An evaluation on potential anti-oxidant and anti-inflammatory effects of Crocin.

Crocin, an active ingredient derived from saffron, is one of the herbal components that has recently been considered by researchers. Crocin has been shown to have many anti-inflammatory and antioxidant properties, and therefore can be used to treat various diseases. It has been shown that Crocin has a positive effect on the prevention and treatment of cardiovascular disease, cancer, diabetes, and kidney disease. In addition, the role of this substance in COVID-19 pandemic has been identified. In this review article, we tried to have a comprehensive review of the antioxidant and anti-inflammatory effects of Crocin in different diseases and different tissues. In conclusion, Crocin may be helpful in pathological conditions that are associated with inflammation and oxidative stress.

Ayurvedic antiviral agents: Overview of medicinal plants perspective

In recent years, it has been reported that many herbal plants contain antiviral agents which combat a human disease that is caused by pathogenic viruses. The natural products which are obtained from plants as antiviral agents against viruses have gone through researches to check the efficacy and potentials of the herbal products in the prevention of viral disorders. On the basis of randomized controlled studies and in-vivo studies, and in-vitro studies, some agents are utilized all across the globe. Progressively numerous studies on therapy of antivirals have been increased. Though, efficacy remains disputable for antiviral drugs that are employed for viral disorders. The viral diseases are challenging for the health of people around the world cause significant increase in mortality and enhance crises. There are many synthetic antiviral drugs that have a large number of side effects and have narrow therapeutic window range, while in the other hand herbal formulations have minimized side effects. The advantages of herbal formulation over synthetic drugs encourage us to devise and expand new herbal moieties against the emerging viral infections. The medicinal plants contain phytochemicals that have antiviral properties. In this paper, the activity of antiviral agents from medicinal plants which have importance in Ayurveda, are discussed along with their source.

In silico evaluation of food-derived carotenoids against SARS-CoV-2 drug targets: Crocin is a promising dietary supplement candidate for COVID-19.

The current COVID-19 pandemic is severely threatening public healthcare systems around the globe. Some supporting therapies such as remdesivir, favipiravir, and ivermectin are still under the process of a clinical trial, it is thus urgent to find alternative treatment and prevention options for SARS-CoV-2. In this regard, although many natural products have been tested and/or suggested for the treatment and prophylaxis of COVID-19, carotenoids as an important class of natural products were underexplored. The dietary supplementation of some carotenoids was already suggested to be potentially effective in the treatment of COVID-19 due to their strong antioxidant properties. In this study, we performed an in silico screening of common food-derived carotenoids against druggable target proteins of SARS-CoV-2 including main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase. Molecular docking results revealed that some of the carotenoids had low binding energies toward multiple receptors. Particularly, crocin had the strongest binding affinity (-10.5 kcal/mol) toward the replication complex of SARS-CoV-2 and indeed possessed quite low binding energy scores for other targets as well. The stability of crocin in the corresponding receptors was confirmed by molecular dynamics simulations. Our study, therefore, suggests that carotenoids, especially crocin, can be considered an effective alternative therapeutics and a dietary supplement candidate for the prophylaxis and treatment of SARS-CoV-2. PRACTICAL APPLICATIONS: In this study, food-derived carotenoids as dietary supplements have the potential to be used for the prophylaxis and/or treatment of SARS-CoV-2. Using in silico techniques, we aimed at discovering food-derived carotenoids with inhibitory effects against multiple druggable sites of SARS-CoV-2. Molecular docking experiments against main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase resulted in a few carotenoids with multitarget inhibitory effects. Particularly, crocin as one of the main components of saffron exhibited strong binding affinities to the multiple drug targets including main protease, helicase, replication complex, mutant spike protein of lineage B.1.351, and ADP-ribose phosphatase. The stability of the crocin complexed with these drug targets was further confirmed through molecular dynamics simulations. Overall, our study provides the preliminary data for the potential use of food-derived carotenoids, particularly crocin, as dietary supplements in the prevention and treatment of COVID-19.

Anti-Depressant Properties of Crocin Molecules in Saffron.

Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-d-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.

Crocetin and related oxygen diffusion-enhancing compounds: Review of chemical synthesis, pharmacology, clinical development, and novel therapeutic applications.

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.

Immunomodulatory and anti-inflammatory potential of crocin in COVID-19 treatment.

The current COVID-19 pandemic is one of the most devastating events in recent history. In the lack of a specific treatment and vaccine for this novel infection, finding effective drugs against this infection is crucial. We suggest the hypothesis that crocin, the main carotenoid of saffron, has the potential to limit the progression and severity of the SARS-CoV2 infection for several reasons: (a) crocin possesses powerful antioxidant properties, (b) crocin can alleviate the uncontrolled cytokine production responsible for acute lung injury, (c) crocin can upregulate PPARγ and downregulate NF-κB expression which leads to a wide range of immunomodulatory and anti-inflammatory effects, and (d) crocin can reduce the viral-induced oxidative stress and downregulates ACE2 expression by activating Nrf2 pathway. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test crocin as a beneficial drug against the SARS-CoV2 infection. PRACTICAL APPLICATIONS: Crocin is a natural antioxidant and the main active carotenoid components of saffron. We suggest the hypothesis that crocin has the potential to limit the progression and severity of the SARS-CoV2 infection because of its antioxidant and anti-inflammatory properties. Furthermore, this compound may prevent viral entry to host cells and reduce SARS-CoV2-induced lung injury. Therefore, we suggest further clinical studies on the effects of crocin against SARS-Cov-2 infection.

Investigation on penetration of saffron components through lipid bilayer bound to spike protein of SARS-CoV-2 using steered molecular dynamics simulation.

A coronavirus identified as COVID-19 is the reason for an infection outbreak which is started in December 2019. NO completely effective drugs and treatments are not recognized for this virus. Recently, saffron and its compounds were used to treat different viral diseases. Saffron extract and its major ingredients have shown antiviral effects. In this study, the steered molecular dynamics simulation was used for investigating the effect of four main components of saffron that include: crocin, crocetin, safranal, and picrocrocin as candidate for drug molecules, on COVID-19. The binding energies between drug molecules and spike protein and the main protease of the virus were evaluated. The obtained results based on Lennard-Jones and electrostatic potentials demonstrated that crocetin has a high affinity towards spike protein and also the main protease of the virus. Also, the quantum mechanics calculations elucidated that the crocetin could overcome energy barrier of lipid bilayer with strong dipole moment and polarizability. The pharmacokinetic and ADMET properties proved that crocetin could be a suitable drug candidate. So, crocetin could be a promising drug for treatment of COVID-19.

Moroccan Medicinal plants as inhibitors against SARS-CoV-2 main protease: Computational investigations.

The new Corona-virus, recently called the severe acute respiratory syndrome Coronavirus (SARS-CoV-2) appears for the first time in China and more precisely in Wuhan (December 2019). This disease can be fatal. Seniors, and people with other medical conditions (diabetes, heart disease…), may be more vulnerable and become seriously ill. This is why research into drugs to treat this infection remains essential in several research laboratories. Natural herbal remedies have long been the main, if not the only, remedy in the oral tradition for treating illnesses. Modern medicine has known its success thanks to traditional medicine, the effectiveness of which derives from medicinal plants. The objective of this study is to determine if the components of natural origin have an anti-viral effect and which can prevent humans from infection by this coronavirus using the most reliable method is molecular docking, which used to find the interaction between studied molecules and the protein, in our case we based on the inhibitor of Coronavirus (nCoV-2019) main protease. The results of molecular docking showed that among 67 molecules of natural origin, three molecules (Crocin, Digitoxigenin, and ß-Eudesmol) are proposed as inhibitors against the coronavirus based on the energy types of interaction between these molecules and studied protein. [Formula: see text] Communicated by Ramaswamy H. SarmaHighlightsDetermine natural compounds that can have an anti-viral effect and which can prevent humans from infection by this coronavirus;Molecular docking to find interaction between the molecules studied and the receptor of COVID-19;The synthesis of these molecules and the evaluation of their in vitro activity against SARS-Cov-2 could be interesting.