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.

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.

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.