Targeted delivery of 5-fluorouracil and shikonin by blended and coated chitosan/pectin nanoparticles for treatment of colon cancer.

Herein, 5-fluorouracil and shikonin (extracted from Fusarium tricinctum) were loaded in chitosan/pectin nanoparticle (CS/PEC-NPs), prepared by blending (B-CS/PEC-NPs) and coating (C-CS/PEC-NPs) methods. The nanoparticles characterized by Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), Energy-dispersive X-ray (EDX), Scanning Electron Microscope (SEM) and Differential Light Scattering (DLS). Then, some properties of the nanoparticles such as drug release rate and the nanoparticles cytotoxicity were studied. The FTIR, XRD, EDX, SEM and DLS results showed that the nanoparticles synthesized properly with an almost spherical morphology, an average size of 82-93 nm for B-CS/PEC-NPs, an average diameter of below 100 nm (mostly 66-89 nm) for C-CS/PEC-NPs, and hydrodynamic diameter of 310-817 nm. The drug release results indicated the lower release rate of drugs for B-CS/PEC-NPs relative to C-CS/PEC-NPs at different pHs, high release rate of drugs for the nanoparticles in the simulated large intestinal fluids containing pectinase, and Korsmeyer-Peppas model for release of the drugs. The results showed more cytotoxicity of B-CS/PEC-NPs containing drugs, especially B-CS/PEC-NPs containing both drugs (B-CS/PEC/5-FU/SHK-NPs) after treating with pectinase (IC50 of 18.6 µg/mL). In conclusion, despite the limitation of C-CS/PEC-NPs for simultaneous loading of hydrophilic and hydrophobic drugs, B-CS/PEC-NPs showed suitable potency for loading and targeted delivery of the drugs.

Investigation the biological activities and the metabolite profiles of endophytic fungi isolated from Gundelia tournefortii L.

Endophytic fungi are microorganisms that are considered as a potential source of natural compounds, and can be applied in various industries. The aims of this research were molecular identification of endophytic fungi isolated from the Gundelia tournefortii stems, and investigation their biological activities as well as phenolic and fatty acid profile. Surface sterilized stems of G. tournefortii were placed on potato dextrose agar (PDA) to isolate the fungal endophytes. Genomic DNA was extracted by CTAB method, and PCR amplification was performed by ITS 1 and ITS 4 as primers. The enzyme production of endophytic fungi was determined based on the formation of a clear zone that appeared around the colonies of fungus. The anti-oxidant activity was evaluated by measuring the amount of free radicals DPPH. Also, the total phenol and flavonoid contents were measured obtained by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Moreover, the separation and identification of phenolic acids and fatty acids were done by HPLC and GC, respectively. Phylogenetic analysis was done based on the Internal Transcribed Spacer (ITS) region, and five isolates were identified as following: Aspergillus niger, Penicillium glabrum, Alternaria alternata, A. tenuissima, and Mucor circinelloides. Evaluation of the enzymatic properties showed that P. gabrum (31 ± 1.9 mm), and A. niger (23 ± 1.7) had more ability for producing pectinase and cellulase. The anti-oxidant activity of isolates showed that A. alternata extract (IC50 = 471 ± 29 µg/mL) had the highest anti-oxidant properties, followed by A. tenuissima extract (IC50 = 512 ± 19 µg/mL). Also, the extract of A. alternata had the greatest amount of total phenols and flavonoids contents (8.2 ± 0.4 mg GAL/g and 2.3 ± 0.3 mg QE/g, respectively). The quantification analysis of phenolic acid showed that rosmarinic acid, para-coumaric acid, and meta-coumaric acid (42.02 ± 1.31, 7.53 ± 0.19, 5.41 ± 0.21 mg/g, respectively) were the main phenolic acids in the studied fungi. The analysis of fatty acids confirmed that, in all fungi, the main fatty acids were stearic acid (27.9-35.2%), oleic acid (11.3-17.3%), palmitic acid (16.9-23.2%), linoleic acid (5.8-11.6%), and caprylic acid (6.3-10.9%). Our finding showed that endophytic fungi are a source of bioactive compounds, which could be used in various industries. This is the first report of endophytic fungi associated with G. tournefortii, which provides knowledge on their future use on biotechnological processes.

How do essential oil composition and phenolic acid profile of Heracleum persicum fluctuate at different phenological stages?

Heracleum persicum, commonly named Persian hogweed, is a principal native medicinal plant in Iran. Collecting H. persicum at the most appropriate growing stage is the key factor to achieve the high phytochemical quality to meet consumer's needs. In the present experiment, the aerial parts of this plant were harvested at up to six different developmental stages during the growing season to determine the phytochemical profiles. Our results indicated that the highest essential oil content was obtained in the mid-mature seed stage (3.5%). The most elevated extract content was recorded in the floral budding stage (10.4%). In the vegetative stage, limonene (18.1%), in floral budding stage, caryophyllene (14.1%), anethole (14.6%), and ß-bisabolene (12.7%), in the full flowering stage, myristicin (15.0%), and hexyl butyrate (9.1%), in the early development of seeds stage, hexyl butyrate (32.1%), and octyl acetate (11.7%), in the mid-mature seeds stage hexyl butyrate (38.8%), octyl acetate (14.5%), in the late-mature/ripe seeds stage, hexyl butyrate (23.6%), and octyl acetate (10.5%) are recorded as the main components. The highest phenolic acids content was obtained in the floral budding stage (287.40 mg/g dried extract). The analysis of phenolic acids demonstrated cinnamic acid (8.0-225.3 mg/g extract), p-coumaric acid (1.7-39.2 mg/g extract), p-hydroxybenzoic acid (0.8-16.8 mg/g extract), and ferulic acid (2.4-15.8 mg/g extract) as the main phenolic acids. Cinnamic acid was found as the major phenolic compound in the vegetative stage following by floral budding, the full flowering stage, the early development of seeds, and late-mature/ripe seeds stages. P-coumaric acid was the most abundant phenolic compounds in the mid-mature seeds stage. In this regard, the harvest time of H. persicum aerial parts can be selected to achieve the highest secondary metabolites of interest. The results of this study can be used as a guideline for grower to obtain the highest possible amount of desirable metabolites, beneficial in both food and pharmaceutical industries as well as their undeniable economical benefits.

Fatty acid profile and in vitro biological properties of two Rosacea species (Pyrus glabra and Pyrus syriaca), grown as wild in Iran.

The high demands for the consumption of edible oils have caused scientists to struggle in assessing wild plants as a new source of seed oils. Therefore, in this study, the oil yield, fatty acid and tocopherol compositions, antioxidant and antibacterial activities of the oils obtained from Iran's two endemic plants (Pyrus glabra and Pyrus syriaca) were investigated. The obtained oil yields from the P. glabra and P. syriaca seeds were 33 ± 0.51 and 26 ± 0.28 w/w%, respectively. Oleic acid (C18:1) with the amount of 49.51 ± 1.05% was the major fatty acid in the P. glabra oil, while the main fatty acids in the P. syriaca seed oil belonged to linoleic acid (C18:2) and oleic acid (C18:1) with the amounts of 46.99 ± 0.37 and 41.43 ± 0.23%, respectively. The analysis of tocopherols was done by HPLC, and the results indicated that the P. glabra and P. syriaca seed oils were rich in α-tocopherol (69.80 ± 1.91 and 45.50 ± 1.86 mg/100 g oil, respectively), constituting 86.24 and 89.01% of total detected tocopherols, respectively. The study on the reducing capacity of the oils indicated that the P. glabra oil had more reducing capacity than the P. syriaca oil. Moreover, the antioxidant activity of the P. glabra seed oil (43.4 ± 0.7 µg/ml) was higher than the P. syriaca seed oil (46.3 ± 1.2 µg/ml). Also, the investigation of the antibacterial activities indicated that the P. glabra and P. syriaca oils have an inhibitory effect on the studied bacteria. The results indicate that the oils of these plants can be appropriate sources of plant oils which can act as natural antibacterial agents.

Molecular identification and phytochemical screening of endophytic fungi isolated from Lithospermum officinale L. roots: A new source of shikonin.

Endophytic fungi are microorganisms located in the inter- or intracellular compartments of plant tissues but with no harmful effects. They are considered a potential source of biological compounds. The present study was conducted to investigate the molecular identification of endophytic fungi isolated from the roots of Lithospermum officinale and their potential production of shikonin. Phylogenetic analysis was performed based on the Internal Transcribed Spacer (ITS) region and the isolates were classified into five genera as follows: Alternaria, Chaetosphaeronema, Fusarium, Mucor, and Trichoderma. The study on the methanol extracts of endophytic fungi indicated that total polyphenol content had a positive relationship with antioxidant activities and the highest antioxidant activity belonged to the methanol extracts of Fusarium tricinctum and Alternaria altenata. Then, to investigate the ability of the fungal isolates to produce shikonin, a naphthoquinone compound with high biological activity, the extracts were subjected to HPLC. The results obtained from HPLC-mass spectrometry showed that shikonin could be produced only by F. tricinctum. Thus, F. tricinctum isolated from the roots of L. officinale can be presented as a new source of shikonin.

Phytochemical Analysis and Various Biological Activities of the Aerial Parts of Scrophularia Atropatana Growing in Iran.

Scrophularia atropatana (S. atropatana), an Iranian plant belonging to the family of Scrophulariaceae, was assigned for its chemical compositions and biological activities of essential oil (EO) and extracts of the aerial parts of the plant during the flowering stage. Combination of GC-MS and GC-FID was assessed for analyzing the chemical compositions of the EO from the aerial parts of S. atropatana. Furthermore, Brine shrimp lethality test and DPPH assay were performed to evaluate general toxicity and free-radical-scavenging properties, respectively. Furthermore, anti-proliferative and antimicrobial activities were assessed by MTT assay and disc diffusion methods correspondingly. Additionally, all the potent samples (extracts) and its fractions in the MTT assay were further studied for the presence of various compounds by GC-MS apparatus. MeOH extract and 40% sep-pak fraction indicated high amounts of total phenolic (TPC), total flavonoid content (TFC), and antioxidant properties. In the case of general toxicity, among the extracts, dichloromethane (DCM) extract showed noticeable effect. Furthermore, DCM extract was indicated potent ability to eliminate breast tumor cells and minimum efficacy on normal cells. Anti-microbial activity of all samples was ignorable. The potent extracts and fractions which had more anti-proliferative activity were further elucidated by GC-MS and showed high amounts of Alkanes and fatty acids. In the case of EO constituents, non-terpenoids were the major compounds. To sum up, it seems BSLT could be a good preliminary approach for evaluating the cytotoxicity in MCF-7 cell line. Additionally, antioxidant activity, TPC, and TFC contents of all samples were in consistent with each other.

Modified rifampin nanoparticles: Increased solubility with slow release Rate.

BACKGROUND: Recent advances in nanotechnology-based drug delivery system have been shown to improve either antibacterial efficacy or pharmacokinetics behavior.The aim of this study was to design a rifampin nanoparticle (RIF-NP) which has a high loading capacity with the slow release profile. MATERIAL AND METHODS: The designed chitosan/gelatin/lecithin (Chg/L) RIF-NPs were prepared by multilamellar vesicle. Thereafter, the particle size, zeta potential, morphology, and release rate were investigated. To optimize the loading capacity and release profiles, different concentrations of lecithin were used. RESULTS: Our results showed a correlation of lecithin concentration with size, zeta potential, and loading capacity of RIF-NPs. Increases in lecithin concentration (0.2-2.0 g) could cause a significant size reduction in NPs (250-150 nm); the amount of zeta potential (from 14 to 49 mV;P < 0.05) and loading capacity increases from 8% to 20% (P < 0.05). Designed NPs had slow drug release profile which was influenced by pH and lecithin concentration. The cumulative percentage of RIF released at pH 7.4 was approximately 93% up to 12 h. In overall, release profile was better than standard drug, even in various pH conditions (pH = 1, 3.4, and 7.4). The Chg/L-RIF NPs may be considered as a promising drug nanocarrier. CONCLUSIONS: These NPs release RIF in slow and constant rate, which effectively might eliminate the bacilli and prevent the formation of RIF-resistant bacilli.