Cinnamon (Cassia)

Trans-cinnamaldehyde (TCA), a natural compound isolated from the stem bark of Cinnamon cassia, has been recognized as a potential therapeutic agent for treating various diseases, including inflammatory conditions and diverse cancers. TNF-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis selectively in cancer cells while sparing normal cells. However, resistance to TRAIL-mediated apoptosis is a significant limitation in cancer therapy. This study aimed to investigate whether TCA could enhance the sensitivity of colorectal cancer cells to TRAIL induced apoptosis and to elucidate the underlying molecular mechanisms involved in this synergistic effect. The study was designed to evaluate the antitumor effects of TCA and TRAIL, both individually and in combination, using colorectal cancer cell lines and in vivo models. Various colorectal cancer cell lines and normal cells were treated with TCA, TRAIL, or their combination. Cell viability assays were conducted to determine the synergistic effects. Western blotting was performed to analyze the expression of ER stress-related proteins. Knockdown of DR5 or CHOP was achieved using siRNA to evaluate its role in the combined anticancer effect. in vivo experiments were conducted to confirm the antitumor effects of the TCA and TRAIL combination. We observed that the combination of TCA and TRAIL exhibits synergistic antitumor effects both in vitro and in vivo. The anticancer effect was notably enhanced when TCA and TRAIL were used to treat various colorectal cancer cell lines, but not normal cells. Additionally, the levels of endoplasmic reticulum (ER) stress-related proteins, such as phosphorylated protein kinase RNA-like ER kinase (PERK), phosphorylation of the eukaryotic initiation factor 2 (eIF2α), and C/EBP homologous protein (CHOP), increased in a dose-dependent manner when treated with TCA. Significantly, TCA elevated DR5 expression levels through ER stress. Knockdown of CHOP reduced the combined effect of TCA and TRAIL. TCA enhances TRAIL-induced apoptosis in colorectal cancer cells by inducing ER stress and upregulating DR5 expression. These findings suggest that TCA is a promising agent for overco

BACKGROUND: Numerous clinical studies have suggested that cinnamon supplementation may be effective for cardiovascular disease risk factors, but the findings are controversial. This comprehensive systematic review and meta-analysis aimed to assess the impact of cinnamon supplementation on cardiovascular disease risk factors. METHODS: Relevant studies were identified through electronic searches of databases, including Web of Science, PubMed, Central, Scopus, and Embase, up to July 2024. RESULTS: Forty-nine studies were included. Cinnamon supplementation significantly reduced WC (SMD = - 0.40; 95% (CI): - 0.73, - 0.06), DBP (SMD = - 1.04; 95% CI: - 1.54, - 0.55), SBP (SMD = - 0.85; 95% CI: - 1.54, - 0.16), fasting glucose (SMD = - 1.28; 95% CI: - 1.65, - 0.90), fasting insulin (SMD = - 0.26; 95% CI: - 0.50, - 0.02), HbA1c (SMD = - 0.71; 95% CI: - 1.02, - 0.40), HOMA-IR (SMD = - 0.54; 95% CI: - 0.82, - 0.26), postprandial blood glucose (SMD = - 2.28; 95% CI: - 3.48, - 1.08), CRP (SMD = - 0.78; 95% CI: - 1.28, - 0.27), LDL-C (SMD = - 0.71; 95% CI: - 1.02, - 0.40), total cholesterol (TC) (SMD = - 1.15; 95% CI: - 1.55, - 0.75), triglycerides (TG) (SMD = - 0.91; 95% CI: - 1.25, - 0.56), and MDA (SMD = - 0.76; 95% CI: - 1.07, - 0.45). Additionally, cinnamon supplementation significantly elevated HDL-C levels (SMD = 0.56; 95% CI: 0.23, 0.89). CONCLUSION: Cinnamon supplementation demonstrated significant benefits in improving cardiovascular risk factors. These findings suggest its potential as an adjunct therapy for improving cardiovascular disease risk factors. © 2025. The Author(s).

BACKGROUND: Diabetes is a serious global health issue and increases the risk of several chronic diseases. However, if hyperglycemia and other metabolic abnormalities related to diabetes are controlled, fewer micro- and macrovascular complications may occur. OBJECTIVE: To investigate whether daily supplementation with berberine in combination with cinnamon could have effect on cardiometabolic risk factors, such as impaired glucose regulation, dyslipidemia, and hypertension in patients with diabetes. METHODS: Patients with type 2 diabetes were recruited to participate in a parallel, double-blind, placebo-controlled, randomized study. Participants were randomized into berberine in combination with cinnamon supplementation or placebo group. Participants were then asked to take a divided daily dose of 1200 mg berberine and 600 mg cinnamon or placebo for 12 weeks. ANCOVA was then performed to evaluate the differences between the two groups, controlling for the respective baseline values. RESULTS: At the end of study, fasting blood sugar (FBS) (P = 0.031) and hemoglobin A1C (HbA1c) (P = 0.013) were significantly lower in participants taking berberine plus cinnamon than those taking the placebo capsules. The results of the serum lipid profile also indicated a significant difference in the level of low density lipoprotein cholesterol (LDL-C) (P = 0.039), while no difference was observed in the levels of total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides between the study groups. In addition, there was no difference in other measured metabolic and anthropometric parameters between the two groups. CONCLUSION: Twelve weeks of berberine plus cinnamon consumption reduced blood FBS, HbA1c and LDL-C concentration in patients with diabetes. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Cinnamon has been studied as a possible way to control blood glucose and serum cholesterol levels. However, there are no well-conducted randomized controlled trials that can accurately measure the lipid and glucose-lowering effects of Cinnamomum zeylanicum (C. zeylanicum) extract. This study primarily aimed to evaluate the effect of a standardized C. zeylanicum extract on serum low-density lipoprotein cholesterol (LDL-C) levels and secondarily on other lipid parameters (high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglycerides), glucose levels, anthropometric measures, blood pressure, and safety outcomes in individuals with an LDL level between 100-190mg/dL. MATERIALS AND METHODS: This was a randomized, double-blinded, placebo-controlled clinical trial. Participants were allocated to either C. zeylanicum extract or placebo group (1:1 allocation ratio). They were advised to take two capsules per day (1000 mg/day, a dose based on prior clinical studies suggesting potential efficacy and safety). Reduction in LDL-C at 12 weeks (from the baseline value) was compared between the two groups using ANCOVA. A complete-case analysis was adhered to in analyzing the outcome data. RESULTS: The mean age (SD) of the 150 participants was 50.4 (10.52) years, and 66% were females. Among the 127 participants assessed at 12 weeks, those in the C. zeylanicum extract arm had a lower LDL-C value than the placebo arm but the difference was not significant (the baseline adjusted mean difference was 6.05mg/dL; 95% CI: -2.43 to 14.52; p = 0.161). However, participants in the C. zeylanicum extract group showed significantly greater reductions in fasting blood sugar (FBS) levels (the baseline adjusted mean difference was 8.59mg/dL; 95% CI: 0.59 to 16.59; p = 0.036). There was a significant interaction effect between the supplement and participants' glycemic status, with individuals with type 2 diabetes mellitus (T2DM) who received C. zeylanicum extract experiencing a notable reduction in FBS levels (standardized coefficient: -63, 95% CI: -102 to -25; p = 0.002). CONCLUSIONS: C. zeylanicum extract did not have significantly reduce LDL-C but demonstrated a s

PURPOSE: Recurrent cystitis, particularly common in women, substantially diminishes patient quality of life and represents a major clinical practice and public health burden. Increasing development of resistance to antibiotics has encouraged the search for alternative treatments. The benefits of a food supplement associating two Lactobacillus strains with proanthocyanidin A-rich cranberry and cinnamon extracts were evaluated in 80 women with a history of cystitis recurrence. MATERIALS AND METHODS: Post-inclusion recurrence frequency was compared between women taking the investigated supplement daily for 6 months and non-supplemented women, based on patient-completed Acute Cystitis Symptom Score (ACSS) questionnaires. RESULTS: Two-thirds (64.9%) of supplemented women experienced no further episodes of cystitis during the first 6 months of the study compared to only one-third (31.6%) of non-supplemented women (p=0.004), the difference between the two groups being significant from 3 months onward. ACSS scores revealed significantly fewer and less severe urinary symptoms in supplemented women, as well as a significantly reduced impact of these symptoms on quality of life (p<0.0001). CONCLUSIONS: The results shown by extensive data on women suffering from recurrent cystitis, collected over 8 months, indicate that taking the tested supplement daily for 6 months can provide significant benefits in terms of recurrence frequency, symptoms, and quality of life. The study is registered on the ClinicalTrials.gov site under the identifier NCT04987164. © The Korean Urological Association.

AIMS: Cinnamon has positive effects on markers of cardiometabolic health, including blood pressure (BP), oxidative stress, and inflammation. Despite the evidence accumulated from meta-analysis studies on the effects of cinnamon on these markers, the reported findings are still controversial. This umbrella review was conducted to evaluate the evidence and provide a definitive clarification. DATA SYNTHESIS: We conducted a systematic search in four scientific databases, including PubMed, Scopus, Web of Science, and Embase electronic databases, up to March 2024 to identify systematic reviews and meta-analyses of randomized clinical trials investigating the impact of cinnamon on blood pressure, oxidative stress, and inflammation. The findings revealed that cinnamon might exert favorable effects on systolic blood pressure (SBP) (ES = -2.36 mmHg; 95% CI: 3.86, -1.40), diastolic blood pressure (DBP) (ES = -1.65 mmHg; 95% CI: 2.41, -0.90), total antioxidant capacity (TAC) (WMD = 0.34; 95% CI: 0.04, 0.64), and interleukin-6 (IL-6) (WMD = -1.48; 95% CI: 2.96, -0.01). However, the results did not show any significant effect of cinnamon on malondialdehyde (MDA) (WMD = -0.47; 95% CI: 0.99, 0.05), C-reactive protein (CRP) (WMD = -1.33; 95% CI: 2.66, 0.00), and intercellular adhesion molecule 1 (ICAM-1) (WMD= 1.53, 95% CI: 12.03, 15.10). CONCLUSIONS: The results of the studies included in this umbrella review support the usefulness of cinnamon consumption in modulating BP as well as improving TAC and IL-6 in metabolic disorders. Due to the limited number of studies, clinical diversity, and other limitations, more high-quality studies must be conducted to provide more precise and comprehensive recommendations. REGISTRATION NUMBER: PROSPERO, CRD42023487350.

CONTEXT: The global prevalence of type 2 diabetes mellitus (DM2) has been rising significantly over the years. Recent studies have shown beneficial effects of cinnamon on metabolic biomarkers. OBJECTIVE: The objective of this review was to assess the effect of cinnamon supplementation on metabolic biomarkers in patients with DM2. DATA SOURCES: The Pubmed/MEDLINE, Cochrane CENTRAL, and Embase databases were searched up to November 10, 2022. DATA EXTRACTION: A systematic search was performed for randomized controlled trials (RCTs) evaluating the effect of cinnamon supplementation on metabolic biomarkers, in adults and the elderly with DM2, and comparing the data for a cinnamon intervention group with that for a placebo group or a control group. The main exclusion criteria were studies (1) with other types of diabetes (ie, gestational diabetes or type 1 diabetes), (2) without cinnamon consumption, (3) that did not evaluate metabolic biomarkers, or (4) in vitro and animal studies. Two researchers independently screened 924 records, evaluated full-text studies, extracted data, and appraised their quality. A third researcher was consulted to resolve any discrepancies. The data were pooled using random-effects models and expressed as the weighted mean difference (WMD) with 95% CI. Heterogeneity was assessed using Cochran's Q test and quantified using I2 statistics. Risk of bias was assessed using the Joanna Briggs Institute (JBI) instrument. Sensitivity analysis and the GRADE system were used to assess the robustness and certainty of the findings. DATA ANALYSIS: In total, 28 RCTs with a duration ranging from 30 to 120 days and a total enrollment of 3054 patients with DM2 were included. Participants consuming cinnamon showed a significant reduction in fasting blood glucose (FBG) (WMD: -15.26 mg/dL; 95% CI: -22.23 to -8.30; I2 = 88%), postprandial glucose (WMD: -39.22 mg/dL; 95% CI: -63.90 to -14.55; I2 = 100%), HbA1c (WMD: -0.56 mg/dL; 95% CI: -0.99 to -0.13; I2 = 94%), and HOMA-IR (WMD = -0.76, 95% CI: -1.13 to -0.39; I2 = 22%) compared with the control group. An intervention of cinnamon in capsule form reduced FBG (WMD:-18.43 mg/dL, 95% CI: -26.32 to -10.53; I2 = 89%)

Erratum in Nutrients. 2024 Nov 05;16(22):3791. doi: 10.3390/nu16223791. Non-communicable diseases (NCDs) place a significant burden on global health and the healthcare systems which support it. Metabolic syndrome is a major risk factor for a large number of NCDs; however, treatments remain limited. Previous research has shown the protective benefits of edible dietary spices on key components of metabolic syndrome. Therefore we performed a 12-week double-blind, placebo-controlled, randomized, clinical trial to evaluate the effect of ginger (Zingiber officinale), cinnamon (Cinnamomum), and black seed (Nigella sativa) consumption on blood glucose, lipid profiles, and body composition in 120 participants with, or at risk of, metabolic syndrome. Each participant consumed 3 g/day of powder (spice or placebo). Data related to different parameters were collected from participants at the baseline, midpoint, and endpoint of the intervention. Over the 12-week interventions, there was an improvement in a number of biochemical indices of metabolic syndrome, including fasting blood glucose, HbA1c, LCL, and total cholesterol associated with supplementation with the spices when compared to a placebo. This study provides evidence to support the adjunct use of supplementation for those at risk of metabolic syndrome and its sequelae.

BACKGROUND: Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES: To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS: Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS: There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI (p < 0.0001), serum insulin (p < 0.05) and the HOMA index (p < 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol (p < 0.005), triglycerides (p < 0.03) and LDL (p < 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters.

Although many randomized controlled trials (RCTs) have revealed the benefits of cinnamon on type 2 diabetes mellitus (T2DM), the effects of cinnamon supplementation on glycemic control in patients with T2DM are inconclusive. Therefore, the aim of this meta-analysis of RCTs was to assess the effects of cinnamon supplementation in managing glycemic control in patients with T2DM. Scientific international databases including Scopus, Web of Sciences, PubMed, Embase, and the Cochrane Library were searched till December 2022. For net changes in glycemic control, standard mean differences (SMDs) were calculated using random-effects models. Findings from 24 RCTs revealed that cinnamon supplementation had a statistically significant reduction in fasting blood sugar (SMD: -1.32; 95% CI: -1.77, -0.87, p < 0.001), Homeostatic Model Assessment for Insulin Resistance (SMD: -1.32; 95% CI: -1.77, -0.87, p < 0.001), and hemoglobin A1C (SMD: -0.67; 95% CI: -1.18, -0.15, p = 0.011) compared with the control group in patients with T2DM. Additionally, cinnamon did not change the serum levels of insulin (SMD: -0.17; 95% CI: -0.34, 0.01, p = 0.058) significantly. Our analysis indicated that glycemic control indicators are significantly decreased by cinnamon supplementation. Together, these findings support the notion that cinnamon supplementation might have clinical potential as an adjunct therapy for managing T2DM. © 2023 John Wiley & Sons Ltd.

AIMS: Cinnamon is a polyphenol-rich spice that has beneficial effects on markers of cardio metabolic health such as lipid profile, oxidative stress, and inflammation. Despite the accumulating evidence from meta-analyses on the effects of cinnamon on these markers, their findings are controversial. Thus, this umbrella meta-analysis was performed to evaluate the present evidence and provide a conclusive clarification. DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049). CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.

BACKGROUND: Supplements are commonly used by individuals with indications for lipid-lowering therapy, but evidence of their effectiveness to lower low-density lipoprotein cholesterol (LDL-C) is lacking, particularly when compared with statins. OBJECTIVES: The trial objective was to compare the efficacy of a low-dose statin with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers. METHODS: This was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased 10-year risk of ASCVD. Participants were randomized to rosuvastatin 5 mg daily, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. The primary endpoint was the percent change in LDL-C from baseline for rosuvastatin 5 mg daily compared with placebo and each supplement after 28 days. The primary endpoint was evaluated in a hierarchical fashion with rosuvastatin first compared with placebo, then each supplement in a prespecified order using analysis of covariance. RESULTS: A total of 190 participants completed the study. The percent LDL-C reduction with rosuvastatin was greater than all supplements and placebo (P < 0.001). The difference in LDL-C reduction with rosuvastatin compared with placebo was -35.2% (95% CI: -41.3% to -29.1%; P < 0.001). None of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo. Adverse event rates were similar across study groups. CONCLUSIONS: Among individuals with increased 10-year risk for ASCVD, rosuvastatin 5 mg daily lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice. (Supplements, Placebo, or Rosuvastatin Study [SPORT]; NCT04846231).

Existing evidence has uncovered the potential health benefits of cinnamon intake; however, its effect on liver function is unclear. Thus, the aim of this systematic review and meta-analysis was to examine the effect of cinnamon supplementation on liver enzymes. Relevant articles were identified through a systematic search in PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase up to September 2020. All trials assessing the effect of oral cinnamon supplementation on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in adults were included. The pooled effect sizes were obtained using the random-effects model and expressed as mean difference (MD) and 95% confidence intervals (CI). A total of seven original trials (nine treatment arms) involving a total of 256 subjects were included in the final analysis. The pooled analysis indicated that cinnamon supplementation had no significant effect on serum levels of ALT, AST, and ALP. However, there was a significant reduction in ALT levels in patients with type 2 diabetes (MD: -4.01 U/L; 95% CI: -6.86, -1.15) and in trials with low-dose supplementation (<1,500 mg/d), follow-up duration longer than 12 weeks, and in the elderly patients (aged>50 years). The beneficial effects of cinnamon intake were also shown in AST levels in patients with type 2 diabetes and trials with long-term follow-up (>12 weeks). Longer-term, oral cinnamon supplementation may improve serum levels of liver enzymes in patients with type 2 diabetes. Further high-quality studies are needed, especially in populations with abnormal liver enzyme levels, to firmly establish the clinical efficacy of cinnamon on liver function. © 2021 John Wiley & Sons Ltd.

This systematic review and meta-analysis aims to summarize and conclude the clinical evidence regarding the use of cinnamon among patients with metabolic diseases. A comprehensive literature search without any limitation on language was conducted using the following bibliographical databases: ISI Web of Science, Embase, Scopus, PubMed, and Google Scholar. Search was conducted up to 23 January 2020. A total of 35 clinical trials were included for final analysis. Pooling of results showed a significant reducing effect of cinnamon on total cholesterol (TC) (weighted mean difference (WMD) = -11.67 mg/dL; P = 0.010), triglyceride (TG) (WMD = -16.27 mg/dL; P < 0.001), low density lipoprotein-cholesterol (LDL-C) (WMD = -6.36 mg/dL; P < 0.001), serum glucose (WMD = -11.39 mg/dL; P < 0.001), serum insulin (WMD = -1.27 μIU/mL; P = 0.028), and waist circumstance (WC) (WMD = -1.68 cm; P = 0.016). These lowering effects on TG, TC, LDL-C, and serum glucose levels were robust in studies that used cinnamon supplementation dose ≤1.5 g. Also, our findings of the present meta-analysis showed that cinnamon supplementation could have favorable effects on high density lipoprotein-cholesterol (HDL-C, WMD = 1.35; P = 0.038) as well as systolic (WMD = -3.95 mmHg; P = 0.018) and diastolic (WMD = -3.36; P = 0.001) blood pressure among patients with metabolic diseases. The present meta-analysis suggests that cinnamon might exert beneficial effects on various cardiometabolic risk factors among patients with metabolic diseases.

AIMS: The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the effect of cinnamon supplementation on liver enzymes. METHODS: A systematic search was performed in electronic databases including PubMed-Medline, Scopus, and ISI Web of Science up to November 2020. We used a random effects model to estimate pooled effect size of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) levels. RESULTS: Seven RCTs (9 treatment arms) fulfilled the eligibility criteria of the present meta-analysis. Overall, meta-analysis could not show any beneficial effect of cinnamon supplementation on AST, ALT, and ALP. Subgroup analyses showed that the effect of cinnamon supplementation on ALT was significant at the dosages of <1500 mg/day (Hedges's: -0.61; 95 % CI: -1.11, -0.10; P = 0.002), in trials lasting>12 weeks (Hedges's: -0.83; 95 % CI: -1.36, -0.30; P = 0.01), and in trials conducted of both gender (Hedges's: -0.72; 95 % CI: -1.45, -0.01; P = 0.04). CONCLUSION: In summary, cinnamon supplementation had no significant effect on liver enzymes in adults. However, the effect of cinnamon on ALT levels was significant at the dosages of <1500 mg/day, in trials lasting>12 weeks, and in trials conducted of both gender. Nevertheless, further studies should be performed to confirm our results.

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

The Middle east and North Africa harbour many native species with pharmaceutical and nutraceutical potential. Since the beginning of history, food and herbal medicinal plants have been an essential part of human lives and the traditional Middle Eastern healthcare system. The notable medicinal plants that have been mentioned in the Bible, which are common in West Asia and some regions of North Africa, are Aloe vera, anise, balm, cassia, cinnamon, cumin, flax, and fig. Chemical components of Aloe vera are aloin, sinapinic acid, catechin, chromone, myricetin, quercitrin and syringic acid. Anethole, safrole, and estragole are the main chemical components of anise. The chemical components of cassia are coumarin, emodin, cinnamyl alcohol, and cinnamaldehyde. The major chemical ingredients of cumin are terpinene, cuminaldehyde, sabinene, thujene, and thymoquinone. The goal of this article is to review the considerable health benefits and pharmaceutical benefits of medicinal herbs and plants that have been neglected and underutilized in the Middle East and North Africa, as well as to promote their utilization. On the basis of the results, the experimented neglected medicinal plant can offer various advantages when used together with conventional medicinal treatments for various health conditions, such as palliative care in managing the side effects of conventional treatments, access to a wider range of treatments, increased patient satisfaction, and improved emotional and mental well-being. Moreover, consuming medicinal plants may help to manage and prevent diabetes, cancer, and heart disease with notable anti-tumor, and anti-inflammatory properties.

In this work, the extract of cinnamon bark was used for the green synthesis of cinnamon-Ag nanoparticles (CNPs) and other cinnamon samples, including ethanolic (EE) and aqueous (CE) extracts, chloroform (CF), ethyl acetate (EF), and methanol (MF) fractions. The polyphenol (PC) and flavonoid (FC) contents in all the cinnamon samples were determined. The synthesized CNPs were tested for the antioxidant activity (as DPPH radical scavenging percentage) in Bj-1 normal cells and HepG-2 cancer cells. Several antioxidant enzymes, including biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH), were verified for their effects on the viability and cytotoxicity of normal and cancer cells. The anti-cancer activity depended on apoptosis marker protein levels (Caspase3, P53, Bax, and Pcl2) in normal and cancerous cells. The obtained data showed higher PC and FC contents in CE samples, while CF showed the lowest levels. The IC50 values of all investigated samples were higher, while their antioxidant activities were lower than those of vitamin C (5.4 g/mL). The CNPs showed lower IC50 value (55.6 µg/mL), whereas the antioxidant activity inside or outside the Bj-1 or HepG-2 was found to be higher compared with other samples. All samples execrated a dose-dependent cytotoxicity by decreasing the cells' viability percent of Bj-1 and HepG-2. Similarly, the anti-proliferative potency of CNPs on Bj-1 or HepG-2 at different concentr

Cinnamomum cassia (C. assia) has long been used in traditional holistic medicine for its medicinal properties. It is used as an antioxidant, antibacterial, anti-inflammatory and anticancer agent. Cinnamon, in particular, the essential oil of C. cassia, has significant biological properties. Despite this, the volatility, stability, and insolubility of C. cassia essential oil (CEO) remain the main disadvantages that limit its application, ultimately affecting its pharmacological efficacy. To find a solution to this problem, we developed the CEO nanoemulsion (CEO-NE). For lipophilic compounds, insoluble nanoemulsion-based formulations are a popular delivery strategy. In this research work, a highly stable dosage form named CEO-NE was successfully developed using polysorbate 80 and water. The findings show that the synthesized CEO has a uniform shape with a PDI of 0.380 and an adequate particle size of 221.8 nm. The antioxidant outcomes show excellent results for CEO-NE compared to CEO against DPPH and hydrogen peroxide. The obtained antibacterial activity of CEO-NE was more efficient than that of CEO against Klebsiella pneumonia (MTCC 8911) with 0.025% and 0.05%, respectively. The CEO-NE preparation was tested against an alveolar lung adenocarcinoma cell line (A549) with an IC50 of 50.21 µg/mL for CEO and 18.05 µg/mL for CEO-NE, respectively. These results are encouraging for future translational studies on CEO-NE use in lung cancer therapy due to its excellent antioxidant, antibacterial, and killing kinetic properties. DOI

The effect of fermentation by Saccharomyces cerevisiae on biological properties of cinnamon (Cinnamomum cassia) was investigated. The study demonstrated that the extract of S. cerevisiae-fermented cinnamon (S.C.FC) has antioxidants higher than non-fermented one. The optimum results for antioxidant yield were noted with 107 CFU S. cerevisiae/10 g cinnamon and 70 mL of dH2O at pH 6 and incubated for 3 d at 35 °C. Under optimum conditions, ABTS, DPPH, and H2O2 radical-scavenging activity increased by 43.8, 61.5, and 71.9%, respectively. Additionally, the total phenols and flavonoids in S.C.FC were increased by 81.3 and 415% compared by non-fermented one. The fermented cinnamon had antimicrobial activity against L. monocytogenes, S. aureus, E. coli, S. typhi, and C. albicans. Also, the anti-inflammatory properties were increased from 89 to 92% after fermentation. The lyophilized extract of S.C.FC showed positive effect against Huh7 cancer cells which decreased by 31% at the concentration of 700 µg/mL. According to HPLC analysis, p-hydroxybenzoic acid, gentisic acid, catechin, chlorogenic acid, caffeic acid, and syringic acid were increased by 116, 33.2, 59.6, 50.6, 1.6, and 16.9%, respectively. Our findings suggest the applicability of cinnamon fermentation using S. cerevisiae as a useful tool for processing functional foods to increase their antioxidant and anti-inflammatory content. © 2023. The Author(s). Conflict of

The aim of this study was to prepare Cinnamomum cassia essential oil (CEO) impregnated chitosan nanoparticles (CS-CEO) and assess its pharmacological activity against breast cancer. Cinnamon oil-loaded chitosan nanoparticles were investigated for their physicochemical properties, stability, and anti-cancer activities both in vitro and in vivo. The prepared CS-CEO nanoparticles have a particle size, zeta-potential, entrapment efficiency and drug loading of (215.40 ± 3.90) nm, (51.70 ± 1.90) mV, (83.37 ± 0.4)% and (26.42 ± 0.65)%, respectively. CS-CEO showed a regular, uniform, and spherical or quasi-spherical structure under a transmission electron microscope. CS-CEO remained stable upon storage at 4 °C. CS-CEO exhibited enhanced in vitro antitumor activity (52 μg/mL) compared to CEO. The mechanism might be related to the up-regulation of Caspase-3 and AIF protein expression. In in vivo experiments, CS-CEO suppressed the growth of 4T1 breast cancer cells transplanted into mice, inhibited tumor cell proliferation, and induced apoptosis by reducing the expression of the Ki-67 protein. These results indicated that CEO encapsulated in chitosan had a higher physical stability and was also more effective against 4T1 breast tumor model, which can be used as a reference for the application of volatile oil components in traditional Chinese medicine.

Coumarins are found in higher plants like Rutaceae and Umbelliferae and essential oils of cinnamon bark, cassia leaf, and lavender oil. Coumarin compounds show different biological properties, viz antimicrobial, antibacterial, antifungal, antioxidant, antitumor, anti-HIV, antihypertension, anticoagulant, anticancer, antiviral, anti-inflammatory, analgesics, antidiabetic, anti-depressive, and other bioactive properties. Coumarin and its derivatives possess anticancer activity against different types of cancers such as prostate, renal, breast, laryngeal, lung, colon, CNS, leukemia, malignant melanoma. In this review, current developments of coumarin-based anticancer agents viz simple coumarin, furanocoumarin, pyranocoumarin, pyrone-substituted coumarin, and their important derivatives have been discussed. The coumarin-triazole, coumarin-chalcone, coumarin-thiosemicarbazone derivatives, and coumarin-metal complexes have been found more potent than coumarin. Hence, further study and structural improvement on coumarin and its derivatives may lead to the design and development of more potent anticancer agents.

Background: Breast cancer has become one of the most common malignant tumors in women owing to its increasing incidence each year. Clinical studies have shown that Cinnamomum cassia (L.) J. Presl (cinnamon) has a positive influence on the prevention and treatment of breast cancer. Aim: We aimed to screen the potential targets of cinnamon in the treatment of breast cancer through network pharmacology and explore its potential therapeutic mechanism through cell experiments. Methods: We used the TCMSP, TCM Database @ Taiwan, and TCMID websites and established the active ingredient and target database of cinnamon. Thereafter, we used the GeneCards and OMIM databases to establish a breast cancer-related target database, which matched the cinnamon target database. Based on the matching results, the STRING database was used to analyze the interaction between the targets, and the biological information annotation database was used to analyze the biological process of the target (gene ontology) and the pathway enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). After establishing the layout of the analysis, we used Cytoscape 3.6.0 software for network analysis. Finally, the cell experiment was used to verify the anti-breast cancer effect of cinnamaldehyde. Results: Our research showed that the main components of cinnamon, including cinnamaldehyde, can play a role in the treatment of breast cancer through 59 possible important targets. Subsequently, enric

BACKGROUND: Cinnamomum cassia (C. cassia) is an evergreen tree in China and Southern and Eastern Asia. In traditional medicine, cinnamon is widely used due to its many bioactivity effects. OBJECTIVE: The present novel study aims to evaluate and make a comparison of antioxidant and antiproliferative activities of different extractions of C. cassia bark using seven solvents having different polarities. Solvents polarity gradients start with the solvent of lower polarity, n-hexane, and end with water as the highest polar solvent. Among the extracts, acetone extract contains the highest phenolic and flavonoid contents; therefore, it is assessed for the ability to protect DNA from damage. METHODS: The extracts are evaluated for total phenolic, flavonoid contents and antioxidant activities, using FRAP, DPPH, superoxide, and hydroxyl and nitric oxide radicals scavenging assays. DNA damage protecting activity of the acetone extract is studied with the comet assay. Each of the extracts is studied for its antiproliferative effect against, MCF-7, MDA-MB-231(breast cancer), and HT29 (colon cancer), using MTT assay. RESULTS: The acetone extract exhibited the highest FRAP value, phenolic and flavonoids contents when compared to the other extracts and could protect 45% mouse fibroblast cell line (3T3-L1) from DNA damage at 30 μg/ml. The lowest IC50 value in DPPH, superoxide, and hydroxyl radicals scavenging was noticed in the ethyl acetate extract. IC50 value obtained for the hexane extract was the lowest compared to the other extracts in scavenging nitric oxide radicals. The hexane extract showed the highest antiproliferative effect against cancer cells

Coumarins are the secondary metabolites of some plants, fungi, and bacteria. Coumarins and the hybrid molecules of coumarins are the compounds which have been widely studied for their potential anticancer effects. They belong to benzopyrone chemical class, more precisely benzo-α-pyrones, where benzene ring is fused to pyrone ring. In nature, coumarins are found in higher plants like Rutaceae and Umbelliferae and some essential oils like cinnamon bark oil, cassia leaf oil and lavender oil are also rich in coumarins. The six main classes of coumarins are furanocoumarins, dihydrofuranocoumarins, pyrano coumarins, pyrone substituted coumarins, phenylcoumarins and bicoumarins. As well as their wide range of biological activities, coumarins and the hybrid molecules of coumarins are proven to have an important role in anticancer drug development due to the fact that many of its derivatives have shown an anticancer activity on various cell lines. Osthol, imperatorin, esculetin, scopoletin, umbelliprenin, angelicine, bergamottin, limettin, metoxhalen, aurapten and isopimpinellin are some of these coumarins. This review summarizes the anticancer effects of coumarins and their hybrid molecules including the novel pharmaceutical formulations adding further information on the topic for the last ten years and basically focusing on the

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, third in the series, considers NFCs composed primarily of constituents with the 3-phenyl-2-propenyl or a cinnamyl functional group, using the procedure outlined in 2005 and updated in 2018 to evaluate the safety of naturally-occurring mixtures for their intended use as flavor ingredients. The procedure reli

Tumor hypoxia is positively correlated with tumor aggressiveness and hence is a negative prognostic factor in cancer. As normal cells usually do not experience such low oxygen levels, hypoxic cell signaling has attracted significant attention for the development of tumor-selective treatment strategies. In response to hypoxia, the master transcriptional regulator, HIF-1α plays central role in cellular adaptation by transactivating several crucial downstream target genes, which are involved in angiogenesis, metastasis, and EMT. In this study, we investigated the effect of cinnamaldehyde (CA), the main active ingredient of Cinnamon cassia bark extract, on hypoxia-induced angiogenesis and metastasis. The study in vitro comprised two cell lines, viz, sarcoma 180 and B16F10 melanoma, which were further confirmed in their respective transplantable in vivo models. Results show that CA administration inhibited tumor angiogenesis, EMT, and metastasis. At the molecular level, this was accompanied by a reduction in VEGF secretion, VEGF receptor (FLK) phosphorylation, matrix metalloproteinase (MMP) expression, and activity as well as a reduction in the EMT-related factors TWIST and ZEB1. Next, we focused our study particularly on the modulation of HIF-1 α by CA, which revealed that CA decreased HIF-1 α protein level by inhibiting its synthesis without affecting its proteasomal degradation. Furthermore, the PI3/Akt/mTOR pathway, which plays an important role in HIF-1α transcription and translation, was also inhibited by CA both in vitro and in vivo. Thus, it can be concluded that CA decreased angiogenesis and metastasis in tumor cells by inhibiting HIF-1α protein accumulation probably by targeting the PI3/Akt/mTOR pathway. © 2019 BioFactors, 45(3

BACKGROUND: Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can

Cinnamon (Cinnamomum cassia) is an important spice which is widely consumed in the Indian subcontinent as well as in several other parts of the world. In the present study, NMR spectroscopy showed the presence of cinnamaldehyde to be the major component of the bark. The possible mutagenic effects of cinnamon bark ethanolic extract (CEE, 0.01-1 mg/plate) cinnamon oil (CNO, 0.125-1 mg/plate), and its active component cinnamadehyde (CLD, 0.125-1 mg/plate) were evaluated. Antimutagenic activity of CEE, CNO, and CLD was also tested against various food borne mutagens (heterocyclic amines and aflatoxin B1 (AFB1)) and sodium azide (SA) using Ames assay. Similarly, the antimicrobial activity was studied using agar well diffusion assay against various pathogens. CEE was non-mutagenic in any of the five tester strains of Salmonella typhimurium (TA97a, TA98, TA100, TA102, and TA104) in Ames test. CEE exhibited antimutagenic activity against all the mutagens tested in the higher doses. Additionally, CEE, CNO, and CLD were effective against various pathogens such as Staphylococcus aureus, Proteus vulgaris, S. typhimurium, Klebsiella pneumoniae, and Escherichia coli in the agar well diffusion assay. Promising antimutagenic and antimicrobial properties were shown by the cinnamon bark ethanolic extract and cinnamaldehyde, respectively. Therefore, their role in cancer chemoprevention, as well as a natural antimicrobial agent must be exploited and studied in depth in in vivo conditions.

BACKGROUND: The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. OBJECTIVE: In the present work, we have evaluated the potential of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. MATERIALS AND METHODS: HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well-known anti-cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. RESULTS: Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of

Herbs and spices have been used for food and medicinal purposes for centuries - the first recorded evidence of their use dates back to 1500BC and the Ebers Papyrus, which mentioned spices such as anise, mustard, saffron, cinnamon, and cassia. Now, in the 21st century, a variety of secondary compounds produced by plants are used in many fields of industry, such as food production (to improve taste, to provide vitamins and macro- and microelements, and also to inhibit food spoilage caused by foodborne bacteria), in medicine (in the treatment of various diseases; in chemoprevention and cancer therapy; as a source of natural antimicrobials for the treatment of infectious disease), and in pharmacology and cosmetology (in dietary supplements, and as a result of the demand for preservative-free cosmetics, to reduce the risk of methylparaben allergies). The aim of this review is to present the major active compounds in herbs and spices and explore their potential applications in industry.

Cinnamon (Cinnamomum zeylanicum and Cinnamon cassia), the eternal tree of tropical medicine, belongs to the Lauraceae family and is one of the most important spices used daily by people all over the world. It contains a lot of manganese, iron, dietary fiber, and calcium. Cinnamon contains derivatives, such as cinnamaldehyde, cinnamic acid, cinnamate, and numerous other components such as polyphenols and antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer effects. Several reports have dealt with the numerous properties of cinnamon in the forms of bark, essential oils, bark powder, and phenolic compounds, and each of these properties can play a key role in human health. Recently, many trials have explored the beneficial effects of cinnamon in Alzheimer's disease, diabetes, arthritis, and arteriosclerosis, but still we need further investigations to provide additional clinical evidence for this spice against cancer and inflammatory, cardioprotective, and neurological disorders.

AIM: Cis-diammine dichloroplatinum (CDDP) is one of the most important chemotherapeutic agents for cancer treatment. Nonetheless, its notable side effect, nephrotoxicity, undermines its clinical use. The current study was undertaken to evaluate the protective potential of the aqueous extract (AEC) of Cinnamomum cassia (cinnamon) against the cytotoxic effect of CDDP in vitro and to elaborate the molecular mechanism underlying protection. METHODS: MTT assay was performed to assess viability of the normal kidney Vero cells treated with CDDP and/or AEC. Cells were stained with Coomassie blue, acridine orange and ethidium bromide to highlight morphological features of apoptosis. Caspase-3 activity, DNA fragmentation and reactive oxygen species (ROS) level were monitored to assess biochemical hallmarks of apoptosis. Quantitative RT-PCR and Western blot analyses were performed to elucidate expression of cellular molecules underlying the protective potential of AEC. RESULTS: CDDP-treated Vero cells exhibited hallmarks of apoptosis; these hallmarks were significantly suppressed in the presence of AEC. AEC did not alter activity of CDDP-induced cytotoxicity of breast and liver cancer cells. AEC treatment of Vero cells prevented CDDP-induced increased expression of mitochondrial Bax protein, release of mitochondrial cytochrome c, caspase-3 activation, DNA fragmentation and generation of ROS. AEC up-regulated expression of the cytoprotective gene (heme o

INTRODUCTION: The islandwide comprehensive supplementary feeding scheme, the 'Thriposha' programme has been in existence in the country for over three decades. However, its effectiveness in improving micronutrient status has not yet been evaluated. OBJECTIVE: We examined the effects of 'Thriposha' on micronutrient status, assessed haematologically and biochemically, in young children. METHODS: Preschool children (aged 3-5 years) from two well-baby clinics were grouped into interventional (n = 137) arm and control (n = 130) arm. Children in the interventional group were fed 'Thriposha' (50 g/day) while the control group of children was fed with 50 g 'Thriposha' made without mineral and vitamin premix, for a period of nine months. Serum calcium, ferritin, folate, freeT4, ceruloplasmin, zinc, vitamin A, vitamin D and haemoglobin (Hb) levels were measured before and one week after completing intervention. RESULTS: The baseline Hb levels of the intervention and control groups were 113.20 (SD10.9) g/l and 112.30 (SD 9.0) g/l respectively. After the intervention, the interventional group showed a significant improvement (repeated measures ANOVA, p = 0.02) in the Hb (mean of 118.10 (7.7) vs. 114.70 (7.0) g/l of the control). The prevalence of anaemia dropped from 37% to 15% in the intervention group (p = 0.03). Serum ferritin and ceruloplasmin levels also improved. CONCLUSION: Regular consumption of conventional 'Thriposha' for 9 months led to improvements in Hb, ferritin and ceruloplasmin levels in the blood.

Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research suggests that pharmacological intervention using dietary factors that activate the redox sensitive Nrf2/Keap1-ARE signaling pathway may represent a promising strategy for chemoprevention of human cancer including CRC. In our search for dietary Nrf2 activators with potential chemopreventive activity targeting CRC, we have focused our studies on trans-cinnamic aldehyde (cinnamaldeyde, CA), the key flavor compound in cinnamon essential oil. Here we demonstrate that CA and an ethanolic extract (CE) prepared from Cinnamomum cassia bark, standardized for CA content by GC-MS analysis, display equipotent activity as inducers of Nrf2 transcriptional activity. In human colon cancer cells (HCT116, HT29) and non-immortalized primary fetal colon cells (FHC), CA- and CE-treatment upregulated cellular protein levels of Nrf2 and established Nrf2 targets involved in the antioxidant response including heme oxygenase 1 (HO-1) and gamma-glutamyl-cysteine synthetase (gamma-GCS, catalytic subunit). CA- and CE-pretreatment strongly upregulated cellular glutathione levels and protected HCT116 cells against hydrogen peroxide-induced genotoxicity and arsenic-induced oxidative insult. Taken together our data demonstrate that the cinnamon-derived food factor CA is a potent activator of the Nrf2-orchestrated antioxidant response in cultured human epithelial colon cells. CA may therefore represent an underappreciated chemopreventive dietary factor targeting colorectal carcinogenesis.

BACKGROUND: Cinnamomum cassia bark is the outer skin of an evergreen tall tree belonging to the family Lauraceae containing several active components such as essential oils (cinnamic aldehyde and cinnamyl aldehyde), tannin, mucus and carbohydrate. They have various biological functions including anti-oxidant, anti-microbial, anti-inflammation, anti-diabetic and anti-tumor activity. Previously, we have reported that anti-cancer effect of cinnamon extracts is associated with modulation of angiogenesis and effector function of CD8+ T cells. In this study, we further identified that anti-tumor effect of cinnamon extracts is also link with enhanced pro-apoptotic activity by inhibiting the activities NFkappaB and AP1 in mouse melanoma model. METHODS: Water soluble cinnamon extract was obtained and quality of cinnamon extract was evaluated by HPLC (High Performance Liquid Chromatography) analysis. In this study, we tested anti-tumor activity and elucidated action mechanism of cinnamon extract using various types of tumor cell lines including lymphoma, melanoma, cervix cancer and colorectal cancer in vitro and in vivo mouse melanoma model. RESULTS: Cinnamon extract strongly inhibited tumor cell proliferation in vitro and induced active cell death of tumor cells by up-regulating pro-apoptotic molecules while inhibiting NFkappaB and AP1 activity and their target genes such as Bcl-2, BcL-xL and survivin. Oral administration of cinnamon extract in melanoma transplantation model significantly inhibited tumor growth with the same mechanism of action observed in vitro. CONCLUSION: Our study suggests that anti-tumor effect of cinnamon extracts is

BACKGROUND: Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. METHODS: The aqueous cinnamon extract (ACE-c) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Deltapsim) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. RESULTS: Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingl

Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.