The growth inhibitory and apoptotic effects of umbelliprenin in a mouse model of systemic candidiasis.

AIMS: Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis. METHODS AND RESULTS: First, an antimicrobial assay via microdilution sensitivity test was performed. Then, twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The ß-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of ß-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1). CONCLUSION: Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis.

Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells.

Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups (5,7-diprenyloxy-4-methyl-coumarin, 4g) or the presence of octyloxy substituent (coumarin 4d) was found to increase the potency of compounds in breast cancer cells, but not against healthy human fibroblasts. The activity of potent compounds on breast cancer cells cultured more similarly to the conditions of the tumour microenvironment was also investigated, and increased toxicity was observed. Results suggest that tested coumarin derivatives could potentially reduce the growth of tumour mass. Moreover, their use as (combination) therapy in cancer treatment might have the potential of causing limited side effects.

UHPLC-UV/Vis Quantitative Analysis of Hydroxylated and O-prenylated Coumarins in Pomegranate Seed Extracts.

A simple and rapid analytical UHPLC methodology with spectrophotometric (UV/Vis) detection, coupled with different extraction procedures, has been perfected to investigate the presence of biologically active O-prenylated umbelliferone derivatives, such as auraptene and umbelliprenin, in pomegranate (Punica granatum L.) seed extracts. Absolute ethanol was the most efficient extraction solvent in terms of yields, after a short ultrasound-assisted. The highest concentration values recorded under these experimental conditions were 1.99 µg/g of dry extract and 6.53 µg/g for auraptene and umbelliprenin, respectively. The parent metabolite umbelliferone was also detected (0.67 µg/g). The extraction and UHPLC analytical methodology set up in the present study proved to be an efficient, powerful, and versatile technique for the simultaneous qualitative analysis and quantification of oxyprenylated coumarins in pomegranate seed extracts. The characterization of such secondary metabolites in the mentioned phytopreparation represents, to the best of our knowledge, the first example in the literature.

HPLC Analysis and Skin Whitening Effects of Umbelliprenin-containing Extracts of Anethum Graveolens, Pimpinella Anisum, and Ferulago Campestris.

Umbelliprenin has recently been shown to have great potential as a skin whitening agent. Wishing to investigate the same effect in plant species known to biosynthesize this coumarin, three plants belonging to the Apiaceae family, namely Anethum graveolens L. (dill), Pimpinella anisum L. (anise), and Ferulago campestris (Besser) Grecescu (field ferula) were screened by HPLC analysis for their respective content of umbelliprenin in extracts obtained with different solvent mixtures and by maceration and ultrasound-assisted processes. EtOH was shown to be the best solvent, providing umbelliprenin yields ranging from 1.7% to 14.4% (with respect to the total amount of extract obtained). Extracts with the highest content of this farnesyloxycoumarin were then assayed as modulators of melanogenesis in cultured murine Melan A cells employing the same umbelliprenin obtained by chemical synthesis as the reference. A parallelism between the content of the coumarin and the recorded depigmenting effect (60% for the EtOH extract of F. campestris as the best value) was revealed for all plants extracts when applied at a dose of 100 µg/mL. Our results demonstrate that the same potential of umbelliprenin can be ascribed also to umbelliprenin-enriched plant extracts which reinforces enforce the widespread use of phyto-preparations for cosmetic purposes (e.g., A. graveolens).

Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti-inflammatory, and immunostimulatory activities in 4T1 tumor-bearing Balb/c mice.

Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary-tumor-bearing mice. Two-hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor-bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor-bearing animals (P < 0.01), and IL-4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki-67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF-κB were significantly decreased in tumors from UMB-treated animals (P < 0.001), whereas E-Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB-administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.

Biological properties and molecular targets of umbelliprenin--a mini-review.

7-Prenyloxycoumarins are a group of secondary metabolites found mainly in plants belonging to the families Rutaceae and Apiaceae. Auraptene, umbelliprenin (UM), and 7-isopentenyloxycoumarin are some examples of prenylated coumarins. UM occurs in various edible plant species including celery, coriander, angelica, lemon, and particularly, Ferula species. Although UM was isolated more than 50 years ago, its biological activities have been studied since the last two decades. Besides anticancer activities, biological activities including anti-inflammatory, antioxidant, and antileishmanial activities have been reported from this natural compound. The present mini-review deals with the biological activities and mechanism of actions reported for UM.

Study of the anti-cancer activity of a mesoporous silica nanoparticle surface coated with polydopamine loaded with umbelliprenin.

A mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and loaded with umbelliprenin (UMB) was prepared and evaluated for its anti-cancer properties in this study. Then UMB-MSN-PDA was characterized by dynamic light scattering (DLS), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and FTIR methods. UV-visible spectrometry was employed to study the percentage of encapsulation efficiency (EE%). UMB-MSN-PDA mediated cell cytotoxicity and their ability to induce programmed cell death were evaluated by MTT, real-time qPCR, flow cytometry, and AO/PI double staining methods. The size of UMB-MSN-PDA was 196.7 with a size distribution of 0.21 and a surface charge of -41.07 mV. The EE% was 91.92%. FESEM and TEM showed the spherical morphology of the UMB-MSN-PDA. FTIR also indicated the successful interaction of the UMB and MSN and PDA coating. The release study showed an initial 20% release during the first 24 h of the study and less than 40% during 168 h. The lower cytotoxicity of the UMB-MSN-PDA against HFF normal cells compared to MCF-7 carcinoma cells suggested the safety of formulation on normal cells and tissues. The induction of apoptosis in MCF-7 cells was indicated by the upregulation of P53, caspase 8, and caspase 9 genes, enhanced Sub-G1 phase cells, and the AO/PI fluorescent staining. As a result of these studies, it may be feasible to conduct preclinical studies shortly to evaluate the formulation for its potential use in cancer treatment.

Umbelliprenin attenuates comorbid behavioral disorders in acetic acid-induced colitis in mice: mechanistic insights into hippocampal oxidative stress and neuroinflammation.

Inflammatory bowel disease (IBD) is often accompanied by psychiatric disorders. Emerging evidence suggests that neuroinflammation and oxidative stress contribute to the psychiatric symptoms associated with IBD. Umbelliprenin (UMB) possesses several pharmacological properties, including anti-inflammatory and antioxidant effects. This study aimed to investigate the protective effects of UMB on comorbid behavioral disorders in a mouse model of experimental colitis, focusing on its potential anti-neuroinflammatory and antioxidant activities. After inducing colitis with acetic acid, male NMRI mice were treated for 7 consecutive days with UMB, saline, or dexamethasone. Behavioral assessments included the forced swimming test (FST), splash test, open field test (OFT), and elevated plus maze (EPM). Histopathological changes in the colon were evaluated, and total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and the expression of inflammatory genes (TNFα, IL1ß, and TLR4) were measured in the hippocampus. Colitis was associated with increased immobility time in the FST, reduced entries and time spent in the open arms of the EPM, decreased grooming behavior in the splash test, and reduced time spent in the central zone of the OFT. Colitis also resulted in a reduction in TAC and an increase in MDA levels and inflammatory gene expression in the hippocampus. UMB treatment mitigated the behavioral disorders associated with colitis, reduced neuroinflammation and oxidative stress in the hippocampus, and alleviated histopathological alterations in the colon. In conclusion, UMB may reduce behavioral disorders induced by colitis by decreasing oxidative stress and neuroinflammation in the hippocampus.

Joining up the scattered anticancer knowledge on auraptene and umbelliprenin: a meta-analysis.

Auraptene (AUR) and umbelliprenin (UMB) are naturally occurring prenylated coumarins that have demonstrated promising anticancer effects across various human cancer cell lines. This meta-analysis aimed to systematically assess, compare, and quantify the anticancer efficacy of AUR and UMB by synthesizing evidence from in vitro studies. A comprehensive literature search identified 27 eligible studies investigating AUR or UMB against cancer cells. Mixed-effects models revealed significant negative associations between coumarin dose and viability for AUR (est. = - 2.27) and UMB (est. = - 3.990), underscoring their dose-dependent cytotoxicity. Meta-regression indicated slightly higher potency for UMB over AUR, potentially due to increased lipophilicity imparted by additional isoprenyl units. Machine learning approaches identified coumarin dose and cancer type as the most influential determinants of toxicity, while treatment duration and the specific coumarin displayed weaker effects. Moderate (AUR) to substantial (UMB) between-study heterogeneity was detected, although the findings proved robust. In summary, this meta-analysis establishes AUR and UMB as promising natural anticancer candidates with clear dose-toxicity relationships across diverse malignancies. The structural insights and quantifications of anticancer efficacy can inform forthcoming efforts assessing therapeutic potential in pre-clinical models and human trials.

Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells.

AIM: To investigate the impact of niosome nanoparticles carrying umbelliprenin (UMB), an anti-angiogenic and anti-inflammatory plant compound, on the expression of vascular endothelial growth factor (VEGF-A) and connective tissue growth factor (CTGF) genes in a human retinal pigment epithelium (RPE)-like retina-derived cell line. METHODS: UMB-containing niosomes were created, optimized, and characterized. RPE-like cells were treated with free UMB and UMB-containing niosomes. The IC50 values of the treatments were determined using an MTT assay. Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis. Niosomes' characteristics, including drug entrapment efficiency, size, dispersion index, and zeta potential were assessed. Free UMB had an IC50 of 96.2 µg/mL, while UMB-containing niosomes had an IC50 of 25 µg/mL. RESULTS: Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells (P=0.001). Additionally, UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells (P=0.05). However, there was no significant reduction in the expression of both genes in cells treated with free UMB. CONCLUSION: Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression. However, the latter demonstrates significantly greater efficacy, potentially due to the lower UMB dosage and gradual delivery. These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

Umbelliprenin via increase in the MECP2 and attenuation of oxidative stress mitigates the autistic-like behaviors in mouse model of maternal separation stress.

Introduction: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition. Maternal separation (MS) stress is an early-life stress factor associated with behaviors resembling Autism. Both MECP2 and oxidative stress are implicated in the pathophysiology of Autism. Umbelliprenin (UMB) is a coumarin compound with various pharmacological properties. Our study aimed to investigate the potential effects of UMB in mitigating autistic-like behaviors in a mouse model subjected to MS stress, focusing on probable alterations in MECP2 gene expression in the hippocampus. Methods: MS paradigm was performed, and mice were treated with saline or UMB. Behavioral tests consisting of the three-chamber test (evaluating social interaction), shuttle box (assessing passive avoidance memory), elevated plus-maze (measuring anxiety-like behaviors), and marble-burying test (evaluating repetitive behaviors) were conducted. Gene expression of MECP2 and measurements of total antioxidant capacity (TAC), nitrite level, and malondialdehyde (MDA) level were assessed in the hippocampus. Results: The findings demonstrated that MS-induced behaviors resembling Autism, accompanied by decreased MECP2 gene expression, elevated nitrite, MDA levels, and reduced TAC in the hippocampus. UMB mitigated these autistic-like behaviors induced by MS and attenuated the adverse effects of MS on oxidative stress and MECP2 gene expression in the hippocampus. Conclusion: In conclusion, UMB likely attenuated autistic-like behaviors caused by MS stress, probably, through the reduction of oxidative stress and an increase in MECP2 gene expression.

Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats.

This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-ß, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.

Umbelliprenin as a novel component of the phytochemical pool from Artemisia spp.

Plants belonging to Artemisia spp. are known to biosynthesize a wide panel of 3,3-dimethylallyl- and sesquiterpenyl- substituted coumarins. In this short communication we applied a novel extraction methodology based on the use of subcritical butane under a counter-current mode to further characterize the presence of selected biologically active oxyprenylated phenylpropanoids, namely coumarins and ferulic acid derivatives, in extracts deriving from aerial parts of Artemisia vulgaris L. (commonly known as "common mugwort") (Asteraceae). In the mean time, we assessed the efficiency of the above mentioned extractive methodology with other routes like maceration and ultrasounds and microwaves-based methods using absolute EtOH as the solvents. UHPLC analysis coupled to UV/Vis detection revealed that, among the 5 pure chemical standard assayed, only umbelliprenin (7-farnesyloxycoumarin) was recorded, while boropinic acid, 4'-geranyloxyferulic acid, 7-isopentenyloxycoumarin, and auraptene were not detected. The best extractive yield (0.18 %) was obtained after extaction with subcritical butane. The presence of umbelliprenin in Artemisia plant species has been reported herein for the first time. This coumarin may represent the biosynthetic precursors of sesquiterpenyloxycoumarins with more complex structures typically found in this genus.

Assessment of the Antitumor Potential of Umbelliprenin, a Naturally Occurring Sesquiterpene Coumarin.

Cancer is one of the greatest causes of mortality worldwide. The prevalence rates of different types of cancer is increasing around the world as well. Limitations in chemotherapy and radiotherapy, owing to multiple side effects including cytotoxic effects of antitumor compounds on normal cells as well as the development of resistance to these treatment options in patients, create a serious threat to successful treatment of cancer. The use of natural compounds to prevent and treat cancers has been found to be quite effective, with fewer adverse effects found in patients. Umbelliprenin (UMB) is a naturally occurring sesquiterpene compound found in Ferula species and recently in Artemisia absinthium. Many studies have highlighted the antitumor potential of UMB in different cancer cell lines as well as in animal models. UMB exerts its anticancer actions by regulating extrinsic and intrinsic apoptotic pathways; causing inhibition of the cell cycle at the G0/G1 phase; and attenuating migration and invasion by modulating the Wnt signaling, NF-ĸB, TGFß, and Fox3 signaling pathways. UMB also affects the key hallmarks of tumor cells by attenuating tumor growth, angiogenesis, and metastasis. This review provides an insight into the role of UMB as a potential antitumor drug for different malignancies and highlights the signaling cascades affected by UMB treatment in diverse tumor cell lines and preclinical models.

7-Farnesyloxycoumarin Exerts Anti-cancer Effects on a Prostate Cancer Cell Line by 15-LOX-1 Inhibition.

BACKGROUND: Prostate cancer is one of the leading causes of cancer related deaths in males worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme and high activity of its metabolic pathway is reported to be a driver for prostate cancer malignancy. Farnesyloxycoumarin derivatives (3f, 4f and 7f) inhibit lipoxygenase enzyme. We hypothesized that farnesyloxycoumarins may exert an anti-cancer effect on prostate cancer cells due to their 15-LOX-1 inhibitory potential. METHODS: The enzyme inhibitory activity of 3f, 4f and 7f was initially evaluated on PC-3 and DU145 prostate cancer cell lines. MTT assay was performed on cancer cell lines and HFF3 cell line to assess cytotoxicity of the compounds. The apoptotic morphology of cells after treatments was assessed by DAPI staining and single cell gel electrophoresis. Propidium iodide staining was also performed to detect cell cycle variations after treatment. RESULTS: 7f inhibited 15-LOX-1 at IC50=4.3 µg/mL, while 3f and 4f did not show high inhibitory activity. 7f reduced cell viability in PC-3 cells at IC50=22-31 µg/mL, however, no significant cytotoxicity was revealed on normal cells. DAPI staining and comet assay confirmed apoptosis and DNA damage in PC-3 cells after 7f treatment, while flow cytometry results revealed G1 arrest in PC-3 cells. CONCLUSION: The results are indicative of a distinctive cytotoxic mechanism for 7f compared to other coumarins, possibly due to its 15-LOX-1 inhibitory potential. Thus, this compound is valued for further assessments with the aim of developing a promising targeted therapy for prostate cancer patients.

Natural oxyprenylated coumarins are modulators of melanogenesis.

Naturally occurring coumarins 7-isopentenyloxycoumarin, auraptene, and umbelliprenin are able to modulate the biosynthesis of melanin in murine Melan-a cells probably through the interaction with selected biological targets like estrogen receptor ß and aryl hydrocarbon receptor. Such a modulation strictly depends on the individual structure of the coumarin: the presence of a 3,3-dimethylallyloxy side chain is a structural determinant for tanning activation whereas a farnesyl one leads to the opposite effect. The parent compound with a free OH group, umbelliferone, did not provide any interaction. Other coumarins assayed, having shorter chains and/or being substituted in other positions, and prenyloxypsoralens, were not active or not further investigated in this context being cytotoxic at low doses.

Cytotoxic activity of the genus Ferula (Apiaceae) and its bioactive constituents.

OBJECTIVE: The genus Ferula L. includes perennial flowering plants belonging to the Apiaceae family. This genus is a rich source of biologically active phytochemicals such as sulfur-containing derivatives, coumarins, sesquiterpenes, sesquiterpene lactones, sesquiterpene coumarins, glucuronic acid, galactose, arabinose, rhamnose, and daucane esters. Over the last decade, considerable attention has been paid to biological activities of these compounds; it is assumed that the most prominent biological features of the genus Ferula are their cytotoxic effects. This article discusses cytotoxic activity of the genus Ferula and their important compounds. MATERIALS AND METHODS: In this mini-review article, papers published from 1990 to April 2016 were included and the following information was discussed; cytotoxic activity of the genus Ferula and their important compounds, the type of cell line used in vitro, concentrations of the extracts/active compound that were used, and the underlying mechanisms of action through which Ferula-related chemicals induced cytotoxicity. In addition, we explained different mechanisms of action through which the active constituents isolated from Ferula, could decrease cellular growth. CONCLUSION: It is highly recommended that potent and effective compounds that were isolated from Ferula plants and found to be appropriate as adjuvant therapy for certain diseases, should be identified. Also, the versatile biological activities of sesquiterpene coumarins suggest them as promising agents with a broad range of biological applications to be used in the future.

Antitumor Effects of Umbelliprenin in a Mouse Model of Colorectal Cancer.

Umbelliprenin is a sesquiterpene coumarin with vitro anti-carcinogenic activities. The aim of this study was to investigate the antitumor effects of umbelliprenin in animal models of colorectal cancer. The cytotoxic effects of umbelliprenin were explored on CT26 and L929by MTT assay. In this study, colorectal tumors developed in mice by intradermal injection of CT26 cell line. Tumor size, serum levels of IFN-γ and IL-4 by ELISA, and Ki-67, MMP2, MMP9, VEGF and E-cadherin markers by IHC method were evaluated. The results showed that umbelliprenin inhibited the cancer cells in a concentration-dependent manner. IC50 Evaluation showed that L929 cells were more resistant to Umbelliprenin than CT26 cells. Umbelliprenin treatment in both tumor-bearing mice and control normal mice showed significantly increased IFN-γ and decreased IL-4(P < 0.05). The pathologic findings had shown that the E-cadherin marker in the umbelliprenin treated cancerous mice were significantly higher compared to the control group (P < 0.05) while the expression of Ki-67 marker was reduced significantly (P < 0.05). Markers involved in angiogenesis including VEGF, MMP2, and MMP-9 in the cancerous mice group treated with umbelliprenin showed a significant decrease compared to the control group (P < 0.05). Metastasis to lung and liver was reduced in umbelliprenin treated group. Our results showed that umbelliprenin inhibited CT26 tumor cells in-vitro. The in-vivo reduction of tumor size, angiogenesis, and proliferation markers and the absence of metastasis represents the antitumor effects of umbelliprenin on colorectal cancer. The results showed that umbelliprenin can be considered as a good candidate for the treatment of colorectal cancer.

Evaluating cytotoxic effect of nanoliposomes encapsulated with umbelliprenin on 4T1 cell line.

Cytotoxicity of umbelliprenin has been found in various cancer cell lines such as, prostate, breast, CLL, and skin. Encapsulating chemotherapeutic agents with nanoliposomes have been resulted in improved cytotoxicity effects than their free forms. However, whether nanoliposomal form of umbelliprenin could have higher cytotoxic effect than free umbelliprenin is not clarified yet. After synthesizing umbelliprenin, different concentrations (3, 6, 12, 25, 50, 100, 200 µg/ml) applied on the mouse mammary carcinoma cell line (4T1) for 24, 48, and 72 h at 37°C. Afterwards, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to analyze cytotoxicity. MTT assay results showed that IC50 of umbelliprenin in dimethyl sulfoxide (DMSO) (30.92, 30.64, and 62.23 for 24, 48, 72 h incubation, respectively) decreased (5.8, 5.0, 3.5 for 24, 48, 72 h incubation, respectively) when encapsulated with nanoliposomes. Nanoliposomal umbelliprenin cytotoxicity affected cell viability in concentration and time-dependent manner. Our study recommended nanoliposomal umbelliprenin as the most effective chemotherapeutic agent against the mouse mammary carcinoma cell line viability. Future in vivo studies and clinical trials are needed.

Phytochemistry and pharmacology of Ferula persica Boiss.: A review.

Ferula persica, is the well-known species of the genus Ferula in Iran and has two varieties: persica and latisecta. They have both been extensively used in traditional medicine for a wide range of ailments. A great number of chemical compounds including sesquiterpene coumarins and polysulfides have been isolated from this plant. Fresh plant materials, crude extracts and isolated components of F. persica have shown a wide spectrum of pharmacological properties including anti-pigmentation in Serratia marcescens, cytotoxic, antibacterial, anti-fungal, anti-leishmanial, cancer chemopreventive, reversal of multi-drug resistance, anti-inflammatory and lipoxygenase inhibitory activity. The present review summarizes the data available regarding the chemical constituents and biological activities of F. persica.