types (tear, paste, and mass) of bitter Ferula assa-foetida Linn. gum.

Ferula assa-foetida gum oleoresin (FAGO) is traditionally used for treatment of different ailments. The subject of this article was to evaluate the chemical composition and antibacterial effects of the different types of bitter FAGO essential oils in the natural habitat of Southwest Iran. α-pinene (38.2%), and (Z)-propenyl sec-butyl disulfide (12.4%) were the main components of F. assa-foetida tear type essential oil, with high antibacterial, anti-biofilm and cytotoxic activities, followed by paste and mass types, respectively. α-pinene (27.8%), and (Z)-propenyl-sec-butyl disulfide (24.2%) were identified as main components of paste type. α-pinene (33.4%), ß-pinene (16.3%), and (Z)-propenyl sec-butyl disulfide (16.1%) were the main components of asafoetida mass type gum oleoresin essential oil. FAGO essential oil specially tear one could serve as suitable candidate for further studies.

Comparative anthelmintic efficacy of Arundo donax, Areca catechu, and Ferula assa-foetida against Haemonchus contortus / Eficácia anthelmíntica comparativa de Arundo donax, Areca catechu e Ferula assa-foetida contra Haemonchus contortus

Abstract In the present study, anthelmintic activities of Arundo (A.) donax L., Areca (Ar.) catechu L., and Ferula (F.) assa-foetida L. were determined. Leaves of A. donax L., latex of F. assa-foetida L. and seeds of Ar. catechu L. in different solvent fractions were subjected to in vitro (egg hatch assay; EHA, and adult motility assay; AMA) and in vivo (faecal egg count reduction test; FECRT) tests of anthelmintic activity using Haemonchus contortus model. In the AMA, crude aqueous methanol extracts (CAME) and ethyl acetate fractions of F. assa-foetida at 10 hr post-treatment showed maximum mortality of H. contortus at 12.5-50 mg mL-1. In the EHA, CAME of F. assa-foetida was identified as a potent ovicide based on its low LC50 (16.9 µg mL-1), followed in order by Ar. catechu and A. donax. Results from the FECRT also showed the extract of F. assa-foetida L. to be more effective than those of Ar. catechu L. and A. donax L., against the gastrointestinal parasitic nematodes. Chloroform and ethyl acetate fractions showed better anthelmintic activities against the adult worms in vitro, while CAME of these plants were better than their crude powders in vivo. It is recommended to document and investigate indigenous knowledge of possible medicinal plants to plan scientific trials that may justify their endorsement.

Resumo No presente estudo, as atividades anti-helmínticas de Arundo (A.) donax L., Areca (Ar.) Catechu L. e Ferula (F.) assa-foetida L. foram determinadas. Folhas de A. donax L., látex de F. assa-foetida L. e sementes de Ar. catechu L. em diferentes frações de solvente foram submetidos a testes in vitro (teste de eclosão de ovos, EHA e ensaio de motilidade em adultos, AMA); e in vivo (teste de redução da contagem de ovos fecais, FECRT) de atividade anti-helmíntica, usando-se Haemonchus contortus. Na AMA, extratos aquosos brutos de metanol (CAME) e frações de acetato de etila de F. assa-foetida. Dez horas pós-tratamento, apresentaram mortalidade máxima de H. contortus em 12,5-50 mg mL-1. No EHA, CAME de F. assa-foetida foi identificado como um ovicida potente baseado em seu baixo LC50 (16,9 µg mL-1), seguido em ordem por Ar. catechu e A. donax. Os resultados do FECRT também mostraram que o extrato de F. assa-foetida L. é mais eficaz do que o de Ar. catechu L. e A. donax L., contra nematoides parasitas gastrointestinais. As frações clorofórmio e acetato de etila mostraram melhores atividades anti-helmínticas contra vermes adultos in vitro, enquanto o CAME dessas plantas foi melhor do que o pó bruto in vivo. Recomenda-se documentar e investigar o conhecimento indígena de possíveis plantas medicinais para planejar ensaios científicos que possam justificar seu endosso.

Metabolomics Approaches for Analyzing Effects of Geographic and Environmental Factors on the Variation of Root Essential Oils of Ferula assa-foetida L.

Environmental factors shape the production and accumulation processes of plant secondary metabolites in medical and aromatic plants and thus their pharmacological and biological activity. Using an environmental metabolomics approach, we determined chemotypes and specific compounds on the basis of essential oils (EOs) from roots of 10 Iranian Ferula assa-foetida L. populations and related them to geographical, climate, and edaphic data. GC-MS revealed three distinct chemotypes characterized by (I) monoterpenes and Z-1-propenyl sec-butyl disulfide; (II) eudesmane sesquiterpenoids and α-agarofuran; and (III) Z- and E-1-propenyl sec-butyl disulfide. NIRS measurements indicated a similar but less distinct pattern. Structural equation models showed that EO constituents and content were directly influenced by edaphic factors (texture, pH, and iron, potassium, and aluminum content) and temperature and predominantly indirectly by latitude, longitude, and altitude. Predicting EO constituents or chemotypes by geographical, climate, and soil factors can be used in F. assa-foetida to select populations with specific EO characteristics.

NMR-based metabolomic study of asafoetida.

Asafoetida, an oleo-gum-resin obtained from the exudates of Ferula assa-foetida L. roots, is traditionally used to treat various diseases including asthma, gastrointestinal disorders, and intestinal parasites. On the basis of Iranian traditional medicine, the main source of asafetida is F. assa-foetida roots. In folk medicine, however, different Ferula species have been used as sources of asafoetida. To identify the original asafoetida that possesses medicinal properties, we should compare metabolic profiles of different asafoetida sources which are commonly used for the oleo-gum-resin preparation.1H-NMR based metabolomics was used to obtain metabolic profiles of eight asafoetida oleo-gum-resin samples and forty-six samples of Ferula species roots from two main regions of Iran. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projection to latent structures discriminant analysis (OPLS-DA) to identify the metabolic differences and similarities between the samples. Asafoetida is usually produced from Ferula species of southern and eastern regions of Iran. A clear metabolic differentiation was evident between asafoetida oleo-gum- resin samples from the southern and those of the eastern Iran. The distinguished metabolites, umbelliprenin, farnesiferol B, farnesiferol C, samarcandin and galbanic acid are significantly found in southern samples. Only southern asafoetida is obtained from F. assa-foetida. Asafoetida from eastern region of Iran is obtained from other species of Ferula such as F. alliacea and its metabolic profile is far different from that of southern asafoetida.

Rheological and functional properties of asafoetida gum.

The asafoetida gum was extracted and purified from oleo-gum-resin of Ferula assa foetida root and characterized by high pressure anions exchange chromatography after acidic hydrolysis. It was composed of Gal:Ara:Rha:GlcA with the ratio 11.5:5.0:2.1:1.0. This monosaccharide composition was found similar to that of a commercial Arabic gum which exhibited a Gal:Ara:Rha:GlcA ratio of 11.7:5.4:3.2:1.0. As the Arabic gum is currently used for its emulsifying properties, the two gums were evaluated for their functional and rheological behaviors. Surface and interfacial tensions values were lower for asafoetida gum compared to Arabic gum. Critical micelle concentration was achieved at concentrations of 0.5% w/w and 1% w/w for asafoetida and Arabic gums, respectively. Values of emulsion capacity, emulsion stability and foaming properties were considerably higher for asafoetida gum in contrast to emulsion activity index that was lower than that of Arabic gum. As those of Arabic gum, solutions of asafoetida gum (2-30% w/w) exhibited Newtonian flow behavior at shear rates between 1 and 500 s-1. Apparent viscosities of Arabic and asafoetida gums were close and logically decreased by increasing temperature (10-80 °C). Higher viscosities were achieved at higher pH and CaCl2 concentrations.

The Effect of Ferula assa-foetida L and Carum copticum Hydroalcoholic Extract on the Expression Levels of Staphylococcus aureus Genes Involved in Quorum Sensing.

BACKGROUND: Quorum sensing is a microbial cell-to-cell communication process. Quorum sensing bacteria produce and release extracellular messenger molecules called autoinducers. Gram-positive and Gram-negative, homoserine lactones, and oligopeptides are autoinducers used to communicate and regulate gene expression. OBJECTIVES: The goal of this study was to assess the impact of subinhibitory concentrations of Ferula assa-foetida l oleo-gum resin and Carum copticum fruit on the expression of tst and hld genes of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains. METHODS: This analytical study was performed using standard strains of MRSA (ATCC 33591) and MSSA (ATCC 29213). Suspensions of MRSA and MSSA bacteria were incubated at 37°C for 7 and 16 hours in the presence of ethanol extracts from F. assa-foetida and C. copticum. The expression of the hld and tst genes was then assessed using the real-time PCR protocol and SYBR Green Master Mix. The data analysis was carried out using the 2-ΔΔCT method. RESULTS: The hld gene expression (RNAIII) of MRSA after 7 and 16 hours of exposure to the sMIC of the F. assa-foetida extract showed a fold change of -1 and 0.08, respectively, in comparison with controls. After 7 and 16 hours of exposure to the sMIC of the C. copticum extract, the fold change was -0.23 and -0.27, respectively. After exposure to the sMIC of the C. copticum extract for 16 hours, the fold change in the expression of the tst (TSST-1) MSSA gene was 0.37 lower than that of the control sample. CONCLUSIONS: The results indicate that sMICs of ethanol extracts from F. assa-foetida and C. copticum can be used to control the expression of virulence genes in pathogenic bacteria, such as MRSA and MSSA.