Ferula Species Research Articles

Sesquiterpene Coumarins, Chromones, and Acetophenone Derivatives with Selective Cytotoxicities from the Roots of Ferula caspica M. Bieb. (Apiaceae).

In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell lines were used to monitor the cytotoxic activity of column fractions and determine the IC50 value of the active compounds. In addition to the seven known (5-11) compounds, four previously unknown compounds: kayserin A (1), kayserin B (2), 8'-epi-kayserin B angelate (3), and 3-epi-ferulin D (4) were isolated from the dichloromethane extract of the roots of F. caspica. Structure elucidation of the isolated compounds was carried out by extensive spectroscopic analyses such as 1D- and 2D-NMR spectroscopy, High-Resolution Mass Spectroscopy (HRMS), IR spectroscopy, and UV spectroscopy. Although all of the isolated compounds showed various degrees of cytotoxic activity on COLO 205, K-562, and MCF-7 cancer cell lines, the most potent compounds were identified in the following order: 1-Hydroxy-1-(1'-farnesyl)-4,6-dihydroxyacetophenone (HFDHAP, 11), 3-epi-ferulin D (3EFD, 4), and 7-desmethylferulin D (7DMFD, 6). The cytotoxic activities of all three compounds were more potent than that of the reference compound cisplatin (Cis) against all tested cancer cell lines. Still, only HFDHAP (11) was more potent than the reference compound doxorubicin (Dox) against the MCF-7 cancer cell line. The mechanism of action of these three compounds was investigated on the COLO 205 cell line. The results indicated that compounds 4, 6, and 11 trigger caspase-3/8/9 activation and suppress the anti-apoptotic protein, Bcl-xL. Molecular docking studies confirmed the interactions of the three cytotoxic molecules with the active site of the Bcl-xL protein.

A Comprehensive Review of the Pharmacological Effects of Genus Ferula on Central Nervous System Disorders.

Plants of the genus Ferula have long been used to treat neurological diseases such as Alzheimer's disease (AD), pain, depression, and seizures. The main compounds include coumarins, monoterpenes, sulfide compounds, and polyphenol compounds, which can improve the functioning of the nervous system. This article has been compiled with the aim of collecting evidence and articles related to the Ferula effects on central nervous system disease. This review article was prepared by searching the terms Ferula and analgesic, anticonvulsant, antidepressant, anti-multiple sclerosis, anti-dementia, and neuroprotective effects.The relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Genus Ferula has a protective effect on nerve cells by reducing cytokines such as IL-6, IL- 1b, and TNF-α. Therefore, the effects of Ferula plants and their effective ingredients can be used to prevent or improve diseases that destroy the nervous system. The members of this genus play a role in strengthening and improving the antioxidant system, reducing the level of oxidative stress, and inhibiting or reducing inflammatory factors in the nervous system. Although the effects of several species of Ferula on the nervous system have been investigated, most studies have not clearly identified the molecular mechanisms as well as the specific functional regions of the brain. The present study was compiled in order to investigate different aspects of the effects of Ferula plants on the central nervous system.

Culture-based diversity of endophytic fungi of three species of Ferula grown in Iran

A total of 1,348 endophytic fungal strains were isolated from Ferula ovina, F. galbaniflua, and F. persica. They included Eurotiales (16 species), Pleosporales (11 species), Botryosphaeriales (1 species), Cladosporiales (2 species), Helotiales (6 species), Hypocreales (31 species), Sordariales (7 species), Glomerellales (2 species), and Polyporales (1 species). F. ovina had the richest species composition of endophytic fungi, and the endophytic fungi were most abundant in their roots compared to shoots. Chao, Margalef, Shannon, Simpson, Berger–Parker, Menhinick, and Camargo indices showed that F. ovina roots had the most endophytic fungal species. The frequency distribution of fungal species isolated from Ferula spp. fell into the log-series model, and F. ovina roots had the highest Fisher alpha. The dominance indices showed that there are no dominant species in the endophytic fungal community isolated from Ferula spp., indicating community stability. Evenness values were 0.69, 0.90, 0.94, and 0.57 for endophytic fungi isolated from F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots, respectively, indicating a species distribution that tends toward evenness. The fungal species community isolated from each of F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots was a diverse species group originating from a homogeneous habitat. Their distribution followed a log-normal distribution, suggesting that the interactions of numerous independent environmental factors multiplicatively control species abundances. Principal component analysis showed that the highest species diversity and dominance were observed in the endophytic fungal community isolated from F. ovina and F. persica roots, respectively.

Phytochemical and Pharmacological Potential ofFerula asafetida“Hing”

Abstract:Asafoetida, also known as Hing, is a resinous gum derived from the roots of Ferula species, specifically Ferula asafetida. From ancient times, it has been employed both in the kitchen as a seasoning and in the practice of traditional medicine. In terms of pharmacognosy, asafoetida is comprised of a number of active chemicals, the most notable of which are coumarins, volatile oils (17%), and ferulic acid (60%). Ferulic acid and coumarins (40%) are two of the components that contribute to the medicinal value of this plant. The volatile oils are responsible for the strong odour and flavour of this plant. It is used for a variety of applications in the medical field. It is not only used as spices and condiments for the goal of imparting taste in curries, but it is also utilised in the treatment of gastrointestinal tract diseases, asthma, whooping cough, hypertension, and a variety of other conditions. The herb has been used to extract a variety of phytochemical components, including sesquiterpene coumarins, coumarins, diterpene coumarins, and chemicals containing sulphur. This manuscript provides a synopsis of the facts concerning the pharmacological activities and bioactive components of Ferula asafetida.

Quality evaluation of four Ferula plants and identification of their key volatiles based on non-targeted metabolomics.

Ferula is a traditional, edible, and important medicinal plant with high economic value. The distinction between edible and non-edible Ferula remains unclear. In this study, headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME/GC-MS) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) non-targeted metabolomics techniques were used to systematically and comprehensively analyse secondary metabolites in the leaves and roots of four species of Ferula, considering their edibility. A total of 166 leaf volatile organic compounds (VOCs) and 1,079 root metabolites were identified. Additionally, 42 potential VOCs and 62 differential root metabolites were screened to distinguish between edible and non-edible Ferula. Twelve volatile metabolites were specific to F. feurlaeoides, and eight compounds were specific to the three edible Ferula species. The results showed that compounds containing sulphur, aldehydes, and ketones, which produce pungent odours, were the primary sources of the strong odour of Ferula. The root differential metabolites include 13 categories, among which the high concentration group is organic acids, amino acids, terpenoids and fatty acids. The bioactive metabolites and VOCs in the roots exhibited species-specific characteristics. VOCs with various odors were linked to the distribution of root metabolites in both edible and non-edible Ferula plants. The screened root markers may contribute to the formation of characteristic VOCs. This study identified the difference in flavour between edible and non-edible Ferula plants and, for the first time, demonstrated the contribution of the efficacy of Ferula root to the unique flavour of the above-ground parts of Ferula. These results provide a theoretical basis for selecting Ferula for consumption and help evaluate the quality of different species of Ferula. Our findings may facilitate food processing and the further development of Ferula.

Features of the distribution of species of the genus Ferula L. on the territory of the Turan lowland

This article presents materials on the study of the distribution area of Ferula species in the flora of the Turonian lowland. The presented materials were obtained as a result of field research. Herbarium materials were collected during our research. The life forms of the plant were studied, and the chemical composition of Ferula species in the area was determined. The importance of Ferula species in agriculture was studied.

Sesquiterpenes and Sesquiterpene Derivatives from Ferula: Their Chemical Structures, Biosynthetic Pathways, and Biological Properties.

Ferula is a genus of flowering plants known for its edible and medicinal properties. Since ancient times, many species of Ferula have been used in traditional medicine to treat various health issues across countries, such as digestive disorders, respiratory problems, and even as a remedy for headaches and toothaches. In addition, they are also used as a flavoring agent in various cuisines. As the main active ingredients in Ferula, sesquiterpenes and their derivatives, especially sesquiterpene coumarins, sesquiterpene phenylpropanoids, and sesquiterpene chromones, have attracted the attention of scientists due to the diversity of their chemical structures, as well as their extensive and promising biological properties, such as antioxidative, anti-inflammatory, antibacterial properties. However, there has not been a comprehensive review of sesquiterpenes and their derivatives from this plant. This review aims to provide an overview of the chemical structures, biosynthetic pathways, and biological properties of sesquiterpenes and sesquiterpene derivatives from Ferula, which may help guide future research directions and possible application methods for this valuable edible and medicinal plant.

The diversity of Ferula species and environmental factors on metabolite composition using untargeted metabolomics

The genus Ferula is widely distributed in Central Asia, and different species of Ferula exhibit significant differences in medicinal efficacy and economic value This study aimed to determine the metabolic composition of different Ferula species using untargeted metabolomics with UHPLC-MS/MS. The study identified 764 metabolites and 56 metabolites as characteristic metabolites of different Ferula species. The study demonstrated the effectiveness of using untargeted metabolomics to screen Ferula quality markers. Furthermore, based on the specific metabolites found, Mantel tests, redundancy analysis, and stepwise regression equation models were jointly affected by soil and terrain factors. These findings provide valuable insights into the rational utilisation and management of Ferula plant resources and artificial cultivation. Overall, this study provides an important contribution to understanding the metabolic differences in Ferula species from different environmental sources and can inform the development of sustainable strategies for the utilisation and management of Ferula plant resources.

In Vitro Evaluation of Ferutinin Rich-Ferula communis L., ssp. glauca, Root Extract on Doxorubicin-Induced Cardiotoxicity: Antioxidant Properties and Cell Cycle Modulation.

The clinical use of anthracycline Doxorubicin as an antineoplastic drug in cancer therapy is limited by cardiotoxic effects that can lead to congestive heart failure. Recent studies have shown several promising activities of different species of the genus Ferula belonging to the Apiaceae Family. Ferula communis is the main source of Ferutinin-a bioactive compound isolated from many species of Ferula-studied both in vitro and in vivo because of their different effects, such as estrogenic, antioxidant, anti-inflammatory, and also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. However, the potential protective role of Ferutinin in myocardium impairment, caused by chemotherapeutic drugs, still represents an unexplored field. The aim of this study was to test the effects of Ferutinin rich-Ferula communis L. root extract (FcFE) at different concentrations on H9C2 cells. Moreover, we evaluated its antioxidant properties in cardiomyocytes in order to explore new potential therapeutic activities never examined before in other experimental works. FcFE, at a concentration of 0.25 µM, in the H9C2 line, significantly reduced the ROS production induced by H2O2 (50 µM and 250 µM) and traced the cell mortality of the H9C2 co-treated with Ferutinin 0.25 µM and Doxorubicin (0.5 µM and 1 µM) to control levels. These results showed that FcFE could protect against Doxorubicin-induced cardiotoxicity. Further molecular characterization of this natural compound may open the way for testing FcFE at low concentrations in vivo and in clinical studies as an adjuvant in cancer therapy in association with anthracyclines to prevent side effects on heart cells.

Review of potential spermatogenic and aphrodisiac effects of the Ferula genus.

Men's sexual health plays an important role in male fertility and childbearing, as it is associated with factors such as sexual desire, healthy spermatogenesis, and erectile function. In various cultures, medicinal plants have been utilized to address male sexual issues, including infertility and erectile dysfunction. Despite recent advancements in medical science for treating male impotence, some men opt for herbal supplements as an alternative, given that numerous herbs have the potential to enhance male sexual performance. The Apiaceae family is one of the oldest plant families used for medicinal purposes. Ferula, a genus within this family, comprises approximately 170 different species worldwide. Members of this genus possess numerous therapeutic properties due to the presence of various compounds. This article aims to explore the potential impacts of Ferula plants on the male reproductive system. This review article was prepared by searching for terms including Ferula and "aphrodisiac," Ferula and "spermatogenesis," and Ferula and "male reproductive system." Relevant information was gathered through electronic databases, including ISI Web of Knowledge, PubMed, and Google Scholar. The findings indicated that relatively comprehensive studies have been conducted in this area, revealing that certain Ferula species have been employed in folk medicine to boost fertility and libido. Recent research has corroborated these effects. It is hoped that new aphrodisiac compounds with fewer side effects can be isolated from Ferula plants in the future.

Antiviral effect of the Ferula Kuhistanica Korovin plant, growing in the high-mountain conditions of the Republic of Tajikistan

This work presents the results of studies on the extract obtained from the root of Ferula kuhistanica Korov, in relation to 2 strains of the influenza virus: A/Vlad/2/09(H1N1) and A/Almaty/8/98(H3N2). It has been shown that the F. kuhistanica Korov extract exhibits selective antiviral activity and primarily acts on the influenza virus strain A/Vlad/2/09(H1N1), not showing an inhibitory effect against another antigenic variant of this virus – the strain A/ Almaty/8/98(H3N2). The tested extract was characterized by high IC50, EC50, and IS50 indicators. Its chemotherapeutic effect (XTI) is 23 times higher than that of the commercial anti-influenza drug - Tamiflu. The data obtained open up prospects for the possible use of extracts obtained from the root of various species of the genus Ferula, growing in our country, in the development of anti-influenza drugs.

Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin.

Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC50 = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (5) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and β-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (5) on cancer cell lines.

Coumarins of genus Ferula L. (Apiaceae Lindl.)

The biologically active coumarins from Ferula L. species of the family Apiaceae Lindl. for the period 1970 to 2022 have been reviewed. The phytochemical investigation of different parts of Ferula L., including gum resin, leaves, fruits, seeds, roots, rhizomes, and resins led to the separation of different types of coumarins. Nearly 185 coumarins were isolated from 35 species of Ferula L. growing in different countries. Coumarins are represented mainly by umbelliferone (7-O-hydroxycoumarin) derivatives substituted in the C-7 position of aglycone, furanocoumarins and metabolites have terpene fragments, esters and glycosides. Umbelliferon is found as a taxon for the genus Ferula L. Some «unusual» metabolites have a furan fragment attached to the pyrone ring. Coumarins are of the psoralen type, containing a furan ring in the C-6 and C-7 positions of the primary skeleton. The rare coumarins with terpene fragments (hemiterpene, monoterpen, sesquiterpene) were reported. The biological activities of some extracts and individual metabolites such as antiinflammatory, cytotoxicity, antibacterial, antileishmanial, antiviral, antigenotoxic, antitumor, anticoagulant, antioxidant, antimycobacterial, inhibition a-glucosidase, antileishmanial were found.

HPLC-MS/MS analysis, antioxidant and α-amylase inhibitory activities of the endemic plant Ferula tunetana using in vitro and in silico methods

Ferula species have occupied great value in traditional medicine in various countries. The aim of the present paper was to assess for the first time to the phytochemical profile of Ferula tunetana Pomel ex Batt. (F. tunetana) seed and leaf extracts using HPLC-MS/MS, as well as to evaluate their antioxidant and anti-α-amylase activities. Therefore, total phenolic and flavonoid amounts of the studied extracts were determined and 38 compounds were detected and quantified (phenolic acids, flavonoids, non-phenolic acid and stilbenes). In addition of their antioxidant potential against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays, in vitro and in silico studies were adopted to evaluate α-amylase inhibitory properties of F. tunetana extracts. Ethyl acetate (EtOAc) seed extract showed the highest total phenolic content, antioxidant potential (IC50 = 19.00 ± 0.37 μg/mL) in terms of free radical scavenging, also for α-amylase inhibition activity with IC50 values of 17.39 ± 0.92 μg/mL. The molecular docking analysis and the drug-likeness prediction of the major selected compounds explained the significant anti-α-amylase activity of the studied extracts. The obtained analysis and results suggest that F. tunetana extracts could be promising candidates to develop a new generation of efficient and especially safe antidiabetic treatments.

Biological Activities of the Fruit Essential Oil, Fruit, and Root Extracts of Ferula drudeana Korovin, the Putative Anatolian Ecotype of the Silphion Plant.

In the present study, preliminary phytochemical investigations were performed on the fruit essential oil and antioxidant-rich methanolic extracts of the fruits and roots of Ferula drudeana, the putative Anatolian ecotype of the Silphion plant, to corroborate its medicinal plant potential and identify its unique characteristics amongst other Ferula species. The essential oil from the fruits of the endemic species Ferula drudeana collected from Aksaray was analyzed by GC and GC/MS. The main components of the oil were determined as shyobunone (44.2%) and 6-epishyobunone (12.6%). The essential oil of the fruits and various solvent extracts of the fruits and roots of F. drudeana were evaluated for their antibacterial and anticandidal activity using microbroth dilution methods. The essential oil of the fruits, methanol, and methylene chloride extracts of the fruits and roots showed weak to moderate inhibitory activity against all tested microorganisms with MIC values of 78-2000 µg/mL. However, the petroleum ether extract of the roots showed remarkable inhibitory activity against Candida krusei and Candida utilis with MIC values of 19.5 and 9.75 µg/mL, respectively. Furthermore, all the samples were tested for their antioxidant activities using DPPH• TLC spot testing, online HPLC-ABTS screening, and DPPH/ABTS radical scavenging activity assessment assays. Methanolic extracts of the fruits and roots showed strong antioxidant activity in both systems.

The plastid genome of twenty-two species from Ferula, Talassia, and Soranthus: comparative analysis, phylogenetic implications, and adaptive evolution

BackgroundThe Ferula genus encompasses 180–185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China.ResultsComprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats.ConclusionPlastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula.

Conferone, a coumarin from Ferula flabelliloba, induced toxic effects on adult T-cell leukemia/lymphoma cells.

Adult T-cell leukemia/lymphoma (ATL) is a lymphoid malignancy caused by HTLV-1 infection, with distinct geographical distribution. Despite advances in cancer treatment, the average survival rate of ATL is low. Conferone is a natural coumarin extracted from Ferula species with a wide range of pharmaceutical effects. In search for a novel chemotherapeutic agent, we investigated the cytotoxicity of conferone on ATL cells. To obtain conferone, the methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography, followed by 1H- and 13C-NMR to confirm its structure. For cytotoxicity assay, MT-2 cells were treated with different concentrations of conferone (2.5, 5, 10, 20, and 40 µM) for 24, 48, and 72 h, and viability was evaluated by a colorimetric assay using alamarBlue. Cell cycle was analyzed by PI staining and flow cytometry, and qPCR was used to study the expression of candidate genes. Obtained findings indicated that conferone induced considerable cytotoxic effects on MT-2 cells in a time- and dose-dependent manner. In addition, accumulation of cells in the sub-G1 phase of the cell cycle was detected upon conferone administration. Moreover, conferone reduced the expression of CDK6, c-MYC, CFLIPL, and NF-κB (Rel-A) in MT-2 cells. Accordingly, conferone could be considered as a potent agent against ATL, although complementary investigations are required to define more precisely its mechanism of action.

The History of Botany (Gifts of Synesius, Bishop of Cyrene)

The article focuses on the identification of silphium — a forgotten precious plant and the symbol of ancient Cyrene — which became extinct in the first century C. E. due to the merciless plunder of local natural resources by Roman governors. However, some scholars believe that silphium survived into the fifth century, with reference to two letters (106 and 134) by Synesius, Bishop of Cyrene (370—413 C. E.). Based on their comparison with other written evidence, the author concludes that, consumed as he was with public duties and church service, Synesius could not fully immerse himself in botanical nuances of the local flora. He therefore identified some other Ferula species, acculturated by his correspondent, as silphium. As a local patriot, Synesius wholeheartedly upheld the legend of the surviving plant, seeing it as a symbol of victory over death, which gave hope to his fellow countrymen in hard times.

Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia.

Natural coumarins are valuable agents that induce anticancer effects and/or enhance sensitivity to therapeutic modalities. Galbanic acid (GBA), auraptene (AUR) and umbelliprenin (UMB) are coumarins derived from Ferula species with various pharmaceutical activities. The aim of the current research was to compare toxic effects of GBA, AUR, and UMB on human lymphoma cells in normoxia and hypoxia. In this regard, GBA and AUR were extracted from the roots of F. szowitsiana and UMB was derived from the roots of F. persica, all by thin-layer chromatography. MT-2 cells were treated with each agent for 3 consequent periods, while exposed to different O2 contents (21% and 2%). By the end of each treatment, the viability of MT-2 cells was determined by resazurindye-based colorimetric assay. Obtained results revealed that low doses of GBA (10 and 20 µM) induced significant (p < 0.0001) toxic effects in hypoxia. However, similar toxicity was observed when cells were treated with 40 µM AUR in normoxia and hypoxia. Notably, UMB was the only coumarin that exerted cytotoxic effects in all time points (48, 72 and 96 h) in normoxia and hypoxia, although its concentration was highest (80 µM). In conclusion, this is the first report indicating GBA was the most toxic coumarin against ATL cells in hypoxia, AUR induced similar effects in normoxia and hypoxia, and low toxicity of UMB was stable during the time and different O2 contents. Future studies on other ATL cell lines are recommended to better evaluate the toxic effects of GBA, AUR and UMB in vitro.

Comparative phytochemical analysis of Ferula assa-foetida with Ferula jaeschkeana and commercial oleo-gum resins using GC–MS and UHPLC-PDA-QTOF-IMS

Ferula assa-foetida is an important species of the genus Ferula, best known for its oleo-gum resin, mainly used as a flavoring agent. Ferula jaeschkeana is another Himalayan medicinal plant of this genus, known for its contraceptive effect but not used in food applications. This study aimed to do a detailed phytochemical analysis of F. assa-foetida growing under controlled conditions in India using GC–MS/headspace and UHPLC-PDA-QTOF-IMS. Further, a comparative analysis of F. assa-foetida was performed with F. jaeschkeana (collected from its natural habitat) and commercial samples of F. assa-foetida oleo-gum resin (collected from the local market). UHPLC-QTOF-IMS profiling of F. assa-foetida led to the identification of foetisulfide C, assafoetidnol A, gumosin, flabellilobin (A/B), and foetisulfide A. In total, 141 metabolites were identified, including vitamins, nucleosides, sulfur compounds, flavonoids, sugars derivatives, and others, using METLIN database. Serine, arginine, asparagine, isoleucine, and phenylalanine were major amino acids quantified among the samples for the nutritional aspect. Characteristic sulfurous compounds (n-propyl-sec-butyl disulfide, trans-propenyl-sec-butyl disulfide, cis-propenyl-sec-butyl disulfide, and bis[1-(methylthio)propyl] disulfide) were identified in all samples except F. jaeschkeana. PCA and cluster analysis showed a significant difference in the volatile constituents of rhizomes of both species. Metabolomics studies also revealed the association of sesquiterpenoid and triterpenoid biosynthesis, phenylpropanoid, flavon, and flavanol biosynthesis. The current study demonstrates, “why only F. assa-foetida is used in culinary applications instead of F. jaeschkeana”?