Investigation of the Antitrichomonal Activity of Cinnamaldehyde, Carvacrol and Thymol and Synergy with Metronidazole.

Objective: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method. Methods: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method. Results: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol. Conclusion: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.

Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells.

Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer. Recently, more attention has been given to natural products (or phytochemicals) as potential anticancer treatments. This study aimed to investigate the synergistic effects of the combination of the phytochemicals chlorogenic acid and cinnamaldehyde (CGA and CA) toward inhibiting metastasis. The hypothesis was that CGA and CA in combination decrease the metastatic potential of breast cancer cells by inhibiting their invasive and migratory abilities as well as the induction of apoptosis via the downregulation of the Akt, disrupting its signal transduction pathway. To test this, wound-healing and Transwell™ Matrigel™ assays were conducted to assess changes in the migration and invasion properties of the cells; apoptosis was analyzed by fluorescence microscopy for Annexin V/propidium iodide; and immunoblotting and FACSort were performed on markers for the epithelial-to-mesenchymal transition status. The results show that CGA and CA significantly downregulated Akt activation by inhibiting phosphorylation. Consequently, increased caspase 3 and decreased Bcl2-α levels were observed, and apoptosis was confirmed. The inhibition of metastatic behavior was demonstrated by the attenuation of N-cadherin, fibronectin, vimentin, and MMP-9 expressions with concomitant increased expressions of E-cadherin and EpCAM. In summary, the present study demonstrated that CGA and CA in combination downregulated Akt activation, inhibited the metastatic potential, and induced apoptosis in different breast cancer cell lines.

Dual-targeted nanoparticulate drug delivery systems for enhancing triple-negative breast cancer treatment.

The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.

Pioneering Topical Ointment Intervention for Unprecedented Antimicrobial and Diabetic Wound Management with Phenylpropanoids and Nano-Silver.

Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating phenylpropanoids-Eugenol and Cinnamaldehyde-with positively-charged silver nanoparticles was synthesized. The process began with the synthesis and characterization of nano-silver, aimed at ensuring the effectiveness and safety of the nanoparticles in biological applications. Subsequent experiments determined the minimum inhibitory concentration (MIC) against pathogens such as Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. These MIC values of all three active leads guided the strategic formulation of an ointment base, which effectively integrated the bioactive components. Evaluations of this nano-ointment revealed enhanced antimicrobial activity against both clinical and reference bacterial strains and it maintained stability after freeze-thaw cycles. Furthermore, the ointment demonstrated superior in-vitro diabetic wound healing capabilities and significantly promoted angiogenesis, as shown by enhanced blood vessel formation in the Chorioallantoic Membrane assay. These findings underscore the formulation's therapeutic potential, marking a significant advance in the use of nanotechnology for topical wound care.

Cinnamaldehyde, A Bioactive Compound from the Leaves of Cinnamomum osmophloeum Kaneh, Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the NLRP3 Inflammasome.

Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the quality of life for affected individuals. The effective management of these conditions remains a persistent challenge. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a complex molecular structure, regulates the production of pro-inflammatory cytokines such as interleukin-1ß. Abnormal activation of the NLRP3 inflammasome plays a pivotal role in the development of IBD, making it a compelling target for therapeutic intervention. Our research revealed that cinnamaldehyde (CA), a major bioactive compound found in the leaves of Cinnamomum osmophloeum kaneh, demonstrated a remarkable ability to alleviate colitis induced by dextran sulfate sodium (DSS) in a mouse model. This effect was attributed to CA's ability to downregulate the activation of the NLRP3 inflammasome and reduce the expression of pro-inflammatory mediators in the colon. In the mechanism study, we observed that CA inhibited the NLRP3 inflammasome in macrophages, at least partially, by enhancing the autophagic response, without reducing mitochondrial damage. These findings collectively suggest that CA holds significant potential as a therapeutic agent for enhancing the management of IBD, offering a promising avenue for further research and development.

Exploring the antibiofilm efficacy of cinnamaldehyde against Malassezia globosa associated pityriasis versicolor.

BACKGROUND: Malassezia globosa is a commensal basidiomycetous yeast occurring on the skin that causes pityriasis versicolor (PV) and seborrheic dermatitis, but that has also been implicated in other dermatoses. Cinnamaldehyde (CM) has antibacterial, antioxidant, and anti-inflammatory activities, but the effect of CM on M. globosa-infected PV has not been clarified. PURPOSE: The study aimed to investigate the possible antifungal and antibiofilm activities of CM against M. globosa-infected PV in vivo and in vitro. METHODS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of CM against M. globosa. The crystal violet staining assay and XTT assay were used to investigate the inhibition of CM on biofilm formation and the eradication of mature biofilms. The visualizations of the biofilm and cell distribution in the biofilm matrix were performed with a scanning electron microscope and confocal laser scanning microscope. The kits of antioxidant kinase were used to determine the activities of oxidative stress markers in M. globosa-stimulated HaCaT cells. Western blot assays were used to evaluate the role of TLR2/NF-κB in vitro. Furthermore, the protective effect of CM was assessed in M. globosa-associated PV mice. The expressions of inflammatory cytokines and apoptosis were screened using ELISA assays. The expressions of interleukin-6 and tumor necrosis factor-α were measured by an immunohistochemistry method in vivo. RESULTS: Our results showed that the MIC of CM against planktonic cells of M. globosa was 4 µg/ml and treatment with 20 × MIC CM eradicated mature biofilms of M. globosa. In vitro, after CM treatment the levels of oxidative stress indicators (i.e., superoxide dismutase, catalase, glutathione) significantly increased, while the levels of malondialdehyde decreased. In addition, the expression of TLR2/NF-κB in HaCaT cells was significantly reduced after CM treatment. On the other hand, an in vivo therapeutic effect of CM was assessed against M. globosa-infected mice. The fungal load on the skin decreased after treatment with CM compared to the M. globosa-infected group. In addition, the uninfected animals showed a normal skin structure, whereas, the M. globosa-infected mice showed extensive infiltration of neutrophils in skin tissues that improved after treatment with CM. Meanwhile, the levels of inflammatory and apoptotic factors improved after CM treatment. CONCLUSION: Our results showed that CM inhibits the biofilm formation of M. globosa and eradicates mature biofilms of M. globosa. Treatment with CM significantly decreased oxidative stress, apoptosis, and inflammatory markers in the skin tissue and HaCaT cells. Hence, this study suggests that CM is a good candidate therapeutic agent against M. globosa-induced PV infections because of its antifungal, antibiofilm, and anti-inflammatory properties.

The role and mechanism of cinnamaldehyde in cancer.

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent. This article aims to explore the multifaceted effects of cinnamaldehyde on cancer cells and shed light on these existing issues. Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, anti-proliferation, anti-inflammatory and antioxidant. In addition, cinnamaldehyde also acts as a reactive oxygen species scavenger, reducing oxidative stress and preventing DNA damage and genomic instability. This article emphasizes the promising therapeutic potential of cinnamaldehyde in cancer treatment and underscores the need for future research to unlock novel mechanisms and strategies for combating cancer. By providing valuable insights into the role and mechanism of cinnamaldehyde in cancer, this comprehensive understanding paves the way for its potential as a novel therapeutic agent. Overall, cinnamaldehyde holds great promise as an anticancer agent, and its comprehensive exploration in this article highlights its potential as a valuable addition to cancer treatment options.

Cinnamaldehyde Protects against P. gingivalis Induced Intestinal Epithelial Barrier Dysfunction in IEC-6 Cells via the PI3K/Akt-Mediated NO/Nrf2 Signaling Pathway.

Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against P. gingivalis (W83) and Pg-derived lipopolysaccharide (Pg-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of P. gingivalis (strain W83, 109 MOI) or Pg-LPS (1, 10, and 100 µg/mL), respectively, between 0-72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. P. gingivalis or Pg-LPS significantly (p < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. Pg-LPS, as well as Pg alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly (p < 0.05) increased with Pg-LPS or Pg infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both Pg- and Pg-LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against Pg infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells.

Gelatin/dextran active films incorporated with cinnamaldehyde and α-tocopherol for scallop (Patinopecten yessoensis) adductor muscle preservation.

Scallops are rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid but perishable due to their microbial growth and lipid oxidation. In this study, gelatin/dextran films containing cinnamaldehyde and α-tocopherol (0% + 0%, 0.3% + 0.3%, 0.6% + 0.6%, 0.9% + 0.9%, and 1.2% + 1.2%, w/w) as active fillers were developed by solution casting method, and their preservation effects on scallop adductor muscle refrigerated at 4°C for 0, 3, 6, 9, and 12 days were evaluated. Inclusion of the two active fillers did not influence the thermal stability of the films but created heterogenous and discontinuous film microstructure and increased the film hydrophobicity. Increase in the concentrations of active fillers lowered the mechanical properties and water vapor permeability of the films but increased their crystallinity, thickness, water contact angle, opacity, antibacterial property, and antioxidant property. The longest release times for both cinnamaldehyde and α-tocopherol were found in 95% (v/v) ethanol solution. The gelatin/dextran films containing 1.2% (w/w) of active fillers (Gelatin [Ge]/Dextran [Dx]/1.2 film) improved the chemical stability of refrigerated scallop adductor muscle. The total viable count (TVC) of the unpackaged scallop adductor muscle exceeded the recommended limit of 7 lg CFU/g on day 6 (7.07 ± 0.50 lg CFU/g), whereas the TVC of the Ge/Dx/1.2 film-packaged scallop adductor muscle was still below the limit on day 9 (5.60 ± 0.50 lg CFU/g). Thus, the Ge/Dx/1.2 film can extend the shelf life of refrigerated scallop adductor muscle by at least 3 days. Overall, the developed gelatin/dextran active packaging films are promising for the preservation of aquatic food products.

Cinnamaldehyde hydrazone derivatives as potential cathepsin B inhibitors: parallel in-vitro investigation in liver and cerebrospinal fluid.

The emergence of cathepsins as a potential target for anticancer drugs has led to extensive research in the development of their inhibitors. In the present study, we designed, synthesized, and characterized several cinnamaldehyde schiff bases employing diverse hydrazines, as potential cathepsin B inhibitors. The parallel studies on cathepsin B isolated from liver and cerebrospinal fluid unveiled the significance of the synthesized compounds as cathepsin B inhibitors at nanomolar concentrations. The compound, 7 exhibited the highest inhibition of 83.48 % and 82.96 % with an IC50 value of 0.06 nM and 0.09 nM for liver and cerebrospinal fluid respectively. The inhibitory potential of synthesized compounds has been extremely effective in comparison to previous reports. With the help of molecular docking studies using iGEMDOCK software, we found that the active site -CH2SH group is involved in the case of α-N-benzoyl-D, l-arginine-b-naphthylamide (BANA), curcumin 2, 3, 6, and 7. For toxicity prediction, ADMET studies were conducted and the synthesized compounds emerged to be non-toxic. The results obtained from the in vitro studies were supported with in silico studies. The synthesized cinnamaldehyde schiff bases can be considered promising drug candidates in conditions with elevated cathepsin B levels.

Mitochondria-mediated self-cycling nanoreactor enabling uninterrupted oxidative damage for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), which employs intracellular H2O2 to produce toxic hydroxyl radicals to kill cancer cells, has received great attention due to its specificity to tumors. However, the relatively insufficient endogenous H2O2 and the short-lifetime and limited diffusion distance of •OH compromise the therapeutic efficacy of CDT. Mitochondria, which play crucial roles in oncogenesis, are highly vulnerable to elevated oxidative stress. Herein, we constructed a mitochondria-mediated self-cycling system to achieve high dose of •OH production through continuous H2O2 supply. Cinnamaldehyde (CA), which can elevate H2O2 level in the mitochondria, was loaded in Cu(II)-containing metal organic framework (MOF), termed as HKUST-1. After actively targeting mitochondria, the intrinsic H2O2 in mitochondria of cancer cells could induce degradation of MOF, releasing the initial free CA. The released CA further triggered the upregulation of endogenous H2O2, resulting in the subsequent adequate release of CA and the final burst growth of H2O2. The cycle process greatly promoted the Fenton-like reaction between Cu2+ and H2O2 and induced long-term high oxidative stress, achieving enhanced chemodynamic therapy. In a word, we put forward an efficient strategy for enhanced chemodynamic therapy.

Biological fate, functional properties, and design strategies for oral delivery systems for cinnamaldehyde.

Cinnamaldehyde (CA) is the main bioactive component extracted from the internal bark of cinnamon trees with many health benefits. In this paper, the bioavailability and biological activities of cinnamaldehyde, and the underlying molecular mechanism are reviewed and discussed, including antioxidant, cardioprotective, anti-inflammatory, anti-obesity, anticancer, and antibacterial properties. Common delivery systems that could improve the stability and bioavailability of CA are also summarized and evaluated, such as micelles, microcapsules, liposomes, nanoparticles, and nanoemulsions. This work provides a comprehensive understanding of the beneficial functions and delivery strategies of CA, which is useful for the future application of CA in the functional food industry.

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde.

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.

Preparation and sustained-release of chitosan-alginate bilayer microcapsules containing aromatic compounds with different functional groups.

This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core materials (benzyl alcohol, eugenol, cinnamaldehyde, and benzoic acid) were synthesized via freeze-drying. Chitosan (CS) and sodium alginate (ALG) were used as wall materials. CS concentration, using orthogonal experiments with the loading ratio as a metric. Under optimal conditions, three other types of microcapsules (cinnamic aldehyde, benzoic acid, and benzyl alcohol) were obtained. The four types of microcapsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA), and their sustained release characteristics were evaluated. The optimal conditions were: CS dosage, 1.2 %; CS-to-eugenol mass ratio, 1:2; and CS-to-ALG mass ratio, 1:1. By comparing the IR spectra of the four types of microcapsules, wall material, and core material, the core materials were revealed to be encapsulated within the wall material. SEM results revealed that the granular protuberances on the surface of the microcapsules were closely aligned and persistent when magnified 2000×. The TEM results indicated that all four microcapsules had a spherical and bilayer structure. The thermal stability and sustained release results showed that the four microcapsules were more resilient and less volatile than the four core materials. The release conformed to first-order kinetics, and the release ratios of the four microcapsules were as follows: benzyl alcohol microcapsules Ëƒ eugenol microcapsules Ëƒ cinnamaldehyde microcapsules Ëƒ benzoic acid microcapsules. The prepared bilayer microcapsules encapsulated four different core materials with good sustained release properties.

Determination of cinnamaldehyde, thymol and eugenol in essential oils by LC-MS/MS and antibacterial activity of them against bacteria.

Plant essential oils contain many secondary metabolites, some of which can effectively inhibit the growth of pathogenic microorganisms, so it is a very promising antibacterial agent. In this study, a qualitative and quantitative method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for the simultaneous determination of three bioactive substances, cinnamaldehyde (CNM), thymol (THY), and eugenol (EUG), in the essential oils of plants. Necessary tests for linearity, limit of quantification, recovery, carryover contamination and precision of the method were carried out. Then, the antibacterial activity of 3 bioactive compounds against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was evaluated by minimal inhibitory concentration and the synergistic antimicrobial effect. The results indicated that CNM, THY and EUG had good antibacterial activity. According to the results of fractional inhibitory concentration index (FICI), it is considered that CNM + THY and CNM + THY + EUG has obvious synergistic inhibitory effect on E. coli, and CNM + THY and CNM + EUG has obvious synergistic inhibitory effect on S. aureus. Finally, we analyzed the effect of the bioactive compounds on trace elements in bacteria and found significant changes in magnesium, calcium, copper and iron.

Hyaluronic acid-based multifunctional bio-active coating integrated with cinnamaldehyde/hydroxypropyl-ß-cyclodextrin inclusion complex for fruit preservation.

Natural preservatives such as cinnamaldehyde (CIN) are garnering increasing interest to replace their synthetic counterparts in maintaining fruit freshness and safety. However, their long-term effectiveness and widespread application have been greatly limited due to high volatility and potent aroma. To address these challenges, we developed a viable and simple strategy to prepare a multifunctional active coating for fruit preservation by incorporating host-guest inclusion complex of CIN and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) CIN@HP-ß-CD into hyaluronic acid (HA), a natural polysaccharide with exceptional film-forming properties. The as-prepared HA/CIN@HP-ß-CD coatings exhibited universal surface affinity, excellent antimicrobial performance, and satisfactory antioxidant properties with no potential toxicity. Release kinetic studies have demonstrated that CIN in the coating is continuously and slowly released. Furthermore, freshness preservation experiments on bananas and fresh-cut apples demonstrated that the developed coating is effective in preserving the color of fruit, decreasing the weight loss rate, preventing the microorganism's growth, and significantly extending the period of freshness, exhibiting the potential for application in fruit preservation.

Cinnamaldehyde ameliorates STZ-induced diabetes through modulation of autophagic process in adipocyte and hepatic tissues on rats.

Type 2 diabetes mellitus is a worldwide public health issue. In the globe, Egypt has the ninth-highest incidence of diabetes. Due to its crucial role in preserving cellular homeostasis, the autophagy process has drawn a lot of attention in recent years, Therefore, the purpose of this study was to evaluate the traditional medication metformin with the novel therapeutic effects of cinnamondehyde on adipocyte and hepatic autophagy in a model of high-fat diet/streptozotocin-diabetic rats. The study was conducted on 40 male albino rats, classified into 2 main groups, the control group and the diabetic group, which was subdivided into 4 subgroups (8 rats each): untreated diabetic rats, diabetic rats received oral cinnamaldehyde 40 mg/kg/day, diabetic rats received oral metformin 200 mg/kg/day and diabetic rats received a combination of both cinnamaldehyde and metformin daily for 4 weeks. The outcomes demonstrated that cinnamaldehyde enhanced the lipid profile and glucose homeostasis. Moreover, Cinnamaldehyde had the opposite effects on autophagy in both tissues; by altering the expression of genes that control autophagy, such as miRNA 30a and mammalian target of rapamycin (mTOR), it reduced autophagy in adipocytes and stimulated it in hepatic tissues. It may be inferred that by increasing the treatment efficacy of metformin and lowering its side effects, cinnamaldehyde could be utilized as an adjuvant therapy with metformin for the treatment of type 2 diabetes.

Olfactory receptors impact pathophysiological processes of lung diseases in bronchial epithelial cells.

BACKGROUND: Therapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are limited. Bronchial epithelial cells are key in the pathogenesis by releasing the central proinflammatory cytokine interleukine-8 (IL-8). Olfactory receptors (ORs) are expressed in various cell types. This study examined the drug target potential of ORs by investigating their impact on associated pathophysiological processes in lung epithelial cells. METHODS: Experiments were performed in the A549 cell line and in primary human bronchial epithelial cells. OR expression was investigated using RT-PCR, Western blot, and immunocytochemical staining. OR-mediated effects were analyzed by measuring 1) intracellular calcium concentration via calcium imaging, 2) cAMP concentration by luminescence-based assays, 3) wound healing by scratch assays, 4) proliferation by MTS-based assays, 5) cellular vitality by Annexin V/PI-based FACS staining, and 6) the secretion of IL-8 in culture supernatants by ELISA. RESULTS: By screening 100 potential OR agonists, we identified two, Brahmanol and Cinnamaldehyde, that increased intracellular calcium concentrations. The mRNA and proteins of the corresponding receptors OR2AT4 and OR2J3 were detected. Stimulation of OR2J3 with Cinnamaldehyde reduced 1) IL-8 in the absence and presence of bacterial and viral pathogen-associated molecular patterns (PAMPs), 2) proliferation, and 3) wound healing but increased cAMP. In contrast, stimulation of OR2AT4 by Brahmanol increased wound healing but did not affect cAMP and proliferation. Both ORs did not influence cell vitality. CONCLUSION: ORs might be promising drug target candidates for lung diseases with non-type 2 inflammation. Their stimulation might reduce inflammation or prevent tissue remodeling by promoting wound healing.

Essential oil from Cinnamomum cassia Presl bark regulates macrophage polarization and ameliorates lipopolysaccharide-induced acute lung injury through TLR4/MyD88/NF-κB pathway.

BACKGROUND: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). PURPOSE: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. METHODS: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. RESULTS: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1ß in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.

Protective effects of EGCG on acrolein-induced Caenorhabditis elegans and its mechanism of life extension.

In this study, it was found that epigallocatechin-3-gallate (EGCG) could extend the lifespan of Caenorhabditis elegans (C. elegans) induced by 100 µM acrolein (ACR) at all test concentrations (300, 400, 500, 600, and 700 µM). Notably, 500 µM EGCG exhibited the most significant mean lifespan extension, increasing it by approximately 32.5%. Furthermore, 500 µM EGCG effectively reduced elevated levels of reactive oxygen species (ROS) and lipofuscin production caused by acrolein. It also bolstered the activity of antioxidant enzymes and mitigated malondialdehyde (MDA) levels compared to the ACR-only group. These effects appeared independent of dietary restrictions. Additionally, qPCR results revealed different changes in the transcription levels of 11 genes associated with antioxidative and anti-aging functions following EGCG treatment. At the expression level, GST-4::GFP, SOD-3::GFP and HSP-16.2::GFP exhibited an initial increase with ACR treatment followed by a decrease with EGCG treatment, while the expression pattern of these three GFPs remained consistent with the enzyme activity and transcription regulation level. EGCG treatment also reduced the nuclear localization of SKN-1 and DAF-16 in the MAPK and IIS pathways that were enhanced by ACR. Moreover, the longevity-promoting effects of EGCG were diminished or absent in 13 longevity gene-deletion mutants. In conclusion, EGCG demonstrates protective effects on ACR-induced C. elegans, with the IIS and MAPK pathways playing a critical role in enhancing resilience to ACR.