Cis-cinnamic Acid Research Articles

Pain healing potential of famous traditional fermented Rhododendron (Lali-Guras) beverages from Indo-Nepal Himalaya: In vitro and in silic o evaluation

Abstract This in vitro and in silico study was designed to validate acclaimed anti-inflammatory or pain-relieving properties of fermented ethnic beverages prepared from Rhododendron or Guras flowers in the Singalila ridge- the famous Rhododendron growing region of the Himalayas. Traditional beverages Guras wine and its distilled version Guras Raksi were considered in this study which were collected from Gairibas, a village situated in Indo-Nepal Singalila Ridge of the Himalayas. In vitro protein (albumin) denaturation inhibition assay was conducted to evaluate anti-inflammatory activity of the samples and later GC-MS analysis was carried out to identify anti-inflammatory compounds present in those beverages. From GC-MS results, eleven major metabolites such as 5-hydroxymethylfurfural; quinic acid; clionasterol; l-(+)-ascorbic acid, 2,6-dihexadecanoate; d-sorbitol; cis-cinnamic acid; tyrosol; lupeol; methyl commate A; 2-hydroxy-gamma-butyrolactone; and 1,3-propanediol, 2-(hydroxymethyl)- 2-nitro- were chosen for molecular docking with human cyclooxygenase-1 (hCOX-1), an important targets in the drug-design for nonsteroidal anti-inflammatory drugs. Among all query compounds, phytosterol- clionasterol and triterpenoid- lupeol and methyl commate A exhibited considerably high binding energy scores (<-8 kcal/mol) even compared to anti-inflammatory drugs- acetaminophen and ibuprofen. Outcome of this research affirmed the potential of Gurasbased traditional drinks in the healing of different forms of high-altitudinal stress induced pain.

Metabolome and Transcriptome Analyses Reveal the Differences in the Molecular Mechanisms of Oat Leaves Responding to Salt and Alkali Stress Conditions

Plant growth and production are more severely inhibited by alkalinity than by salinity. However, the metabolites responsible for the reduced growth caused by alkalinity are largely unknown. Here, the Illumina RNA-Seq analysis and targeted metabolome were used to identify the differentially expressed genes and metabolites responding to salt and alkali stresses. The expression levels of eight genes related to photosynthesis and some genes related to chlorophyll synthesis decreased under alkali stress, whereas no changes were detected under salt stress, which may explain the observed lower level of photosynthetic rate in alkalinity than in salinity. Under alkali stress, significant decreases in the relative abundances of cis-cinnamic acid and scopoline were observed, which correlated with the high levels of reactive oxygen species (ROS). The levels of protocatechuic acids decreased, correlating with the observed decrease in the chlorophyll content. Alkalinity markedly increased the production of o-coumaric acid, which contributes to growth inhibition. No significant changes in cis-cinnamic acid, scopoline, and o-coumaric acid were detected in salinity, which may be the reason for the stronger growth inhibition due to alkali stress than salt stress. The accumulation of citric acid, serotonin, pyroglutamic acid, L-citrulline, ferulic acid, and caffeic acid was detected under salt and alkali stress conditions, indicating high free radical scavenging capacity. The enhancement of mevalonic acid and salicylic acid levels was detected under alkali stress, which could have facilitated chlorophyll accumulation. Salt and alkali stress conditions also led to the accumulation of cyclic AMP related to inorganic ion regulation and betaine-related osmoregulation. Benzamide, phenethylamine, N-feruloyltyramine, chrysoeriol 6-C-hexoside, 1,3-o-di-p-coumaroyl glycerol, cordycepin, and 1-o-p-cumaroylglycerol were identified to be accumulated in response to alkali stress.

Phlogacanthus cornutus: chemical profiles and antioxidant effects

Phlogacanthus cornutus is a rare species and the chemical profiles and the bioactivities of this plant are unknown. In present study, the chemical components of the acetone extract as well as the antioxidant activity of acetone extract and its fractions such as n-hexane, chloroform and ethyl acetate of P. cornutus were firstly reported. A total of 33 constituents were identify in the acetone extract of this plant using Gas Chromatography/Mass Spectrometry assay, in which trans-cinnamic acid (21.26%), neophytadiene (6.36%), linolenic acid (5.86%), dihydroagathic acid (5.71%), n-hexadecanoic acid (5.53%), phytol (4.14%) and cis-cinnamic acid (3.23%) were the major compounds. The acetone extract and its fractions such as n-hexane, chloroform and ethyl acetate of P. cornutus showed DPPH radical scavenging activity with IC50 value of 234.31, 185.95, 758.65 and 458.52 µg/mL respectively.

A New Series of Strigolactone Analogs Derived From Cinnamic Acids as Germination Inducers for Root Parasitic Plants.

Root parasitic plants such as Striga and Orobanche cause significant damage on crop production, particularly in sub-Saharan Africa. Their seeds germinate by sensing host root-derived signaling molecules called strigolactones (SLs). SL mimics can be used as suicidal germination inducers for root parasitic plants. Previous attempts to develop such chemicals have revealed that the methylbutenolide ring (D-ring), a common substructure in all the naturally occurring SLs, is critical for SL agonistic activity, suggesting that it should be possible to generate new SL mimics simply by coupling a D-ring with another molecule. Because structural information regarding SLs and their receptor interaction is still limited, such an approach might be an effective strategy to develop new potent SL agonists. Here, we report development of a series of new SL analogs derived from cinnamic acid (CA), the basis of a class of phenylpropanoid natural products that occur widely in plants. CA has an aromatic ring and a double-bond side-chain structure, which are advantageous for preparing structurally diverse derivatives. We prepared SL analogs from cis and trans configuration CA, and found that all the cis-CA-derived SL analogs had stronger activities as seed germination inducers for the root parasitic plants, Orobanche minor and Striga hermonthica, compared with the corresponding trans-CA-derived analogs. Moreover, introduction of a substitution at the C-4 position increased the germination-stimulating activity. We also found that the SL analogs derived from cis-CA were able to interact directly with SL receptor proteins more effectively than the analogs derived from trans-CA. The cis isomer of CA was previously reported to have a growth promoting effect on non-parasitic plants such as Arabidopsis. We found that SL analogs derived from cis-CA also showed growth promoting activity toward Arabidopsis, suggesting that these new SL agonists might be useful not only as suicidal germination inducers for root parasitic weeds, but also as plant growth promoters for the host plants.

Seedling developmental defects upon blocking CINNAMATE-4-HYDROXYLASE are caused by perturbations in auxin transport.

The phenylpropanoid pathway serves a central role in plant metabolism, providing numerous compounds involved in diverse physiological processes. Most carbon entering the pathway is incorporated into lignin. Although several phenylpropanoid pathway mutants show seedling growth arrest, the role for lignin in seedling growth and development is unexplored. We use complementary pharmacological and genetic approaches to block CINNAMATE-4-HYDROXYLASE (C4H) functionality in Arabidopsis seedlings and a set of molecular and biochemical techniques to investigate the underlying phenotypes. Blocking C4H resulted in reduced lateral rooting and increased adventitious rooting apically in the hypocotyl. These phenotypes coincided with an inhibition in AUX transport. The upstream accumulation in cis-cinnamic acid was found to be likely to cause polar AUX transport inhibition. Conversely, a downstream depletion in lignin perturbed phloem-mediated AUX transport. Restoring lignin deposition effectively reestablished phloem transport and, accordingly, AUX homeostasis. Our results show that the accumulation of bioactive intermediates and depletion in lignin jointly cause the aberrant phenotypes upon blocking C4H, and demonstrate that proper deposition of lignin is essential for the establishment of AUX distribution in seedlings. Our data position the phenylpropanoid pathway and lignin in a new physiological framework, consolidating their importance in plant growth and development.

ON THE THERMODYNAMICS OF ANTIOXIDANT ACTION OF NATURALLY OCCURRING HYDROXYDERIVATIVES OF CIS-CINNAMIC ACID

Antioxidant activity represents one of the important features of phenolic acids, such as hydroxyderivatives of cinnamic acid. However, in the case of cis-cinnamic acid derivatives, corresponding thermochemistry data can be still considered scarce. This work is focused on the two most relevant mechanisms of primary antioxidant action in gas-phase, non-polar benzene and in aqueous solution. Reaction enthalpies describing thermodynamics of Hydrogen Atom Transfer (HAT) and Sequential Proton-Loss – Electron Transfer (SPLET) mechanisms were theoretically investigated using (SMD) M06-2X/6-311++G(d,p) method for cis-ortho-coumaric, cis-meta-coumaric, cis-para-coumaric, cis-ferulic, cis-sinapic and cis-caffeic acid and their carboxylate anions. The effect of carboxyl COOH group deprotonation on the thermodynamics of studied mechanisms was assessed for the three environments.

Cis-Cinnamic acid is a natural plant growth-promoting compound.

Agrochemicals provide vast potential to improve plant productivity, because they are easy to implement at low cost while not being restricted by species barriers as compared with breeding strategies. Despite the general interest, only a few compounds with growth-promoting activity have been described so far. Here, we add cis-cinnamic acid (c-CA) to the small portfolio of existing plant growth stimulators. When applied at low micromolar concentrations to Arabidopsis roots, c-CA stimulates both cell division and cell expansion in leaves. Our data support a model explaining the increase in shoot biomass as the consequence of a larger root system, which allows the plant to explore larger areas for resources. The requirement of the cis-configuration for the growth-promoting activity of CA was validated by implementing stable structural analogs of both cis- and trans-CA in this study. In a complementary approach, we used specific light conditions to prevent cis/trans-isomerization of CA during the experiment. In both cases, the cis-form stimulated plant growth, whereas the trans-form was inactive. Based on these data, we conclude that c-CA is an appealing lead compound representing a novel class of growth-promoting agrochemicals. Unraveling the underlying molecular mechanism could lead to the development of innovative strategies for boosting plant biomass.

Cis-Cinnamic Acid Is a Novel, Natural Auxin Efflux Inhibitor That Promotes Lateral Root Formation.

Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.

Synthesis of fluorescent molecular probes based on cis-cinnamic acid and molecular imaging of lettuce roots

We synthesized azo dye- and fluorescence-labeled cis-cinnamic acid analogues possessing inhibitory activity against lettuce root growth and a trans-isomer without bioactivity as a control probe. The radicles incubated with the azo dye-labeled analogue were stained red, with their tips especially deeply dyed. The fluorescent images of the radicles incubated with each of these molecular probes depicted that the root cap was fluorescence-stained. However, images of the control radicles prepared by staining with the trans-isomer fluorescent probe did not show emission at the root cap. These contrasts suggest specific localization of the cis-cinnamate analogue at the columella cells.

Solid-state photochemistry of cis-cinnamic acids: a competition between [2 + 2] addition and cis–trans isomerization

With three examples, we have established that cis-cinnamic acids can dimerize via a diradical intermediate in the crystalline state provided that the intermolecular distance is less than 4.2 A. In the excited state of cis-isomers, C–C bond formation with an adjacent molecule competes with geometric isomerization.

Cis-Cinnamic acid selective suppressors distinct from auxin inhibitors.

The activity of cis-cinnamic acid (cis-CA), one of the allelochemicals, in plants is very similar to that of indole-3-acetic acid (IAA), a natural auxin, and thus cis-CA has long been believed to be an analog of auxin. We have reported some structure-activity relationships studies by synthesizing over 250 cis-CA derivatives and estimating their inhibitory activities on root growth inhibition in lettuce. In this study, the compounds that showed low- or no-activity on root growth inhibition were recruited as candidates suppressors against cis-CA and/or auxin and tested for their activity. In the presence of cis-CA, lettuce root growth was inhibited; however, the addition of some cis-CA derivatives restored control-level root growth. Four compounds, (Z)-3-(4-isopropylphenyl)acrylic acid, (Z)-3-(3-butoxyphenyl)acrylic acid, (Z)-3-[3-(pentyloxy)phenyl]acrylic acid, and (Z)-3-(naphthalen-1-yl)acrylic acid were selected as candidates for a cis-CA selective suppressor they allowed the recovery of root growth from inhibition by cis-CA treatment without any effects on the IAA-induced effect or elongating activity by themselves. Three candidates significantly ameliorated the root shortening by the potent inhibitor derived from cis-CA. In brief, we have found some cis-CA selective suppressors which have never been reported from inactive cis-CA derivatives for root growth inhibition. cis-CA selective suppressors will play an important role in elucidating the mechanism of plant growth regulation.

Design and synthesis of conformationally constrained analogues of cis-cinnamic acid and evaluation of their plant growth inhibitory activity.

1-O-cis-Cinnamoyl-β-D-glucopyranose is known to be one of the most potent allelochemical candidates and was isolated from Spiraea thunbergii Sieb by Hiradate et al. (2004), who suggested that it derived its strong inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity. In this study, key structural features and substituent effects of cis-cinnamic acid (cis-CA) on lettuce root growth inhibition was investigated. These structure-activity relationship studies indicated the importance of the spatial relationship of the aromatic ring and carboxylic acid moieties. In this context, conformationally constrained cis-CA analogues, in which the aromatic ring and cis-olefin were connected by a carbon bridge, were designed, synthesized, and evaluated as plant growth inhibitors. The results of the present study demonstrated that the inhibitory activities of the five-membered and six-membered bridged compounds were enhanced, up to 0.27 μM, and were ten times higher than cis-CA, while the potency of the other compounds was reduced.

Substituent effects of cis-cinnamic acid analogues as plant growh inhibitors.

1-O-cis-Cinnamoyl-β-D-glucopyranose is one of the most potent allelochemicals that has been isolated from Spiraea thunbergii Sieb by Hiradate et al. It derives its strong inhibitory activity from cis-cinnamic acid (cis-CA), which is crucial for phytotoxicity. By preparing and assaying a series of cis-CA analogues, it was previously found that the key features of cis-CA for lettuce root growth inhibition are a phenyl ring, cis-configuration of the alkene moiety, and carboxylic acid. On the basis of a structure-activity relationship study, the substituent effects on the aromatic ring of cis-CA were examined by systematic synthesis and the lettuce root growth inhibition assay of a series of cis-CA analogues having substituents on the aromatic ring. While ortho- and para-substituted analogues exhibited low potency in most cases, meta-substitution was not critical for potency, and analogues having a hydrophobic and sterically small substituent were more likely to be potent. Finally, several cis-CA analogues were found to be more potent root growth inhibitors than cis-CA.

Acylated Flavonoid from Vaccinium Corymbosum (Ericaceae) Flowers with Yeast α-Glucosidase Inhibitory Activity

Purpose: To isolate and identify chemical constituents with yeast α-glucosidase inhibitory activity from the methanol extract of V. myrtillus (blueberry) flowers.Methods: The active fraction (ethyl acetate extract) were chromatographed on C18 MPLC column, Sephadex LH-20 column and semi-preparative HPLC column. The isolated compounds were identified by the extensive 1H-nuclear magnetic resonance spectroscopy (NMR), 13C-NMR, 2D-NMR and high resolution mass spectral (HR-MS) analyses.Results: Two phenolic compounds, an acylated flavonoid and a coumaric acid derivative, were isolated and identified as isorhamnetin-3-O-(6''-O-coumaroyl)-β-D-glucoside (1) and cis-cinnamic acid methyl (2). Compound 1 showed powerful α-glucosidase inhibitory activity and in this regard, was superior to the positive drug, acarbose.Conclusion: Compounds 1 and 2 were isolated for the first time from this species and the genus of Vaccinium. This is the first report on characterization of these phenolic compounds and the possible utilization of blueberry flowers for nutraceutical and functional food applications.Keywords: Vaccinium corymbosum, Blueberry, Acylated flavonoid, Yeast α-Glucosidase, Inhibitory activity, Nutraceuticals

High Purity cis-Cinnamic Acid Preparation for Studying Physiological Role of trans-Cinnamic and cis-Cinnamic Acids in Higher Plants

Fil: Salum, Maria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina;

Root-specific induction of early auxin-responsive genes in Arabidopsis thaliana by cis-cinnamic acid

Root-specific induction of early auxin-responsive genes in Arabidopsis thaliana by cis-cinnamic acid

Synthesis of cis-Cinnamic Acid from trans-Cinnamaldehyde over Ag+-Exchanged Beta-Zeolite in Toluene

With a view to promoting green chemistry, cis-cinnamic acid (cis-CA) has been synthesized by using Ag-exchanged zeolites (AGZ). cis-CA [(Z)-3-phenyl-2-propenoic acid] and derivatives are physiologically active substances having plant growth regulatory activity, and have recently been isolated from plants[1,2]. Methods of synthesizing cis-CA reported up to now include photoisomerization of trans-cinnamic acid [the (E)-form, trans-CA], the method of reacting (Z)-2-bromostyrene with carbon monoxide in the presence of a palladium triphenylphosphine phasetransfer catalyst[3], and the method of electrolytic carboxylation of 2-bromostyrene using a nickel catalyst[4]. On the other hand, silver ion (Ag) -exchanged zeolite, silver ion supported on porous material[5] and complex membranes made up of amino acids and silver polymers[6] and the like have been utilized as olefin separation agents. In the present study, cis-CA was prepared in one pot synthesis using AGZ in toluene by novel methods of isomerization and oxidation of trans-cinnamaldehyde (TCA) to cis-CA exploiting the fact that Ag soft Lewis acid on AGZ forms a π -complex with the olefin double bond of TCA and reacts as the oxidant. (Scheme 1)

Key structural features of cis-cinnamic acid as an allelochemical.

1-O-cis-cinnamoyl-β-D-glucopyranose is one of the most potent allelochemicals isolated from Spiraea thunbergii Sieb. It is suggested that it derives its strong inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity. It was synthesized to confirm its structure and bioactivity, and also a series of cis-cinnamic acid analogues were prepared to elucidate the key features of cis-cinnamic acid for lettuce root growth inhibition. The cis-cyclopropyl analogue showed potent inhibitory activity while the saturated and alkyne analogues proved to be inactive, demonstrating the importance of the cis-double bond. Moreover, the aromatic ring could not be replaced with a saturated ring. However, the 1,3-dienylcyclohexene analogue showed strong activity. These results suggest that the geometry of the C-C double bond between the carboxyl group and the aromatic ring is essential for potent inhibitory activity. In addition, using several light sources, the photostability of the cinnamic acid derivatives and the role of the C-C double bond were also investigated.

Stereoselective synthesis of β-glycosyl esters of cis-cinnamic acid and its derivatives using unprotected glycosyl donors

The β-glycosyl esters of cis-cinnamic acid were synthesized directly using Hannesian’s unprotected glycosyl donor and the carboxylic acid in toluene. This protocol does not require protecting groups on the glycosyl donors, and high stereoselectivity was achieved. The first synthesis of a potent allelochemical, 1- O- cis-cinnamoyl-β- d-glucopyranose, is also described.

A comparative study on the effectiveness of cis- and trans-form of cinnamic acid treatments for inhibiting invasive activity of human lung adenocarcinoma cells

Lung cancer is the major cause of tumor-related death, and approximately 70% of lung cancer patients die from metastasis. Evidence that phenolic compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. Cinnamic acid is a member of phenolics which having several isoforms in nature. The trans-cinnamic acid ( t-CA) has been investigated extensively for its potential pharmacological effects whereas the study of cis-cinnamic acid ( c-CA) is limited because pure c-CA was hard to obtain. We had developed a practicable method previously to transform and obtain pure c-CA, and the pure compound was used to evaluate the anti-invasive effect on human adenocarcinoma A549 cells. The A549 cells were treated with 0–200 μM of c-CA and t-CA in the presence of 200 nM phorbol-12-myristate-13-acetate (PMA) at 37 °C for 24 h, and matrix metalloproteinase (MMP)-2, MMP-9, adhesive, migratory, and invasive activities of the cells were determined. The results showed that the treatment of c-CA and t-CA dose-dependently reduced the PMA-induced MMP-2 and -9 activities but without significant effect on the adhesive activity of cells. The PMA-induced motility was suppressed in a dose-dependent manner by a 24-h treatment with c-CA and t-CA. The invasive ability was significantly ( p < 0.05) reduced to 68% and 65%, respectively, relative to PMA treatment alone after treatment of PMA-treated A549 cells with either 50 μM c-CA or 100 μM t-CA for 24 h. The results suggest that both of the c-CA and t-CA are inhibitors for invasion of A549 cells and the activity of c-CA seems to be higher than t-CA.