Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches.

Our study focuses on synthesizing and exploring the potential of three N-(4) substituted thiosemicarbazones derived from cinnamic aldehyde, alongside their Ru(II)-(η6 -p-cymene)/(η6-benzene) complexes. The synthesized compounds were comprehensively characterized using a range of analytical techniques, including FT-IR, UV-visible spectroscopy, NMR (1H, 13C), and HRMS. We investigated their electronic and physicochemical properties via density functional theory (DFT). X-ray crystal structures validated structural differences identified by DFT. Molecular docking predicted promising bioactivities, supported by experimental observations. Notably, docking with EGFR suggested an inhibitory potential against this cancer-related protein. Spectroscopic titrations revealed significant DNA/BSA binding affinities, particularly with DNA intercalation and BSA hydrophobic interactions. RuPCAM displayed the strongest binding affinity with DNA (Kb = 6.23 × 107 M-1) and BSA (Kb = 9.75 × 105 M-1). Assessed the cytotoxicity of the complexes on cervical cancer cells (HeLa), and breast cancer cells (MCF-7 and MDA-MB 231), revealing remarkable potency. Additionally, selectivity was assessed by examining MCF-10a normal cell lines. The active complexes were found to trigger apoptosis, a vital cellular process crucial for evaluating their potential as anticancer agents utilizing staining assays and flow cytometry analysis. Intriguingly, complexation with Ru(II)-arene precursors significantly amplified the bioactivity of thiosemicarbazones, unveiling promising avenues toward the creation of powerful anticancer agents.

Effects of monoglycerides of short and medium chain fatty acids and cinnamaldehyde blend on the growth, survival, immune responses, and tolerance to hypoxic stress of Pacific white shrimp (Litopenaeus vannamei).

Free fatty acids have long been used as dietary supplements in aquaculture, but the application of monoglycerides has increased interest in more recent times. The study aimed to investigate the effects of dietary short- and medium-chain fatty acid monoglyceride and cinnamaldehyde (SMMG) on the growth performance, survival, immune responses, and tolerance to hypoxic stress of Pacific white shrimp (Litopenaeus vannamei). In Experiment 1, shrimp post-larvae were divided into 4 groups with 6 replicates and fed with diets supplemented with 0 (control), 0.3, 0.4, and 0.5% diet for 30 days. The final body weight and survival rate were determined. In Experiment 2, the juvenile shrimp from Experiment 1 were subjected to hypoxic stress conditions (dissolved oxygen level 2-2.5 mg/L) for 14 days, then the specific growth rate (SGR), survival rate, intestinal Vibrio spp. count, immune responses, and histopathological change of the hepatopancreas were analyzed. Following the 30-day feeding trial, the results revealed that the final body weight and survival of the 0.3-0.5% SMMG groups (2.81-3.06 g and 74.00-84.33%, respectively) were significantly higher than the control shrimp (1.96 g and 68.33%, respectively). In the hypoxic stress experiment, the survival rates of shrimp fed 0.4-0.5% SMMG (71.67-80.00%) were significantly higher than the control (51.67%). Although the SGR were not affected by SMMG supplementation, all immune parameters evaluated were significantly enhanced, and the intestinal Vibrio spp. counts were significantly decreased in the 0.4-0.5% SMMG-fed shrimp; the histopathological structure of the hepatopancreas was also improved in these shrimp compared to the control. Our findings indicated that SMMG as a feed additive has beneficial effects in improving shrimp health and increasing tolerance to hypoxic conditions.

Enzymatic Acrolein Production System and Its Impact on Human Cells.

Acrolein is an environmental toxicant and is also generated by microbial metabolism in the intestinal tract. Aqueous acrolein rapidly dissipates from standard human cell culture media with nondetectable levels after 8 h, hindering cell-based studies to understand its biological impacts. Thus, we developed an extracellular acrolein biosynthesis system to continuously produce acrolein compatible with human cell culture conditions. The approach uses spermine as a precursor, amine oxidase found in fetal calf serum, and catalase to remove the hydrogen peroxide byproduct. We confirmed amine oxidase activity of calf serum using a colorimetric assay and further tested the requirement for catalase in the system to mitigate hydrogen peroxide-induced cytotoxicity. We calibrated responses of human colon cells to this enzymatic acrolein production system by comparing transcriptional responses, DNA adduct formation and cytotoxicity responses to either this system or pure acrolein exposures in a human colon cell line. Several genes related to oxidative stress including HMOX1, and the colorectal cancer-related gene SEMA4A were upregulated similarly between the enzymatic acrolein production system or pure acrolein. The acrolein-DNA adduct γ-OH-Acr-dG increased in a dose-dependent manner with spermine in the enzymatic acrolein production system, producing a maximum of 1065 adducts per 108 nucleosides when 400 µM spermine was used. This biosynthetic production method provides a relevant model for controlled acrolein exposure in cultured human cells and overcomes current limitations due to its physical properties and limited availability.

The Combined Use of Cinnamaldehyde and Vitamin C Is Beneficial for Better Carcass Character and Intestinal Health of Broilers.

The use of cinnamaldehyde and Vitamin C can improve immunity and intestinal health. A two-way factorial design was employed to investigate the main and interactive effects of cinnamaldehyde and vitamin C on the growth, carcass, and intestinal health of broiler chickens. A total of 288 one-day-old female Arbor Acres broiler chicks were randomly distributed among four treatment groups, consisting of six replicate cages with 12 birds each. Four treatments were basal diet or control (CON), supplemental cinnamaldehyde (CA) 300 g/ton (g/t), vitamin C (VC) 300 g/t, and cinnamaldehyde 300 g/t, and vitamin C 300 g/t (CA + VC), respectively. The results showed that supplemental CA did not affect the growth performance or slaughter performance of broilers at 21 days (d), 42 days (d), and 1-42 days (d); however, it could improve intestinal barrier function at 42 d of age and reduce the mRNA expression of inflammatory factors in the intestine at 21 d and 42 d of age. Supplemental VC showed a trend towards increasing body weight gain (BWG) at 21 d (p = 0.094), increased breast muscle rate (at 21-d 5.33%, p < 0.05 and at 42-d 7.09%, p = 0.097), and decreased the abdominal fat (23.43%, p < 0.05) and drip loss (20.68%, p < 0.05) at 42-d. Moreover, VC improves intestinal morphology and intestinal barrier function and maintains a balanced immune response. The blend of CA and VC significantly upregulated the mRNA expression of myeloid differentiation factor 88 (MyD-88) in the intestine at 21 d of age, the mRNA expression of catalase (CAT), Occludin, Claudin-1, Mucin-2, nuclear factor-kappa B (NF-κB) and toll-like receptor 4 (TLR-4) in the intestine at 42 d of age (p < 0.01), and downregulated the mRNA expression of interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) in the intestine at 21-d and 42-d of age, and interleukin-1 beta (IL-1ß) mRNA in intestine at 42 d of age (p < 0.01). This study suggested that the combination of CA and VC had the potential to regulate intestinal health and result in better carcass character of broilers.

Capture of single or multiple reactive carbonyl species by mangiferin under high temperatures.

Reactive carbonyl species (RCS), including acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO), are typically generated in food processing and accumulate in the body for ages, triggering various chronic diseases. Here, we investigated the capture capability and reaction pathways of mangiferin one-to-one and one-to-many on RCS in high temperatures using UPLC-MS/MS. We found that mangiferin can capture ACR/MGO/GO to form their adducts, yet, the ability to capture RCS is arranged in different orders, with ACR > MGO > GO for a single RCS and MGO > ACR > GO for multiple RCS. After synthesizing and identifying the structures of the ACR- and MGO-adducts of MGF, our results indicated that MGF-ACR-MGO produced in the multiple-RCS-MGF system was formed by capturing MGO through MGF-ACR rather than through MGF-MGO capturing ACR, which resulting in higher inhibitory activity of MGF against MGO than against ACR. Then, the capture ability and path of MGF on RCS were verified in the coffee-leaves tea and cake.

Cinnamaldehyde activates AMPK/PGC-1α pathway via targeting GRK2 to ameliorate heart failure.

BACKGROUND: According to recent research, treating heart failure (HF) by inhibiting G protein-coupled receptor kinase 2 (GRK2) to improve myocardial energy metabolism has been identified as a potential approach. Cinnamaldehyde (CIN), a phenylpropyl aldehyde compound, has been demonstrated to exhibit beneficial effects in cardiovascular diseases. However, whether CIN inhibits GRK2 to ameliorate myocardial energy metabolism in HF is still unclear. PURPOSE: This study examines the effects of CIN on GRK2 and myocardial energy metabolism to elucidate its underlying mechanism to treat HF. METHODS: The isoproterenol (ISO) induced HF model in vivo and in vitro were constructed using Sprague-Dawley (SD) rats and primary neonatal rat cardiomyocytes (NRCMs). Based on this, the effects of CIN on myocardial energy metabolism and GRK2 were investigated. Additionally, validation experiments were conducted after interfering and over-expressing GRK2 in ISO-induced NRCMs to verify the regulatory effect of CIN on GRK2. Furthermore, binding capacity between GRK2 and CIN was explored by Cellular Thermal Shift Assay (CETSA) and Microscale Thermophoresis (MST). RESULTS: In vivo and in vitro, CIN significantly improved HF as demonstrated by reversing abnormal changes in myocardial injury markers, inhibiting myocardial hypertrophy and decreasing myocardial fibrosis. Additionally, CIN promoted myocardial fatty acid metabolism to ameliorate myocardial energy metabolism disorder by activating AMPK/PGC-1α signaling pathway. Moreover, CIN reversed the inhibition of myocardial fatty acid metabolism and AMPK/PGC-1α signaling pathway by GRK2 over-expression in ISO-induced NRCMs. Meanwhile, CIN had no better impact on the stimulation of cardiac fatty acid metabolism and the AMPK/PGC-1α signaling pathway in ISO-induced NRCMs when GRK2 was disrupted. Noticeably, CETSA and MST confirmed that CIN binds to GRK2 directly. The binding of CIN and GRK2 promoted the ubiquitination degradation of GRK2 mediated by murine double mimute 2. CONCLUSION: This study demonstrates that CIN exerts a protective intervention in HF by targeting GRK2 and promoting its ubiquitination degradation to activate AMPK/PGC-1α signaling pathway, ultimately improving myocardial fatty acid metabolism.

Cinnamon extracts, trans-cinnamaldehyde and trans-cinnamic acid inhibit HDAC 1 activity.

Histone deacetylase (HDAC) enzymes play a key role in cell function and are implicated in several diseases such as inflammation, cancer, and neurodegeneration. Studies on natural products have revealed their potential and have led to increased research on natural HDAC inhibitors. Since the progression of these diseases is a prolonged process, dietary supplements and nutraceuticals consisting of plant extracts may be beneficial against HDAC related diseases. Beyond nutritional purposes, cinnamon (Cinnamomum cassia (L.) J. Presl), as a regularly consumed dietary additive due to its rich flavor, may present co-benefits during lifelong use. In this study, cinnamon extracts of differing polarities, trans-cinnamaldehyde and trans-cinnamic acid were evaluated for HDAC 1 inhibitory activity. The total phenol and flavonoid contents were quantified by spectrophotometry, while cinnamaldehyde and cinnamic acid analyses were performed using UPLC-DAD, ESI-MS/MS. Ethanol and dichloromethane extracts yielded the highest cinnamaldehyde and cinnamic acid contents of 389.17 mg per g extract and 11.85 mg per g extract, respectively. The essential oil (IC50: 51.11 µg ml-1) and 70% ethanol extract (IC50: 107.90 µg ml-1) showed the most potent HDAC 1 inhibitory activity. Individually, cinnamaldehyde and cinnamic acid were determined to have IC50 values of 7.58 µg ml-1 and 9.15 µg ml-1, respectively. As the 70% ethanol extract was able to yield remarkably lower cinnamaldehyde and cinnamic acid amounts, the potential of other moderately polar phenolic compounds for HDAC 1 inhibitory activity was revealed. The essential oil and 70% ethanol extracts of Cinnamomum cassia bark can be further evaluated in future studies for use in products against HDAC 1 related diseases.

Novel fluorescent nanoplatform for all-in-one sensing and removal of acrolein: An ultrasensitive probe to evaluate its removal efficiency.

As a highly toxic aldehyde, acrolein is widely found in diet and environment, and can be produced endogenously, posing a serious threat to human health. Herein, we designed a novel fluorescent nanoplatform integrating carbon dots­manganese dioxide (CDs-MnO2) and glutathione (GSH) for all-in-one sensing and removal of acrolein. By converting Mn4+ to free Mn2+, GSH inhibited the inner filter effect (IFE) of MnO2 nanosheets, and the Michael addition of acrolein with GSH inhibited the GSH-induced Mn4+ conversion, forming an "off-on-off" fluorescence response of CDs. The developed fluorescent nanoplatform exhibited high sensitivity (LOD was 0.067 µM) and selectivity for the simultaneous detection and removal of acrolein. The combination of CDs-MnO2 hydrogels with smartphones realized the point-of-care detection of acrolein, yielding satisfactory results (recovery rates varied between 97.01-104.65%, and RSD ranged from 1.42 to 4.16%). Moreover, the capability of the nanoplatform was investigated for on-site evaluating acrolein scavengers' efficacy, demonstrating excellent potential for practical application.

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 µl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1ß-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways.

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1ß on chondrocytes. We stimulated chondrocytes with IL-1ß to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1ß on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1ß on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.

Cinnamaldehyde protects SH-SY5Y cells against advanced glycation end-products induced ectopic cell cycle re-entry.

Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.

Cinnamaldehyde: Pharmacokinetics, anticancer properties and therapeutic potential (Review).

Cancer incidence is increasing globally, presenting a growing public health challenge. While anticancer drugs are crucial in treatment, their limitations, including poor targeting ability and high toxicity, hinder effectiveness and patient safety, requiring relentless scientific research and technological advancements to develop safer and more effective therapeutics. Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications. CA has potential in treating a wide array of conditions, including cardiovascular diseases, diabetes, inflammatory disorders and various forms of cancer. The present review comprehensively summarizes the physicochemical and pharmacokinetic profiles of CA, and delves into the latest advancements in elucidating its potential mechanisms and targets across various cancer types. CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis. Additionally, the present review explores targeted formulations of CA, laying a scientific foundation for further exploration of its implications in cancer prevention and treatment strategies.

Determination of in vitro synergy and antibiofilm activities of antimicrobials and essential oil components.

Using existing adrentimicrobials with essential oil components to prevent antimicrobial resistance is an alternative strategy. This study aimed to evaluate the resistance status, synergistic combinations, and in vitro biofilm formation activities of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia and Candida albicans against antimicrobial agents and cinnamaldehyde, carvacrol, eugenol, limonene and eucalyptol. Antimicrobial activities were evaluated by microdilution, cytotoxicity by XTT, synergy by checkerboard and time-kill, and biofilm inhibition by microplate methods. Cinnamaldehyde and carvacrol showed strong antimicrobial activity. Synergistic effects were observed when using all essential oils with antimicrobials. Only two C. albicans isolates showed antagonism with cinnamaldehyde and fluconazole. The constituents showed cytotoxic effects in the L929 cell line (except limonene). A time-kill analysis revealed a bacteriostatic effect on S. maltophilia and MRSA isolates and a fungicidal effect on C. albicans isolates. These results are important for further research to improve antimicrobial efficacy or to develop new agents.

Organic nanoparticles incorporated starch/carboxymethylcellulose multifunctional coating film for efficient preservation of perishable products.

Most of postharvest agricultural produces are perishable due to microorganisms infections and physiological change. Herein, one kind of multifunctional coating film of SC-ECCNPs was developed by incorporating organic nanoparticles of ECCNPs into starch/carboxymethylcellulose (SC) to prolong shelf life of food with excellent performances. The SC-ECCNPs coating was prepared with starch and sodium carboxymethylcellulose as film substrate (SC) to incorporate with organic nanoparticles of ECCNPs formed by integrating epigallocatechin-3-gallate (EGCG), cysteine (Cys), and cinnamaldehyde (CA). The incorporation of ECCNPs improves the UV-resistance and physical properties of SC-ECCNPs coating and also endows it with excellent antioxidative and broad-spectrum antibacterial activity. The application possibilities of SC-ECCNPs coating were explored with strawberries and oranges as samples, validating that the SC-ECCNPs coating can prolong the shelf life of fruits at room temperature. The biosafety of the coating was further confirmed with hemolysis and MTT experiments. The SC-ECCNPs coating film was prepared with natural substrates via a simple and green method. The investigation provides an instructive way for developing advanced packaging materials with high performances.

Sodium alginate/chitosan-based intelligent multifunctional bilayer film for shrimp freshness retention and monitoring.

Developing bifunctional innovative food packaging for maintaining and monitoring food freshness is crucial for food safety. Here, we prepared tannic acid cinnamaldehyde nanoemulsions through self-assembly and ionic cross-linking between the natural emulsifiers tannic acid and cinnamaldehyde, and were incorporated into chitosan as a protective outer layer. Sodium alginate anchored with alizarin was employed as the sensing inner layer. A pH-sensitive bilayer film integrating real-time monitoring and maintenance of food fresh food freshness was designed using layer-by-layer assembly (LBL) technology. The prepared bilayer film exhibited 100 % UV protection, >99 % antimicrobial effect, and 94.86 % and 97.91 % clearance rates for DPPH and ABTS free radicals, respectively. In addition, the bilayer film exhibited high biosafety and sensitive, reversible, and rapid response to pH/NH3. Shrimp preservation experiments showed that the smart bilayer film could effectively slow down the growth of microorganisms on the surface of shrimp, extend the freshness period of shrimp, and could monitor the freshness of shrimp in real-time through color changes. In conclusion, the prepared SL-CCT bilayer film has excellent potential for food preservation and freshness monitoring, providing a new perspective for design and development of multifunctional smart food packaging films.

Antibacterial activity of t-cinnamaldehyde: An approach to its mechanistic principle towards enterohemorrhagic Escherichia coli (EHEC).

BACKGROUND: Compounds of natural origin are potent source of drugs with unique mechanisms of action. Among phytochemicals, trans-cinnamaldehyde (t-CA) exhibits a wide range of biological activity, thus has been used for centuries to fight bacterial and fungal infections. However, the molecular basis of these properties has not been fully covered. Considering that difficult-to-control infections are becoming a rising global problem, there is a need to elucidate the molecular potential of t-CA. PURPOSE: To evaluate the antibacterial activity of t-CA against Shiga-toxigenic E. coli strains and elucidate its mechanism of action based on the inhibition of the virulence factor expression. METHODS: The antimicrobial potential of t-CA was assessed with two-fold microdilution and time-kill assays. Further evaluation included bioluminescence suppression assays, quantification of reactive oxygen species (ROS) and assessment of NAD+/NADH ratios. Morphological changes post t-CA exposure were examined using transmission electron microscopy. RNA sequencing and radiolabeling of nucleotides elucidated the metabolic alterations induced by t-CA. Toxin expression level was monitored through the application of fusion proteins, monitoring of bacteriophage development, and fluorescence microscopy studies. Lastly, the therapeutic efficacy in vivo was assessed using Galleria mellonella infection model. RESULTS: A comprehensive study of t-CA's bioactivity showed unique properties affecting bacterial metabolism and morphology, resulting in significant bacterial cell deformation and effective virulence inhibition. Elucidation of the underlying mechanisms indicated that t-CA activates the global regulatory system, the stringent response, manifested by its alarmone, (p)ppGpp, overproduction mediated by the RelA enzyme, thereby inhibiting bacterial proliferation. Intriguingly, t-CA effectively downregulates Shiga toxin gene expression via alarmone molecules, indicating its potential for therapeutic effect. In vivo validation demonstrated a significant improvement in larval survival rates post- t-CA treatment with 50 mg/kg (p < 0.05), akin to the efficacy observed with azithromycin, thus indicating its effectiveness against EHEC infections (p < 0.05). CONCLUSIONS: Collectively, these results reveal the robust antibacterial capabilities of t-CA, warranting its further exploration as a viable anti-infective agent.

Tenuazonic acid-induced mycotoxicosis in an immunosuppressed mouse model and its prophylaxis with cinnamaldehyde.

Patients with impaired immune systems are particularly vulnerable to infections. With the increasing number of immunocompromised patients, it becomes necessary to design studies that evaluate the effects of toxic contaminants that are a part of our daily lives. Simultaneously, the management of these toxic components also becomes essential. Therefore, the present study evaluated the possible protective role of cinnamaldehyde (Cin) against tenuazonic acid-induced mycotoxicosis in the immunosuppressed murine model. Tenuazonic acid (TeA), a toxin usually produced by Alternaria species, is a common contaminant in tomato and tomato-based products. Evaluating the potential toxicity of a hazardous chemical necessitates the use of in vitro, in vivo, and in silico methods. Here, the immunomodulatory effect of TeA was assessed in vitro using mouse splenocytes. In silico docking was carried out for the tumour markers of eight organs and TeA. The haematological, histopathological, and biochemical aspects were analysed in vivo. The sub-chronic intoxication of mice with TeA showed elevated malondialdehyde, reduced catalase, and superoxide dismutase production, along with abnormal levels of aspartate aminotransferase and alanine transaminase. The treatment with Cin prevented TeA-induced alterations of antioxidant defense enzyme activities and significantly forbade TeA-induced organ damage, showing therapeutic effects and toxicity reduction in TeA-induced mycotoxicosis.

Puerarin inhibits HDAC1-induced oxidative stress disorder by activating JNK pathway and alleviates acrolein-induced atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.

Trans-Cinnamaldehyde Inhibition of Pyruvate Dehydrogenase: Effects on Streptococcus mutans Carbohydrate Metabolism.

Dental caries is a chronic oral infectious disease, and Streptococcus mutans (S. mutans) plays an important role in the formation of dental caries. Trans-cinnamaldehyde (CA) exhibits broad-spectrum antibacterial activity; however, its target and mechanism of action of CA on S. mutans needs to be further explored. In this study, it was verified that CA could inhibit the growth and biofilm formation of S. mutans. Further proteomic analysis identified 33, 55, and 78 differentially expressed proteins (DEPs) in S. mutans treated with CA for 1, 2, and 4 h, respectively. Bioinformatics analysis showed that CA interfered with carbohydrate metabolism, glycolysis, pyruvate metabolism, and the TCA cycle, as well as amino acid metabolism of S. mutans. Protein interactions suggested that pyruvate dehydrogenase (PDH) plays an important role in the antibacterial effect of CA. Moreover, the upstream and downstream pathways related to PDH were verified by various assays, and the results proved that CA not only suppressed the glucose and sucrose consumption and inhibited glucosyltransferase (GTF) and lactate dehydrogenase (LDH) activities but also decreased the ATP production. Interestingly, the protein interaction, qRT-PCR, and molecular docking analysis showed that PDH might be the target of CA to fight S. mutans. In summary, the study shows that CA interferes with the carbohydrate metabolism of bacteria by inhibiting glycolysis and the tricarboxylic acid (TCA) cycle via binding to PDH, which verifies that PDH is a potential target for the development of new drugs against S. mutans.