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.
Introduction
The genus Crocus is a member of the Iridaceae (subfamily Crocoideae) and consists of about 100 species that occur in the wild. These are mainly found in central-southern Europe (Balkan Peninsula), North Africa, and Western Asia . Several species of this genus are currently used in gardens and parks as ornamental plants for their colorful flowers, while Crocus sativus L. (saffron) is the only species that is cultivated for the edible purpose.
The use of saffron is very ancient: its earliest representation appeared approximately 4000 years ago in some paintings and ceramics of the Minoan civilization in the region of Crete. The stigmas from flowers are traditionally handpicked at dawn to preserve all the aroma and organoleptic characteristics. Then the stigmas are dried in the shade and finally powdered. Due to its distinctive flavor and yellow-orange color, it has an ancient use as spice in Arab, European, Indian, and Persian cuisine. It is also used in liquors, candies, food supplements, and medical and coloring qualities.
Among the phytoconstituents, there have been described several compounds that are thought to be the chemical determinants of the bitterness, scent, and color of saffron. These are formally terpenoids or thought to be derived from terpenoid precursors. In particular, these are the apocarotenoids such as trans-crocetin and its glycosylated forms (crocins), especially trans-crocetin di-(β-D-gentiobiosyl) ester and trans-crocetin (β-D-gentiobiosyl)-(β-D-glucosyl) ester, together with picrocrocin and safranal (Figure 1), formerly a monoterpene glycoside and a monoterpene, respectively, and believed to be degradation products of zeaxanthin.
As minor components, which also contribute to the spice color and biological effects, there are a series of glycosidic derivatives of kaempferol (Figure 1) and quercetin. Other minor components that contribute to the peculiar aroma of saffron are volatile compounds related to isophorone.
Obviously, several of the medicinal and healthpromoting properties attributed to saffron are due to the presence of these compounds. For example, safranal, in addition to its antioxidant and radical-scavenger properties, is useful as an anticonvulsant and antidepressant in preclinical models. Due to the high added value of saffron as a spice and of its chemical constituents mainly related to the healthy properties, the studies on saffron and its plant source (C. sativus) are in the limelight, especially concerning the analytical methods used to evaluate the quality and to identify marker compounds related to the country of origin.
In this updated review, the following aspects of Crocus plants are considered: traditional uses, phytochemical composition, pharmacological properties with mechanisms evidenced from in vitro and in vivo studies, clinical studies, toxicological data, and upcoming clinical perspectives.