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

Abstract

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.

Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview

“…A systems pharmacology approach was employed between the major compounds of Iranian Chrysanthemum cultivars and known breast cancer drugs with breast cancer-related targets to analyze the mechanism. Among the major compounds of these cultivars, rutin has shown anticancer activity against MCF-7 cell line [ 117 ]. The systems pharmacology approach gives an idea of the target compound network as well as the signaling pathways associated with treating complex diseases like breast cancer apart from the confirmation study of the chosen target [ 118 ].…”

Chemical Antioxidant Quality Markers of Chrysanthemum morifolium Using a Spectrum-Effect Approach

“…The Compendium of Materia Medica records that CM can benefit the five veins, regulate the extremities, and cure the head wind heat tonic. Modern pharmacological researches also show that CM possesses heat dissipation, detoxification, brightening eyes, lowering blood pressure and other effects (Hodaei et al, 2021a). The main active ingredients of CM include flavonoids (luteolin), phenolic acids (chlorogenic acid), and polysaccharides (Hodaei et al, 2018;Tian et al, 2020), and Chrysanthemum extracts containing different components have the ability to improve myocardial nutrition, remove reactive oxygen radicals, strengthen vascular resistance, and lower blood lipids (Zhang et al, 2019).…”