A new sesquiterpene coumarins from Ferula bungeana Kitagawa.

A new sesquiterpene coumarin, bungeanin A (1), together with four known sesquiterpene coumarins, were isolated from the whole plants of Ferula bungeana Kitagawa. The structure of bungeanin A was elucidated by analysis of its spectroscopic data, including UV, IR, HR-ESI-MS, and extensive 1D and 2D NMR spectroscopy.

A histological examination of the effects of Ferula elaeochytris extract on kidney and liver tissues in myoglobinuric acute renal failure.

Myoglobinuric acute renal failure (MARF) is a structural and functional disorder that occurs in the kidney following the release of muscle cell contents into the circulation. In this present study, possible protective and curative effects of Ferula elaeochytris extract against kidney and liver damage in experimentally induced MARF in a rat model were investigated. 3-4 Month-old, 200-250 g Sprague Dawley rats were divided into 8 equal groups with 7 rats per group. Group I was a no-intervention Control group. All groups except for the Group I were dehydrated for 16 hours. Following this dehydration, 50% v/v aqueous glycerol solution was injected into both hind leg muscles of the animals, at a dose of 8 ml/kg. The rats were given physiological saline (SF) once orally before the model was administered (Group II) and after the model was administered (Group V). Similarly, two different doses of Ferula elaeochytris root extract (40 mg/kg and 80 mg/kg) were dissolved in 2 ml of SF and administered orally before (Groups III and IV) and after (Group VI, VII) the model was created. Following the experimental period, kidney and liver tissues were removed from all groups, and fixed in 10% neutral formaldehyde solution for light microscopic examinations. Intracellular vacuolization, enlargement in the Bowman's space, widespread atrophy in the tubular structures, luminal enlargement, and desquamation were detected in the kidney tissue sections of all the experimental model groups. In the liver tissue sections, was detected hepatocyte degeneration, intracellular vacuolization, irregularity in cell membrane borders, and apoptotic bodies. These histopathological consequences of MARF were evaluated for all groups, and whereas a curative effect of Ferula elaeochytris could be seen, its protective effect was higher than its curative effect.

Investigation of physio-mechanical, antioxidant and antimicrobial properties of starch-zinc oxide nanoparticles active films reinforced with Ferula gummosa Boiss essential oil.

The production of surface compounds coated with active substances has gained significant attention in recent years. This study investigated the physical, mechanical, antioxidant, and antimicrobial properties of a composite made of starch and zinc oxide nanoparticles (ZnO NPs) containing various concentrations of Ferula gummosa essential oil (0.5%, 1%, and 1.5%). The addition of ZnO NPs improved the thickness, mechanical and microbial properties, and reduced the water vapor permeability of the starch active film. The addition of F. gummosa essential oil to the starch nanocomposite decreased the water vapor permeability from 6.25 to 5.63 g mm-2 d-1 kPa-1, but this decrease was significant only at the concentration of 1.5% of essential oils (p < 0.05). Adding 1.5% of F. gummosa essential oil to starch nanocomposite led to a decrease in Tensile Strength value, while an increase in Elongation at Break values was observed. The results of the antimicrobial activity of the nanocomposite revealed that the pure starch film did not show any lack of growth zone. The addition of ZnO NPs to the starch matrix resulted in antimicrobial activity on both studied bacteria (Staphylococcus aureus and Escherichia coli). The highest antimicrobial activity was observed in the starch/ZnO NPs film containing 1.5% essential oil with an inhibition zone of 340 mm2 on S. aureus. Antioxidant activity increased significantly with increasing concentration of F. gummosa essential oil (P < 0.05). The film containing 1.5% essential oil had the highest (50.5%) antioxidant activity. Coating also improved the chemical characteristics of fish fillet. In conclusion, the starch nanocomposite containing ZnO NPs and F. gummosa essential oil has the potential to be used in the aquatic packaging industry.

Dauferulins A-L, daucane-type sesquiterpenes from the roots of Ferula communis: Their structures and biological activities.

Phytochemical study on the roots of a medicinal plant Ferula communis L. (Apiaceae) resulted in the isolation of 20 sesquiterpenes including 12 previously undescribed compounds, dauferulins A-L (1-12). The detailed spectroscopic analysis revealed 1-12 to be daucane-type sesquiterpenes with a p-methoxybenzoyloxy group at C-6. The absolute configurations of 1-12 were deduced by analysis of the ECD spectra. Dauferulins A-L (1-12), known sesquiterpenes (13-20), and analogues (14a-14l) derived from 6-O-p-methoxybenzoyl-10α-angeloyloxy-jeaschkeanadiol (14) were evaluated for their effects on AMPK phosphorylation in human hepatoma HepG2 cells as well as inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and IL-1ß production from LPS-treated murine microglial cells.

Characterization and investigation of cytotoxicity and antimicrobial properties of coencapsulated limonene and thymol into the Ferula assafoetida gum microparticles.

Thymol (Th) and d-limonene (L) exhibit low stability and are prone to oxidation when exposed to air, light, humidity, and high temperatures. This study examined the coencapsulation of Th and L into Ferula assafoetida gum (AFG) microparticles. Scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA) were done to characterize the obtained complexes. Furthermore, the encapsulation efficiency, antibacterial properties, cytotoxicity, and anticancer properties of both the free and encapsulated forms of L and Th were measured. For all samples, by increasing the percentage of bioactive compound (L, Th, and L-Th) from 2.5 to 5 % w/w, the EE was increased. FTIR and XRD analysis results demonstrated that Th and L were successfully incorporated into the AFG. Additionally, thermogravimetric analysis showed that in the thermal graphs of all samples, the first weight loss occurred between 30 °C and 160 °C, which was due to the evaporation of water. In the free L and Th graph, a sharp reduction peak was observed in which 80 % of compounds were lost. These reduction peaks disappeared in the thermal graphs of L: AFG and Th: AFG revealing that the thermal stability of Th and L was significantly increased upon their incorporation into the AFG. The inclusion of Th into the AFG also led to an increase in its antibacterial activity, while L exhibited acceptable antibacterial activity, albeit not as high as Th. Additionally, according to the MIC results, Th: AFG had the best antibacterial activity among all compounds, especially on gram-positive bacteria. According to the result of the MTT assay, there was a significant difference between the IC50 of free Th (123.4 µg/ml) and Th: AFG (2312 µg/ml), and free L (1762 µg/ml) and L: AFG (2480 µg/ml) showing that encapsulated Th and L into the AFG has decreased the cytotoxicity of free compounds against L929 cell line. Also, Th: AFG had the best anticancer activity against Hella and CT26 cell lines among all compounds. Finally, the flow cytometry analysis demonstrated that the encapsulated particles effectively eliminated cancer cells. The outcomes imply that AFG can be employed as a suitable delivery system to enhance the use of Th and L into the food and pharmaceutical industries.

Exploring the anticancer properties of the gum of Ferula gummosa: impact on cytotoxicity, caspase 3/7 activity and apoptosis, and gene expression in SW-480 cells.

Ferula gummosa Boiss. is a well-known Iranian endemic plant that grows in the north and northeast regions of Iran. In Iranian traditional medicine, its gum is utilized to treat inflammation, pain, and infections of the gastrointestinal system. However, no studies have been conducted to investigate the anticancer potential of its gum against colorectal cancer cells. This study aimed to identify the chemical components of the gum of F. gummosa and investigate its effects on SW-480 cells. The experiments included MTT, clonogenic, micronucleus formation, acridine orange/ethidium bromide stain, DNA degradation, caspase 3/7 activity assay, and in vitro wound-healing experiment and investigating the expression of BAX, BCL2, MTOR, and PTEN genes. Chemical analysis using GC/MS identified 102 compounds. The gum had a significant cytotoxic effect on SW-480 cells, with an IC50 value of 1.8 µg/ml for 48 hours. The gum induced apoptosis. Microscopic observations revealed a decrease in cell proliferation, as evidenced by nuclear condensation, increased micronucleus formation, and inhibition of colony formation. Additionally, the gum suppressed cell migration, induced the expression of PTEN and BAX, and down-regulated MTOR and BCL2 genes. These findings suggest that Ferula gummosa has strong cytotoxic properties and warrants further investigation.

Chimgin from Ferula haussknechtii as AChE inhibitor and confirmation of the absolute configuration.

Alzheimer's disease (AD) is the most common cause of dementia worldwide and is classified as a neurodegenerative disorder. From a drug design perspective, natural products (NPs) are more drug-like and are highly compatible with biological systems compared to most synthetic libraries. NPs provide a more efficient and cost-effective approach to new drug discovery. However, the complexity of NPs makes their identification a challenging task. Chimgin, a bicyclic monoterpene with three chiral centers, exhibits a wide range of biological activity. Despite this, the exact structure of chimgin has remained unclear until now. In this study, we quantified the amount of chimgin in Ferula haussknechtii using analytical Reversed-phase high-pressure liquid chromatography equipped with photodiode array detector (RP-HPLC-PDA). Furthermore, we determined the absolute configuration of chimgin through electronic circular dichroism (ECD) spectroscopy and time-dependent density functional theory (TDDFT) calculations. Finally, we evaluated its inhibitory effect on AChE through in vitro and in silico studies. The extraction process yielded an output of 2.82 ± 0.10% with an exact amount of 0.62 ± 0.04 mg of chimgin per 100 g of plant. Based on the results of ECD and TDDFT calculation, the absolute configuration of chimgin was determined to be 1S, 2S, 4S. Chimgin exhibited an inhibitory effect on AChE with an IC50 of 37.43 µM and its mechanism of action was found to be competitive. HighlightsChimgin was isolated from the roots of Ferula haussknechtii.The amount of chimgin in the plant was determined by RP-HPLC-PDA.Its absolute configuration of chimgin was determined using ECD.In vitro acetylcholinesterase activity of the chimgin was evaluated.The docking and molecular dynamic simulation of chimgin was done.Communicated by Ramaswamy H. Sarma.

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.

In vitro Evaluation of the Potent Antileishmanial Activity of Ferula tabasensis Alone or in Combination with Shark Cartilage Extract Against the Standard Iranian Strain of Leishmania major (MRHO/IR/75/ER).

Background: The available drugs for the treatment of leishmaniasis are highly toxic and extremely expensive, with low efficiency; therefore, the development of effective therapeutic compounds is essential. Objectives: The present study aimed to explore the antileishmanial effects of ethyl acetate extract, methanol extract, and fractions 1-4 (F1-F4) of Ferula tabasensis, alone or in combination with shark cartilage extract (ShCE), on L. major in vitro. Methods: In this study, ethyl acetate, methanol, and n-hexane extracts were extracted from the aerial roots of F. tabasensis by the maceration method. The silica gel column chromatography was used to separate n-hexane extracts at varying polarities (F1-F4 fractions). Subsequently, the effects of extracts and fractions against promastigotes were assessed by the parasite counting method microscopic inhibition test and MTT assay. Besides, their effects on the infected macrophage cells and the number of amastigotes were investigated. Cytotoxicity was evaluated in non-infected J774A.1 macrophage cells. Finally, apoptosis induction of promastigotes, including infected and non-infected macrophages, was evaluated. Results: The results indicated the highly potent activity of F. tabasensis extracts and F1-F4 fractions, alone or in combination with ShCE, against L. major promastigotes and amastigotes in a dose-dependent manner (P < 0.05). The F1 fraction and methanol extract showed markedly higher toxicity compared to the other extracts and fractions, with 50% inhibitory concentrations (IC50/72h) of 2.4 ± 0.29 and 2.9 ± 0.55 µg/mL against promastigotes and 1.79 ± 0.27 µg/mL and 1.39 ± 0.27 µg/mL against amastigotes (P < 0.001). Moreover, they had a high selectivity index (SI) due to the low toxicity of macrophages (P < 0.0001). The results of flow cytometry indicated that the percentages of apoptotic promastigote cells in contact with IC50 concentrations of F1 and methanol extract alone after 72 h were 43.83 and 43.93%, as well as 78.4%, and 65.45% for their combination with ShCE, respectively.Also, apoptosis of infected macrophages induced by F1 and methanol extracts was estimated at 68.5% and 83.7%, respectively. Conclusions: In this study, the F1 fraction and methanol extract of F. tabasensis showed potent efficacy against L. major, associated with low toxicity and apoptosis induction. Therefore, they can be promising therapeutic candidates in future animal and even human studies.

Isolation, Identification, Anti-Inflammatory, and In Silico Analysis of New Lignans from the Resin of Ferula sinkiangensis.

Ferula sinkiangensis K. M. Shen (Apiaceae) is distributed in arid desert areas of Xinjiang, and its resin is a traditional Chinese medicine to treat gastrointestinal digestive diseases. To explore bioactive components from F. sinkiangensis, three new lignans and thirteen known components were isolated. The structural elucidation of the components was established utilizing spectroscopic analyses together with ECD calculations. Griess reaction results indicated new compounds 1 and 2 significantly decreased NO production in LPS-stimulated RAW 264.7 macrophages, and ELISA results indicated that they effectively attenuated LPS-induced inflammation by inhibiting TNF-α, IL-1ß, and IL-6 expressions. The in silico approach confirmed that compound 1 docked into the receptors with strong binding energies of -5.84~-10.79 kcal/mol. In addition, compound 6 inhibited the proliferation of AGS gastric cancer cells with IC50 values of 15.2 µM by suppressing the cell migration and invasion. This study disclosed that F. sinkiangensis might be a promising potential resource for bioactive components.

Effects of silver nanoparticles prepared by aqueous extract of Ferula communis on the developing mouse embryo after maternal exposure.

Green synthesis of silver nanoparticles (AgNPs) from aqueous silver nitrate has been achieved using an extract of Ferula communis leaf as a capping, reducing, and stabilizing agent. The formation and stability of the green synthesized silver nanoparticles in the colloidal solution were monitored by absorption measurements. Silver nanoparticles were characterized by different analyses such as X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and FT-IR spectroscopy. The average particle size of silver nanoparticles was determined by high-resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM) analyses. In this experiment, pregnant female mice were divided into four groups (G); G1 was the control and received phosphate-buffered saline, G2 received orally aqueous extract of F. communis leaf, G3 received orally AgNPs chemically prepared by NaBH4, and G4 received orally AgNPs prepared by aqueous extract of F. communis leaf. The diameter of AgNPs was 20 nm. AgNPs exhibited good catalytic reduction ability toward methyl orange in the presence of sodium borohydride with a rate constant of 2.95 x 10-4 s-1. The results revealed the occurrence of resorbed embryos in G2, G3, and G4 with different percentages. The livers of mothers and embryos at E14.5 in G2, G3, and G4 showed different levels of histopathological alteration and increase in GFAP and CTGF expressions compared with the control group. The study concluded that the oral administration of small-sized AgNPs (20 nm) prepared by Ferula extract had less toxicity than those prepared by the chemical method.

Ag/g-C3N4 nanocomposite: Green fabrication and its application as a catalyst in the synthesis of new series of depsipeptides as biologically active compounds and investigation on their anti-breast cancer activity.

In this study, we bring forward a green and novel eco-friendly strategy for the fabrication of Ag/g-C3N4 nanocomposite via a fast in-situ generation method using Ferula Gummosa extracts as both stabilizer and reducing agent. Ag/g-C3N4 nanocomposite was analyzed by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX-MAP), and transmission electron microscopy (TEM). After procurement and characterization, the catalytic activity of the prepared reagent was surveyed in the synthesis of a new series of depsipeptides using aspirin/ketoprofen, cyclohexyl isocyanide, and aryl aldehydes at ambient temperature in EtOH/H2O as a green media. Taking into account the economic and environmental facets, the method bestows some advantages such as using plant extracts as green media for the preparation of Ag nanoparticles, simple work-up procedure, mild reaction conditions, short reaction times, and high yields of the products. Additionally, the Ag/g-C3N4 nanocomposite catalyst can be recycled effectually and reused several times without a substantial loss in reactivity.

A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.

Efficacy of topical galbanum oil with dry cupping in hospitalized COVID-19 patients: A randomized open-label clinical trial.

Objective: This study was designed to detect the therapeutic effects of galbanum oil plus dry cupping (a Persian medicine-based method) in hospitalized patients with coronavirus disease-2019 (COVID-19). Materials and Methods: In this randomized controlled trial, 60 hospitalized COVID-19 patients with positive polymerase chain reaction test (PCR), pulmonary involvement and blood oxygen saturation (SpO2) ≤93 mmHg, were randomly assigned into two groups to take the standard therapeutic regimen alone or alongside cupping and topical galbanum oil (Ferula gommosa oleo-gum resin) for 3-5 days. The SpO2 level, the severity of signs and symptoms of patients and laboratory parameters were compared between the two groups. Results: Fifty-eight patients were analyzed. The SpO2 level changed from 89.27±3.82 to 90.29±3.09 mmHg (p=0.038) in control group, while it increased from 88.74±3.45 to 94.23±2.1 mmHg (<0.001) in galbanum group with a significant difference between the groups (p<0.001). Fever, cough, dyspnea, and anorexia alleviated in the galbanum group more than the control (p=0.003, 0.001, 0.01, and 0.04, respectively). No adverse effects were reported due to galbanum oil and cupping therapy. Conclusion: Dry cupping with galbanum oil alongside the routine therapeutic regimen could be more effective than the routine therapeutic regimen alone for improving SpO2 level and alleviating fever, cough, and dyspnea in COVID-19 patients.

Antioxidant, cytotoxic, and genotoxic potentials of the gum of Ferula gummosa Boiss on PC-3 cells.

Objective: Ferula gummosa Boiss is a well-known Iranian endemic plant that has been used in Iranian traditional medicine against various diseases. This study aimed to evaluate the antioxidant and cytotoxic capacity of F. gummosa gum on prostate cancer PC-3 cells. Materials and Methods: In this study, we evaluated the total phenolic and flavonoid contents, and antioxidant potentials of the gum. The MTT experiment was conducted to assess the cytotoxic potential of the gum on PC-3 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of PC-3 cells. DNA degradation and caspase 3/7 activity evaluations were used to assess apoptosis. The inhibitory effect on the migration of PC-3 cells was examined by in vitro wound-healing experiment. Results: Total phenolic and flavonoid contents, and antioxidant potential of the gum were 9.22 mg of gallic acid equivalent (GAE)/g, 3.6 mg of quercetin equivalents (QE) /g of the extract, and 13 µg/ml, respectively (compared to gallic acid and quercetin, respectively) (p<0.05). The IC50 value was 9.14 µg/ml for 48 hours (compared to non-treated cells) (p<0.01). The pattern of DNA degradation, and caspase 3/7 activity levels (compared to non-treated cells) (p<0.05) proposed decreased cell viability that may be due to apoptosis induction. Microscopic observations revealed nuclear condensation, a significant increase in the formation of micronuclei, and inhibition of forming colonies (compared to non-treated cells) (p<0.01) in PC-3 cells treated with 8 and 10 µg/ml of the gum. Wound-healing assessment showed the migration suppression potentials of the gum (compared to non-treated cells) (p<0.05). Conclusion: These results indicate that F. gummosa has considerable antioxidant and cytotoxic properties that can make it a good nominee for subsequent investigations.

"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.

Molecular Docking and Molecular Dynamics Studies Reveal the Anticancer Potential of Medicinal-Plant-Derived Lignans as MDM2-P53 Interaction Inhibitors.

The interaction between the tumor suppressor protein p53 and its negative regulator, the MDM2 oncogenic protein, has gained significant attention in cancer drug discovery. In this study, 120 lignans reported from Ferula sinkiangensis and Justicia procumbens were assessed for docking simulations on the active pocket of the MDM2 crystal structure bound to Nutlin-3a. The docking analysis identified nine compounds with higher docking scores than the co-crystallized reference. Subsequent AMDET profiling revealed satisfactory pharmacokinetic and safety parameters for these natural products. Three compounds, namely, justin A, 6-hydroxy justicidin A, and 6'-hydroxy justicidin B, were selected for further investigation due to their strong binding affinities of -7.526 kcal/mol, -7.438 kcal/mol, and -7.240 kcal/mol, respectively, which surpassed the binding affinity of the reference inhibitor Nutlin-3a (-6.830 kcal/mol). To assess the stability and reliability of the binding of the candidate hits, a molecular dynamics simulation was performed over a duration of 100 ns. Remarkably, the thorough analysis demonstrated that all the hits exhibited stable molecular dynamics profiles. Based on their effective binding to MDM2, favorable pharmacokinetic properties, and molecular dynamics behavior, these compounds represent a promising starting point for further refinement. Nevertheless, it is essential to synthesize the suggested compounds and evaluate their activity through in vitro and in vivo experiments.

Fractura de mandíbula en pacientes parcialmente edéntulos. Alternativa de tratamiento cerrado. Serie de casos / Mandibular fractures in partially edentulous patients. Closed treatment alternatives. A Cases series

Para el tratamiento de fracturas mandibulares existen protocolos cuyo propósito primordial es la función temprana. Existen diversos motivos por los cuales no se puede ejecutar ciertas técnicas en Venezuela, principalmente por problemas económicos para la adquisición de materiales de osteosíntesis especializados. Por esta razón, se ha recurrido a técnicas quirúrgicas antiguas. Se presenta un estudio con diseño longitudinal de tipo descriptivo, para el reporte de serie de 5 casos clínicos de fracturas de mandíbula, con los siguientes criterios de inclusión: presentar fractura mandibular en pacientes dentados parcialmente con imposibilidad al acceso al material de osteosíntesis del sistema de cargas soportadas. Tratados bajo procedimiento quirúrgico cerrado, la condición de edentulismo parcial confiere a la fractura de mandíbula inestabilidad, dificulta la reducción anatómica, pérdida de dimensión vertical y transversal, las que se recuperan a través de la elaboración de férulas tipo Gunning modificadas. Estas férulas se mantuvieron en posición con alambrados de suspensión ósea tipo circummandibulares y circumzigomáticos, como medios para establecer estabilidad en el tiempo. Se obtuvieron resultados satisfactorios, por lo que, aún hoy en día se pueden plantear como opciones de tratamiento.

For the treatment of mandibular fractures, there are protocols whose primary purpose is early function. However, several reasons prevent the execution of these techniques in Venezuela, mainly due to economic problems regarding the acquisition of specialized osteosynthesis materials. As a result, there is a necessity to resort to old surgical techniques. A study with a descriptive longitudinal design is presented, reporting 5 clinical cases of jaw fractures with the following inclusion criteria: presenting a mandibular fracture in partially dentate patients with impossibility of accessing the osteosynthesis material of the load-bearing system. The treatment conducted under closed surgical procedures. The condition of partial edentulism confers instability to the mandible fracture, hindering anatomical reduction and causing a loss of vertical and transverse dimension. These issues are addressed through the utilization of modified Gunning-type splints, which help in recovery. The splints were maintained in position with circum-mandibular and circum-zygomatic bone suspension wiring as a means to establish stability over time. Satisfactory results were obtained, indicating that these techniques can still be considered as treatment options today.

Novel Cytotoxic Sesquiterpene Coumarin Ethers and Sulfur-Containing Compounds from the Roots of Ferula turcica.

Six new sesquiterpene coumarin ethers, namely turcicanol A (1), turcicanol A acetate (2), turcicanol B (3), turcica ketone (4), 11'-dehydrokaratavicinol (5), and galbanaldehyde (6), and one new sulfur-containing compound, namely turcicasulphide (7), along with thirty-two known secondary metabolites were isolated from the root of the endemic species Ferula turcica Akalin, Miski, & Tuncay through a bioassay-guided isolation approach. The structures of the new compounds were elucidated by spectroscopic analysis and comparison with the literature. Cell growth inhibition of colon cancer cell lines (COLO205 and HCT116) and kidney cancer cell lines (UO31 and A498) was used to guide isolation. Seventeen of the compounds showed significant activity against the cell lines.

Assessment of the acute and subacute toxicity of the aqueous extract of Moroccan Ferula communis fruit in a mouse model.

Ferula communis L. is thought to possess a wide range of therapeutic qualities. This plant's safety is critical regarding its potential uses as a medicine. Using the techniques outlined in the OECD recommendations, the present study aimed to assess the acute and subacute toxicity profiles of Ferula communis aqueous extract (FC-Ext) in mice. In the acute study, the FC-Ext was administered to adult male and female Swiss albino mice through oral and intraperitoneal routes at doses of 0-4 g/kg. The general behavioral effects, mortality rates, and latency of mortality were evaluated for a period of 14 days. For the sub-acute dose study, the FC-Ext was administered orally to adult mice at doses of 125, 250, and 500 mg/kg on a daily basis for 28 days. Body weight and selected biochemical and hematological parameters were measured, and histological examinations of the liver, kidney, and spleen were conducted to assess any signs of organ damage at the end of the treatment period. The results of the acute toxicity study demonstrated that the LD50 values for the oral and intraperitoneal administration of FC-Ext were 3.6 g/kg and 2.3 g/kg, respectively. In the subacute toxicity study of FC-Ext, no significant changes in body weight were observed. However, a substantial increase in the weights of the liver, kidney, and spleen was observed in male mice. The administration of FC-Ext to mice at doses higher than 250 mg/kg resulted in a decrease in white blood cells and platelets in both sexes and a reduction in red blood cells and mean corpuscular hemoglobin concentration in males and hemoglobin in females. No changes in biochemical parameters were observed. Microscopic examination of vital organs such as the liver, kidney, and spleen revealed no significant injuries. Based on the current results, the aqueous extract of Ferula communis has low toxicity. These findings provide important information about the toxicity profile of the traditional medicine plant Ferula communis.