The Potential of Cinnamon Extract (Cinnamomum burmanii) as Anti-insomnia Medication through Hypothalamus Pituitary Adrenal Axis Improvement in Rats.

OBJECTIVE: This study aimed to explore the efficacy of cinnamon extract as an anti-insomnia medication in experimental animals by evaluating the levels of hormones and neurotransmitters related to insomnia. MATERIALS AND METHODS: A total of 30 male Wistar rats were divided into six groups. Induction of insomnia in animal models was done by administration of p-chloro-phenylalanine (PCPA) compounds. Estazolam was administrated to the positive control group. Cinnamon extract administration was divided into 3 doses, namely: 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW. Evaluation of the organ coefficient was conducted to evaluate drug toxicity to the organs. The enzyme-linked-immunoassay method assessed hormones and neurotransmitters in the serum and hypothalamus related to insomnia. RESULTS: There was a decrease in the adrenal coefficient in the cinnamon extract group compared to the PCPA group (0.011+0.001, P<0.05). In addition, there was a decrease in the corticotropin-releasing hormone, adrenocorticotropin hormone, and corticosterone levels in the serum of animals who received cinnamon extract. Our study found a dose of cinnamon extract of 50 mg/kg BW was the best dose to balance neurotransmitter levels in insomniac rats. CONCLUSION: The cinnamon extract increased serotonin and melatonin levels and decreased norepinephrine levels in the insomnia-induced group. Cinnamon extract has potential as an anti-insomnia medication through hypothalamus-pituitaryadrenal axis improvement and brain neurotransmitter regulation in an animal model of insomnia.

Transcriptome and metabolome reveal the accumulation of secondary metabolites in different varieties of Cinnamomum longepaniculatum.

BACKGROUND: Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li, whose leaves produce essential oils, is a traditional Chinese medicine and economically important tree species. In our study, two C. longepaniculatum varieties that have significantly different essential oil contents and leaf phenotypes were selected as the materials to investigate secondary metabolism. RESULT: The essential oil content and leaf phenotypes were different between the two varieties. When the results of both transcriptome and metabolomic analyses were combined, it was found that the differences were related to phenylalanine metabolic pathways, particularly the metabolism of flavonoids and terpenoids. The transcriptome results based on KEGG pathway enrichment analysis showed that pathways involving phenylpropanoids, tryptophan biosynthesis and terpenoids significantly differed between the two varieties; 11 DEGs (2 upregulated and 9 downregulated) were associated with the biosynthesis of other secondary metabolites, and 12 DEGs (2 upregulated and 10 downregulated) were related to the metabolism of terpenoids and polyketides. Through further analysis of the leaves, we detected 196 metabolites in C. longepaniculatum. The abundance of 49 (26 downregulated and 23 upregulated) metabolites differed between the two varieties, which is likely related to the differences in the accumulation of these metabolites. We identified 12 flavonoids, 8 terpenoids and 8 alkaloids and identified 4 kinds of PMFs from the leaves of C. longepaniculatum. CONCLUSIONS: The combined results of transcriptome and metabolomic analyses revealed a strong correlation between metabolite contents and gene expression. We speculate that light leads to differences in the secondary metabolism and phenotypes of leaves of different varieties of C. longepaniculatum. This research provides data for secondary metabolite studies and lays a solid foundation for breeding ideal C. longepaniculatum plants.

Transcriptome analysis of Cinnamomum migao seed germination in medicinal plants of Southwest China.

BACKGROUND: Cinnamomum migao is an endangered evergreen woody plant species endemic to China. Its fruit is used as a traditional medicine by the Miao nationality of China and has a high commercial value. However, its seed germination rate is extremely low under natural and artificial conditions. As the foundation of plant propagation, seed germination involves a series of physiological, cellular, and molecular changes; however, the molecular events and systematic changes occurring during C. migao seed germination remain unclear. RESULTS: In this study, combined with the changes in physiological indexes and transcription levels, we revealed the regulation characteristics of cell structures, storage substances, and antioxidant capacity during seed germination. Electron microscopy analysis revealed that abundant smooth and full oil bodies were present in the cotyledons of the seeds. With seed germination, oil bodies and other substances gradually degraded to supply energy; this was consistent with the content of storage substances. In parallel to electron microscopy and physiological analyses, transcriptome analysis showed that 80-90 % of differentially expressed genes (DEGs) appeared after seed imbibition, reflecting important development and physiological changes. The unigenes involved in material metabolism (glycerolipid metabolism, fatty acid degradation, and starch and sucrose metabolism) and energy supply pathways (pentose phosphate pathway, glycolysis pathway, pyruvate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation) were differentially expressed in the four germination stages. Among these DEGs, a small number of genes in the energy supply pathway at the initial stage of germination maintained high level of expression to maintain seed vigor and germination ability. Genes involved in lipid metabolism were firstly activated at a large scale in the LK (seed coat fissure) stage, and then genes involved in carbohydrates (CHO) metabolism were activated, which had their own species specificity. CONCLUSIONS: Our study revealed the transcriptional levels of genes and the sequence of their corresponding metabolic pathways during seed germination. The changes in cell structure and physiological indexes also confirmed these events. Our findings provide a foundation for determining the molecular mechanisms underlying seed germination.

A polyphenolic cinnamon fraction exhibits anti-inflammatory properties in a monocyte/macrophage model.

Periodontal diseases are bacteria-induced inflammatory disorders that lead to the destruction of the tooth-supporting tissues. Active compounds endowed with a capacity to regulate the inflammatory response are regarded as potential therapeutic agents for the treatment of periodontal diseases. The aim of this study was to characterize the anti-inflammatory properties of a polyphenolic cinnamon fraction. Chromatographic and mass spectrometry analyses of the polyphenolic composition of the cinnamon fraction revealed that phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins make up 9.22%, 0.72%, and 10.63% of the cinnamon fraction, respectively. We used a macrophage model stimulated with lipopolysaccharides (LPS) from either Aggregatibacter actinomycetemcomitans or Escherichia coli to show that the cinnamon fraction dose-dependently reduced IL-6, IL-8, and TNF-α secretion. Evidence was brought that this inhibition of cytokine secretion may result from the ability of the fraction to prevent LPS-induced NF-κB activation. We also showed that the cinnamon fraction reduces LPS binding to monocytes, which may contribute to its anti-inflammatory properties. Lastly, using a competitor assay, it was found that the cinnamon fraction may represent a natural PPAR-γ ligand. Within the limitations of this in vitro study, the cinnamon fraction was shown to exhibit a therapeutic potential for the treatment of periodontal diseases due to its anti-inflammatory properties.

The in vitro and in vivo anti-virulence activities of Cinnamomum bejolghota by inhibiting type three secretion system effector proteins of Salmonella.

The bark of Cinnamomum bejolghota (Buch.-Ham.) Sweet (C. bejolghota) is widely used as medicine to treat bacterial diarrhea in Myanmar. We previously reported that the bark extract of C. bejolghota significantly inhibited secretion effector proteins of the type three secretion system (T3SS) in Salmonella. This study is designed to investigate the anti-virulence potential of the C. bejolghota bark extract against Salmonella Typhimuriumin in in vivo and in vitro experiments. The results suggested that the polar fraction Fr.M1 inhibited the secretion of effector proteins SipA, SipB, SipC and SipD without affecting bacteria growth and the translocation of SipC into MDA-MB-231 cells. In addition, Fr.M1 alleviated inflammatory symptoms of mice in Salmonella-infected mouse model. Overall, the results provide evidence for medicinal usage of C. bejolghota bark to treat diarrhea in Myanmar.

Antichemotactic and Antifungal Action of the Essential Oils from Cryptocarya aschersoniana, Schinus terebinthifolia, and Cinnamomum amoenum.

The purpose of this work was to determine the chemical composition and evaluate the antichemotactic, antioxidant, and antifungal activities of the essential oil obtained from the species Cryptocarya aschersoniana Mez, Cinnamomum amoenum (Ness & Mart.) Kosterm., and Schinus terebinthifolia Raddi, as well as the combination of C. aschersoniana essential oil and terbinafine against isolates of dermatophytes. Allo-aromadendrene, bicyclogermacrene, and germacrene B were identified as major compounds in essential oils. The essential oil of C. aschersoniana shown 100 % inhibitory effect on leukocyte migration at the concentration of 10 µg/mL while S. terebinthifolia oil presented 80.1 % inhibitory effect at the same concentration. Only S. terebinthifolia oil possessed free-radical-scavenging activity which indicates its antioxidant capacity. The essential oils were also tested against fungal isolates of dermatophyte species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum), resulting in MIC ranging from 125 µg/mL to over 500 µg/mL. C. aschersoniana oil combined with terbinafine resulted in an additive interaction effect. In this case, the essential oil may act as a complement to conventional therapy for the topical treatment of superficial fungal infections, mainly because it is associated with an anti-inflammatory effect.

Identification of novel Nrf2 activators from Cinnamomum chartophyllum H.W. Li and their potential application of preventing oxidative insults in human lung epithelial cells.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, ß-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3', 4, 4'-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 protein-protein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue.

Antileukemic activity of lignans and phenylpropanoids of Cinnamomum parthenoxylon.

In this study, we evaluated the in vitro cytotoxicity of fractions and isolated constituents from Cinnamomum parthenoxylon woods against human leukemia HL-60 and U937 cells. The n-Hex, EtOAc, and MeOH-H2O fractions of the woods inhibited cell proliferation in both cell lines. Our phytochemical investigation of the n-Hex and EtOAc fractions led to the isolation of lignans and phenylpropanoids, whose chemical structures were confirmed by spectroscopic analyses. All isolated compounds were evaluated for their in vitro antileukemic activity; especially, hinokinin and cubebin exhibited strong inhibition toward U937 cell proliferation. Morphological observation indicated that these cytotoxic actions were mediated by apoptosis. Our findings suggested that an oxygenated functional group at the C-9 position in dibenzylfuran skeleton contributed their potency. In addition, these results enhanced the ethnopharmacological value of C. parthenoxylon.

Direct analysis in real time by mass spectrometric technique for determining the variation in metabolite profiles of Cinnamomum tamala Nees and Eberm genotypes.

Cinnamomum tamala Nees & Eberm. is an important traditional medicinal plant, mentioned in various ancient literatures such as Ayurveda. Several of its medicinal properties have recently been proved. To characterize diversity in terms of metabolite profiles of Cinnamomum tamala Nees and Eberm genotypes, a newly emerging mass spectral ionization technique direct time in real time (DART) is very helpful. The DART ion source has been used to analyze an extremely wide range of phytochemicals present in leaves of Cinnamomum tamala. Ten genotypes were assessed for the presence of different phytochemicals. Phytochemical analysis showed the presence of mainly terpenes and phenols. These constituents vary in the different genotypes of Cinnamomum tamala. Principal component analysis has also been employed to analyze the DART data of these Cinnamomum genotypes. The result shows that the genotype of Cinnamomum tamala could be differentiated using DART MS data. The active components present in Cinnamomum tamala may be contributing significantly to high amount of antioxidant property of leaves and, in turn, conditional effects for diabetic patients.

Insecticidal activities of leaf essential oils from Cinnamomum osmophloeum against three mosquito species.

The larvicidal activities of leaf essential oils and their constituents from six chemotypes of indigenous cinnamon (Cinnamomum osmophloeum Kaneh.) trees were evaluated against three mosquito species. Results of larvicidal tests demonstrated that the leaf essential oils of cinnamaldehyde type and cinnamaldehyde/cinnamyl acetate type had an excellent inhibitory effect against Aedes albopictus larvae, and their LC(50) values in 24h were 40.8 microg/ml (LC(90)=81.7 microg/ml) and 46.5 microg/ml (LC(90)=83.3 microg/ml), respectively. Results of the 24-h mosquito larvicidal assays also showed that the effective constituents in leaf essential oils were trans-cinnamaldehyde and benzaldehyde and that the LC(50) values of these constituents against A. albopictus larvae were below 50 mug/ml. In addition, cinnamaldehyde type leaf essential oil and trans-cinnamaldehyde have also exhibited great larvicidal performance against Culex quinquefasciatus and Armigeres subalbatus larvae. Comparisons of mosquito larvicidal activity of trans-cinnamaldehyde congeners revealed that alpha-methyl cinnamaldehyde, benzaldehyde, and trans-cinnamaldehyde exhibited strong mosquito larvicidal activity.

Antioxidant activities of ethanolic extracts from the twigs of Cinnamomum osmophloeum.

Cinnamomum osmophloeum Kaneh. is an indigenous tree species in Taiwan. In this study, phytochemical characteristics and antioxidant activities of ethanolic extracts from the twigs of C. osmophloeum were investigated for the first time. The extracts were obtained successively using liquid-liquid partition to yield n-hexane (Hex), ethyl acetate (EtOAc), n-butanol (BuOH) and water fractions. The antioxidant activities of C. osmophloeum twig extracts were examined using various antioxidant assays, such as DPPH, NBT, reducing power, lipid peroxidation using mouse brain homogenates, metal chelating ability, and photochemiluminescence (PCL). In addition, total phenolic contents were also determined. Results revealed that the BuOH fraction exhibited the best performance in DPPH assay, NBT assay, reducing power assay and lipid peroxidation using mouse brain homogenates assay. Furthermore, the BuOH fraction has the highest total phenolic contents (496.7 mg of GAE/g). Consequently, kaempferol-7-O-rhamnoside was also isolated from the antioxidative BuOH fraction and its activity was also confirmed. These results demonstrated that ethanolic extracts of C. osmophloeum twigs have excellent antioxidant activities and thus it has great potential as a source for natural health products.

Microwave-assisted isolation of essential oil of Cinnamomum iners Reinw. ex Bl.: comparison with conventional hydrodistillation.

Microwave-assisted hydrodistillation was used to isolate an essential oil from the leaves of Cinnamomum iners Reinw. ex Bl., and the results compared with those obtained by conventional hydrodistillation. The composition of the oil from both methods was found to be similar, and (-)-linalool was found as the main component (30-50%). The antioxidant activity of the essential oil obtained by both methods was evaluated using DPPH, ABTS, FRAP and lipid peroxidation methods, all of which indicated the same but insignificant activity.