The Pharmacological Activities of Crocus sativus L.: A Review Based on the Mechanisms and Therapeutic Opportunities of its Phytoconstituents

Abstract

Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western Asia, used in gardens and parks as ornamental plants, while Crocus sativus L. (saffron) is the only species that is cultivated for edible purpose. The use of saffron is very ancient; besides the use as a spice, saffron has long been known also for its medical and coloring qualities. Due to its distinctive flavor and color, it is used as a spice, which imparts food preservative activity owing to its antimicrobial and antioxidant activity. This updated review discusses the biological properties of Crocus sativus L. and its phytoconstituents, their pharmacological activities, signaling pathways, and molecular targets, therefore highlighting it as a potential herbal medicine. Clinical studies regarding its pharmacologic potential in clinical therapeutics and toxicity studies were also reviewed. For this updated review, a search was performed in the PubMed, Science, and Google Scholar databases using keywords related to Crocus sativus L. and the biological properties of its phytoconstituents. From this search, only the relevant works were selected. The phytochemistry of the most important bioactive compounds in Crocus sativus L. such as crocin, crocetin, picrocrocin, and safranal and also dozens of other compounds was studied and identified by various physicochemical methods. Isolated compounds and various extracts have proven their pharmacological efficacy at the molecular level and signaling pathways both in vitro and in vivo. In addition, toxicity studies and clinical trials were analyzed. The research results highlighted the various pharmacological potentials such as antimicrobial, antioxidant, cytotoxic, cardioprotective, neuroprotective, antidepressant, hypolipidemic, and antihyperglycemic properties and protector of retinal lesions. Due to its antioxidant and antimicrobial properties, saffron has proven effective as a natural food preservative. Starting from the traditional uses for the treatment of several diseases, the bioactive compounds of Crocus sativus L. have proven their effectiveness in modern pharmacological research. However, pharmacological studies are needed in the future to identify new mechanisms of action, pharmacokinetic studies, new pharmaceutical formulations for target transport, and possible interaction with allopathic drugs.

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines

“…With reference to the previous data, saffron and its major constituents present a rather safe pharmacokinetic profile, even in healthy volunteers, as according to the toxicity classification, substances with a LD 50 value within the range of 0.5–5 g/kg are considered practically low-toxic and substances with LD 50 > 5 g/kg may be considered practically non-toxic [ 23 , 25 , 147 , 178 , 179 , 180 , 181 ]. In the current study, although a wide range of concentrations was used, i.e., 0.179–22.85 mg/mL for CRCs and 0.09–11.429 for DMCRT, such high concentrations were also employed in studies of saffron metabolites on hormone-insensitive prostate cancer cells (22rv1, C4–2B, DU145, PC3 cells), lung adenocarcinoma cells (A549, SPC-A1), HL-60 leukemia cells, HCT116 colorectal carcinoma and gastric adenocarcinoma (BGC-823, SGC-7901) cells.…”

“…Constituents and metabolites of saffron are relatively safe as demonstrated in several studies on animal models, in terms of acute, subacute, sub chronic and chronic exposure. Saffron and its metabolites did not cause any significant hematological or biochemical toxic effects, nor were associated with histotoxicity in heart, liver, spleen and kidney, or genotoxic and mutagenic effects [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. CRCs in preclinical mice models were well tolerated in doses up to 3 g/kg, in intraperitoneal or oral administration for acute exposure and 400 mg/kg in intraperitoneal administration for subacute exposure (3–4 weeks) [ 26 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Untargeted Metabolomics Analysis of Crocus cancellatus subsp. damascenus (Herb.) B. Mathew Stigmas and Their Anticarcinogenic Effect on Breast Cancer Cells

“…In recent years, C. sativus stigmas have been widely researched for their potential effects on cancer and other diseases [4,32]. According to the identification of the main bioactive constituents of saffron, the antiproliferative effect of C. cancellatus stigmas extract in both 2D monolayer and 3D cell cultures of MDA-MB-231 and MCF-7 human breast Evidence-Based Complementary and Alternative Medicine cancer cells were examined for the first time.…”

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine

“…Colchicine is an alkaloid derived from the colchicum genus, derived from the autumn crocus ( Colchicum autumnale ) and Glory Lilly ( Gloriosa Superba ) plants, found primarily in Europe and North America (Additional file 1 ). Colchicine has been used in medications approved by the US Food and Drug Administration since 2009 [ 66 ]. It is a plant water-soluble alkaloid, odourless, with pale yellow needles or powder.…”