Bioactive compounds of cinnamon and their effect on decreasing metabolic syndrome: systematic review / Compuestos bioactivos de canela y su efecto en la disminución del síndrome metabólico: revisión sistemática

Introducción. El síndrome metabólico (SM) aumenta el ingreso hospitalario y el riesgo de desarrollar COVID-19, los fármacos utilizados para su tratamiento ocasionan efectos secundarios por lo que se ha optado por la búsqueda de alternativas terapéuticas a base de compuestos bioactivos contenidos en plantas medicinales. La canela se utiliza como agente terapéutico debido a sus propiedades comprobadas con diversos mecanismos de acción reportados en el tratamiento de varias patologías. Objetivo. Documentar los estudios in vitro, in vivo, estudios clínicos y los mecanismos de acción reportados del efecto de la administración de extractos y polvo de canela en las comorbilidades relacionadas con el SM. Materiales y métodos. Revisión sistemàtica de artículos en bases de datos electrónicas, incluyendo estudios de canela en polvo, extractos acuosos, de acetato de etilo y metanol de la corteza de canela, período de 5 años, excluyendo todo artículo relacionado a su efecto antimicrobiano, antifúngico y aceite de canela. Resultados. Las evidencias de los principales compuestos bioactivos contenidos en la canela validan su potencial en el tratamiento de enfermedades relacionadas al SM, con limitados estudios que indagan en los mecanismos de acción correspondientes a sus actividades biológicas. Conclusiones. Las evidencias de las investigaciones validan su potencial en el tratamiento de estas patologías, debido a sus principales compuestos bioactivos: cinamaldehído, transcinamaldehído, ácido cinámico, eugenol y, antioxidantes del tipo proantocianidinas A y flavonoides, los cuales participan en diversos mecanismos de acción que activan e inhiben enzimas, con efecto hipoglucemiante (quinasa y fosfatasa), antiobesogénico (UPC1), antiinflamatorio (NOS y COX), hipolipemiante (HMG-CoA) y antihipertensivo (ECA)(AU)

Introduction. Metabolic syndrome (MS) increases hospital admission and the risk of developing COVID-19. Due to the side effects caused by the drugs used for its treatment, the search for therapeutic alternatives based on bioactive compounds contained in medicinal plants has been chosen. Cinnamon is used as a therapeutic agent due to its proven properties with various mechanisms of action reported in the treatment of various pathologies. Objective. To document the in vitro and in vivo studies, clinical studies and the mechanisms of action reported on the effect of the administration of cinnamon extracts and powder on comorbidities related to MS. Materials and methods. Systematic review of articles in electronic databases, including studies of cinnamon powder, aqueous extracts, ethyl acetate and methanol from cinnamon bark, over a period of 5 years, excluding all those articles related to its antimicrobial, antifungal and antimicrobial effect. cinnamon oil. Results. The evidence of the main bioactive compounds contained in cinnamon validates its potential in the treatment of diseases related to MS, with limited studies that investigate the mechanisms of action corresponding to its biological activities. Conclusions. Research evidence validates its potential in the treatment of these pathologies, due to its main bioactive compounds: cinnamaldehyde, transcinnamaldehyde, cinnamic acid, eugenol, and antioxidants of the proanthocyanidin A type and flavonoids, which participate in various mechanisms of action that activate and they inhibit enzymes, with hypoglycemic (kinase and phosphatase), antiobesogenic (UPC1), anti-inflammatory (NOS and COX), lipid-lowering (HMG-CoA) and antihypertensive (ACE) effects(AU)

Bioactive Compositions of Cinnamon (Cinnamomum verum J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals.

Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals was investigated. Twenty-seven and twenty-three compounds were tentatively identified in cinnamon water and ethanol extracts, respectively. Seven compounds, including saccharumoside C, two emodin-glucuronide isomers, two physcion-glucuronide isomers, and two type-A proanthocyanidin hexamers, were first reported in cinnamon. Cinnamon water and ethanol extracts suppressed the binding of SARS-CoV-2 spike protein to ACE2 and inhibited ACE2 activity in a dose-dependent manner. Cinnamon ethanol extract had total phenolic content of 36.67 mg gallic acid equivalents (GAE)/g and free radical scavenging activities against HO• and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) of 1688.85 and 882.88 µmol Trolox equivalents (TE)/g, which were significantly higher than those of the water extract at 24.12 mg GAE/g and 583.12 and 210.36 µmol TE/g. The free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) of cinnamon ethanol extract was lower than that of the water extract. The present study provides new evidence that cinnamon reduces the risk of SARS-CoV-2 infection and COVID-19 development.

Structural interactions of phytoconstituent(s) from cinnamon, bay leaf, oregano, and parsley with SARS-CoV-2 nucleocapsid protein: A comparative assessment for development of potential antiviral nutraceuticals.

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin > catechin > apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin > cinnamic acid > catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.

In silico identification of potential inhibitors from Cinnamon against main protease and spike glycoprotein of SARS CoV-2.

Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In the present study, 48 isolates compounds from Cinnamon retrieved from the PubMed database, are subjected to docking analysis. Docking study was performed using Autodock vina and PyRx software. Afterwards, admetSAR, as well as DruLiTo servers, were used to investigate drug-likeness prophecy. Our study shows that the nine phytochemicals of Cinnamon are very likely against the main protease enzyme of COVID-19. Further MD simulations could identify Tenufolin (TEN) and Pavetannin C1 (PAV) as hit compounds. Utilizing contemporary strategies, these phyto-compounds from a natural origin might establish a reliable medication or support lead identification. Identified hit compounds can be further taken for in vitro and in vivo studies to examine their effectiveness versus COVID-19.

Cinnamon and its possible impact on COVID-19: The viewpoint of traditional and conventional medicine.

The COVID-19 global epidemic caused by coronavirus has affected the health and other aspects of life for more than one year. Despite the current pharmacotherapies, there is still no specific treatment, and studies are in progress to find a proper therapy with high efficacy and low side effects. In this way, Traditional Persian Medicine (TPM), due to its holistic view, can provide recommendations for the prevention and treatment of new diseases such as COVID-19. The muco-obstruction of the airway, which occurs in SARS-CoV-2, has similar features in TPM textbooks that can lead us to new treatment approaches. Based on TPM and pharmacological studies, Cinnamomum verum (Darchini)'s potential effective functions can contribute to SARS-CoV-2 infection treatment and has been known to be effective in corona disease in Public beliefs. From the viewpoint of TPM theories, Cinnamon can be effective in SARS-CoV-2 improvement and treatment through its anti-obstructive, diuretic, tonic and antidote effects. In addition, there is pharmacological evidence on anti-viral, anti-inflammatory, antioxidant, organ-o-protective and anti-depression effects of Cinnamon that are in line with the therapeutic functions mentioned in TPM.Overall, Cinnamon and its ingredients can be recommended for SARS-CoV2 management due to multi-targeting therapies. This review provides basic information for future studies on this drug's effectiveness in preventing and treating COVID-19 and similar diseases.

Cinnamon: A Promising Natural Product Against COVID-19.

COVID-19 is a pandemic and acute respiratory disease. Every day, all around the world, researchers are endeavoring to find effective or potential adjuvant therapies. Studies illustrate that essential oils from cinnamon and derivatives such as cinnamaldehyde and cinnamic acid possess numerous biological activities. In this paper, we have reviewed the possible mechanisms of cinnamon on the inflammatory cascade as a potential alternative therapy to decrease oxidative stress and inflammation in COVID-19 patients.

Trachyspermum ammi and Cinnamomum verum as nutraceuticals: Spices rich in therapeutically significant protein tyrosine phosphatases.

Nutraceuticals need special attention as preventive molecules to create a natural barrier against various dreadful diseases like cancer and to regulate metabolism. In the present study, two spices, Trachyspermum ammi and Cinnamomum verum, been identified as excellent Protein Tyrosine Phosphatases (PTPases) sources that play significant role in the regulation of cell signal transduction and developmental processes in plants as well as animals, being lucrative and potential targets for pharmacological modulation. PTPases from both cases were partially purified into 0%-40% and 40%-80% fractions based on ammonium sulfate saturation levels. Fraction (40%-80%) exhibited a purification level of 4.44-fold and 2.86-fold with specific activity of 44.06 and 23.33 U/mg for PTPases from T. ammi and C. verum, respectively. PTPases being found to be thermally stable up to 70°C imply their industrial significance. Kinetic studies showed Km values to be 7.14 and 8.33 mM, whereas the activation energy (Ea ) values were 25.89 and 29.13 kJ/mol, respectively. Divalent cations: Cu2+ , Zn2+ , and Mn2+ acted as inhibitors of PTPases, from both sources. The Ki values of inhibitors varied from 0.014-0.125 mM in the descending order Cu2+  > Zn2+  > Mn2+ and Mn2+  > Cu2+  > Zn2+ for PTPases from T. ammi and C. verum, respectively. The inhibitory effect of sodium metavanadate aligns with prominent PTPase characteristics. In addition to these properties, the thermostability of PTPases from two spices enhances their significance in industries with therapeutically vital products. Although the source of PTPases is culinary spices, further studies are required to establish the utilization of PTPases as nutraceuticals and in therapeutic formulations. PRACTICAL APPLICATIONS: For a healthy lifestyle, awareness needs to be created by humankind towards food habits to minimize illnesses. Numerous studies have explored the consumption of nutraceutical products acts as a natural barrier and immune booster for various human ailments including SARS-COV-2. PTPases play important roles in regulating intracellular signaling and, ultimately, biological function along with their structural features. The importance of PTPases and their inhibitors has been implicated in various diseases like cancer, diabetes, and obesity. Further investigations need to be undertaken to explore the therapeutic properties of PTPases in both in vivo and in vitro for their clinical significance.