Uncovering the Mechanisms of Cinnamic Acid Treating Diabetic Nephropathy Based on Network Pharmacology, Molecular Docking, and Experimental Validation.

BACKGROUND: Cinnamic acid (Cinn) is a phenolic acid of Cinnamomum cassia (L.) J. Presl. that can ameliorate diabetic nephropathy (DN). However, comprehensive therapeutic targets and underlying mechanisms for Cinn against DN are limited. OBJECTIVE: In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy. METHODS: The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn. RESULTS: Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice. CONCLUSION: This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.

Changes in the Antioxidant Potential of Camellia sinensis Cultures under the Influence of Phenolic Precursors.

The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine-3 mM, trans-cinnamic acid-1 mM, naringenin-0.5 mM). According to the data obtained, the effect of precursors on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of certain phenolics classes accumulation in plant cells.

Hydroxyl-rich ferrofluid for efficient liquid phase microextraction of cinnamic acid derivatives in traditional Chinese medicine.

In this study, a hydroxyl-rich ferrofluid was prepared by dispersing silica-coated magnetic nanoparticles into a methyltrioctylammonium chloride-glycerol deep eutectic solvent and then employed in the preconcentration of trace-level of cinnamic acid derivatives (caffeic acid, p-hydroxycinnamic acid, ferulic acid, and cinnamic acid) in traditional Chinese medicine prior to high-performance liquid chromatography analysis. The structures of the synthesized materials were characterized by X-ray diffraction and infrared spectroscopy. The experimental parameters affecting the extraction performance, such as deep eutectic solvent composition, dosage of ferrofluid, pH of aqueous sample solution, salt concentration, extraction time, type, and volume of desorption solvent, were studied and optimized. Under the optimum conditions, the enrichment factors of four cinnamic acid derivatives were in the range of 107-114. Low detection limits (0.2-0.9 ng/mL), good precisions (relative standard deviations 1.2%-9.5%), and satisfactory recoveries (96.0%-104.7%) were achieved. Subsequently, the possible microextraction mechanism of the proposed method was explored and elucidated. It showed that the prepared ferrofluid is easily dispersed in the aqueous sample and achieved recovery after the extraction. The developed approach is a simple, convenient, and efficient method for preconcentration and determination of cinnamic acid derivatives in complex matrices.

Biological evaluation of 1,3-benzodioxole acids points to 3,4-(methylenedioxy) cinnamic acid as a potential larvicide against Aedes aegypti (Diptera: Culicidae).

Aedes aegypti serves as the primary vector for viruses like dengue, Chikungunya, Zika, and yellow fever, posing a significant public health challenge in Brazil. Given the absence of approved vaccines for these diseases, effective mosquito control becomes paramount in preventing outbreaks. However, currently available chemical insecticides face issues related to toxicity and the emergence of resistance, necessitating the exploration of new active compounds. Drawing inspiration from natural products, we identified the 1,3-benzodioxole group as a key pharmacophore associated with insecticidal activity. Therefore, this study aimed to synthesize and assess the larvicidal activity of 1,3-benzodioxole acids against Ae. aegypti, as well as their toxicity in mammals. Among the compounds evaluated, 3,4-(methylenedioxy) cinnamic acid (compound 4) demonstrated larvicidal activity. It exhibited LC50 and LC90 values of 28.9 ± 5.6 and 162.7 ± 26.2 µM, respectively, after 24 h of exposure. For reference, the positive control, temephos, displayed both LC50 and LC90 values below 10.94 µM. These findings underline the significance of the 3,4-methylenedioxy substituent on the aromatic ring and the presence of a double bond in the aliphatic chain for biological activity. Furthermore, compound 4 exhibited no cytotoxicity towards human peripheral blood mononuclear cells, even at concentrations up to 5200 µM. Lastly, in mice treated with 2000 mg kg-1, compound 4 showed mild behavioral effects and displayed no structural signs of toxicity in vital organs such as the kidney, liver, spleen, and lungs.

[A new cinnamic acid ester derivative from Liquidambaris Resina].

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17ß-hydroperoxide(4), erythrodiol(5), 13ß,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3ß)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) µmol·L~(-1), respectively.

Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders.

Background: Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this work, we identify herbal compounds that are potential inhibitors of CA VI. Methods: We used the AutoDock tool to evaluate binding affinity between the CA VI active site and 79 metabolites derived from flavonoids, anthraquinones, or cinnamic acids. Compounds ranked at the top were chosen for molecular dynamics (MD) simulations. Interactions between the best CA VI inhibitors and residues within the CA VI active site were examined before and after MD analysis. Additionally, the effects of the most potent CA VI inhibitor on cell viability were ascertained in vitro through the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: Kaempferol 3-rutinoside-4-glucoside, orientin, kaempferol 3-rutinoside-7-sophoroside, cynarin, and chlorogenic acid were estimated to establish binding with the CA VI catalytic domain at the picomolar scale. The range of root mean square deviations for CA VI complexes with kaempferol 3-rutinoside-4-glucoside, aloe-emodin 8-glucoside, and cynarin was 1.37 to 2.05, 1.25 to 1.85, and 1.07 to 1.54 Å, respectively. The MTT assay results demonstrated that cynarin had a substantial effect on HCT-116 cell viability. Conclusion: This study identified several herbal compounds that could be potential drug candidates for inhibiting CA VI.

Mesenchymal stem cell-derived rapid drug screening system for Alzheimer's disease for the identification of novel drugs.

A reliable and efficient in vitro model is needed to screen drugs for Alzheimer's disease (AD), as many drugs are currently in the developmental stage. To address this, we developed an in vitro model using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) to screen novel drugs for AD. We differentiated AM-MSCs into neurons and degenerated them using beta amyloid1-42 (Aß). We then tested AD drugs, which are commercially available such as donepezil, rivastigmine, memantine, citicoline, and two novel drugs, that is, probucol, an anti-hyperlipidaemic drug, and NMJ-2, a cinnamic acid analogue for their potential to protect the cells against neurodegeneration. We used gene expression and immunofluorescence staining to assess the neuroprotective ability of these drugs. We also measured the ability of these drugs to reduce lactate dehydrogenase, reactive oxygen species, and nitric oxide levels, as well as their ability to stabilize the mitochondrial membrane potential and increase acetylcholine (ACh) levels. The AD drugs and novel drugs reduced cytotoxicity and oxidative stress, stabilized mitochondrial membrane potential, and restored ACh levels. Furthermore, they reduced BACE1 expression, with a concomitant increase in the expression of cholinergic markers. This AM-MSCs-based AD-like model has immense potential to be an accurate human model and an alternative to animal models for testing a large number of lead compounds in a short time. Our results also suggest that the novel drugs probucol and NMJ-2 may protect against Aß-induced neurodegeneration.

Development of sodium alginate-pectin biodegradable active food packaging film containing cinnamic acid.

Plastics are still the most popular food packaging material and many of them end up in the environment for a long period. Due to packaging material's inability to inhibit microbial growth, beef often contains microorganisms that affect its aroma, colour and texture. Cinnamic acid is categorized as generally recognised as safe and is permitted for use in food. The development of biodegradable food packaging film with cinnamic acid has never been conducted before. This present study was aimed to develop a biodegradable active packaging material for fresh beef using sodium alginate and pectin. The film was successfully developed with solution casting method. The films' thickness, colour, moisture level, dissolution, water vapour permeability, bending strength and elongation at break were comparable to those of polyethylene plastic film in terms of these attributes. The developed film also showed the degradability in soil of 43.26% in a duration of 15 days. Fourier Transform Infrared (FTIR) spectra showed that cinnamic acid was successfully incorporated with the film. The developed film showed significant inhibitory activity on all test foodborne bacteria. On Hohenstein challenge test, a 51.28-70.45% reduction on bacterial growth was also observed. The antibacterial efficacy of the established film by using fresh beef as food model. The meats wrapped with the film showed significant reduction in bacterial load throughout the experimental period by 84.09%. The colour of the beef also showed significant different between control film and edible film during 5 days test. Beef with control film turned into dark brownish and beef with cinnamic acid turn into light brownish. Sodium alginate and pectin film with cinnamic acid showed good biodegradability and antibacterial activity. Further studies can be conducted to investigate the scalability and commercial viability of this environmental-friendly food packaging materials.

Cinnamic acids as promising bioactive compounds for cancer therapy by targeting MAPK3: a computational simulation study.

OBJECTIVES: Mitogen-activated protein kinase-3 (MAPK3) is the upstream regulator in the MAPK cascade and is involved in many critical signaling pathways and biological processes, such as cell proliferation, survival, and apoptosis. MAPK3 overexpression is linked to onset, development, metastasis, and drug resistance in several human cancers. Thus, identifying novel and effective MAPK3 inhibitors is highly demanded. Herein, we aimed to discover organic compounds from cinnamic acid derivatives as potential MAPK3 inhibitors. METHODS: The binding affinity of 20 cinnamic acids to the MAPK3 active site was tested using the AutoDock 4.0 software. Top-ranked cinnamic acids were ranked based on the ΔG binding values between the ligands and the receptor's active site. Interaction modes between top-ranked cinnamic acids and MAPK3 catalytic site were indicated using the Discovery Studio Visualizer tool. Molecular dynamics (MD) simulation was carried out to study the stability of the docked pose for the most potent MAPK3 inhibitor in this study. RESULTS: Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate exhibited a salient binding affinity to the MAPK3 active site with the criteria of ΔG binding <-10 k cal/mol. Further, the inhibition constant value for cynarin was calculated at the picomolar concentration. The docked pose of cynarin within the MAPK3 catalytic domain was stable in 100 ns simulation. CONCLUSIONS: Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate might be helpful in cancer therapy by inhibiting MAPK3.

Anti-tyrosinase and antimelanogenic effect of cinnamic acid derivatives from Prunus mahaleb L.: Phenolic composition, isolation, identification and inhibitory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunus species against skin diseases and especially for skin lightning cosmeceutical purposes is widespread in many cultures. Prunus mahaleb L. is a well known food plant and used in the baking industry for flavoring. The fruit kernels (endocarp) are used in India for hyperpigmentation. AIM OF THE STUDY: To investigate the chemical composition with the antimelanogenesis effect of P. mahaleb seed and kernel extracts and isolated compounds. MATERIALS AND METHODS: Isolation studies performed from the methanol extracts obtained from kernels and structures were determined using NMR and MS analysis. Antimelanogenesis effect was determined by mushroom tyrosinase assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. RESULTS: Five cinnamic acid derivatives were isolated and their structures (2-O-ß-glucopyranosyloxy-4-methoxy-hydrocinnamic acid (1), cis-melilotoside (2), dihydromelilotoside (3), trans-melilotoside (4), 2-O-ß-glucosyloxy-4-methoxy trans-cinnamic acid (5)) were elucidated using advanced spectroscopic methods. Mushroom tyrosinase enzyme inhibition of extracts, fractions and pure compounds obtained from P. mahaleb kernels were investigated and structure-activity relationship revealed. According to a detailed, comprehensive and validated LC-MS/MS technique analysis, vanilic acid (41.407 mg/g), protocatechuic acid (8.992 mg/g) and ferulic acid (4.962 mg/g) in the kernel ethylacetate fraction; quinic acid (14.183 mg/g), fumaric acid (8.349 mg/g) and aconitic acid (5.574 mg/g) were found as major phenolic compounds in the water fraction. The correlation of trace element copper content in extracts and fractions with mushroom enzyme activity was determined. By examining the enzyme kinetics of the compounds with effective cinnamic acid derivatives, inhibition types and enzyme binding constants Ki were calculated. Compounds 1,3 and 5 exhibited high noncompetitive tyrosinase inhibitory activity against L-tyrosine substrates, with IC50 values of 0.22, 0.31 and 0.37 mM respectively. In addition compounds 1, 3 and 5 showed dose-dependent inhibitory effects on intracellular tyrosinase and melanin levels in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. CONCLUSIONS: Potent tyrosinase inhibitory compounds and extracts of P. mahaleb kernels suggest that it could be a new, non-toxic and inexpensive resource for the cosmeceutical industry and in skin diseases associated with hyperpigmentation.

Changes in polyphenolic compounds and antioxidant activities of seed-used pumpkin during hydrothermal treatment.

An environmentally friendly physical processing method, hydrothermal treatment (HT), was used to increase the content of specific compounds and antioxidant activities of seed-used pumpkin byproducts. The influence of hydrothermal temperature (80 °C-160 °C) and time (30-150 min) on changes in polyphenols and antioxidation was evaluated. The results revealed that the maximum free polyphenol content (140 °C for 120 min) was 3.96-fold higher than the untreated samples. Elevated temperature and long duration changed phenolic acid contents. For example, p-coumaric acid, rutin and chlorogenic acid exhibited a decreasing trend, and p-hydroxybenzoic acid, quercetin and cinnamic acid showed an increasing trend. Compared to controls, HT was significantly associated with increased antioxidant activities. To comprehensively reveal the influence of hydrothermal temperature and time on changes in polyphenolic content, back propagation artificial neural network (BP-ANN) models with accurate prediction ability were developed, and the results exhibited well-fitted and strong approximation ability (R2 > 0.95 and RMSE < 2 %) and stability.

Cinnamomum verum extract inhibits NOX2/ROS and PKCδ/JNK/AP-1/NF-κB pathway-mediated inflammatory response in PMA-stimulated THP-1 monocytes.

BACKGROUND: Cinnamomum verum J. Presl (Cinnamon) is widely used in the food and pharmaceutical industries. C. verum exhibits various biological activities. However, it is unclear whether C. verum can inhibit NOX, a major source of ROS generation, and exert anti-inflammatory and antioxidant effects in PMA-stimulated THP-1 cells. PURPOSE: This study investigates the anti-inflammatory and antioxidant effects of C. verum in PMA-stimulated THP-1 cells. METHODS: The MeOH extract of C. verum was analyzed using UPLC-QTOF/MS. Anti-inflammatory and antioxidant effects of C. verum extract were examined by DCF-DA staining, immunofluorescence staining, RT-PCR, and immunoblotting in PMA-stimulated THP-1 cells. RESULTS: C. verum and its components, cinnamic acid and coumarin, significantly attenuated the expression of IL-1ß, IL-8, CCL5, and COX-2 in PMA-stimulated THP-1. C. verum decreased ROS levels via NOX2 downregulation, as well as ameliorated plasma membrane translocation of PKCδ and decreased JNK phosphorylation. Besides, C. verum suppressed the nuclear translocation of AP-1 and NF-κB, which modulates diverse pro-inflammatory genes. CONCLUSION: C. verum effectively inhibits inflammation and oxidative stress during monocyte-macrophage differentiation and downregulates inflammatory mediators via NOX2/ROS and PKCδ/JNK/AP-1/NF-κB signaling.

Chemical Composition, Antimicrobial and Antioxidant Bioautography Activity of Essential Oil from Leaves of Amazon Plant Clinopodium brownei (Sw.).

The Amazonian region of Ecuador has an extremely rich vegetal biodiversity, and its inhabitants have proven to have a millennial ancestral knowledge of the therapeutic and medicinal use of these resources. This work aimed to evaluate the chemical composition and biological activity of the essential oil obtained from the medicinal plant Clinopodium brownei (Sw.) Kuntze, which is widely spread in tropical and subtropical America. This species is traditionally used for treating respiratory and digestive diseases and is also known for its analgesic properties. Most of the molecules detected on a non-polar column were ethyl cinnamate 21.4%, pulegone 20.76%, methyl cinnamate 16.68%, caryophyllene 8.17%, ß-selinene 7.92% and menthone 7.51%, while those detected on a polar column were: pulegone 29.90%, ethyl cinnamate 18.75%, methyl cinnamate 13.82%, caryophyllene 10.0% and menthone 8.04%. The antioxidant activity by the assays, DPPH (2.2-diphenyl-1-picrylhydrazyl) and ABTS (2.2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), shows the following values of 50% inhibition of oxidation, IC50 DPPH 1.77 mg/mL, IC50 ABTS 0.06 mg/mL, which, compared to the essential oil of Thymus vulgaris (natural positive control), turn out to be less active. Bioautography indicates that the molecules responsible for the antioxidant activity are derived from cinnamic acid: ethyl cinnamate and methyl cinnamate, and caryophyllene. The antimicrobial activity on the nine microorganisms evaluated shows bacterial growth inhibitory concentrations ranging from 13.6 mg/mL for Staphylococcus epidermidis ATCC 14990 to 3.1 mg/mL for Candida albicans ATCC 10231; the results are lower than those of the positive control. Bioautography assigns antimicrobial activity to caryophyllene. The results indicate a very interesting activity of the essential oil and several of its molecules, validating the traditional use and the importance of this medicinal plant from Ecuador.

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study.

The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 µM), followed by compound 4 (672.83 µM) and compound 3 (726.36 µM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 µM), followed by compound 9 (550.96 µM) and compound 6 (626.62 µM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.

Discovery of new cinnamic derivatives as anti-inflammatory agents for treating acute lung injury in mice.

The blockade of the overexpression of pro-inflammatory cytokines by anti-inflammatory natural products has been proven therapeutically beneficial in the treatment of acute lung injury (ALI). Given the fact that cinnamic acid has been proven to have significant anti-inflammatory activity, we selected it as a promising lead compound to develop more effective analogs in treating ALI. Learning from the symmetric structure of curcumin, 32 new symmetric cinnamic derivatives were designed, synthesized, and evaluated for their anti-inflammatory activity. Among them, 6h not only displayed a remarkable inhibitory activity in vitro (85.9% and 65.7% for  IL-6 and TNF-α, respectively) without cytotoxicity but also possessed chemical structure stability. Furthermore, an in vivo study in mice revealed that the administration of 6h significantly attenuated lipopolysaccharide-induced ALI, providing new lead structures for the development of anti-inflammatory drugs for the treatment of ALI.

Antiglycation potential and antioxidant activity of genipap (Genipa americana L.) in oxidative stress mediated by hydrogen peroxide on cell culture.

Genipa americana L. is a plant widely used by folk medicine for the prevention and as an aid in the treatment of various diseases. In this work, we evaluated the anti-glycant and antioxidant activities of genipap fruit juice, as well as the influence of different temperatures (-6 °C and -80 °C) on the preservation of phenolic compounds. Purified extract from G. americana showed anti-glycant activity reducing the formation of fructosamine by up to 53% and recovered viability of cells under oxidative stress induced by H2O2. HPLC/UV-Vis analysis identified cinnamic acid as a bioactive substance and possibly responsible for the biological activities described above. Taken together, these results indicate that G. americana is a rich source of cinnamic acid with appreciable antioxidant and anti-glycant potential.

The ethnobotany, phytochemistry, and biological properties of genus Phagnalon (Asteraceae): a review.

The genus Phagnalon Cass., included within the Asteraceae family, has a wide distribution, expanding from Macaronesia in the West to the Himalayas in the East, from S. France and N. Italy to Ethiopia and Arabian Peninsula. Various species of Phagnalon have been used in the popular medicine of several countries as medicinal herbs and food. This literature review, the first one of the Phagnalon genus, includes publications with the word 'Phagnalon', and considers the extracts and the single metabolites identified, characterized, and tested to evaluate their biological potential. The extracts and the secondary metabolites, have a varied application spectrum at a biological level, with antimicrobial, antioxidant, antidiabetic, antitumor, etc. properties having been reported. Unfortunately, in vitro tests have not always been accompanied by in vivo tests, and this is the major critical aspect that emerges from the study of the scientific aspects related to this genus.

Synthesis and Anti-Inflammatory Activity of 1-Methylhydantoin Cinnamoyl Imides.

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans-cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1ß in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1ß. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.

Effects of Extraction Methods on Phenolic Content in the Young Bamboo Culm Extracts of Bambusa beecheyana Munro.

Nowadays, many studies focus on the potential of bamboo as a source of bioactive compounds and natural antioxidants for nutraceutical, pharmaceutical, and food sources. This study is a pioneering effort to determine the total phenolic content, total flavonoid content and free radical scavenging activity, as well as the phenolic identification and quantification of Bambusa beecheyana. The study was conducted by using ethanol, methanol, and water for solvent extraction by applying cold maceration, Soxhlet, and ultrasonic-assisted extraction techniques. The results showed that Soxhlet and ultrasonic-assisted Bambusa beecheyana culm extracts had an increase in the extract's dry yield (1.13-8.81%) but a constant p-coumaric acid (4) content (0.00035 mg/g) as compared to the extracts from the cold maceration. The ultrasonic-assisted extraction method required only a small amount (250 mL) of solvent to extract the bamboo culms. A significant amount of total phenolics (107.65 ± 0.01 mg GAE/g) and flavonoids (43.89 ± 0.05 mg QE/g) were found in the Soxhlet methanol culm extract. The extract also possessed the most potent antioxidant activity with an IC50 value of 40.43 µg/mL as compared to the positive control, ascorbic acid. The UHPLC-ESI-MS/MS analysis was carried out on the Soxhlet methanol extract, ultrasonic-assisted extract at 40 min, and cold methanol extract. The analysis resulted in the putative identification of a total of five phenolics containing cinnamic acid derivatives. The two cinnamic acid derivatives, p-coumaric acid (4) and 4-methoxycinnamic acid (5), were then used as markers to quantify the concentration of both compounds in all the extracts. Both compounds were not found in the water extracts. These results revealed that the extract from Soxhlet methanol of Bambusa beecheyana could be a potential botanical source of natural antioxidants. This study provides an important chemical composition database for further preclinical research on Bambusa beecheyana.

Cinnamic acid preserves against myocardial ischemia/reperfusion injury via suppression of NLRP3/Caspase-1/GSDMD signaling pathway.

BACKGROUND: Cinnamic acid (CA) is an active organic acid compound extracted from Cinnamomi ramulus that has various biological activities. There is growing studies have shown that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome significantly contributes to sterile inflammatory response and pyroptosis in myocardial ischemia/reperfusion injury (MI/RI). However, whether CA has any influence on NLRP3 inflammasome and pyroptosis during MI/RI are not fully elucidated. PURPOSE: In the present study, we investigated whether NLRP3 inflammasome activation and pyroptosis were involved in the cardioprotective effect of CA against MI/RI. METHODS: Male Sprague-Dawley rats were intragastrically administered either with CA (75 and 150 mg/kg, daily) or vehicle for 7 successive days prior to ligation of coronary artery, and then rats were subjected to ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min to evoke MI/RI. RESULTS: Our results demonstrated that CA could significantly improve cardiac diastolic function, decrease cardiac infarct size and myocardial injury enzymes, inhibit cardiomyocyte apoptosis, attenuate cardiac structure abnormality, and mitigate oxidative stress and inflammatory response. We also found that MI/RI activate NLRP3 inflammasome as evidenced by the upregulation levels of NLRP3, pro-caspase-1, caspase-1, and ASC proteins and mRNA. More importantly, MI/RI trigger pyroptosis as indicated by increased DNA fragmentation, membrane pore formation, and mitochondrial swelling as well as increased levels of pyroptosis-related proteins and mRNA, including GSDMD, N-GSDMD, IL-18, and IL-1ß. As expected, all these deleterious alterations were prominently reversed by CA pretreatment. CONCLUSIONS: These findings indicate that CA effectively protected cardiomyocytes against MI/RI by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway, and it is worthy of more investigations for its therapeutic potential for extenuating ischemic heart disease.