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  1. Cheah HL, Lim V, Sandai D
    PLoS One, 2014;9(4):e95951.
    PMID: 24781056 DOI: 10.1371/journal.pone.0095951
    Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis.
    Matched MeSH terms: Cinnamates/pharmacology
  2. Ngo YL, Lau CH, Chua LS
    Food Chem Toxicol, 2018 Nov;121:687-700.
    PMID: 30273632 DOI: 10.1016/j.fct.2018.09.064
    Rosmarinic acid is a bioactive phytochemical that can be found in many herbs as ethnomedicines. It possesses remarkable pharmacological activities, and thus leading to its exploration as a therapeutic drug in diabetes treatment recently. This article reviews the extraction and fractionation techniques for plant-based natural rosmarinic acid and its anti-diabetic potential based on literature data published in journals, books, and patents from 1958 to 2017. Factors affecting the performance of rosmarinic acid extraction and fractionation such as operating temperature, time, solvent to sample ratio and eluent system are compiled and discussed in detail. The inhibitory action of rosmarinic acid against sugar digestive enzymes, and protective action towards pancreatic β-cell dysfunction and glucolipotoxicity mediated oxidative stress are also critically reviewed. The optimal parameters are largely dependent on the applied extraction and fractionation techniques, as well as the nature of plant samples. Previous studies have proven the potent role of rosmarinic acid to control plasma glucose level and increase insulin sensitivity in hyperglycemia. Although rosmarinic acid is readily absorbed by human body, its mechanism after consumption is remained unclear. Intensive studies should be well planned to determine the dosage and toxicity level of rosmarinic acid for efficacy and safe consumption.
    Matched MeSH terms: Cinnamates/pharmacology*
  3. Rajendran K, Anwar A, Khan NA, Shah MR, Siddiqui R
    ACS Chem Neurosci, 2019 06 19;10(6):2692-2696.
    PMID: 30970208 DOI: 10.1021/acschemneuro.9b00111
    Primary amoebic meningoencephalitis (PAM), a deadly brain infection, is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin, and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95%. Moreover, severe adverse side effects are associated with these drugs. Nanotechnology has provided several advances in biomedical applications especially in drug delivery and diagnosis. Herein, for the first time we report antiamoebic properties of cinnamic acid (CA) and gold nanoparticles conjugated with CA (CA-AuNPs) against N. fowleri. CA-AuNPs were successfully synthesized by sodium borohydride reduction of tetrachloroauric acid. Size and morphology were determined by atomic force microscopy (AFM) while the surface plasmon resonance band was analyzed by ultraviolet-visible (UV-vis) spectrophotometry for the characterization of the nanoparticles. Amoebicidal and cytopathogenicity (host cell cytotoxicity) assays revealed that both CA and CA-AuNPs displayed significant anti- N. fowleri properties ( P < 0.05), whereas nanoparticles conjugation further enhanced the anti- N. fowleri effects of CA. This study established a potential drug lead, while CA-AuNPs appear to be promising candidate for drug discovery against PAM.
    Matched MeSH terms: Cinnamates/pharmacology*
  4. Choo WS, Birch EJ, Stewart I
    Lipids, 2009 Sep;44(9):807-15.
    PMID: 19727883 DOI: 10.1007/s11745-009-3334-2
    Lipase-catalyzed transesterification of flaxseed oil with cinnamic acid (CA) or ferulic acid (FA) using an immobilized lipase from Candida antarctica (E.C. 3.1.1.3) was conducted to evaluate whether the lipophilized products provided enhanced antioxidant activity in the oil. Lipase-catalyzed transesterification of flaxseed oil with CA or FA produced a variety of lipophilized products (identified using ESI-MS-MS) such as monocinnamoyl/feruloyl-diacylglycerol, dicinnamoyl-monoacylglycerol and monocinnamoyl-monoacylglycerol. The free radical scavenging activity of the lipophilized products of lipase-catalyzed transesterification of flaxseed oil with CA or FA toward 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) were both examined in ethanol and ethyl acetate. The polarity of the solvents proved important in determining the radical scavenging activity of the substrates. Unesterified FA showed the highest free radical scavenging activity among all substrates tested while CA had negligible activity. The esterification of CA or FA with flaxseed oil resulted in significant increase and decrease in the radical scavenging activity compared with the native phenolic acid, respectively. Based on the ratio of a substrate to DPPH. concentration, lipophilized FA was a much more efficient free radical scavenger compared to lipophilized CA and was able to provide enhanced antioxidant activity in the flaxseed oil. Lipophilized cinnamic acid did not provide enhanced radical scavenging activity in the flaxseed oil as the presence of natural hydrophilic antioxidants in the oil had much greater radical scavenging activity.
    Matched MeSH terms: Cinnamates/pharmacology*
  5. Anwar A, Siddiqui R, Shah MR, Khan NA
    PMID: 29967024 DOI: 10.1128/AAC.00630-18
    trans-Cinnamic acid (CA) is a natural organic compound. Using amoebicidal assays, for the first time we showed that CA affected the viability of the protist pathogen Acanthamoeba castellanii Conjugation with gold nanoparticles (AuNPs) enhanced the antiamoebic effects of CA. CA-coated AuNPs (CA-AuNPs) also exhibited significant excystation and encystation activity, compared to CA and AuNPs alone. Pretreatment of amoebae with CA-AuNPs inhibited A. castellanii-mediated host cell cytotoxicity. Moreover, CA-AuNPs exhibited potent effects against methicillin-resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1 and protected host cells against bacteria-mediated host cell death.
    Matched MeSH terms: Cinnamates/pharmacology*
  6. Adewoyin M, Mohsin SM, Arulselvan P, Hussein MZ, Fakurazi S
    Drug Des Devel Ther, 2015;9:2475-84.
    PMID: 25995619 DOI: 10.2147/DDDT.S72716
    BACKGROUND: Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA.

    METHODS: In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined.

    RESULTS: Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only.

    CONCLUSION: The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control.

    Matched MeSH terms: Cinnamates/pharmacology*
  7. Ee SF, Mohamed-Hussein ZA, Othman R, Shaharuddin NA, Ismail I, Zainal Z
    ScientificWorldJournal, 2014;2014:840592.
    PMID: 24678279 DOI: 10.1155/2014/840592
    Polygonum minus is an aromatic plant, which contains high abundance of terpenoids, especially the sesquiterpenes C15H24. Sesquiterpenes were believed to contribute to the many useful biological properties in plants. This study aimed to functionally characterize a full length sesquiterpene synthase gene from P. minus. P. minus sesquiterpene synthase (PmSTS) has a complete open reading frame (ORF) of 1689 base pairs encoding a 562 amino acid protein. Similar to other sesquiterpene synthases, PmSTS has two large domains: the N-terminal domain and the C-terminal metal-binding domain. It also consists of three conserved motifs: the DDXXD, NSE/DTE, and RXR. A three-dimensional protein model for PmSTS built clearly distinguished the two main domains, where conserved motifs were highlighted. We also constructed a phylogenetic tree, which showed that PmSTS belongs to the angiosperm sesquiterpene synthase subfamily Tps-a. To examine the function of PmSTS, we expressed this gene in Arabidopsis thaliana. Two transgenic lines, designated as OE3 and OE7, were further characterized, both molecularly and functionally. The transgenic plants demonstrated smaller basal rosette leaves, shorter and fewer flowering stems, and fewer seeds compared to wild type plants. Gas chromatography-mass spectrometry analysis of the transgenic plants showed that PmSTS was responsible for the production of β -sesquiphellandrene.
    Matched MeSH terms: Cinnamates/pharmacology
  8. Ghasemzadeh A, Jaafar HZ
    PMID: 24289290 DOI: 10.1186/1472-6882-13-341
    Phytochemicals and antioxidants from plant sources are of increasing interest to consumers because of their roles in the maintenance of human health. Most of the secondary metabolites of herbs are used in a number of pharmaceutical products.
    Matched MeSH terms: Cinnamates/pharmacology*
  9. Hafizur RM, Hameed A, Shukrana M, Raza SA, Chishti S, Kabir N, et al.
    Phytomedicine, 2015 Feb 15;22(2):297-300.
    PMID: 25765836 DOI: 10.1016/j.phymed.2015.01.003
    Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.
    Matched MeSH terms: Cinnamates/pharmacology*
  10. Gautam RK, Gupta G, Sharma S, Hatware K, Patil K, Sharma K, et al.
    Int J Rheum Dis, 2019 Jul;22(7):1247-1254.
    PMID: 31155849 DOI: 10.1111/1756-185X.13602
    AIM: The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum.

    METHOD: Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated.

    RESULTS: Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P 

    Matched MeSH terms: Cinnamates/pharmacology*
  11. Kim RP, Bihud V, Bin Mohamad K, Leong KH, Bin Mohamad J, Bin Ahmad F, et al.
    Molecules, 2012 Dec 21;18(1):128-39.
    PMID: 23344192 DOI: 10.3390/molecules18010128
    Eleven compounds:goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC(50)value of 64.17 ± 5.60 µM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC(50) of 0.207 µM.
    Matched MeSH terms: Cinnamates/pharmacology
  12. Hsieh CF, Jheng JR, Lin GH, Chen YL, Ho JY, Liu CJ, et al.
    Emerg Microbes Infect, 2020 Dec;9(1):1194-1205.
    PMID: 32397909 DOI: 10.1080/22221751.2020.1767512
    Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, Salvia miltiorrhiza (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and in vivo mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed to be refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.
    Matched MeSH terms: Cinnamates/pharmacology
  13. Yusoff MM, Ibrahim H, Hamid NA
    Chem Biodivers, 2011 May;8(5):916-23.
    PMID: 21560240 DOI: 10.1002/cbdv.201000270
    Two poorly studied, morphologically allied Alpinia species endemic to Borneo, viz., A. ligulata and A. nieuwenhuizii, were investigated here for their rhizome essential oil. The oil compositions and antimicrobial activities were compared with those of A. galanga, a better known plant. A fair number of compounds were identified in the oils by GC-FID and GC/MS analyses, with large differences in the oil composition between the three species. The rhizome oil of A. galanga was rich in 1,8-cineole (29.8%), while those of A. ligulata and A. nieuwenhuizii were both found to be extremely rich in (E)-methyl cinnamate (36.4 and 67.8%, resp.). The three oils were screened for their antimicrobial activity against three Gram-positive and three Gram-negative bacteria and two fungal species. The efficiency of growth inhibition of Staphylococcus aureus var. aureus was found to decline in the order of A. nieuwenhuizii>A. ligulata ∼ A. galanga, while that of Escherichia coli decreased in the order of A. galanga>A. nieuwenhuzii ∼ A. ligulata. Only the A. galanga oil inhibited the other bacteria and the fungi tested.
    Matched MeSH terms: Cinnamates/pharmacology
  14. Umar MI, Asmawi MZ, Sadikun A, Majid AM, Al-Suede FS, Hassan LE, et al.
    Clinics (Sao Paulo), 2014 Feb;69(2):134-44.
    PMID: 24519205 DOI: 10.6061/clinics/2014(02)10
    The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga.
    Matched MeSH terms: Cinnamates/pharmacology*
  15. Srivastava N, Mishra S, Iqbal H, Chanda D, Shanker K
    J Ethnopharmacol, 2021 May 10;271:113911.
    PMID: 33571614 DOI: 10.1016/j.jep.2021.113911
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog). Although ethnomedicinal properties have extensively been demonstrated in traditional medicines of south-east countries i.e. China, India, Indonesia, and Malaysia, the chemico-biological validation are still lacking.

    AIM OF THE STUDY: Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action.

    MATERIALS AND METHODS: A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. The vasorelaxation effect of major phytochemicals of KGR was evaluated on the main mesenteric arteries isolated from male Wistar rats. Specific BKca channel blocker tetraethylammonium (TEA), receptor antagonist, nitric oxide scavenging capacity, and antioxidant potential were also evaluated for its plausible mechanism.

    RESULTS: Present validated HPLC method facilitates simultaneous quantitation of EPMC and EC faster than classical GC techniques. EPMC has shown a dose-dependent relaxation in rat main mesenteric arteries (MMA) contracted by U46619 with an Emax of 58.68 ± 3.31%. Similarly, in endothelium-denuded MMA rings, relaxation was also observed (Emax of 61.83 ± 3.38%). Moreover, relaxation response to EPMC has strongly inhibited (Emax 14.76 ± 2.29%) when the tissue exposed to depolarizing high K+ containing buffer for the contraction. The point correlation dimension (pD2) values were also significantly decreased in high K+ treated arterial rings compared to control. Interestingly, when MMA rings incubated with a specific BKca channel blocker (TEA, 1 mM), the relaxation response to EPMC was also significantly blocked.

    CONCLUSIONS: The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.

    Matched MeSH terms: Cinnamates/pharmacology*
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