RESUMO
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.
Assuntos
Acroleína , Antineoplásicos , Neoplasias , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Acroleína/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
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.
Assuntos
Acroleína , Acroleína/análogos & derivados , Adipócitos , Autofagia , Diabetes Mellitus Experimental , Fígado , Metformina , Animais , Acroleína/farmacologia , Acroleína/uso terapêutico , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Metformina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Estreptozocina , Glicemia/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Cinnamaldehyde (CA) showed potent activity against melanoma in our previous study, and the structure of unsaturated aldehydes is envisaged to play a role. Nevertheless, its limited drug availability restricts its clinical application. Therefore, a series of CA analogues were synthesized to evaluate their anti-melanoma activities across various melanoma cell lines. These compounds were also tested for their toxicity against the different normal cell lines. The compound with the most potential, CAD-14, exhibited potent activity against the A375, A875 and SK-MEL-1 cells, with IC50 values of 0.58, 0.65, and 0.82 µM, respectively. A preliminary molecular mechanism study of CAD-14 indicated that it could inhibit the p38 pathway to induce apoptosis, and suppress tumor growth by inhibiting the expression of ENO1. Furthermore, an acute toxicity study depicted that CAD-14 has better safety and tolerability than CA in vivo. These findings indicate that CAD-14 might be a lead compound for exploring effective anti-melanoma drugs.
Assuntos
Antineoplásicos , Melanoma , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Melanoma/metabolismo , Acroleína/farmacologia , Acroleína/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Objective: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,ß-unsaturated aldehyde, is a common dietary and environmental pollutant. Design: The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models. Methods: Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system. Results: We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function. Conclusions: These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.
Assuntos
Carnosina , Diabetes Mellitus , Nefropatias Diabéticas , Poluentes Ambientais , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Acroleína/metabolismo , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Carnosina/metabolismo , Carnosina/farmacologia , Carnosina/uso terapêutico , Citocinas , Diabetes Mellitus/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Poluentes Ambientais/metabolismo , Poluentes Ambientais/farmacologia , Poluentes Ambientais/uso terapêutico , Células HEK293 , Humanos , Hidralazina/metabolismo , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Rim/metabolismo , Camundongos , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêuticoRESUMO
Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.
Assuntos
Antineoplásicos , Fumar Cigarros , Neoplasias da Bexiga Urinária , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Camundongos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Bioactive dietary constituents activating Transient receptor potential (TRP) channels have emerged as promising candidates for the prevention of metabolic disorders. OBJECTIVE: The present study is an attempt to evaluate anti-obesity potential of a dietary TRP-based tri-agonist, combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist), and cinnamaldehyde (TRPA1 agonist) in high-fat diet (HFD)-fed mice. DESIGN: Male C57BL/6 J mice divided into three groups (n = 8), were fed on normal pellet diet (NPD), or high-fat diet (HFD) (60% energy by fat) and HFD + CB (combination of capsaicin 0.4 mg/Kg, menthol 20 mg/Kg, and cinnamaldehyde 2 mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied. RESULTS: Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis, and adipose tissue hypertrophy. Tri-agonist supplementation was found to induce browning of white adipose tissue and promote brown adipose tissue activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with a tri-agonist. CONCLUSION: The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/agonistas , Acroleína/administração & dosagem , Acroleína/análogos & derivados , Acroleína/uso terapêutico , Animais , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/métodos , Modelos Animais de Doenças , Mentol/administração & dosagem , Mentol/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL/crescimento & desenvolvimento , Camundongos Endogâmicos C57BL/metabolismo , Fenótipo , Canais de Potencial de Receptor Transitório/farmacologiaRESUMO
Background: Trans-cinnamaldehyde (tCA), a bioactive component found in Cinnamomum cassia, has been reported to exhibit anti-inflammatory and antioxidant effects, but its efficacy in muscle cells has yet to be found. In this study, we investigated the inhibitory effect of tCA on inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in C2C12 mouse skeletal myoblasts. Methods: To investigate the anti-inflammatory and antioxidant effects of tCA in LPS-treated C2C12 cells, we measured the levels of pro-inflammatory mediator, cytokines, and reactive oxygen species (ROS). To elucidate the mechanism underlying the effect of tCA, the expression of genes involved in the expression of inflammatory and oxidative regulators was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of tCA against LPS in the zebrafish model. Results: tCA significantly inhibited the LPS-induced release of pro-inflammatory mediators and cytokines, which was associated with decreased expression of their regulatory genes. tCA also suppressed the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor, and attenuated the nuclear translocation of nuclear factor-kappa B (NF-κB) and the binding of LPS to TLR4 on the cell surface in LPS-treated C2C12 cells. Furthermore, tCA abolished LPS-induced generation of ROS and expression levels of ROS producing enzymes, NADPH oxidase 1 (NOX1) and NOX2. However, tCA enhanced the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated C2C12 myoblasts. In addition, tCA showed strong protective effects against NO and ROS production in LPS-injected zebrafish larvae. Conclusions: Our findings suggest that tCA exerts its inhibitory ability against LPS-induced inflammatory and antioxidant stress in C2C12 myoblasts by targeting the TLR4/NF-κB, which might be mediated by the NOXs and Nrf2/HO-1 pathways.
Assuntos
Acroleína/análogos & derivados , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Mioblastos , NF-kappa B/metabolismo , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/metabolismo , Peixe-ZebraRESUMO
Parkinson's disease (PD) is the most common neurodegenerative movement disorder with obscure etiology and no disease-modifying therapy to date. Hence, novel, safe, and low cost-effective approaches employing medicinal plants are currently receiving increased attention. A growing body of evidence has revealed that cinnamon, being widely used as a spice of unique flavor and aroma, may exert neuroprotective effects in several neurodegenerative diseases, including PD. In vitro evidence has indicated that the essential oils of Cinnamomum species, mainly cinnamaldehyde and sodium benzoate may protect against oxidative stress-induced cell death, reactive oxygen species generation, and autophagy dysregulation, thus acting in a potentially neuroprotective manner. In vivo evidence has demonstrated that oral administration of cinnamon powder and sodium benzoate may protect against dopaminergic cell death, striatal neurotransmitter dysregulation, and motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse models of PD. The underlying mechanisms of its action include autophagy regulation, antioxidant effects, upregulation of Parkin, DJ-1, glial cell line-derived neurotrophic factor, as well as modulation of the TLR/NF-κB pathway and inhibition of the excessive proinflammatory responses. In addition, in vitro and in vivo studies have shown that cinnamon extracts may affect the oligomerization process and aggregation of α-synuclein. Herein, we discuss recent evidence on the novel therapeutic opportunities of this phytochemical against PD, indicating additional mechanistic aspects that should be explored, and potential obstacles/limitations that need to be overcome, for its inclusion in experimental PD therapeutics.
Assuntos
Acroleína/análogos & derivados , Cinnamomum zeylanicum/química , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/tratamento farmacológico , Acroleína/química , Acroleína/uso terapêutico , Animais , Humanos , Camundongos , Fármacos Neuroprotetores/química , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/patologiaRESUMO
Diarrhetic shellfish toxins (DSTs), some of the most important phycotoxins, are distributed almost all over the world, posing a great threat to human health through the food chain. Therefore, it is of great significance to find effective methods to reduce toxin accumulation in shellfish. In this paper, we observed the effects of four phytochemicals including cinnamaldehyde (CA), quercetin, oridonin and allicin on the accumulation of DSTs in the digestive gland of Perna viridis after exposure to the DSTs-producing Prorocentrum lima. We found that, among the four phytochemicals, CA could effectively decrease the accumulation of DSTs (okadaic acid-eq) in the digestive gland of P. viridis. Further evidence demonstrated that CA could reduce the histological alterations of the digestive gland of a mussel caused by DSTs. RT-qPCR showed that CA could suppress the CYP3A4 induction by DSTs, suggesting that the DSTs' decrease induced by CA might be related to the inhibition of CYP3A4 transcription induction. However, further studies on the underlying mechanism, optimal treatment time, ecological safety and cost should be addressed before cinnamaldehyde is used to decrease the accumulation of DSTs in field.
Assuntos
Acroleína/análogos & derivados , Diarreia/tratamento farmacológico , Sistema Digestório/efeitos dos fármacos , Toxinas Marinhas/antagonistas & inibidores , Perna (Organismo)/efeitos dos fármacos , Intoxicação por Frutos do Mar/tratamento farmacológico , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Diarreia/metabolismo , Diarreia/patologia , Sistema Digestório/metabolismo , Sistema Digestório/patologia , Toxinas Marinhas/metabolismo , Perna (Organismo)/metabolismo , Frutos do Mar , Intoxicação por Frutos do Mar/metabolismo , Intoxicação por Frutos do Mar/patologiaRESUMO
Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci's impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it's impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM.
Assuntos
Acroleína/análogos & derivados , Diabetes Gestacional/tratamento farmacológico , Hipóxia Fetal/prevenção & controle , Neovascularização Patológica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Placenta/efeitos dos fármacos , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Gestacional/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Hipóxia Fetal/metabolismo , Neovascularização Patológica/metabolismo , Estresse Oxidativo/fisiologia , Placenta/irrigação sanguínea , Placenta/metabolismo , Gravidez , Ratos , Ratos WistarRESUMO
Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on neurodegenerative diseases. This review will discuss an herbal constituent known as cinnamaldehyde (CA) with the neuroprotective potential to treat neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Accumulating evidence supports the notion that CA displays neuroprotective effects in AD and PD animal models by modulating neuroinflammation, suppressing oxidative stress, and improving the synaptic connection. CA exerts these effects through its action on multiple signaling pathways, including TLR4/NF-κB, NLRP3, ERK1/2-MEK, NO, and Nrf2 pathways. To summarize, CA and its derivatives have been shown to improve pathological changes in AD and PD animal models, which may provide a new therapeutic option for neurodegenerative interventions. To this end, further experimental and clinical studies are required to prove the neuroprotective effects of CA and its derivatives.
Assuntos
Acroleína/análogos & derivados , Inflamação/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Acroleína/química , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Inflamação/complicações , Doenças Neurodegenerativas/complicações , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and reperfusion for 2 h. The results indicated that pretreatment with 10 or 40 mg/kg of CA attenuated morphological damage in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly restored the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mesenteric I/R-injured liver tissues, indicating the improvement of hepatic function. CA also significantly attenuated the inflammation via reducing myeloperoxidase (MOP) activity and downregulating the expression of inflammation-related proteins, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (Cox-2), and tumor necrosis factor receptor type-2 (TNFR-2) in both lung and liver tissues of mesenteric I/R-injured rats. Pretreatment with CA significantly downregulated nuclear factor kappa B- (NF-κB-) related protein expressions (NF-κB p65, NF-κB p50, I kappa B alpha (IK-α), and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß)) in both lung and liver tissues of mesenteric I/R-injured rats. CA also significantly downregulated the protein expression of p53 family members, including caspase-3, caspase-9, Bax, and p53, and restored Bcl-2 in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly reduced TUNEL-apoptotic cells and significantly inhibited p53 and NF-κB p65 nuclear translocation in both lung and liver tissues of mesenteric I/R-injured rats. CA neither induced pulmonary and hepatic histological alterations nor affected the parameters of inflammation and apoptosis in sham rats. We conclude that CA alleviated mesenteric I/R-induced pulmonary and hepatic injuries via attenuating apoptosis and inflammation through inhibition of NF-κB and p53 pathways in rats, suggesting the potential role of CA in remote organ ischemic injury protection.
Assuntos
Acroleína/análogos & derivados , Isquemia Mesentérica/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/patologia , Inflamação/prevenção & controle , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/patologia , Hepatopatias/etiologia , Hepatopatias/patologia , Hepatopatias/prevenção & controle , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Masculino , Isquemia Mesentérica/complicações , Isquemia Mesentérica/patologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologiaRESUMO
Oxidative stress, which is characterized by overproduction of reactive oxygen species (ROS), is considered a major risk factor associated with fibroblast death in severe lung diseases such as idiopathic pulmonary fibrosis. trans-Cinnamaldehyde (tCA), the major phytochemical constituent in cinnamon, is known to possess strong anti-oxidant activity. However, whether tCA can defend lung fibroblasts against oxidative injury remains to be elucidated. Therefore, this study was conducted to investigate the protective effects of tCA on oxidative stress in V79-4 Chinese hamster lung fibroblasts. The current results showed that tCA inhibited hydrogen peroxide (H2O2)-induced cytotoxicity by blocking abnormal accumulation of ROS in V79-4 Chinese hamster lung fibroblasts. tCA attenuated apoptosis by suppressing of mitochondrial dysfunction and cytosolic release of cytochrome c, increasing the rate of Bcl-2/Bax expression and reducing the activity of caspase-9 and caspase-3 in H2O2-stimulated V79-4 cells, suggesting that tCA protected V79-4 cells from the induction of mitochondria-mediated apoptosis by H2O2. Additionally, the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) was markedly promoted by tCA in the presence of H2O2, which was associated with the enhanced expression of heme oxygenase-1 (HO-1). However, inhibiting the activity of HO-1 by zinc protoporphyrin IX, a potent inhibitor of HO-1, eliminated the ROS scavenging and protective effects of tCA, indicating that tCA was able to protect V79-4 lung fibroblasts from H2O2-induced oxidative stress by activating the Nrf2 signaling pathway. Therefore, it is suggested that tCA may be useful as a candidate for the treatment of oxidative stress-mediated lung injuries in the future.
Assuntos
Acroleína/análogos & derivados , Antioxidantes/farmacologia , Heme Oxigenase-1/metabolismo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Heme Oxigenase-1/antagonistas & inibidores , Humanos , Peróxido de Hidrogênio/metabolismo , Fibrose Pulmonar Idiopática/patologia , Pulmão/citologia , Pulmão/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Protoporfirinas/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Cinnamaldehyde (CA), as an active compound isolated from the bark of Cinnamomum cassia, has been reported to possess the anti-fungal, anti-bacterial, anti-inflammatory, anti-mutagenic, and anti-oxidant properties. However, the possible effects and underlying mechanisms of CA on rheumatoid arthritis (RA) have not been revealed yet. In the present study, we found that CA obviously improved the type II collagen-induced RA in rats, accompanied with decreasing pro-inflammatory factors, proliferation and metastasis. In addition, CA decreased the expression levels of TNF-α, IL-1ß, and IL-6 in RA-FLSs. Besides, CA remarkably inhibited the proliferation, downregulated the EdU-positive cells, and promoted apoptosis of RA-FLSs by CCK-8, EdU and flow cytometry analysis. Moreover, the results of wound healing, transwell migration and invasion assays showed that CA inhibited the migration and invasion of RA-FLSs. Further, western blot experiment showed CA inhibited the activation of PI3K/AKT signaling pathway in RA-FLSs. Finally, 740Y-P, the PI3K/AKT signaling pathway activator, could reverse the effects of CA on the proliferation and metastasis in RA-FLSs. In conclusion, we confirmed that CA exhibited potential therapeutic properties against RA via suppressing proliferation and metastasis of RA-FLSs by blockage of PI3K/AKT signaling pathway. Therefore, our study provides evidence that CA may emerge as a therapeutic option for RA treatment.
Assuntos
Acroleína/análogos & derivados , Artrite Experimental/prevenção & controle , Artrite Reumatoide/prevenção & controle , Progressão da Doença , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
One hundred and twenty one-day-old chukar partridges were randomly divided into eight groups which received diets with different supplementations. There were four unchallenged groups. One group received salinomycin (50 ppm), two groups received cinnamaldehyde (CINN) (100 and 200 mg/kg of diet), and another one received only the basal diet from the 1st to the 31st day. There were also four corresponding groups orally challenged by 3 × 105Eimeria kofoidi sporulated oocysts at the 21st day. Three samplings were done at the 24th, 26th, and 31st days of rearing for pathological and biochemical assessments. Fecal samples were daily taken to check the pattern of oocyst shedding from the 26th to 31st day. The body weight of birds was measured at 21st and 31st days. Along with the in vivo experiment, an in vitro sporulation inhibition test was carried out. The in vitro results showed that CINN decreased sporulation rate at 1 and 0.5 mg/ml. In vivo, it was found that CINN did not prevent the oocyst shedding. Furthermore, the histopathological findings revealed that CINN and salinomycin had no effect on infection establishment. However, our findings showed that CINN (200 mg/kg of diet) could enhance the body weight and improve antioxidant status. Although our results did not support the in vivo anticoccidial activity of CINN, it had a promising potential to improve antioxidant status and body weight in the chukar partridge.
Assuntos
Acroleína/análogos & derivados , Doenças das Aves/parasitologia , Coccidiose/veterinária , Eimeria/efeitos dos fármacos , Galliformes/parasitologia , Acroleína/farmacologia , Acroleína/uso terapêutico , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Doenças das Aves/tratamento farmacológico , Peso Corporal , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Fezes/parasitologia , Galliformes/crescimento & desenvolvimento , Intestinos/parasitologia , Intestinos/patologia , Contagem de Ovos de Parasitas/veterinária , Piranos/farmacologia , Piranos/uso terapêutico , Distribuição Aleatória , Esporos de Protozoários/efeitos dos fármacos , Esporos de Protozoários/fisiologia , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVES: This review assesses the polypharmacy reduction potential of cinnamic acids (CAs) and some related compounds in managing three or more of the cluster of seven, pre- and post-type 2 diabetes mellitus (T2DM)-related features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation). METHODS: Google scholar and Pubmed were searched for cinnam*, chlorogenic acid, ferulic acid, and caffeic acid in conjunction with each of pre- and post-onset T2DM, central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation. The study was divided into an introduction followed by findings on the impacts of each of the CAs including trans-CA acid, the E isomer of a CA-based thiazolidinedione and a metabolite of that isomer, as well as p-methoxy CA, various cinnamic amides and some other CA-related compounds (chlorogenic acid, cinnamaldehyde, ferulic and caffeic acid). RESULTS: Trans-CA has a potential to manage three, while each of chlorogenic acid, cinnamalde-hyde, caffeic acid and ferulic acid has a potential to manage all seven members of the cluster. Other CA-related compounds identified may manage only one or two of the cluster of seven. CONCLUSIONS: Much of the work has been done in animal models of pre- and post-onset T2DM and non-pre- or post-onset T2DM humans and animals, along with some cell culture and in vitro work. Very little work has been done with human pre- and post-onset T2DM. While there is potential for managing 3 or more members of the cluster with many of these compounds, a definitive answer awaits large pre- and post-T2DM onset clinical trials with humans.
Assuntos
Acroleína/análogos & derivados , Ácidos Cafeicos/uso terapêutico , Ácido Clorogênico/uso terapêutico , Cinamatos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Inflamação/tratamento farmacológico , Obesidade Abdominal/tratamento farmacológico , Polimedicação , Acroleína/uso terapêutico , Animais , HumanosRESUMO
BACKGROUND: This systematic review aims to assess the effect of cinnamaldehyde on Cav-1 and Survivin expression in epilepsy. METHODS: We will search Cochrane Library, PUBMED, EMBASE, CINAHL, Web of Science, Google Scholar, PsycINFO, WANGFANG, VIP, CBM, and CNKI from their inceptions to the March 31, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. RevMan 5.3 software will be used for statistical analysis. RESULTS: This systematic review will investigate whether cinnamaldehyde is effective on Cav-1 and Survivin expression in epilepsy. CONCLUSION: Its findings will provide helpful evidence for the effect of cinnamaldehyde on Cav-1 and Survivin expression in epilepsy.Systematic review registration: INPLASY202040152.
Assuntos
Acroleína/análogos & derivados , Caveolina 1/análise , Epilepsia/sangue , Expressão Gênica/efeitos dos fármacos , Survivina/análise , Acroleína/uso terapêutico , Protocolos Clínicos , Epilepsia/epidemiologia , Expressão Gênica/fisiologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Previous reports found that cinnamaldehyde has effects on anti-respiratory syncytial virus (ARSV). However, their results are still contradictory. Therefore, this study will systematically address the effects of cinnamaldehyde on ARSV. METHODS: The following electronic bibliographic databases will be retrieved from their outset to the March 31, 2020: MEDLINE, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Technology Periodical Database, China Biology Medicine, and China National Knowledge Infrastructure. No language and publication time limitations will be exerted in this study. All relevant case-controlled studies or randomized controlled studies exploring the effects of cinnamaldehyde on ARSV will be included. Study quality of case-controlled studies will be assessed by Newcastle-Ottawa scale, and that of randomized controlled studies will be identified by Cochrane risk of bias tool. All data pooling and analysis will be performed using RevMan 5.3 software. RESULTS: This study will summarize the up-to-date high-quality evidence to synthesize outcome data on the effects of cinnamaldehyde on ARSV. CONCLUSION: Findings of this study may provide beneficial evidence for both clinicians and future studies regarding the effects of cinnamaldehyde on ARSV. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040074.
Assuntos
Acroleína/análogos & derivados , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Acroleína/administração & dosagem , Acroleína/efeitos adversos , Acroleína/uso terapêutico , Apoptose , Western Blotting , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Metanálise como AssuntoRESUMO
Cinnamaldehyde (CA) is an essential component of cinnamon (Cinnamomum cassia Presland), which is often used as a flavoring condiment in beverages, pastries, perfumes, etc. Cinnamon is also used as herbal medicine in China and Southeast Asia to treat rheumatoid arthritis. However, the molecular mechanism is unclear. In this study, we aim to investigate its anti-inflammatory effects against Rheumatoid arthritis (RA) using activated macrophages (Raw246.7) in vitro and adjuvant arthritis rats (AA) in vivo. The results demonstrated that CA significantly reduced synovial inflammation in AA rats, possibly due to suppression of the expressions of pro-inflammatory cytokines, especially the IL-1ß. Further investigation found that CA also suppressed the activity of HIF-1α by inhibiting the accumulation of succinate in cytoplasm. As we know, the reduction of HIF-1α nucleation slows down IL-1ß production, because HIF-1α activates the expression of NLRP3, which is involved in the assembly of inflammasome and processing of IL-1ß. In addition, CA also inhibited the expression of the succinate receptor GPR91, which in turn inhibited the activation of HIF-1α. In conclusions, our results suggested that CA might be a potential therapeutic compound to relieve rheumatoid arthritis progress by suppressing IL-1ß through modulating succinate/HIF-1α axis and inhibition of NLRP3.
Assuntos
Acroleína/análogos & derivados , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Interleucina-1beta/imunologia , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Células RAW 264.7 , Ratos Sprague-Dawley , Ácido Succínico/imunologiaRESUMO
Percutaneous absorption of drugs can be enhanced by ethosomes, which are nanocarriers with excellent deformability and drug-loading properties. However, the ethanol within ethosomes increases phospholipid membrane fluidity and permeability, leading to drug leakage during storage. Here, we developed and characterized a new phospholipid nanovesicles that is co-hybridized with hyaluronic acid (HA), ethanol and the encapsulated volatile oil medicines (eugenol and cinnamaldehyde [EUG/CAH]) for transdermal administration. In comparison with EUG/CAH-loaded ethosomes (ES), the formulation stability and percutaneous drug absorption of EUG/CAH-loaded HA-immobilized ethosomes (HA-ES) were significantly improved. After transdermal administration of HA-ES, the interstitial cells of Cajal in the colon of rats with trinitrobenzene sulfonate-induced ulcerative colitis (UC) were significantly increased, and the stem cell factor/c-kit signaling pathway was partly repaired. Overall, HA-ES possesses excellent deformability and showed improved efficacy against UC compared with ES, which is demonstrated as a promising transdermal delivery vehicle for volatile oil medicines.