Cationic Okra gum coated nanoliposomes as a pH-sensitive carrier for co-delivery of hesperetin and oxaliplatin in colorectal cancers.

Oxaliplatin (OXP) is the typical treatment for colorectal cancer. Combining chemotherapeutic drugs can reduce drug resistance and side effects. In the present study, the co-delivery of OXP with Hesperetin (HSP), a natural anti-cancer flavonoid, by nanoliposomes was studied against HT-29 colon cancer cells. Cationic Okra gum (COG) was synthesized to coat nanoliposomes. The successful synthesis of COG was confirmed by NMR spectroscopy. Liposomes were prepared by thin film hydration technique. Formulations containing 0.5, 1, and 2 mg·ml-1 COG, had particle sizes ranging from 145 to 175 nm and zeta potentials for uncoated and coated formulations changed between -29 and -0.403 mV. Coated liposomes released 98 and 66% of HSP and OXP, respectively during 24 h pH-dependently. Cationic Okra gum enhanced the physical stability of the liposomes for about 30 days. The composite liposomes containing OXP and HSP at final concentrations of 1.125 and 125 µM, respectively could generate significant cytotoxicity at 48 h in comparison to each drug alone. Extracted drug-target interactions from the STITCH database, showed that Catalase (CAT) is the common target between OXP and HSP drugs. Measurement of the CAT activity may be used as an indicator to investigate the mechanism of action of these drugs in subsequent experiments.

Variation in bioactive compounds, antioxidant and antibacterial activity of Iranian Chrysanthemum morifolium cultivars and determination of major polyphenolic compounds based on HPLC analysis.

In this study, chemical profiling, phenolic and flavonoid contents, as well as the antibacterial and antioxidant activity of 17 Iranian Chrysanthemum morifolium cultivars were evaluated. The high performance liquid chromatography analysis revealed the presence of eight compounds with the major constituents including chlorogenic acid (0-934.7 mg/100 g), ferulic acid (12.7-171.6 mg/100 g), rutin (0-225.8 mg/100 g) and luteolin (2.83-213.5 mg/100 g). The cultivar "Ashna" with 63.6 mg tannic acid equivalents g-1 DW had the highest amount of total phenol, while the highest flavonoid content (13.52 mg quercetin equivalents g-1DW) was observed in cultivar "Shokoh". The antioxidant activities of the samples were determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the reducing power assay. The results showed that the cultivars "Poya3" (IC50 = 385.7) and "Dorna2" (IC50 = 489.4) possessed a higher antioxidant activity than the others in DPPH model system. Antimicrobial activity was also evaluated based on minimal inhibitory concentration (MIC) and minimal bactericidal concentration values. MIC values were in the range of 5-10 mg ml-1 against Salmonella enterica and Bacillus cereus and 10-20 mg ml-1 against Staphylococcus aureus and Escherichia coli. Finally, Chrysanthemum cultivars with high bioactive compounds were introduced for beneficial usage in food and industrial applications.

Anticancer drug discovery from Iranian Chrysanthemum cultivars through system pharmacology exploration and experimental validation.

Breast cancer is the most common carcinoma in women, and natural products would be effective preventing some side effects of cancer treatment. In the present study, cytotoxic activities of different Iranian Chrysanthemum morifolium cultivars were evaluated in human breast cancer cell lines (MCF-7) and human lymphocytes. A systems pharmacology approach was employed between major compounds of these cultivars (chlorogenic acid, luteolin, quercetin, rutin, ferulic acid, and apigenin) and known breast cancer drugs (tucatinib, methotrexate, tamoxifen, and mitomycin) with 22 breast cancer-related targets to analyze the mechanism through which Chrysanthemum cultivars act on breast cancer. Target validation was performed by the molecular docking method. The results indicated that Chrysanthemum extracts inhibited the proliferation of MCF7 cells in a dose- and cultivar-dependent manner. In all studied cultivars, the most effective extract concentration with the lowest viability of MCF-7 cells, was as much as 312 µg ml-1. Also, higher concentrations of the extracts (> 1000 µg ml-1) reduced the lymphocyte cell viability, demonstrating that these doses were toxic. The gene ontology analysis revealed the therapeutic effects of Chrysanthemum's active compounds on breast cancer by regulating the biological processes of their protein targets. Moreover, it has been documented that rutin, owing to its anticancer effects and several other health benefits, is a promising multi-targeted herbal ingredient. Finally, the present study compared different Iranian Chrysanthemum cultivars to provide new insights into useful pharmaceutical applications.