4-methoxycinnamic Acid Research Articles

CREATING CO-CRYSTAL SALTS: Synthesis, Crystal Structure, Hirshfeld Surface Analysis and Quantum Chemical Calculations of Pyrimethamine and their Potential Anti- SARS-Cov-2 Activity

Although the COVID-19 pandemic is over but the clouds of next pandemic can't be ignored and therefore, search for new effective and more safe drug candidates against SARS-CoV-2 is the need of time. The presented study investigates the potential for designing new least toxic but more effective drug candidates with enhanced therapeutic properties against SARS-CoV-2. Pyrimethamine, which was once a cornerstone in malaria treatment, has lost its effectiveness due to the development of drug resistance. Despite this, significant interest remains in modifying and repurposing the drug within medicinal chemistry. The presented study has demonstrated the synthesis of three novel organic co-crystal salts derived from pyrimethamine and the coformers homophthalic acid, chlorosalicylic acid, and 4-methoxy cinnamic acid via reflux method to obtain co-crystal salt I (PYM: HOM), II (PYM: CSAL), and III (PYM: MCIN), in a 1:1 stoichiometric ratio. Single-crystal X-ray diffraction, vibrational spectroscopy, and DSC/TGA analysis were used for the structural characterization and confirmation. Moreover, quantum chemical calculations were carried out to evaluate the structural and electronic properties of the binary complex of the co-crystals and crystal supercells. The interaction energies of the binary complexes were also computed to assess the relative stability of the crystal salts while comparing them with TGA/DTG data. As the COVID-19 pandemic has infected millions of people with mortality exceeding >1 million. There is an urgent need to find therapeutic agents that can help with virus eradication to prevent severe disease and deaths. These co-crystal salts were evaluated for their potential to inhibit SARS-CoV-2 propagation. Co-crystal salt II was observed as the most significant inhibitor at all the treatment points such as prophylactic, entry, and therapeutic (post-entry). Furthermore, pyrimethamine and coformers were also found to be effective at different targets as well. The identification of co-crystal salt II, comprising pyrimethamine and the coformers, shows promising antiviral activity against SARS-CoV-2, potentially laying the groundwork for the development of new drug candidates.

4-Methoxycinnamic acid ameliorates post-traumatic stress disorder-like behavior in mice by antagonizing the CRF type 1 receptor

AimsPosttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric illness caused by traumatic or life-threatening events and manifesting as various symptoms, including intrusive re-experiences of trauma, avoidance behaviors, hyperarousal, and negative changes in perception and mood. Main methodsCurrent monoamine-based medications commonly exhibit limited efficacy and significant side effects, which hamper their clinical utility. To address this unmet need, we explored 4-methoxycinnamic acid (4-MCA) as a potential novel treatment for PTSD in a single prolonged stress (SPS)-induced animal model. Key findingsAdministration of 4-MCA (3 and 10 mg/kg, p.o.) significantly mitigated anxiety-like behaviors, alleviated depression-like behaviors, and improved cognitive function in an SPS-treated PTSD mouse model. Further, 4-MCA treatment effectively rectified the fear extinction deficits in the fear conditioning test. Molecular analyses revealed that 4-MCA normalized the elevated corticotropin-releasing hormone (CRH) levels as well as the phosphorylation of protein kinase A (PKA) and cAMP response element-binding protein (CREB) in the amygdala, a pivotal region for fear memory formation. Co-administration of 4-MCA and the CRFR1 antagonist antalarmin at subeffective doses facilitated fear memory extinction. SignificanceThese findings suggest that 4-MCA alleviates SPS-induced PTSD-like behaviors by regulating the CRH-CRFR1-PKA-CREB signaling pathway in the amygdala, and that 4-MCA may be a potential candidate for future PTSD treatment.

Biodiversity and Bioprospecting of Fungal Endophytes from Houttuynia cordata Thunb. as a Potential Antibacterial and Anticancer Agent.

Endophytic fungi are considered a new source of bioactive compounds that have important applications in agriculture and medicine. This study aims to investigate the biodiversity and potential of endophytic fungi isolated from Houttuynia cordata Thunb. as antimicrobials and anticancer agents. Out of ten isolated endophytes, four species have never been reported to be associated with H. cordata: Ceratobasidium sp., Cladosporium sp., Phomopsis sp., and Fusarium sp. The antibacterial activity assay revealed that the ethyl acetate extract of Ceratobasidium sp. HCS-3 possessed most potent antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, its cytotoxic activity test showed the promising anticancer activity on lung cancer A549, osteosarcoma MG-63, and cervical cancer HeLa cells with IC50 of 4.55±1.16, 32.14±2.78, and 1.54±0.66 ppm, respectively. Furthermore, metabolite profiling identified 66 compounds suggesting that benzoic acid, farnesol, and cyclopeptides may contribute to the antibacterial activity, while 4-methoxycinnamic acid may have anticancer potential.

Exploring induced smectic phases of hydrogen bond liquid crystals for nonlinear optical applications: Theoretical (DFT) and experimental approach

A new intermolecular hydrogen bond liquid crystal (HBLC) complex has been isolated and characterized. The HBLC complex is synthesized by mixing of non mesogenic (E)-3-(3,4,5-trimethoxyphenyl)prop‑2-enoic acid (3,4,5-Trimethoxycinnamic acid, TMCA) and mesogenic (E)-3-(4-Methoxyphenyl)prop‑2-enoic acid (4-Methoxycinnamic acid, 4MCA). Mesogenic textures and its LC parameters are analyzed using polarizing optical microscope (POM) and differential scanning calorimeter (DSC). The manifestation of cyclic dimer H-bonds between TMCA and 4MCA is confirmed via FTIR spectrum by observing peak at 3593cm−1 (OH) and C = O at 1683cm−1. It is noteworthy to observe that the induced smectic A (Sm A) with batonnets texture (during cooling cycle) at 129.3 °C and smectic G (Sm G) with multi color mosaic texture at 116.5 °C in TMCA+4MCA, while compared to its individuals. To understand the molecular level modifications in the LC phases, with the aid of density functional theory (DFT), the nature (H-bond length, MEP, FMO, QTAIM, etc.,) and strength of intermolecular H-bonds are explored. The NLO parameters of HBLC complex have been discussed. In this present paper, the DFT result is compared with experimental observations and the special significances are studied to identify the potent applications of HBLCs.

In silico Evaluation of Ferulic Acid Based Multifunctional Conjugates as Potential Drug Candidates.

Recent research has shown that ferulic acid (FA, trans-4-hydroxy-3- methoxycinnamic acid) has remarkable antioxidant properties and a wide range of biological activities. Conjugation of two or more biologically active compounds to produce a novel molecular scaffold is justified by the need to enhance biological activity against a single target or obtain a conjugate that behaves as a multi-target-directed ligand. In addition, the conjugation strategy decreases dose-dependent side effects by promoting the use of smaller doses of conjugated components to treat the disease. Moreover, the patient's compliance is positively affected when conjugating two active compounds into a single more active compound as this reduces the number of pills to be taken daily. This study aims to shed light on studies that design and synthesize FA-based hybrid compounds with enhanced biological activities and to in silico assess these compounds as potential drug candidates. The conjugate compounds were found by searching the literature using the keywords (ferulic acid-based hybrid or ferulic acid-based conjugate). To study conjugate pharmacokinetic parameters and toxicity (ADMET), software suites from Biovia Inc. (San Diego, California) were integrated into Discovery Studio 4.5. The structures were created using ChemDraw Ultra 7.0. 14 conjugates exhibiting variable biological activities were collected and three of them (compounds 3,5, and 6) in addition to the cis FA (compound 12) are the best-predicted compounds with low Daphnia toxicity and hepatotoxicity with acceptable pharmacokinetic properties. Cis FA, FA conjugates 3,5, and 6 act as good drug candidates that can be used to modify new hits.

Serum metabolome and gut microbiome alterations are associated with low handgrip strength in older adults.

Handgrip strength (HGS), which represents global muscle strength, is a powerful indicator of disability and mortality in older adults; it is also used for the diagnosis of possible- or probable- sarcopenia and physical frailty. This study aimed to explore the metabolic mechanisms and potential biomarkers associated with declining HGS among older adults. We recruited 15 age- and environment-matched inpatients (age, 77-90 years) with low or normal HGS. Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal DNA (rDNA) gene sequencing were performed to analyze the metabolome of serum and stool samples and the gut microbiome composition of stool samples. Spearman's correlation analysis was used to identify the potential serum and fecal metabolites associated with HGS. We assessed the levels of serum and fecal metabolites belonging to the class of cinnamic acids and derivatives and reported that the levels of carboxylic acids and their derivatives decreased in the low-HGS group. Serum levels of microbial metabolites, including cinnamoylglycine, 4-methoxycinnamic acid, and (e)-3,4,5-trimethoxycinnamic acid, were positively correlated with HGS. We found that gut microbial α-diversity was significantly higher in the low-HGS group, whereas higher β-diversity was observed in the normal group. The relative abundances of the genera Parabacteroides and Intestinibacter increased significantly in the low-HGS group and were negatively correlated with the serum levels of cinnamoylglycine. The identified metabolites whose levels were markedly altered, and intestinal flora associated with these metabolites suggest the potential metabolic underpinnings for HGS and provide a basis for the further identification of biomarkers of muscle strength decline in older adults.

Genomic insight into O-demethylation of 4-methoxybenzoate by a two-component system from Amycolatopsis magusensis KCCM40447

Cytochrome P450 monooxygenases perform a multitude of roles, including the generation of hydroxylated aromatic compounds that might be utilized by microorganisms for their survival. WGS data of Amycolatopsis magusensis KCCM40447 revealed a complete circular genome of 9,099,986 base pairs and functionally assigned 8601 protein-encoding genes. Genomic analysis confirmed that the gene for 4-methoxybenzoate monoxygenase (CYP199A35) was conserved in close proximity to the gene for 4-hydroxybenzoate transporter (PcaK). The co-localized genes encoding CYP199A35, and ferredoxin-NAD(P) reductase (Mbr) represent a two-component system for electron transfer. CYP199A35 was specific for O-demethylation of para O-methyl substituted benzoic acid derivatives, 4-methoxybenzoate (4 MB), and 4-methoxycinnamic acid (4MCA) using the native redox partner (Mbr); two-component system and non-physiological redox partners (Pdr/Pdx); three-component system. The catalytic efficiency for O-demethylation of 4 MB using Mbr and Pdr/Pdx was 0.02 ± 0.006 min−1 μM−1 and 0.07 ± 0.02 min−1 μM−1 respectively. Further, sequence annotation and function prediction by RAST and KEEG analysis revealed a complete catabolic pathway for the utilization of 4 MB by strain KCCM40447, which was also proved experimentally.

New europium(III) methoxycinnamates complex: synthesis, thermal and luminescence properties

A method was proposed for the preparative synthesis of mixed-ligand Eu(III) compounds with para -methoxycinnamic acid, ligands from the sodium salt of para -methoxycinnamic acid. It was found that europium(III) methoxycinnamate with hexamethylphosphotriamide has the highest luminescence intensity. Luminescent polymer materials with synthesized europium(III) methoxycinnamates were obtained.

Anti-inflammatory activity via NO production inhibition of compounds from Vietnamese Lycopodium casuarinoides Spring

In our investigation of the methanol extract derived from the aerial parts of Vietnamese Lycopodium casuarinoides Spring, we successfully isolated two novel secondary metabolites: 3β,21α,24-trihydroxyserrat-14-en-29-yl-E-4′-hydroxy-3′-methoxycinnamate (1) and lycocasuarinol A (2), and eight known compounds, namely α-onocerin (3), salcolin A (4), salcolin B (5), (2 R,3 R)-dihydrokaempferol (6), apigenin (7), huperzinine (8), 4-methoxycinnamic acid (9), and (E)-p-coumaric acid (10). The structural elucidation of these compounds was accomplished through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy techniques. All isolates were tested for their potential to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, the flavonoids (2 R,3 R)-dihydrokaempferol (6) and apigenin (7) exhibited significant inhibitory activity against NO production, with IC50 values of 3.4 µM and 3.0 µM, respectively. These values surpassed the inhibition observed with the positive control, celastrol. Furthermore, a comparison of the guaiacyl glyceryls salcolin A (4) and salcolin B (5), differing in their threo-β- and erythro-guaiacyl glyceryl moieties, revealed potential structure-activity relationships. These findings suggest that the extract from Lycopodium casuarinoides and its phytochemical constituents hold promise as potential anti-inflammatory agents

Experimental and theoretical (DFT) approaches on novel ternary liquid crystals derived from asymmetric aromatic dicarboxylic acid

Novel ternary liquid crystal (TLC) homologues series was designed and prepared from 4-methoxycinnamic acid (4MCA), homophthalic acid (HPA) and 4-n-alkyloxybenzoic acids (nOBA, where n = 6 to 12). The mesogenic behaviour, phase transition temperature, thermal span width and thermal stability factor of TLC (homologues series) were studied by polarising optical microscopy (POM) and differential scanning calorimetry (DSC) techniques. A noteworthy observation is that, TLC induces smectic A (batonnets texture) along with nematic and smectic F phases whereas, the Sm A is not perceived in the individual compounds while compared with the TLC. Further, the existence of smectic phases (Sm A and Sm F) are identified by temperature dependent X-ray diffraction (XRD) analysis. The same are correlated with DSC observations. Density functional theory (DFT) is used to optimize the molecular geometry of TLC. FMO and MEP study explores the molecular environment and quantum chemical behaviour of TLC. NBO, QTAIM and RDG analysis explicate the charge transfer with stabilization energy and non-covalent interactions. Density functional theory (DFT) calculations confirm the possible conformer of TLC.

Chemical constituents of Pteris ensiformis from Guizhou

The phytochemical investigation of Pteris ensiformis from Guizhou has resulted in the isolation of 15 phenolic compounds (1–15), including kaempferol-3-O-glucoside (1), kaempferol-3-O-rhamnoside (2), kaempferol-4′,7-dimethyl ether-3-O-glucoside (3), apigenin-7-O-glucopyranoside (4), diosmetin-7-O-glucoside (5), esculetin (6), 4-methoxycinnamic acid (7), (+)-pinoresinol (8), bockioside B (9), 7-O-caffeoyl-hydroxymaltol-3-O-glucopyranoside (10), cylindol B (11), salicylic acid (12), vanillin (13), vanillic acid (14) and catechol (15). The structures of these compounds were determined based on the analysis of spectroscopic data and comparison with the data reported in literatures. Compounds 1–9, 11–15 were isolated from P. ensiformis for the first time. In addition, the chemotaxonomic significance of the isolated compounds was discussed.

Potential transformation of seagrass (Syringodium isoetifolium) into a bioactive food ingredient using different extraction techniques

Background: Syringodium isoetifolium is a seagrass that grows abundantly in Indonesian territorial waters and has been known to be of high significance not only for the seawater ecosystem, but also for human beings (as food, nutritional and pharmaceutical products). In this study, the bioactive constituent of Syringodium isoetifolium was extracted using several different techniques to recover a maximum yield. Methods: Extraction was carried out by conventional and non-conventional (Microwave-assisted extraction, ultrasound-assisted extraction-bath system, and ultrasound-assisted extraction- (UAE) probe system) techniques with green solvents (water, 50% ethanol, and 100% ethanol). Results: As a result, 50% ethanol and water extracts exhibited a significantly higher yield. Total phenol content was significantly higher for 50% ethanol extract. Different extraction techniques (using 50% ethanol solvent) showed that the UAE-probe was the best technique since it yielded the highest total phenol (17.37 ± 2.16 mg GAE/g) and the richest bioactive compounds (Choline, betaine, 3,5-di-tert-butyl-4-hydroxybenzoic acid, 7-Hydroxycoumarine, 4-Methoxycinnamic acid, Zearalenone, Caffeic acid, Levalbuterol, Phloretin, Dihydrocaffeic acid, Quercetin-3β-D-glucoside and Quercetin). Interestingly, choline was the most abundant compound in the extract obtained with different extraction techniques. In this in silico assay, choline from seagrass extract was shown as an anti-inflammatory. The interaction pathway of the choline compound with receptors (TNF-α, IL-1β, and IL6) had a higher binding affinity value than the inhibitor-receptor interaction (i.e. -3.4, -3.0, and -2.8 kcal/mol). The cytotoxicity test on TIG-1 cells showed that the extract did not have a toxic effect on them. Conclusions: These findings support the potential use of Syringodium isoetifolium as a bioactive food ingredient.

Stability improvement of UV-filter between methoxy cinnamic acid derivatives and cyclodextrins inclusion complexes based on DFT and TD-DFT investigations

Structures and UV–vis absorption spectra of the host-guest interaction of the methoxy cinnamic acid (MCA) derivatives and cyclodextrins (CDs) were performed by using the density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. All geometries of MCA derivatives (4-MCA, 245-MCA, 246-MCA), three types of CD (αCD, βCD, γCD), and five host-guest inclusion complexes between MCA and CD consisting of 4-MCA/αCD (1), 4-MCA/βCD (2), 245-MCA/βCD (3), 246-MCA/βCD (4), and 246-MCA/γCD (5) were fully optimized by using the M06-2X/6-31G (d,p) levels of theory. Two orientations (A and B) of the MCA guest molecule were considered. Upon examining the optimized geometry, five complexes of the methoxy cinnamic acid molecules are located inside the cavity of CD. Orientation B was more stable than orientation A because of the stronger intermolecular hydrogen bonds between the hydroxyl group of CD and the carboxylic group of MCA. The results indicated that the intermolecular hydrogen bond is mainly the driving force of formation between methoxy cinnamic acid and cyclodextrins. To reveal the host-guest interaction that is relevant to UV-filter compounds, the UV–vis absorption spectra were performed using TD-DFT calculations. The obtained results confirmed that orientation B is the most stable orientation and can absorb in both UVB and UVA regions which is similar to the parent MCA. Therefore, this knowledge will bring to understand the host-guest interaction between methoxy cinnamic acid and cyclodextrin complexes. The theoretical results are expected to provide valuable information for improving the stability of further UV-filter compounds.

Phytocompounds, antioxidant potential, and inhibitory actions of ethanolic leaf fraction of Sida linifolia Linn. (Malvaceae) on enzymes linked to inflammation, diabetes, and neurological disorders

Abstract Background Sida linifolia L. is a weed ubiquitously found in Africa with several folkloric applications. Traditional healers in the Southeastern part of Nigeria employ the alcoholic concoction of S. linifolia leaves as antidepressants, anti-malaria, antihypertensive, anti-abortifacients, and for managing painful whitlow; however, these claims lack scientific validation. The present study was aimed to explore the phytochemical profile of the plant, S. linifolia with special emphasis to its antioxidant and inhibitory actions on enzymes linked to inflammation, diabetes, and neurological disorders. Phytochemical profiling and in vitro antioxidant and enzyme inhibition assays were employed to assess the pharmacological profile of S. linifolia ethanolic leaf fraction (SLELF). Results Preliminary phytochemical screening of SLELF revealed appreciable amounts of total phenolics (91.64 ± 7.61 mg GAE/g), total tannins (62.44 ± 3.86 mg TAE/g), and total flavonoids (27.35 ± 1.48 mg QE/g) present in SLELF. Results of HPLC analysis of SLELF revealed rich composition in bioactive compounds such as ellagic acid, quercetin, ferulic acid, 3,4-dimethoxy benzoic acid, gallic acid, 4-methoxy cinnamic acid, sinapic acid, vanillic acid, and chlorogenic acid. Enzymatic antioxidants (catalase and superoxide dismutase), non-enzymatic antioxidants (reduced glutathione (GSH), Vit A, C, and E), elemental minerals (Cu, Mn, Zn, Cr, Fe, and Ca), and γ-aminobutyric acid (GABA) were present in SLELF in appreciable levels. At various concentrations (0.2–1.0 mg/ml), SLELF exhibited potent and concentration-dependent hydrogen peroxide (H2O2) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) radical scavenging activities and exerted moderate inhibitory actions on enzymes associated with inflammation (cyclooxogenase-2 (COX-2) and lipoxygenases (LOXs), diabetes (α-amylase, α-glucosidase), and neurological disorders (butyrylcholinesterase (BChE) and γ-aminobutyric acid transaminase (GABA-T), compared to respective standards (ascorbic acid, acarbose, indomethacin, galanthamine, and vigabatrin). Perhaps, the observed potent pharmacological activities of SLELF could be anchored to its phytoconstituents. Furthermore, the slightly higher ranges of IC50 values (0.57–0.87 mg/ml) of SLELF compared to standards (0.44–0.68 mg/ml) suggest moderation in enzyme inhibition that may preclude adverse side effects. Conclusion This study lends credence to the folklore claims of S. linifolia leaves and revealed its potential as possible source of bioactive compounds for medicinal and pharmaceutical exploration.

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes.

Identification of Differential Compositions of Aqueous Extracts of Cinnamomi Ramulus and Cinnamomi Cortex

Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.

Dynamic changes in the bacterial communities and metabolites of Moringa oleifera leaves during fermentation with or without pyroligneous acid

In this study, Moringa oleifera leaves (MOL) were fermented with or without pyroligneous acid (PA) for 3, 7, 14, and 30 days. PA addition enhanced the contents of acetic acid and true protein (P < 0.01) and decreased pH (P < 0.01) and the contents of coliform bacteria, nonprotein nitrogen (P < 0.01), and ammonium nitrogen (P < 0.01). With the addition of PA, the abundance of Lactobacillus increased, but the abundance of Enterobacter decreased. A total of 754 metabolites were identified. In the MOL fermented with PA, the contents of apigenin, arbutin, 2-methoxy-4-vinyl phenol, and 4-methoxy cinnamic acid increased, while the content of skatole decreased compared with the contents for the MOL fermented without PA. The detected metabolites were correlated with bacterial communities, especially Lactobacillus and Weissella. In conclusion, the addition of PA improves the fermentation quality and protein preservation and affects the microbial communities and metabolites of fermented MOL.

The therapeutic role and mechanism of 4-Methoxycinnamic acid in fungal keratitis

Fungal keratitis is an infectious vision-threatening disease that has a poor prognosis, and the clinical therapeutic drugs have multiple limitations, such as epithelial toxicity and low bioavailability. Therefore, new antifungal treatment strategies must be developed.4-Methoxycinnamic acid (MCA) is a widely occurring natural phenolic acid that has been proven to have multiple effects, such as antibacterial, antifungal, anti-inflammatory, neuroprotective, and inhibiting cancer. In this research, we explored the effects and underlying mechanisms of MCA on A. fumigatus keratitis and the antifungal effects of the combination of MCA and natamycin (NATA) on A. fumigatus. We found that MCA exerts antifungal effects by inhibiting the synthesis of the fungal cell wall, changing the permeability of fungal cell membranes. Moreover, the MCA-NATA combination exhibited synergy for A. fumigatus.In addition, MCA exerted an anti-inflammatory effect by downregulating the inflammatory factors (IL-1β, TNF-α, IL-6, and iNOS) in C57BL/6 mice and RAW264.7 cells. The anti-inflammatory mechanism of MCA was associated with the Mincle signal pathway.In summary, MCA acts as a potential therapeutic drug for fungal keratitis and a potential antifungal sensitizer for natamycin. MCA inhibits fungal cell wall synthesis, destroys the permeability of fungal cell membranes, and mediates the anti-inflammatory, immune response of the host.

Correlation between Chemical Profile of Georgian Propolis Extracts and Their Activity against Helicobacter pylori.

Helicobacter pylori (H. pylori) is considered the most common bacterial pathogen colonizing stomach mucosa of almost half the world's population and is associated with various gastrointestinal diseases (from digestive problems and ulcers to gastric cancer). A lack of new drugs and a growing number of H. pylori antibiotic-resistant strains is a serious therapeutic problem.As a mixture of natural compounds, propolis has antimicrobial activity based on high concentrations of bioactive polyphenols (mainly flavonoids and phenolic acid derivates). The chemical composition of tested Georgian propolis is characterized by the presence of flavonoids aglycones, and phenolic acid monoesters, e.g., pinobanksin-5-methyl ether, pinobanksin, chrysin, pinocembrin, galangin, pinobanksin-3-O-acetate, pinostrobin and pinobanksin-3-O-butanoate, or isobutanoate and methoxycinnamic acid cinnamyl ester. The anti-H. pylori activity of 70% ethanol water extracts of 10 Georgian propolis samples was evaluated in vitro by MIC (minimal inhibitory concentration) against the reference strain (H. pylori ATCC 43504) and 10 clinical strains with different antibiotic-resistance patterns. The strongest anti-Helicobacter activity (MIC and MBC = 31.3 µg/mL) was observed for propolis from Orgora, Ota, and Vardzia and two from Khaheti. Lower levels of activity (MIC = 62.5 µg/mL) were found in propolis obtained from Qvakhreli and Pasanauri, while the lowest effect was observed for Norio and Mestia (MIC = 125.0 µg/mL). However, despite differences in MIC, all evaluated samples exhibited bactericidal activity. We selected the most active propolis samples for assessment of urease inhibition property. Enzyme activity was inhibited by propolis extracts, with IC50 ranging from 4.01 to 1484.8 µg/mL. Principal component analysis (PCA) and hierarchical fuzzy clustering (dendrograms) coupled with matrix correlation analysis exhibited that the strongest anti-Helicobacter activity was connected with black poplar origin and high flavonoid content of propolis. Samples with lower activity contained higher presence of aspen markers and/or dominance of non-flavonoid polyphenols over flavonoids. In summary, Georgian propolis can be regarded as a source bioactive compounds that can be used as adjuvant in therapy of H. pylori infection.

Penetration study of p-methoxycinnamic acid (PMCA) in nanostructured lipid carrier, solid lipid nanoparticles, and simple cream into the rat skin

This study compared the ability of Nanostructured Lipid Carrier (NLC), Solid Lipid Nanoparticles (SLN), and Cream systems in delivering para Methoxycinnamic Acid (PMCA) to the dermis layer of the skin. Wistar rats were used as research subjects. NLC and SLN were made by applying the high shear homogenization method. Nile red was used as a penetration indicator based on its fluorescence. The interaction between fluorescence labeled NLC, SLN, or Cream and rat skin was visualized by fluorescence microscopy. Observations were made after 2 and 4.5 h of smearing the test sample. From the observations, it was known that the system/lipid base could penetrate the stratum corneum for delivering drugs. Penetration speed differs among systems as does the number of PMCAs that can be delivered. In this study, it can be concluded that the NLC system is able to deliver PMCA more quickly and in greater quantities to the dermis than SLN and Cream.