2-methoxycinnamaldehyde and cinnamaldehyde

Skeletal muscle atrophy, associated with increased morbidity, mortality and poor quality of life, is a metabolic disorder with no FDA approved drug. Oxidative stress is one of the key mediators of atrophy that influences various cell signaling molecules. The goal of this study is to identify potential antioxidant agents that could be used to treat atrophy. In this study in vitro and in situ screening of different cinnamaldehyde (CNA) derivatives for their antioxidant effects was done along with computational analysis to understand the relationship between their chemical structure and biological activity. Data show that 2-hydroxycinnamaldehyde (2HCNA) worked better than other CNA analogues at physiological pH, while 4-Fluoro-2-methoxycinnamaldehyde (4FoCNA) showed the maximum antioxidant activity under acidic conditions. However, these derivatives (2HCNA and 4FoCNA) were found to be toxic to the cultured myotubes (mature myofiber) under both physiological and pathophysiological conditions. Immunofluorescence, bright-field microscopic and biochemical studies conducted using live C2C12 cells showed that pre-incubation with other CNA analogues i.e. 2-methoxycinnamaldehyde (2MeCNA) and 2-benzyloxycinnamaldehyde (2BzCNA) not only maintained the normal morphology of myotubes but also protected them from H2O2-induced atrophy. These compounds (2MeCNA and 2BzCNA) showed higher stability and antioxidant potential, as indicated by computer simulation data analyzed by Density Functional Theory (DFT) based molecular modeling. Overall, the chemical, biological, and computational studies reveal the therapeutic potential of CNA analogues (BzCNA and MeCNA) against oxidative-stress induced muscle atrophy in C2C12 cells.

Topics: Antioxidants; Computer Simulation; Humans; Hydrogen Peroxide; Muscle Fibers, Skeletal; Muscular Atrophy; Oxidative Stress; Protective Agents; Quality of Life

The appropriate selection of quality marker (Q-marker) for performing the comprehensive quality evaluation of traditional Chinese medicines (TCMs) has much more significance. Wu-Wei-Wen-Tong Capsule (WWWTC), a TCMs prescription, is mainly utilized to treat rheumatoid arthritis (RA) in China. However, the comprehensive quality control for WWWTC has not been achieved because of lacking system analysis for the Q-marker. In this study, a dual wavelength, 203 and 270 nm, was selected based on the feature of 15 Q-markers, and a reliable UHPLC-UV fingerprinting approach was established, achieving the comprehensive quality evaluation of WWWTC. First, we identified 91 prototypes in rat plasma after administering a set amount of WWWTC by using UHPLC-QTOF/MS technique and selected them as the candidate Q-markers. Next, based on the "five principles" of Q-marker selection, 15 absorbed components among them including coumarin, cinnamic acid, cinnamaldehyde, cinnamic alcohol, and 2-methoxycinnamaldehyde derived from Monarch medicine of Cmnamomi Mmulus; epimedin C, icariin, baohuoside I, and anhydroicaritin derived from Monarch medicine Epimedii Folium; germacrone, the sesquiterpene compound in Minister medicine Rhizoma Wenyujin Concisum; pachymic acid, the tetracyclic triterpenoid acids in Assistant medicine Poria; baicalin, baicalein, wogonin, and wogonoside in Guide medicine Scutellariae Radix, respectively, were seriously chosen as the Q-markers, indicating preferable pharmacological effect on RA, characterization of transitivity and traceability as well as measurable components in WWWTC. The effective and meaningful strategy displayed a unique perspective for the exploration of Q-markers in the quality evaluation and further ensured efficacy and safety of the TCMs.

Topics: Acrolein; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers, Pharmacological; Chromatography, High Pressure Liquid; Cinnamates; Coumarins; Drug Development; Drugs, Chinese Herbal; Flavanones; Humans; Medicine, Chinese Traditional; Propanols; Quality Control; Rats; Tandem Mass Spectrometry; Triterpenes

It is still a challenge to discover and identify individual bioactive compounds directly in multicomponent mixtures. Current workflows are too tedious for routine use. Hence, the hyphenation of separation and detection techniques is a powerful tool to maximize the information obtained by a single sample run. A robust eight-dimensional (8D) hyphenation was developed. Orthogonal separations, biological assay detection, analyte trapping, desalting, and physico-chemical detections were arranged in the following order, i.e. 1) normal phase high-performance thin-layer chromatography (NP-HPTLC) separation, 2) Vis detection, 3) UV detection, 4) fluorescence detection (FLD), 5) bioassay for effect-directed analysis (EDA), 6) heart-cut trapping/desalting/elution to reversed phase high-performance liquid chromatography (RP-HPLC) separation, 7) photodiode array (PDA) and 8) mass spectrometry (MS) detection. For the first time, the hyphenation exploited online analyte trapping to desalt the eluted bioactive zone from the plate containing highly salted bioassay media. Subsequent valve switching guided the trapped analyte(s) to the main column, followed by multiple detection. As proof-of-principle, cinnamon samples were analyzed by NP-HPTLC-UV/Vis/FLD-EDA-RP-HPLC-PDA-MS, whereby a bioactive zone was separated into two distinct peaks detected by PDA and MS to be 2-methoxy cinnamaldehyde and cinnamaldehyde. The developed 8D hyphenation is applicable for routine, allowing the non-target high-throughput screening of complex samples for individual bioactive compounds.

Topics: Acrolein; Biological Assay; Chromatography, Liquid; Mass Spectrometry; Models, Chemical; Sodium Chloride

Information is scarce regarding pharmacokinetic-based herb-drug interactions (HDI) with

Topics: Acrolein; Area Under Curve; Cinnamomum zeylanicum; Cytochrome P-450 CYP2A6; Drug Evaluation, Preclinical; Herb-Drug Interactions; Humans; Letrozole; Microsomes, Liver; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Nicotine; Recombinant Proteins

Chronic inflammation is a contributing factor in many age-related diseases. In a previous study, we have shown that Sri Lankan cinnamon (C. zeylanicum) was one of the most potent anti-inflammatory foods out of 115 foods tested. However, knowledge about the exact nature of the anti-inflammatory compounds and their distribution in the two major cinnamon species used for human consumption is limited. The aim of this investigation was to determine the anti-inflammatory activity of C. zeylanicum and C. cassia and elucidate their main phytochemical compounds. When extracts were tested in LPS and IFN-γ activated RAW 264.7 macrophages, most of the anti-inflammatory activity, measured by down-regulation of nitric oxide and TNF-α production, was observed in the organic extracts. The most abundant compounds in these extracts were E-cinnamaldehyde and o-methoxycinnamaldehyde. The highest concentration of E-cinnamaldehyde was found in the DCM extract of C. zeylanicum or C. cassia (31 and 34 mg g(-1) of cinnamon, respectively). When these and other constituents were tested for their anti-inflammatory activity in RAW 264.7 and J774A.1 macrophages, the most potent compounds were E-cinnamaldehyde and o-methoxycinnamaldehyde, which exhibited IC₅₀ values for NO with RAW 264.7 cells of 55 ± 9 μM (7.3 ± 1.2 μg mL(-1)) and 35 ± 9 μM (5.7 ± 1.5 μg mL(-1)), respectively; and IC₅₀ values for TNF-α of 63 ± 9 μM (8.3 ± 1.2 μg mL(-1)) and 78 ± 16 μM (12.6 ± 2.6 μg mL(-1)), respectively. If therapeutic concentrations can be achieved in target tissues, cinnamon and its components may be useful in the treatment of age-related inflammatory conditions.

Topics: Acrolein; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cinnamomum aromaticum; Cinnamomum zeylanicum; Dietary Supplements; Ethnopharmacology; Macrophage Activation; Macrophages; Medicine, Traditional; Mice; Molecular Structure; Nitric Oxide; Plant Bark; Plant Extracts; Sri Lanka; Stereoisomerism; Tumor Necrosis Factor-alpha

In a prior study on electronic cigarette (EC) refill fluids, Cinnamon Ceylon was the most cytotoxic of 36 products tested. The purpose of the current study was to determine if high cytotoxicity is a general feature of cinnamon-flavored EC refill fluids and to identify the toxicant(s) in Cinnamon Ceylon. Eight cinnamon-flavored refill fluids, which were screened using the MTT assay, varied in their cytotoxicity with most being cytotoxic. Human embryonic stem cells were generally more sensitive than human adult pulmonary fibroblasts. Most products were highly volatile and produced vapors that impaired survival of cells in adjacent wells. Cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol, and vanillin were identified in the cinnamon-flavored refill fluids using gas chromatography–mass spectrometry and high-pressure liquid chromatography (HPLC). When authentic standards of each chemical were tested using the MTT assay, only CAD and 2MOCA were highly cytotoxic. The amount of each chemical in the refill fluids was quantified using HPLC, and cytotoxicity correlated with the amount of CAD/product. Duplicate bottles of the same product were similar, but varied in their concentrations of 2MOCA. These data show that the cinnamon flavorings in refill fluids are linked to cytotoxicity, which could adversely affect EC users.

Topics: Acrolein; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Cinnamomum zeylanicum; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Embryonic Stem Cells; Fibroblasts; Flavoring Agents; Gas Chromatography-Mass Spectrometry; Humans; Lung; Neural Stem Cells; Spectrophotometry, Ultraviolet; Tetrazolium Salts; Thiazoles; Tobacco Products

A pressurized liquid extraction and GC-MS method was developed for simultaneous quantitative determination of the seven components, including cinnamaldehyde, copaene, cinnamic acid, coumarin, 2-methoxycinnamaldehyde, 2-methoxycinnamic acid and safrole in Cinnamomum cassia. The results showed that methanol and ethanol was not available for extraction of cinnamaldehyde and 2-methoxycinnamaldehyde due to aldol reaction. The developed method was validated to be sensitive, accurate and simple, and was successfully employed for the analysis of 15 samples of C. cassia. The contents of the investigated components were significantly variant and cinnamaldehyde is the most abundant compound, but safrole was not detected in all samples.

Topics: Acrolein; Analytic Sample Preparation Methods; Chemical Fractionation; Cinnamates; Cinnamomum aromaticum; Coumarins; Gas Chromatography-Mass Spectrometry; Molecular Structure; Pressure; Safrole; Sesquiterpenes; Stereoisomerism

The antifungal activity of the essential oil from Cinnamomum cassia, alone or combined with amphotericin B, a drug widely used for most indications despite side-effects was investigated. The composition of the oil was analysed by GC/MS and characterized by its very high content of cinnamaldehyde (92.2%). The minimal inhibitory concentration (MIC 80%), used to evaluate the antifungal activity against Candida albicans, was determined by a macrobroth dilution method followed by a modelling of fungal growth. The essential oil of Cinnamomum cassia exhibited strong antifungal effect (MIC 80% = 0.169 microL/mL and K(aff) = 18,544 microL/mL). A decrease of the MIC 80% of amphotericin B was obtained when the culture medium contained essential oil concentrations ranging from 0.08 to 0.1 microL/mL. The strongest decrease (70%) was obtained when the medium contained 0.1 microL/mL of essential oil. This potentiation of amphotericin B obtained in vitro may show promise for the development of less toxic and more effective therapies especially for the treatment of HIV infection.

Topics: Acrolein; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cinnamates; Cinnamomum aromaticum; Drug Synergism; Gas Chromatography-Mass Spectrometry; Microbial Sensitivity Tests; Oils, Volatile; Phytotherapy; Plant Extracts; Regression Analysis

Nuclear factor (NF)-cB is a transcription factor regulating the expression of inflammatory and immune genes. In the present study, an extract from stem bark of Cinnamomum cassia Blume(Lauraceae) was discovered to have an inhibitory effect on LPS-induced NF-KB transcriptional activity, which was determined using macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter construct containing four copies of the NF-KB binding KB sequence. Following activity-guided fractionation, trans-cinnamaldehyde and 2-methoxycinnamaldehyde were identified as the NF-KB inhibitors from C cassia with IC50 values of 43 MM and 31 pM, respectively. As a positive control, caffeic acid phenethyl ester (CAPE) showed an IC50 value of 2 uM on NF-KB transcriptional activity. Both trans-cinnamaldehyde and 2-methoxycinnamaldehyde inhibited LPS-induced DNA binding activity of NF-KB in addition to NF-KB transcription-al activity.

Topics: Acrolein; Animals; Cinnamomum aromaticum; Inhibitory Concentration 50; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Plant Stems