Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

A Systematic Review Evaluating Cinnamon's Effects on Glucose Utilizing a Ranking System to Assess Bias and Study Quality.

In the context of diabetes, the use of cinnamon continues to be among the most popular supplements taken by patients for glucose control. To strategically evaluate the available literature comparing various cinnamon species and statistically significant glucose effects after ranking studies based on two tools to assess bias and overall study quality, to clarify cinnamon's role in glucose control. The authors performed a systematic search based upon PRISMA guidelines. The search was conducted utilizing PubMed, AMED, CINAHL, EMBASE, Cochrane, and Medline databases, with the final search performed in September 2022 with restrictions to human subjects and English language. Electronic searches were conducted utilizing the keywords "diabetes mellitus" combined with Cinnamomum zeylanicum/Cinnamomum cassia/Cinnamomum verum combined with blood glucose (BG). A second search utilized "cinnamomum zeylanicum/cinnamomum cassia/cinnamomum verum" combined with "blood glucose," and a final search utilized "diabetes mellitus" combined with "cinnamon." Data extraction and ranking of included studies utilizing the risk of bias 2 tool and modified Heyland Methodological Quality Scoring tool were performed independently by two review authors. These authors compared their results and reconciled any differences in scoring to generate a final ranking of studies. A third author was available for any discrepancies that could not be resolved but was not needed. Forty-five studies were included in the review and were scored for bias and quality. Overall 62% demonstrated statistical significance for positive effects in at least one parameter around BG control. Applying the ranking systems reduced the percentage closer to 50%. Safety was extremely well documented across studies with few adverse effects. Results are limited by heterogeneity of glucose parameters, leading to studies being ranked individually and not synthesized. Cinnamon supplementation likely has a modest positive effect on BG. Based upon the strong safety profile, utilization of this spice as an adjunct to pharmacologic therapy is reasonable.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

Bioactive Piperazic Acid-Bearing Cyclodepsipeptides, Lydiamycins E-H, from an Endophytic Streptomyces sp. Associated with Cinnamomum cassia.

A chemical investigation of the endophytic Streptomyces sp. HBQ95, associated with the medicinal plant Cinnamomum cassia Presl, enabled the discovery of four new piperazic acid-bearing cyclodepsipeptides, lydiamycins E-H (1-4), and one known compound (lydiamycin A). Their chemical structures, including absolute configurations, were defined by a combination of spectroscopic analyses and multiple chemical manipulations. Lydiamycins F-H (2-4) and A (5) exhibited antimetastatic activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

Chemical profiling and identification of anti-osteoporosis chemical-markers of Cinnamomum cassia (L.) presl extracts using GC-MS and spectrum-activity analyses.

Cinnamomum cassia (L.) Presl (cinnamon), an important folk medicine is widely used to prevent osteoporosis for long time in China. Our study aimed to investigate the anti-osteoporosis activity and mechanisms of cinnamon extracts obtained by supercritical CO2 extraction (SFE) and identify activity associated chemical components by gas chromatography-mass spectrometry. The cinnamon SFE exhibited superior anti-osteoporosis efficacy in an ovariectomised mice model to common alcohol extracts. It could induce calcified nodules and ALP activity, upregulate the mRNA expression of ALP, BMP-2, and RUNX2 in MC3T3-E1 cells. The major chemical classes of cinnamon extracts were alcohol esters (28.2%), and terpenes (16.1%). The spectrum-activity analysis indicated that the potential chemical-markers of extracts could be (E)-Cinnamaldehyde, γ-Sitosterol, and (Z, Z)-9,12-Octadecadienoic acid, which could induce the proliferation and ALP activity in MC3T3-E1 cells. Our study revealed the promising applications of the cinnamon SFE in prevention of osteoporosis, and identified its anti-osteoporosis associated compounds.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Molecular Mechanism of Cinnamomum cassia against Gastric Damage and Identification of Active Compounds.

Cinnamomum cassia is a natural product found in plants that has been used as a folk remedy for inflammation. In this study, we investigated the mechanism underlying the anti-inflammatory and antioxidant properties of C. cassia extract (ECC) in lipopolysaccharide (LPS)-induced murine RAW 264.7 cells, in comparison with 4-hydroxycinnamaldehyde, a C. cassia extract component. ECC and 4-hydroxycinnamaldehyde inhibited the production of nitrite oxide in a dose-dependent manner and did not show any change in cellular toxicity when treated with the same dose as that used in the nitrite assay. Moreover, they attenuated ROS accumulation after lipopolysaccharide (LPS) stimulation. ECC and 4-hydroxycinnamaldehyde decreased the mRNA and protein expression levels of inflammatory mediators (iNOS and COX-2) and cytokines such as TNF and IL-6. We also found that ECC and 4-hydroxycinnamaldehyde mitigated the phosphorylation of ERK, JNK, and transcription factors, such as NF-κB and STAT3, suppressing NF-κB nuclear translocation in LPS-activated macrophages. In addition, administration of ECC in a Sprague Dawley rat model of acute gastric injury caused by indomethacin significantly increased the gastric mucus volume. Analysis of serum and tissue levels of inflammatory mediators revealed a significant decrease in serum PGE2 and myeloperoxidase levels and a reduction in gastric iNOS, COX-2, and p65 protein levels. Collectively, these results suggest that ECC has antioxidant and anti-inflammatory effects and is a potential candidate for curing gastritis.

A new megastimane sesquiterpenoid from the leaves of Cinnamomum cassia.

A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2-6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1-6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.

Cinnamomum cassia and Syzygium aromaticum Essential Oils Reduce the Colonization of Salmonella Typhimurium in an In Vivo Infection Model Using Caenorhabditis elegans.

The regulation of intestinal colonization in livestock by means of non-bactericidal additives is an important management lever for zoonotic bacteria such as Salmonella spp. Caenorhabditis elegans is proposed here as a model for the evaluation of five essential oils (EOs) as anti-colonization products against Salmonella Typhimurium. An evaluation of the toxicity of EOs for C. elegans showed LD50 values ranging from 74.5 ± 9.6 µg/mL for Cinnamomum cassia (CEO) to 271.6 ± 14.9 µg/mL for Syzygium aromaticum (SyEO). Both EOs significantly inhibited bacterial colonization in the digestive tract of C. elegans with reductions of 0.88 and 0.70 log CFU/nematode at nontoxic concentrations of 50 µg/mL and 150 µg/mL, respectively. With the minimal bactericidal concentrations of CEO and SyEO against S. Typhimurium being 312.5 µg/mL and 625 µg/mL, respectively, an antibacterial effect can be excluded to explain the inhibition of the bacterial load. The anti-colonizing activity of these two EOs could, however, be related to an inhibition of the swimming motility, which was significantly reduced by 23.47% for CEO at 50 µg/mL and 19.56% for SyEO at 150 µg/mL. This study shows the potential of C. elegans as a predictive in vivo model of anti-colonizing activities that is suitable for the evaluation of essential oils.

The Extracts of Angelica sinensis and Cinnamomum cassia from Oriental Medicinal Foods Regulate Inflammatory and Autophagic Pathways against Neural Injury after Ischemic Stroke.

The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of ischemic stroke. In the study, we investigate the effects and mechanisms of the extracts of Angelica sinensis and Cinnamomum cassia (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral artery occlusion model. Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKKß and IκBα, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-α, IL-1ß, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased. Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function poststroke. Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for ischemic stroke treatment.

Acaricidal activity of Cinnamomum cassia (Chinese cinnamon) against the tick Haemaphysalis longicornis is linked to its content of (E)-cinnamaldehyde.

BACKGROUND: The tick Haemaphysalis longicornis (Neumann) is a well-known vector of numerous pathogens of veterinary and medical importance. Various control strategies, including the use of synthetic pesticides, have been developed to control this tick species. However, demand for effective and safe alternative pesticides is increasing due to the adverse effects associated with the intensive and injudicious use of synthetic pesticides, which include undesirable effects on non-target species and environmental pollution. Hence, the acaricidal activity of the extract and the essential oil of Cinnamomum cassia (Chinese cinnamon) and their major components, and the underlying mechanisms of this activity, were evaluated against unfed larvae and nymphs of H. longicornis. METHODS: The components of the extract and essential oil of C. cassia were determined by gas chromatography-mass spectrometry, and their larvicidal and nymphicidal activity were evaluated using the larval and nymphal packet test. The underlying detoxification mechanism was elucidated by targeting in vivo esterase and monooxygenase activity, and the toxicological effect was assessed on non-target Tenebrio molitor and Harmonia axyridis by topical application in open Petri dishes. RESULTS: (E)-cinnamaldehyde was the predominant component of the extract (50.79%) and essential oil (89.95%). The 50% lethal concentration (LC50) for larvae and nymphs treated with the extract was 11.56 and 49.18 mg/mL, respectively. The essential oil, (E)-cinnamaldehyde and fenvalerate exhibited acaricidal activity, with LC50 values of 3.81, 3.15, and 0.14 mg/mL, respectively, against the larvae, and 21.31, 16.93, and 1.89 mg/mL, respectively, against the nymphs. (E)-cinnamaldehyde significantly increased esterase and monooxygenase activity in both larvae and nymphs. Unlike fenvalerate, C. cassia essential oil and (E)-cinnamaldehyde did not cause mortality of T. molitor or H. axyridis adults. CONCLUSIONS: This study demonstrates that C. cassia essential oil and (E)-cinnamaldehyde have the potential to be developed into botanical-based larvicidal and nymphicidal agents for tick control.

Study on the experimental verification and regulatory mechanism of Rougui-Ganjiang herb-pair for the actions of thermogenesis in brown adipose tissue based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Rougui) has character of xin、gan、wen, belongs to Jing of heart、lung、bladder, and has the effect of dispersing cold and relieving pain. It is widely used to resolve the exterior and dissipate cold in Treatise on Febrile Diseases (Shang Han Lun), such as Chaihu Guizhi Ganjiang Tang and Guizhi Renshen Tang. Both these two prescriptions contain Cinnamomum cassia Presl and Zingiber officinale Rosc (Ganjiang). Rougui-Ganjiang herb-pair (RGHP) can warm viscera and remove cold, which is widely used in Shang Han Lun. And in modern times, recent studies have showed that cinnamon and ginger also have the effect of thermogenesis and regulating the body temperature, respectively. AIM OF THE STUDY: To maintain the body thermal homeostasis and prevent cold invasion of main organs, in this study, we assessed the underlying physiological changes induced by RGHP in mice exposed to -20 °C and explored the mechanisms for the thermogenic actions of RGHP in brown adipose tissue (BAT) by network pharmacology and molecular docking. MATERIALS AND METHODS: Male Kunming (KM) mice were fed normal diet with orally administration of distilled water or ethanol RGHP extract (three doses: 375,750 and 1500 mg/kg) for 21 days, once per day and then exposed to -20 °C for 2 h. The core temperature, activity ability and the degree of frostbite in mice, morphological and ATP content of adipocytes were measured. In addition, the network pharmacology was employed to predict the targets of RGHP' s thermogenesis effect on BAT. Pathway analysis and biological process with key genes was carried out through KEGG and GO analysis, respectively. Furthermore, the core ingredients and targets obtained by network pharmacology were verified by molecular docking and Western blot assays. RESULTS: RGHP can significantly increase the core body temperature, reduce the degree of frostbite and enhance the activity ability of mice after cold exposure. Meanwhile, it can also improve the lipid morphology and decrease ATP production in BAT. A network pharmacology-based analysis identified 246 ingredients from RGHP (two herbs), which related to 222 target genes. There were 8 common genes between 222 compounds target genes and 62 thermogenesis associated target genes, which linked to 49 potential compounds. There are 24 ingredients which degree are greater than the average. Among them, we found that oleic acid, EIC, 6-gingerol, eugenol, isohomogenol and sitogluside could be detected in mice plasma. The cAMP-PPAR signaling pathway was enriched for thermogenesis after KEGG analysis with 8 genes. Molecular docking analysis and Western blot assay further confirmed that oleic acid, 6-gingerol, eugenol and isohomogenol were potential active ingredients for RGHP's heat production effect. And UCP1, PGC-1α, PPARα and PPARγ are key thermogenesis proteins. CONCLUSIONS: RGHP treatment can significantly maintain the rectal temperature of mice by enhancing the BAT heat production. RGHP exhibited the heat production effect, which might be mainly attributed to increasing thermogenesis through the cAMP-PPAR signaling pathway in cold exposure mice. Oleic acid, 6-gingerol, eugenol and isohomogenol might be considered the potential therapeutic ingredients which affect the key targets of thermogenesis effect.

Anti-inflammatory, and anti-arthritic effects by the twigs of Cinnamomum cassia on complete Freund's adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The young branches of C. cassia Blume (Cinnamomi Ramulus; Guizhi; ; C. cassia twigs) have long been used as an anti-pyretic, anti-rheumatic, anti-spasmodic and stomachic in traditional medicine. AIM OF THE STUDY: The aim of this study was to test the anti-inflammatory, anti-nociceptive, and anti-arthritic effects of Cinnamomum cassia twigs in acute and chronic arthritis rats. MATERIALS AND METHODS: Subcutaneous injection of carrageenan for acute inflammation and complete Freund's adjuvant (CFA) for chronic arthritis was carried out in the hind paw of SD rats. The paw volume was measured by a plethysmometer; thermal hyperalgesia was tested using a thermal plantar tester; hyperalgesia was evaluated by ankle flexion evoked vocalizations. The c-Fos expression in the lumbar spinal cord was measured with the avidin-biotin-peroxidase technique. The nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW 264.7 cells was tested by Griess assay. RESULTS AND DISCUSSION: An 80% ethanoic extract of the C. cassia twigs exhibited chronic anti-inflammatory and anti-arthritic activities by reducing the edema volume in the paws of CFA-induced chronic arthritis in rats. In addition, it showed analgesic effects through the recovery of the paw withdrawal latency stimulated by thermal hyperalgesia, and suppressing the vocalization scores evoked by ankle flexion in the hind paws of the arthritis rats. It also controlled c-Fos expression in the lumbar spinal cord of the arthritis rats. Moreover, the addition its 80%-ethanoic extract, specifically, its ethyl acetate fraction, powerfully suppressed the paw swelling in carrageenan-stimulated arthritis and the NO production in LPS-induced murine immune cells. CONCLUSION: C. cassia twigs may act as a viably sufficient therapeutic or preventive candidate for osteoarthritis and rheumatoid arthritis; additionally, it could prevent gastrointestinal damage with its gastric protection.

Interstrains comparison of the antimicrobial effect and mode of action of a Vietnamese Cinnamomum cassia essential oil from leaves and its principal component against Listeria monocytogenes.

The antibacterial activity of a Cinnamomum cassia essential oil (EO) and of its main component trans-cinnamaldehyde (90% w/w) was examined against five Listeria monocytogenes strains. The minimal inhibitory concentrations (MICs) of C. cassia EO against the five L. monocytogenes strains were identical (250 µg ml-1 ), while the minimal bactericidal concentrations (MBCs) ranged between 800 and 1200 µg ml-1 . In order to study if this EO and trans-cinnamaldehyde altered the five strains at the membrane level, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured in presence of different concentrations (1/2MIC, MIC, 2MIC) of these antibacterial agents. A concentration-dependent increase of fluorescence anisotropy of DPH in their presence reflecting a rigidification of the membrane was observed for the five strains. This modification of the membrane fluidity was associated with a perturbation of the selective membrane permeability, as a perturbation of the gradient between intracellular and extracellular pH was also observed.

Microdesigned Nanocellulose-Based Flexible Antibacterial Aerogel Architectures Impregnated with Bioactive Cinnamomum cassia.

This work is strategically premeditated to study the potential of a herbal medicinal product as a natural bioactive ingredient to generate nanocellulose-based antibacterial architectures. In situ fibrillation of purified cellulose was done in cinnamon extract (ciE) to obtain microfibrillated cellulose (MFC). To this MFC suspension, carboxylated cellulose nanocrystals (cCNCs) were homogeneously mixed and the viscous gel thus obtained was freeze-dried to obtain lightweight and flexible composite aerogel architectures impregnated with ciE, namely, ciMFC/cCNCs. At an optimal concentration of 0.3 wt % cCNCs (i.e., for ciMFC/cCNCs_0.3), an improvement of around 106% in compressive strength and 175% increment in modulus were achieved as compared to pristine MFC architecture. The efficient loading and interaction of ciE components, specifically cinnamaldehyde, with MFC and cCNCs resulted in developing competent antibacterial surfaces with dense and uniform microstructures. Excellent and long-term antimicrobial activity of the optimized architectures (ciMFC/cCNCs_0.3) was confirmed through various antibacterial assays like the zone inhibition method, bacterial growth observation at OD600, minimum inhibitory concentration (MIC, here 1 mg/mL), minimum bactericidal concentration (MBC, here 3-5 mg/mL), and Live/Dead BacLight viability tests. The changes in the bacterial morphology with a disrupted membrane were further confirmed through various imaging techniques like confocal laser scanning microscopy, FESEM, AFM, and 3D digital microscopy. The dry composite architecture showed the persuasive capability of suppressing the growth of airborne bacteria, which in combination with antibacterial efficiency in the wet state is considered as an imperative aspect for a material to act as the novel biomaterial. Furthermore, these architectures demonstrated excellent antibacterial performance under real "in use" contamination prone conditions. Hence, this work provides avenues for the application of crude natural extracts in developing novel forms of advanced functional biomaterials that can be used for assorted biological/healthcare applications such as wound care and antimicrobial filtering units.

Network pharmacology-based research uncovers cold resistance and thermogenesis mechanism of Cinnamomum cassia.

BACKGROUND: Cinnamomum cassia (L.) J.Presl (Cinnamon) was known as a kind of hot herb, improved circulation and warmed the body. However, the active components and mechanisms of dispelling cold remain unknown. METHODS: The effects of several Chinses herbs on thermogenesis were evaluated on body temperature and activation of brown adipose tissue. After confirming the effect, the components of cinnamon were identified using HPLC-Q-TOF/MS and screened with databases. The targets of components were obtained with TCMSP, SymMap, Swiss and STITCH databases. Thermogenesis genes were predicted with DisGeNET and GeneCards databases. The protein-protein interaction network was constructed with Cytoscape 3.7.1 software. GO enrichment analysis was accomplished with STRING databases. KEGG pathway analysis was established with Omicshare tools. The top 20 targets for four compounds were obtained according to the number of edges of PPI network. In addition, the network results were verified with experimental research for the effects of extracts and major compounds. RESULTS: Cinnamon extract significantly upregulated the body temperature during cold exposure.121 components were identified in HPLC-Q-TOF/MS. Among them, 60 compounds were included in the databases. 116 targets were obtained for the compounds, and 41 genes were related to thermogenesis. The network results revealed that 27 active ingredients and 39 target genes. Through the KEGG analysis, the top 3 pathways were PPAR signaling pathway, AMPK signaling pathway, thermogenesis pathway. The thermogenic protein PPARγ, UCP1 and PGC1-α was included in the critical targets of four major compounds. The three major compounds increased the lipid consumption and activated the brown adipocyte. They also upregulated the expression of UCP1, PGC1-α and pHSL, especially 2-methoxycinnamaldehyde was confirmed the effect for the first time. Furthermore, cinnamaldehyde and cinnamon extract activated the expression of TRPA1 on DRG cells. CONCLUSION: The mechanisms of cinnamon on cold resistance were investigated with network pharmacology and experiment validation. This work provided research direction to support the traditional applications of thermogenesis.

Cinnamomum cassia extract promotes thermogenesis during exposure to cold via activation of brown adipose tissue.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (L.) J.Presl (Lauraceae), a widely used traditional Chinese medicine, is well known to exert hot property. It is recorded as dispelling cold drug in ancient Chinese monographs, such as Synopsis of golden chamber published in Han dynasty. According to Chinese Pharmacopoeia (2015), Cinnamomum cassia (L.) J.Presl (Cinnamon) has the functions of dispersing cold, relieving pain, warming meridians and promoting blood circulation. AIM OF THE STUDY: The aim of this study is to evaluate the effect of Cinnamon extract (CE) on cold endurance and the mechanism of thermogenesis activity. MATERIALS AND METHODS: The improving effect of hypothermia were evaluated with body temperature by infrared camera and multi-thermo thermometer. In vivo, the thermogenic effect was observed with energy metabolism and substrate utilization. The activation of brown adipose tissue (BAT) was evaluated with the histomorphology and expression of thermogenic protein. In vitro, the uncoupling effect on mitochondrial was evaluated with Seahorse and fluorescent staining. The mechanism of thermogenesis was explored in brown adipocyte. RESULTS: The body temperature and energy expenditure were significantly increased by CE administration in cold environment. In morphology, lipid droplets were reduced and the number of mitochondrial was increased. CE significantly increased the non-shivering thermogenesis via upregulating the expression of thermogenic protein. In vitro, the uncoupling effect was obviously along with the decreased mitochondrial membrane potential and ATP production. It was confirmed that the thermogenesis effect was induced via lipolysis and energy metabolism. In addition, CE also alleviated myocardium injury in the morphology in cold environment. Moreover, the major constituent was identified as (1) coumarin, (2) cinnamic acid, (3) cinnamaldehyde and (4) 2-methoxy cinnamaldehyde. CONCLUSIONS: The mechanism of improving cold tolerance was related to lipolysis and activation of BAT. Meanwhile, we provided a kind of potential prevention methods for cold injury.

Study of Antioxidant, Antiproliferative and DNA Damage Protecting Activities of Cinnamomum cassia Extracts Obtained by Sequential Extraction.

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 followed by the chloroform extract. The ethyl acetate extract inhibited the proliferation of only MCF-7 by IC50 of 100 µg/ml, while the other extracts exhibited no IC50 in all the cancer cells. CONCLUSION: C. cassia showed promising antioxidant and anticancer activities with significant DNA damage protecting effect.

Anti-proliferation and anti-migration effects of an aqueous extract of Cinnamomi ramulus on MH7A rheumatoid arthritis-derived fibroblast-like synoviocytes through induction of apoptosis, cell arrest and suppression of matrix metalloproteinase.

CONTEXT: Cinnamomi ramulus, the dry twig of Cinnamomum cassia Presl. (Lauraceae), has been reported to exert several activities such as antitumor, anti-inflammatory, and analgesic effects. OBJECTIVE: This study investigates the effects of an aqueous extract of Cinnamomi ramulus (ACR) on rheumatoid arthritis (RA). MATERIALS AND METHODS: TNF-α-induced RA-derived fibroblast-like synoviocyte MH7A cells were incubated with ACR (0.1-2 mg/mL) for 24 h. The proliferation was tested using CCK-8 and colony formation assays. The migration and invasion abilities were measured using transwell tests and wound healing assays. Apoptosis and cell cycle were examined by flow cytometry. The potential mechanisms were determined by western blotting and quantitative real-time PCR. UPLC-QE-MS/MS was used for chromatographic analysis of ACR and its compounds were identified. Molecular docking strategy was used to screen the potential anti-RA active compounds of ACR. RESULTS: We found that ACR induced apoptosis in MH7A cells at concentrations of 0.4, 0.8, and 1.2 mg/mL. The proliferation of MH7A cells was reduced and the cell cycle was blocked in the G2/M phase at concentrations of 0.2, 0.4, 0.6 mg/mL. Migration and invasion of MH7A cells were reduced through inhibiting the expression of MMP-1, MMP-2, and MMP-3. The molecular docking strategy results showed that 9 compounds in ACR have good affinity with protein crystal, and benzyl cinnamate (10-100 µg/mL) could inhibit cell migration and induce apoptosis. CONCLUSIONS: The anti-RA effect of ACR may be attributed to its anti-proliferative and anti-migration effects on synovial fibroblasts. These data suggest that Cinnamomi ramulus may have therapeutic value for the treatment of RA.

Insecticidal activity and mechanism of cinnamaldehyde in C. elegans.

Cinnamon is the dried bark of Cinnamomum cassia Presl, and its main component is cinnamaldehyde (CA). Decades of synthetic pesticide use to control parasitic nematodes that can harm plants has seriously polluted the environment and poses a risk to soil ecology, highlighting the need to develop natural biological pesticides. Some species classified under Nematoda are highly similar, therefore we used the model organism C. elegans to explore the effect of cinnamaldehyde, a plant-derived natural product, on C. elegans viability. We found that the lethal dose of cinnamaldehyde for C. elegans treatment for 4 h at a concentration of 800 mg/L. Sequencing-based transcriptome data revealed differences between the cinnamaldehyde treatment and control groups. RNA-seq analysis showed that C. elegans exposed to cinnamaldehyde had significantly altered expression of metabolic genes, particularly for genes involved in glutathione metabolism (gst-1, gst-2, gst-4, gst-5, gst-6, gst-7, gst-8, gst-25, gst-30, gst-38, gst-44, and gcs-1). Therefore, glutathione metabolism is altered in C. elegans upon exposure to cinnamaldehyde. Based on the above results, treatment with 800 mg/L of cinnamaldehyde for 4 h was selected for all experiments in nematodes. Given these findings, cinnamaldehyde may be a promising natural alternative to synthetic pesticides for controlling plant parasitic nematodes with low cost, high efficiency, and diminished environmental pollution.