Regulation of overexpressed efflux pump encoding genes by cinnamon oil and trimethoprim to abolish carbapenem-resistant Acinetobacter baumannii clinical strains.

Resistance mechanisms are a shelter for Acinetobacter baumannii to adapt to our environment which causes difficulty for the infections to be treated and WHO declares this organism on the top of pathogens priority for new drug development. The most common mechanism that develops drug resistance is the overexpression of the efflux pump, especially Resistance-nodulation-cell division (RND) family, to almost most antibiotics. The study is designed to detect RND efflux pump genes in A. baumannii, and its correlation to multidrug resistance, in particular, the carbapenems resistance Acinetobacter baumannii (CRAB), and using different inhibitors that restore the antibiotic susceptibility of imipenem. Clinical A. baumannii isolates were recovered from different Egyptian hospitals in Intensive care unit (ICU). The expression of genes in two strains was analyzed using RT-PCR before and after inhibitor treatment. About 100 clinical A. baumannii isolates were recovered and identified and recorded as MDR strains with 75% strains resistant to imipenem. adeB, adeC, adeK, and adeJ were detected in thirty- seven the carbapenems resistance Acinetobacter baumannii (CRAB) strains. Cinnamomum verum oil, Trimethoprim, and Omeprazole was promising inhibitor against 90% of the carbapenems resistance Acinetobacter baumannii (CRAB) strains with a 2-6-fold decrease in imipenem MIC. Downregulation of four genes was associated with the addition of those inhibitors to imipenem for two the carbapenems resistance Acinetobacter baumannii (CRAB) (ACN15 and ACN99) strains, and the effect was confirmed in 24 h killing kinetics. Our investigation points to the carbapenems resistance Acinetobacter baumannii (CRAB) strain's prevalence in Egyptian hospitals with the idea to revive the imipenem activity using natural and chemical drugs as inhibitors that possessed high synergistic activity.

Proposal of novel ApoE4 inhibitors from the natural spice Cinnamon for the treatment of Alzheimer's disease: Ab initio molecular simulations.

Alzheimer's disease (AD), one of the most common neurodegenerative diseases, is a major factor contributing to cognitive impairment in older adults. Current therapeutic treatments can only relieve the symptoms of AD, but they cannot stop the progression of the disease because it takes a long time for clinical symptoms to manifest. Therefore, it is essential to develop effective diagnostic strategies for early detection and treatment of AD. As the most common genetic risk factor for AD, apolipoprotein E4 (ApoE4) is present in more than half of patients with AD, and it can be a target protein for AD therapy. We used molecular docking, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations to investigate the specific interactions between ApoE4 and Cinnamon-derived compounds. Of the 10 compounds, epicatechin was found to have the highest binding affinity to ApoE4 because the hydroxyl groups of epicatechin form strong hydrogen bonds with the Asp130 and Asp12 residues of ApoE4. Therefore, we proposed some epicatechin derivatives by adding a hydroxyl group to epicatechin and studied their interactions with ApoE4. The FMO results indicate that the addition of a hydroxyl group to epicatechin increases its binding affinity to ApoE4. It is also revealed that the Asp130 and Asp12 residues of ApoE4 are important for the binding between ApoE4 and the epicatechin derivatives. These findings will help propose potent inhibitors against ApoE4, leading to a proposal for effective therapeutic candidates for AD.

Edible coating enriched with cinnamon oil reduces the oxidative stress and improves the quality of strawberry fruit stored at room temperature.

BACKGROUND: The present study aimed to assess the impact of a starch/gelatine coating containing cinnamon oil on selected quality attributes and redox status in strawberry fruit stored at room temperature (72 h). RESULTS: Research showed that the application of cinnamon oil to an edible coating allows an improvement of the quality of strawberry fruit stored at room temperature. The cinnamon oil coating inhibits the development of yeast and mould, and reduces loss of soluble solids and ascorbic acid during 72 h storage at room temperature. Moreover, the coating with cinnamon oil clearly reduced the level of oxidative stress, which was manifested by a lower level of reactive oxygen species, as well as a lower activity of antioxidant enzymes. The elimination of oxidative stress in the cinnamon oil-coated fruit also contributed to lower PARP1 mRNA expression, inhibiting the metabolism of NAD+ and reducing ATP losses. CONCLUSION: The coating of strawberry fruit with a starch/gelatine biofilm containing cinnamon oil is an effective method for delaying postharvest senescence of fruit and the storage degradation of tissue. © 2023 Society of Chemical Industry.

Protective effects of cinnamon on acetylcholinesterase activity and memory dysfunction in diabetic rats.

OBJECTIVES: Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes. METHODS: Forty-seven male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups. RESULTS: Vs. the control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group. CONCLUSIONS: These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury.

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.

Structural interactions of phytoconstituent(s) from cinnamon, bay leaf, oregano, and parsley with SARS-CoV-2 nucleocapsid protein: A comparative assessment for development of potential antiviral nutraceuticals.

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin > catechin > apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin > cinnamic acid > catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.

Cinnamon Infusion Reduces Satiety and Increases Energy Intake: A Randomized Crossover Trial.

BACKGROUND/AIMS: This study aimed to evaluate the effects of the intake of a single dose of cinnamon infusion on energy metabolism, appetite responses, and food intake in healthy individuals. METHODS: This was an open randomized crossover clinical trial, with a minimum washout of 7 days, in which two standardized breakfasts were served randomly: one with cinnamon infusion (2 g, Cinnamomum sp.) and one with water (control). The study included 21 healthy volunteers. Energy expenditure (EE), diet-induced thermogenesis (DIT), respiratory quotient (RQ), substrate oxidation, and appetite responses were evaluated, as well as prospective food intake. RESULTS: Ingestion of cinnamon infusion did not alter EE, DIT, RQ, or substrate oxidation. The incremental area under the curve for hunger, satiety, and desire to eat did not differ between the treatment with cinnamon infusion and water; however, there was a reduction in the feeling of satiety (p = 0.021) compared to the control treatment. The energy consumption of the first meal after treatment was higher (p = 0.05) in the treatment with cinnamon infusion than in the control treatment. Regarding macronutrients or food intake throughout the day, there was no difference between treatments. CONCLUSIONS: Although it did not affect energy metabolism, consuming a single dose of cinnamon infusion promoted less feeling of satiety and increased energy intake in the first meal after treatment. The study protocol was registered at the Brazilian Clinical Trials Registry Platform (RBR-5ftg3z).

Therapeutic Potential and Safety of the Cinnamomum zeylanicum Methanolic Extract Against Chronic Toxoplasma gondii Infection in Mice.

Background: This experimental study determined the in vitro, in vivo, and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection. Methods: The in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR. Results: CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1ß, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 µg/ml. Conclusion: The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.

Combined efficacy of Cinnamomum zeylanicum and doxorubicin against leukemia through regulation of TRAIL and NF-kappa B pathways in rat model.

BACKGROUND: Recent discoveries in cancer therapeutics have proven combination therapies more effective than individual drugs. This study describes the efficacy of the combination of Cinnamomum zeylanicum and doxorubicin against benzene-induced leukemia. METHODS AND RESULTS: Brine shrimp assay was used to assess the cytotoxicity of C. zeylanicum, doxorubicin and their combination. After AML induction in Sprague Dawley rats, the same drugs were given to rat groups. Changes in organ weight, haematological profile, and hepatic enzymes were determined. Real-time PCR was used to elucidate the effect on the expression of STMN1, GAPDH, P53 and various TRAIL and NF-kappaB components. C. zeylanicum reduced the cytotoxicity of doxorubicin. The combination treatment showed better anti-leukemic results than any of the individual drugs as evident from STMN1 expression (p < 0.001). It was particularly effective in reducing total white blood cell counts and recovering lymphocytes, monocytes and eosinophils along with hepatic enzymes ALT and AST (p < 0.001). All doses recovered relative organ weights and improved blood parameters. The combination therapy was particularly effective in inducing apoptosis, inhibition of proliferation marker GAPDH (p < 0.001) and NF-kappaB pathway components Rel-A (p < 0.001) and Rel-B (p < 0.01). Expressions of TRAIL components c-FLIP (p < 0.001), TRAIL ligand (p < 0.001) and caspase 8 (p < 0.01) were also altered. CONCLUSION: Cinnamomum zeylanicum in combination with doxorubicin helps to counter benzene-induced cellular and hepatic toxicity and improves haematological profile. The anti-leukemic effects are potentially due to inhibition of GAPDH and NF-kappa B pathway, and through regulation of TRAIL pathway. Our data suggests the use of C. zeylanicum with doxorubicin to improve anti-leukemic therapeutic regimes.

Diabetic cardiomyopathy was attenuated by cinnamon treatment through the inhibition of fibro-inflammatory response and ventricular hypertrophy in diabetic rats.

Diabetic cardiomyopathy (DCM) is a chronic complication of diabetes that emphasizes the urgency of developing new drug therapies. With an illustrious history in traditional medicine to improve diabetes, cinnamon has been shown to possess blood lipids lowering effects and antioxidative and anti-inflammatory properties. However, the extent to which it protects the diabetic heart has yet to be determined. Forty-eight rats were administered in the study and grouped as: control; diabetic; diabetic rats given 100, 200, or 400 mg/kg cinnamon extract, metformin (300 mg/kg), valsartan (30 mg/kg), or met/val (combination of both drugs), via gavage for six weeks. Fasting blood sugar (FBS) and markers of cardiac injury including creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were evaluated in blood samples. Malondialdehyde (MDA) levels, the total contents of thiol, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Histopathology study and gene expression measurement of angiotensin II type 1 receptor (AT1), atrial natriuretic peptide (ANP), beta-myosin heavy chain (ß-MHC), and brain natriuretic peptide (BNP) were done on cardiac tissue. FBS and cardiac enzyme indicators were reduced in all treated groups. A reduction in MDA level and enhancement in thiol content alongside with increase of SOD and CAT activities were observed in extract groups. The decrease of inflammation and fibrosis was obvious in treated groups, notably in the high-dose extract group. Furthermore, all treated diabetic groups showed a lowering trend in AT1, ANP, ß-MHC, and BNP gene expression. Cinnamon extract, in addition to its hypoglycemic and antioxidant properties, can prevent diabetic heart damage by alleviating cardiac inflammation and fibrosis. PRACTICAL APPLICATIONS: This study found that cinnamon extract might protect diabetic heart damage by reducing inflammation and fibrosis in cardiac tissue, in addition to lowering blood glucose levels and increasing antioxidant activity. Our data imply that including cinnamon in diabetic participants' diets may help to reduce risk factors of cardiovascular diseases.

Cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats.

Obesity is a health and medical problem and is known as the accumulation of fat that increases the risk of cardiovascular, type 2 diabetes mellitus, and infertility. Cinnamon is a spice that is used mainly as a flavoring additive and folk remedies to treat diabetes. Molecular mechanisms of its effects on hepatic lipogenesis and beta-oxidation, inflammation, and oxidative damage are not fully understood. Therefore, the aim of this study was to evaluate the protective and therapeutic effect of different doses of cinnamon in obese male rats. Forty-eight adult male Wister rats were randomly assigned into eight controlled and treated groups. Serum levels of lipid, glucose, and insulin profiles were measured along with liver levels of antioxidant enzymes, MDA and TNF-α. Hepatic expression of genes involved in beta-oxidation, lipogenesis, oxidative stress, and inflammation was also evaluated. Hepatic levels of oxidative and inflammatory biomarkers and serum levels of glucose, liver enzymes, insulin, and lipid profiles increased significantly in obese rats. Moreover, hepatic expression of SREBP-1c and NF-κB increased, and PPAR-alpha, CD36, FAS, CPT-1, and Nrf-2 decreased in obese rats. However, pretreatment and treatment with different doses of cinnamon in obese rats could significantly ameliorate them in obese rats. It can be concluded that cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats. PRACTICAL APPLICATIONS: Obesity as a medical and psychiatric problem is seen in more than a third of the world's population. Obesity leads to cardiovascular disease, diabetes, and in some cases even death. Cinnamon as a spice and folk remedy has long been used as a treatment for obesity and liver disease. Cinnamon has received a great of attention from the past to the present due to its pharmacological properties and in addition to its availability, cheapness and low side effects. Cinnamon can prevent dyslipidemia, hyperglycemia, oxidative damage, and inflammation by modulating multiple signaling pathways. Our results showed that cinnamon could improve hepatic steatosis caused by HFD via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation. Therefore, it can be recommended that cinnamon and its products can be used as a very suitable option for the production of pharmaceutical supplements for the prevention and treatment of metabolic diseases.

Retention of sulfamethoxazole by cinnamon wood biochar and its efficacy of reducing bioavailability and plant uptake in soil.

The objective of this research was to evaluate the efficacy of cinnamon wood biochar (CWBC) in adsorbing sulfamethoxazole (SUL), which alleviates bioavailability and plant uptake. Batch studies at various pH, contact times, and initial SUL loading were used to study SUL adsorption in CWBC, soil, and 2.5% CWBC amended soil. SUL mitigation from plant uptake were examined using Ipomoea aquatica at different SUL contamination levels in the soil. The kinetic results were described by pseudo-second-order with maximum adsorption capacities (Qmax) of 95.64 and 0.234 mg/g for pristine CWBC and amendment, respectively implying that chemical interactions are rate-determining stages. Hill and Toth's model described the isotherm data for pristine CWBC, soil and CWBC amended soil as Qmax of 113.44, 0.72, and 3.45 mg/g. Column data showed a great mobilization of SUL in loamy sand; however, when CWBC was added to the loamy sand, the mobilization was drastically reduced by 98.8%. The Ipomoea aquatica showed a great potential to SUL uptake and it depended on the contamination level; the SUL accumulation in plant was 9.6-13.8 and 19.1-48 mg/kg when soil was spiked with 5 and 50 mg/kg, respectively. The addition of 2.5% CWBC reduced root and shoot uptake by 30 and 95%, respectively in 5 mg/kg of SUL, whereas with 50 mg/kg of SUL, the root and shoot uptake was reduced by 60 and 61%, respectively. The current study suggested CWBC as a possible adsorbent that may be employed to reduce SUL bioavailability in environmental matrices.

Testing the Effects of Cinnamon Extract Supplementation on Inflammation and Oxidative Stress Induced by Acrylamide.

We investigated the effects of cinnamon water extract supplementation on inflammation and oxidative stress induced by acrylamide in rats. This revealed acrylamide-intoxicated control group had significant higher levels of malondialdehyde, tumor necrosis factor-alpha (TNF-α), high-sensitive C-reactive protein (hs-CRP), leptin and alanine transaminase, and lower levels of total antioxidant capacity compared to the negative control group. In contrast, cinnamon extract administration remedied the levels of total antioxidant capacity, malondialdehyde, TNF-α, hs-CRP, and leptin in the treatment groups. However, there was no significant effect on adiponectin or liver enzymes. This chapter presents a protocol involving production of the acrylamide-induced oxidative stress model, the aqueous extraction of cinnamon powder, and measurement of inflammatory and oxidative stress markers.

Multifunctional poly(vinyl alcohol) films using cellulose nanocrystals/oregano and cellulose nanocrystals/cinnamon Pickering emulsions: Effect of oil type and concentration.

Poly (vinyl alcohol) (PVA) films with high transparency, UV-barrier, antioxidant, and antimicrobial properties were prepared using oregano essential oil (OEO) and cinnamon essential oil (CEO) Pickering emulsions. The effect of Pickering emulsion type and concentration on the PVA film properties was studied. Cellulose nanocrystals (CNCs) were used as a natural stabilizer to prepare OEO and CEO Pickering emulsions. Both emulsions showed spherical droplets with diameters of 155-291 nm, zeta potential of -36.2 to -49.6 mV, minimum inhibition concentration of 6.25-12.5 µL/mL, and inhibition zone of 40-65 mm, depending on oil type. Morphology and FTIR analysis showed that OEO and CEO Pickering emulsions were compatible with the PVA matrix. The UV-transmittance of PVA films decreased from 77.3% to 30.4% and 2.0% without sacrificing the transparency after adding OEO and CEO Pickering emulsions, respectively. Antimicrobial results showed that E. coli was more sensitive to CEO, while S. aureus was sensitive to OEO Pickering emulsion. PVA/CEO film displayed higher properties than PVA/OEO film.

Cinnamic Aldehyde, the main monomer component of Cinnamon, exhibits anti-inflammatory property in OA synovial fibroblasts via TLR4/MyD88 pathway.

Cinnamon is a wildly used traditional Chinese herbal medicine for osteoarthritis (OA) treatment, but the underlying mechanism remains ambiguous. The purpose of this study is to explore the mechanism of cinnamic aldehyde (CA), a bioactive substance extracted from Cinnamon, on synovial inflammation in OA. A total of 144 CA-OA co-targeted genes were identified by detect databases (PubChem, HIT, TCMSP, TTD, DrugBank and GeneCards). The results of GO enrichment analysis indicated that these co-targeted genes have participated in many biological processes including 'inflammatory response', 'cellular response to lipopolysaccharide', 'response to drug', 'immune response', 'lipopolysaccharide-mediated signalling pathway', etc. KEGG pathway analysis showed these co-targeted genes were mainly enriched in 'Toll-like receptor signalling pathway', 'TNF signalling pathway', 'NF-kappa B signalling pathway', etc. Molecular docking demonstrated that CA could successfully bind to TLR2 and TLR4. The results of in vitro experiments showed no potential toxicity of 10, 20 and 50 µM/L CA on human OA FLS, and CA can significantly inhibit the inflammation in LPS-induced human FLS. Further experimental mechanism evidence confirmed CA can inhibited the inflammation in LPS-induced human OA FLS via blocking the TLR4/MyD88 signalling pathway. Our results demonstrated that CA exhibited strong anti-inflammation effect in OA FLS through blocking the activation of TLR4/MyD88 signalling pathway, suggesting its potential as a hopeful candidate for the development of novel agents for the treatment of OA.

Comprehensive feature-based molecular networking and metabolomics approaches to reveal the differences components in Cinnamomum cassia and Cinnamomum verum.

Cinnamon was been a widely used plant in medicinal and spices for a long time and has spread all over the world. However, the differences in the components of the bark from Cinnamomum cassia and Cinnamomum verum, the two most common types of cinnamon, have not been thoroughly investigated. In the present experiment, ultra-high-performance liquid chromatography LTQ-Orbitrap Velos Pro hybrid mass spectrometer-based metabolomics coupled with chemometrics and feature-based molecular networking were employed to dramatically distinguish and annotate Cinnamomum cassia Bark and Cinnamomum verum bark. As a consequence, principal component analysis, orthogonal projection to latent structures discriminates analysis, and heat map analysis demonstrated clear discrimination between the profiles of metabolites in cinnamon. Besides, as the known compounds, proanthocyanidins (cinnamtannin B1 and procyanidin B2) and alkaloids (norboldine, norisoboldine) with variable importance in the projection scores >6, and an unknown alkaloid (formula C24 H33 NO6 ) were selected as the best markers to discriminate cinnamon. Furthermore, large numbers of proanthocyanidins and alkaloids components were identified through feature-based molecular networking for the first time. Our investigation provides new ideas for the discovery of quality markers and identification of unknown components in natural products.

Trachyspermum ammi and Cinnamomum verum as nutraceuticals: Spices rich in therapeutically significant protein tyrosine phosphatases.

Nutraceuticals need special attention as preventive molecules to create a natural barrier against various dreadful diseases like cancer and to regulate metabolism. In the present study, two spices, Trachyspermum ammi and Cinnamomum verum, been identified as excellent Protein Tyrosine Phosphatases (PTPases) sources that play significant role in the regulation of cell signal transduction and developmental processes in plants as well as animals, being lucrative and potential targets for pharmacological modulation. PTPases from both cases were partially purified into 0%-40% and 40%-80% fractions based on ammonium sulfate saturation levels. Fraction (40%-80%) exhibited a purification level of 4.44-fold and 2.86-fold with specific activity of 44.06 and 23.33 U/mg for PTPases from T. ammi and C. verum, respectively. PTPases being found to be thermally stable up to 70°C imply their industrial significance. Kinetic studies showed Km values to be 7.14 and 8.33 mM, whereas the activation energy (Ea ) values were 25.89 and 29.13 kJ/mol, respectively. Divalent cations: Cu2+ , Zn2+ , and Mn2+ acted as inhibitors of PTPases, from both sources. The Ki values of inhibitors varied from 0.014-0.125 mM in the descending order Cu2+  > Zn2+  > Mn2+ and Mn2+  > Cu2+  > Zn2+ for PTPases from T. ammi and C. verum, respectively. The inhibitory effect of sodium metavanadate aligns with prominent PTPase characteristics. In addition to these properties, the thermostability of PTPases from two spices enhances their significance in industries with therapeutically vital products. Although the source of PTPases is culinary spices, further studies are required to establish the utilization of PTPases as nutraceuticals and in therapeutic formulations. PRACTICAL APPLICATIONS: For a healthy lifestyle, awareness needs to be created by humankind towards food habits to minimize illnesses. Numerous studies have explored the consumption of nutraceutical products acts as a natural barrier and immune booster for various human ailments including SARS-COV-2. PTPases play important roles in regulating intracellular signaling and, ultimately, biological function along with their structural features. The importance of PTPases and their inhibitors has been implicated in various diseases like cancer, diabetes, and obesity. Further investigations need to be undertaken to explore the therapeutic properties of PTPases in both in vivo and in vitro for their clinical significance.

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We studied the effects of urease/nitrification inhibitor combinations on urea hydrolysis and nitrification, aiming to screen out the effective inhibitor combinations for black soil and cinnamon soil in Northeast China. Urease inhibitor, N-butyl thiophosphate-triamine (NBPT), and its combination with nitrification inhibitor dicyandiamide (DCD), 3, 4-dimethylpyrazole phosphate (DMPP), 2-chloro-6 (trichloromethyl)-pyridine (CP), 2-amino-4-chloro-6-methylpyrimidine (AM) and 3-methylpyrazole (MP) were added to urea separately. Samples were collected 15 times in each of all the treatments during 125 days. We examined the changes of urea nitrogen, ammo-nium, nitrate, and nitrification inhibition rate in the two soils. Our results showed the hydrolysis of urea in black soil and cinnamon soil was about 7 d, and the addition of NBPT with or without diffe-rent nitrification inhibitors slowed down the hydrolysis to 21 d at least. Compared with the treatment with common urea, inhibitor addition significantly increased soil NH4+-N, decreased soil NO3--N, and maintained the high NH4+-N content in soil for a longer time. In black soil, application with nitrification inhibitor inhibited soil nitrification significantly and lasted for more than 125 d. DMPP and CP combined with NBPT increased the NH4+-N content in black soil by 1.6-1.8 times, while the nitrification inhibition rate was 47.9% and 24.1% at 125 d, respectively. In the cinnamon soil, the application of nitrification inhibitor could prolong the duration of ammonium oxidation from 80 d to 110 d. DCD and DMPP combined with NBPT increased the NH4+-N content in cinnamon soil by 2.1-3.4 times, while the nitrification inhibition rates at 125 d were 25.3% and 23.2%, respectively. Therefore, NBPT+DMPP combination with urea was recommended for utilization in black soil, followed by NBPT+CP. In cinnamon soil, NBPT+DCD combination with urea was recommended, followed by NBPT+DMPP.

Chemical composition, antioxidant and antimicrobial activity of essential oils from tangerine (Citrus reticulata L.), grapefruit (Citrus paradisi L.), lemon (Citrus lemon L.) and cinnamon (Cinnamomum zeylanicum Blume).

The phytochemical and biological properties of tangerine (Citrus reticulata L.), grapefruit (Citrus paradisi L.), lemon (Citrus lemon L.) and cinnamon (Cinnamomum zeylanicum Blume) essential oils were examined. The chemical composition of the essential oils determined using chromatography analysis revealed that D-limonene and cis-cinnamaldehyde were the main components. The antioxidant and antimicrobial activities of the essential oils have been studied by the DPPH radical-scavenging assay and the disc-diffusion method, respectively. All essential oils had antimicrobial activity against saprophytic (Bacillus subtilis, Penicillium chrysogenum, Fusarium moniliforme, Aspergillus niger, Aspergillus flavus, Saccharomyces cerevisiae) and pathogenic microorganisms (Escherichia coli, Salmonella abony, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans), with the highest inhibitory activity being observed in cinnamon oil, followed by grapefruit zest oil, tangerine zest oil and lemon zest oil; the MIC ranging from 6 to 60 ppm. In addition, they exhibited high antioxidant activity with the highest antioxidant activity being determined for the grapefruit zest essential oil, followed by the lemon zest essential oil, the tangerine zest essential oil and the cinnamon essential oil. The demonstrated promising results for the antioxidant and antimicrobial activity of the studied essential oils would give reason for their inclusion in the development of bio-preservation strategies for food emulsion preservation.

A novel W/O/W double emulsion co-delivering brassinolide and cinnamon essential oil delayed the senescence of broccoli via regulating chlorophyll degradation and energy metabolism.

The postharvest senescence accompanied by yellowing limited the shelf-life of broccoli. In this study, we developed a novel W/O/W double emulsion co-delivering brassinolide and cinnamon essential oil and applied it to broccoli for preservation. Results showed that double emulsion prepared by whey protein concentrate-high methoxyl pectin (1:3) exhibited best storage stability with largest particle size (581.30 nm), lowest PDI (0.23) and zeta potential (-40.31 mV). This double emulsion also exhibited highest encapsulation efficiency of brassinolide (92%) and cinnamon essential oil (88%). The broccoli coated with double emulsion maintained higher chlorophyll contents and activities of chlorophyllase and magnesium-dechelatase were reduced by 9% and 24%, respectively. The energy metabolic enzymes (SDH, CCO, H+-ATPase, Ca2+-ATPase) were also activated, inducing higher level of ATP and energy charge. These results demonstrated W/O/W double emulsion co-delivering brassinolide and cinnamon essential delayed the senescence of broccoli via regulating chlorophyll degradation and energy metabolism.