The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

With cancer being a leading cause of death globally, there is an urgent need to improve therapeutic strategies and identify effective chemotherapeutics. This study aims to highlight the potential of crocetin, a natural product derived from certain plants, as an anticancer agent. It was  conducted an extensive review of the existing literature to gather and analyze the most recent data on the chemical properties of crocetin and its observed effects in various in vitro and in vivo studies. The study  particularly focused on studies that examined crocetin\'s impact on cell cycle dynamics, apoptosis, caspases and antioxidant enzyme levels, tumor angiogenesis, inflammation, and overall tumor growth. Crocetin exhibited diverse anti-tumorigenic activities including inhibition of tumor cell proliferation, apoptosis induction, angiogenesis suppression, and potentiation of chemotherapy. Multiple cellular and molecular pathways such as the PI3K/Akt, MAPK and NF-κB were modulated by it. Crocetin demonstrates promising anti-cancer properties and offers potential as an adjunctive or alternative therapy in oncology. More large-scale, rigorously designed clinical trials are needed to establish therapeutic protocols and ascertain the comprehensive benefits and safety profile of crocetin in diverse cancer types.

The potential therapeutic benefits of saffron and its active constituents have been investigated for the treatment of numerous illnesses. In this review, the impacts of saffron and its essential components on the levels of microRNAs (miRNAs) in different diseases have been delineated. Relevant articles were obtained through databases such as PubMed, Web of Sciences, Scopus, and Google Scholar up to the end of November 2022. miRNA expression has been altered by saffron and its active substances (crocin, crocetin, and safranal) which has been of great advantage in treating diseases such as cardiovascular, type 2 diabetes, cancers, gastrointestinal and liver disorders, central and peripheral nervous system disorders, asthma, osteoarthritis, ischemic-reperfusion induced injury conditions, and renal disorder. This study uncovered the potential restorative advantages of saffron and its derivatives, in miRNA imbalances in a variety of diseases.

Saffron (Crocus sativus) is a natural compound and its constituents such as crocin, crocetin, and safranal have many pharmacological properties such as anti-oxidant, anti-inflammatory, antitumor, antigenotoxic, anti-depressant, hepatoprotective, cardioprotective, and neuroprotective. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays an important role against inflammation, oxidative stress, and carcinogenesis. In the regulation of the Nrf2 signaling pathway, kelch-like ECH-associated protein 1 (keap1) is the most studied pathway. In this review, we gathered various studies and describe the pharmacological effects of saffron and its constituents with their related mechanisms of action, particularly the Nrf2 signaling pathway. In this review, we used search engines or electronic databases including Scopus, Web of Science, and Pubmed, without time limitation. The search keywords contained saffron, \"Crocus sativus\", crocetin, crocin, safranal, picrocrocin, \"nuclear factor erythroid 2-related factor 2\", and Nrf2. Saffron and its constituents could have protective properties through various mechanisms particularly the Nrf2/HO-1/Keap1 signaling pathway in different tissues such as the liver, heart, brain, pancreas, lung, joints, colon, etc. The vast majority of studies discussed in this review indicate that saffron and its constituents could induce the Nrf2 signaling pathway leading to its anti-oxidant and therapeutic effects.

Diabetes mellitus is one of the most prevalent metabolic disorders that affect people of all genders, ages, and races. Medicinal herbs have gained attention from researchers and have been widely investigated for their antidiabetic potential. Saffron (Crocus sativus L.) and its main constituents, that is, crocin and crocetin, are natural carotenoid compounds, widely known to possess a wide spectrum of properties and induce pleiotropic anti-inflammatory, anti-oxidative, and neuro-protective effects. An increasing number of experimental, animal and human studies have investigated the effects and mechanism of action of these compounds and their potential therapeutic use in the treatment of diabetes. This narrative review presents the key findings of published clinical studies that examined the effects of saffron and/or its constituents in the context of diabetes mellitus. Moreover, an overview of the proposed underlying mechanisms mediating these effects, the medicinal applications of saffron, and the new findings regarding its effect on diabetes and various cellular and molecular mechanisms of action will be debated.

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.

Crocus sativus L. (Iridaceae), known as saffron, is widely used as a coloring agent, food additive, and medicinal spice. Saffron can be beneficial for treating convulsions, tumors, oxidative-related diseases, inflammation, memory impairments, and depression. These effects are due to its chemical components like anthocyanins, flavonoids and terpenoids. Saffron has been shown to be of benefit for treating skin diseases as a result of its anti-oxidant, anti-microbial, depigmenting, and repairing activities. Therefore, it is used for formulating various lotions, creams, and cosmetics emulsions, namely sunscreens, moisturizers, and anti-spot and anti-aging products. In this review, we have presented various skin protective effects of saffron and its components.

Crocins, as a kind of water-soluble carotenoid pigment, are a series of ester compounds formed from crocetin and gentibiose or glucose, and mainly distributed among Crocus sativus L. (CSL), Gardenia jasminoides Ellis. (GJE). Crocins exhibit a wide range of pharmacological effects on neurodegeneration, cardiovascular disease, cerebrovascular disease, depression, liver disease, arthritis, tumor, diabetes, etc. This review systematically discussed the pharmacologic study of crocins in the aspect of structural characteristic and pharmacokinetics, and summarized the mechanism of treating disease. It summarized the abundant research of crocins from 1984 to 2020 based on the above aspects, which provide a reference for the deeply development and application of crocins.

The current pandemic forced us to introspect and revisit our armamentarium of medicinal agents which could be life-saving in emergency situations. Oxygen diffusion-enhancing compounds represent one such class of potential therapeutic agents, particularly in ischemic conditions. As rewarding as the name suggests, these agents, represented by the most advanced and first-in-class molecule, trans-sodium crocetinate (TSC), are the subject of intense clinical investigation, including Phase 1b/2b clinical trials for COVID-19. Being a successor of a natural product, crocetin, TSC is being investigated for various cancers as a radiosensitizer owing to its oxygen diffusion enhancement capability. The unique properties of TSC make it a promising therapeutic agent for various ailments such as hemorrhagic shock, stroke, heart attack, among others. The present review outlines various (bio)synthetic strategies, pharmacological aspects, clinical overview and potential therapeutic benefits of crocetin and related compounds including TSC. The recent literature focusing on the delivery aspects of these compounds is covered as well to paint the complete picture to the curious reader. Given the potential TSC holds as a first-in-class agent, small- and/or macromolecular therapeutics based on the core concept of improved oxygen diffusion from blood to the surrounding tissues where it is needed the most, will be developed in future and satisfy the unmet medical need for many diseases and disorders.

Natural products with high pharmacological potential and low toxicity have been considered as the novel therapeutic agents. Crocetin is an active constituent of saffron (Crocus sativus L.) stigma, which in its free-acid form is insoluble in water and most organic solvents. Crocetin exhibits various health-promoting properties including anti-tumor, neuroprotective effects, anti-diabetics, anti-inflammatory, anti-hyperlipidemia, etc. These therapeutic effects can be achieved with different mechanisms such as improvement of oxygenation in hypoxic tissues, antioxidant effects, inhibition of pro-inflammatory mediators, anti-proliferative activity and stimulation of apoptosis in cancer cells. It is also worth considering that crocetin could be tolerated without major toxicity at therapeutic dosage in experimental models. In the present review, we discuss the biosynthesis, pharmacokinetic properties of crocetin and provide a comprehensive study on the biological activities and toxicity along with the mechanism of actions and clinical trials data of crocetin.