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Protective Role of Ternatin Anthocyanins and Quercetin Glycosides from Butterfly Pea ( Clitoria ternatea Leguminosae) Blue Flower Petals against Lipopolysaccharide (LPS)-Induced Inflammation in Macrophage Cells
Abstract
From the blue flowers of Clitoria ternatea twelve phenolic metabolites (9 Ternatin anthocyanins and 3 glycosylated quercetins) were identified by high- performance liquid chromatography diode array detection and electrospray ionization/mass spectrometry (HPLC-DAD-ESI/MSn). Three anthocyanins not reported in this species before show fragmentation pattern of the Ternatin class. Extracts were fractionated in fractions containing flavonols (F3) and Ternatin anthocyanins (F4). In general, Clitoria ternatea polyphenols showed anti-inflammatory properties in LPS-induced inflammation in RAW 264.7 macrophage cells with distinct molecular targets. Flavonols (F3) showed strong inhibition of COX-2 activity and partial ROS suppression. On the other hand the Ternatin anthocyanins (F4) inhibited nuclear NF-κB translocation, iNOS protein expression and NO production through a non-ROS suppression mechanism. Accordingly, quercetin glycosides and Ternatin anthocyanins from the blue flower petals of Clitoria ternatea may be useful in developing drugs or nutraceuticals for protection against chronic inflammatory diseases by suppressing the excessive production of pro-inflammatory mediators from macrophage cells.
... C. ternatea has a high level of availability and is easy to cultivate. C. ternatea flowers contain alkaloids, saponins, terpenoids, phenols, flavonoids, and glycosides (Cahyaningsih et al., 2019;Escher et al., 2020;Nair et al., 2015). Several studies reported that the content of C. ternatea flower extract, especially flavonoids, was effective as an anti-inflammatory (Al-Snafi, 2016; Cahyaningsih et al., 2019). ...
... Flavonoid compounds have anti-inflammatory effects by inhibiting the release of proinflammatory cytokines (Ginwala et al., 2019). The potential of C. ternatea flower as a nutraceutical material for protection against chronic inflammatory diseases by suppressing the excessive production of pro-inflammatory mediators from macrophage cells (Nair et al., 2015). Research by (Thilavech et al., 2021), reported that oral administration of a 2 g daily dose of C. ternatea flower extract reduced levels of proinflammatory cytokines (IL-6 and TNF-) in obese male patients after consuming a high-fat diet. ...
... Research conducted by (Thilavech et al., 2021), reported that the anti-inflammatory effect of C. ternatea flower in this study could be through changes in the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kB (NF-kB) indicating a cytoprotective and antiinflammatory role in the pathology of obesity. Meanwhile, in this study, the mechanism used to suppress inflammation, the effect of flavonoid and phenolic content in C. ternatea flower inhibits the cyclooxygenation enzyme so that arachidonic acid metabolism can be inhibited thereby preventing the inflammatory process (Nair et al., 2015). By inhibiting the metabolism of arachidonic acid and the scavenging of free radicals that play a role, the process of prostaglandin formation will be inhibited so that the inflammatory process in the tissue is reduced. ...
Reversal reaction is a type IV cellular hypersensitivity reaction in leprosy. Interleukin-6 is a mediator with a pleiotropic effect on inflammation and immune response. Steroids are the standard therapy in the treatment of reaction reversal. Clitoria ternatea flower extract has anti-inflammatory properties. Long-term use of steroids can cause side effects. Therefore, it is necessary to give adjuvant therapy that can shorten the treatment period. This study aims to analyze the effect of adjuvant therapy of Clitoria ternatea extract to reduce IL-6 levels in reversal reaction. Experimental research design with pre and post-randomized single-blinded controlled trial, involving 22 subjects with reversal reaction. The control group received standard therapy and the treatment group received standard and adjuvant therapy with Clitoria ternatea extract. IL-6 levels were measured by ELISA. Data analysis used the Wilcoxon test and Independent T-test. The results showed a significant difference in treatment group (p=0.003) and control group (p=0.016). The mean decrease in serum IL-6 levels in treatment group was 81.35 pg/ml and in control group was 24.30 pg/ml (p=0.027). Clitoria ternatea showed a significant IL-6-lowering effect in patients with reversal reactions. This study has demonstrated the potential of Clitoria ternatea extract as adjuvant therapy in patients with leprosy reactions.
... The healing properties of Clitori aextracts used in traditional medicine have been confirmed by the results of current research. Nair et al. [35] identified twelve phenolic metabolites (nine ternatin anthocyanins and three glycosylated quercetins) in Clitoria ternatea blue flower extracts. All Clitoria ternatea polyphenols exhibited antiinflammatory properties in macrophage-mediated inflammation caused by lipopolysaccharides (LPS). ...
... It has been shown that Clitoria ternatea flower extracts strongly inhibit the activity of cyclooxygenase-2 (COX-2), reduce the release of free oxygen radicals, and reduce the production of nitric oxide by reducing the expression of nitric oxide synthase (iNOS). The available research results [32,[35][36][37][38] of extracts from other plants rich in ternatins indicate that they are a very good source of natural antioxidants, thanks to which they have a strong anti-inflammatory and antianaphylactic effect [32,[35][36][37][38]. ...
... It has been shown that Clitoria ternatea flower extracts strongly inhibit the activity of cyclooxygenase-2 (COX-2), reduce the release of free oxygen radicals, and reduce the production of nitric oxide by reducing the expression of nitric oxide synthase (iNOS). The available research results [32,[35][36][37][38] of extracts from other plants rich in ternatins indicate that they are a very good source of natural antioxidants, thanks to which they have a strong anti-inflammatory and antianaphylactic effect [32,[35][36][37][38]. ...
Color is an important food attribute which increases its attractiveness, thus influencing consumer preferences and acceptance of food products. The characteristic color of fresh, raw food is due to natural dyes present in natural food sources. Food loses its natural color during processing or storage. Loss of natural color (e.g., graying) often reduces the appeal of a product to consumers. To increase the aesthetic value of food, natural or synthetic dyes are added to it. Interestingly, the use of food coloring to enhance food attractiveness and appetizing appearance has been practiced since antiquity. Food coloring can also cause certain health effects, both negative and positive. Dyes added to food, both natural and synthetic, are primarily chemical substances that may not be neutral to the body. Some of these substances have strong antioxidant properties. Thanks to this activity, they can also perform important pro-health functions, including antiallergic ones. On the other hand, as foreign substances, they can also cause various adverse food reactions, including allergic reactions of varying severity and anaphylactic shock. This article discusses food dyes of plant origins with antioxidant properties (anthocyanins, betanins, chlorophylls, carotenoids, and curcumin) and their relationship with allergy, both as sensitizing agents and immunomodulatory agents with potential antiallergic properties.
... The LC-MS analysis was conducted for the anthocyanin extracts obtained by hot water extraction, ultrasound, microwave, 1.5% (w/v) pectinase-assisted extraction with optimum extraction conditions (1: 15 (w/v) substrate: solvent ratio, at 50 °C for 30 min). Individual compounds were recognized using mass-to-charge ( m/z ) ratio and retention time using LC-MS according to the method of Nair et al. (2015) with slight modifications. Chromatographic separations were performed on an Agilent 1290 Infinity LC system with Agilent 6520 Accurate-Mass quadrupole time-of-flight (Q-TOF) mass spectrometer that has a dual electrospray ionization (ESI) source (Thermo Finnigan, San Jose, CA, USA), connected with a Surveyor 2000 quaternary pump, and a Surveyor UV 2000 photodiode-array detector using an Agilent ZORBAX Eclipse XDB-C18 analytical column, 150 mm × 4.6 mm, 5 μm. ...
... The highest extraction yield obtained in this study was 78.4 ± 3.6%. Nair et al. (2015) reported an extraction yield of 72% for blue pea flower anthocyanins but freeze-dried petal powder of blue pea flower was extracted using 5:4:1 of methanol/acetone/water for a period of 24 h at room temperature. The reason for the lower extraction yield could be the lower extraction temperature used by Nair et al. (2015) . ...
... Nair et al. (2015) reported an extraction yield of 72% for blue pea flower anthocyanins but freeze-dried petal powder of blue pea flower was extracted using 5:4:1 of methanol/acetone/water for a period of 24 h at room temperature. The reason for the lower extraction yield could be the lower extraction temperature used by Nair et al. (2015) . When the extraction time was 30 min and the temperature was 60 °C, the extraction yield significantly decreased ( p < 0.05) when the substrate: solvent ratio changed from 1:15 to 1:20 ( Table 1 ). ...
... Butterfly pea flowers, known Clitoria ternatea L., area plant species belonging to the Fabaceae family [1]. In Vietnam, butterfly pea flowers are usually used as food drinks and as a colorant. ...
... Structures 1-6 are recognized as delphinidin 3malonylglucoside with 3′-GCGC-5′-G, 3′-GCGCG5′-G, 3′-GC-5′-G, 3′-GCG-5′-G, 3′-G-5′-G, and 3′-GC-5′-GC, and compounds 7 and 8 as delphinidin 3-glucoside with 3′-GCG-5′-GCG and 3′-GCG-5′-G are the side chains, respectively. Then, Nair et al. [1] went on to identify other delphinidin derivatives. Azima et al. [6] also found only anthocyanidin, delphinidin, but not cyanidin, as in some other ingredients containing anthocyanins. ...
... The modifications of these anthocyanins were mainly glycosylation and acylation. In other studies, some delphinidin derivatives were also found in butterfly pea flowers but these compounds had larger sizes, as evidenced by the larger m/z values of the [M + H] + ion, for example 950, 1296, 1534 [1] or 830.21, 1551.42, 903.22 [22]. ...
Butterfly pea flower have great sensory attraction, but they have not yet been used widely in Vietnam. Extracts of butterfly pea flowers can be used conveniently as a natural blue colorant for food products. In this study, the identification of anthocyanin compounds in butterfly pea flowers was performed by UPLC coupled with a UV and Mass spectrometer instrument. Positive and negative ion electrospray MS/MS chromatograms and spectra of the anthocyanin compounds were determined. By analyzing the chromatograms and spectra for each ion, five anthocyanins were identified in the butterfly pea flower extract; these were delphinidin-3-(6”‐p-coumaroyl)-rutinoside, cyanidin 3-(6”-p-coumaroyl)-rutinoside, delphinidin-3-(p-coumaroyl) glucose in both cis- and trans- isomers, cyanidin-3-(p-coumaroyl-glucoside) and delphinidin-3-pyranoside. Additionally, based on their intensity, it was determined that cyanidin-3-(p-coumaroyl-glucoside) was the most abundant anthocyanin, followed by cyanidin 3-(6”-p-coumaroyl)-rutinoside, delphinidin-3-(p-coumaroyl-glucoside), delphinidin-3-(6”-p-coumaroyl)-rutinoside and delphinidin-3-pyranoside. In this study, cyanidin derivatives were discovered in butterfly pea flower extract, where these compounds had not been detected in previous studies.
... The biological functions of anthocyanin are associated with a significant role in the modulation of oxidative stress and inflammation, perhaps delaying the onset of noncommunicable chronic diseases [1]. Typically, anthocyanin from the butterfly pea, Clitoria ternatea, is a potent inhibitor of nuclear NF-κB translocation and possesses a non-ROS suppression mechanism because of its high ternatin (polyacylated anthocyanin pigment) content [2]. The aqueous extract of butterfly pea petals lowers blood pressure, controls diabetes, and has a protective effect on human erythrocytes against hemolysis [3]. ...
... For double emulsions with 5% w/v PGPR, the particle size decreased with increasing concentrations of NCC, whereas the trend was irregular for 3% w/v PGPR with increasing concentrations of NCC. Figure 1C demonstrates the change in mean diameters of the particle size based on weighted volume at day 1 and after 7 days of storage, where there was a significant increase in the particle diameter after storage. Likewise, the mean diameters of the particle size based on weighted area, which is denoted as D [3,2], of the BPE-loaded double emulsion showed similar trends concerning the different concentrations of PGPR and NCC (Table 2). A narrow distribution of particle size was observed, with a shift to a lower particle size with the increasing NCC concentration ( Figure S2). ...
Butterfly pea petal extract (BPE)-loaded water-in-oil-in-water (W/O/W) emulsions were fabricated using nanocrystalline cellulose (NCC) as a hydrophilic stabilizer and polyglycerol polyrici-noleate (PGPR) as a hydrophobic emulsifier. The impact of different concentrations of NCC and PGPR in different phase proportions on the emulsion formation, rheology, and stability of an anthocyanin-loaded (pH ≈ 7.0) emulsion was investigated. The mean droplet size of the emulsions increased as the NCC concentration increased, while color intensity (greenness) decreased as the PGPR and NCC concentrations increased. A microscopic examination confirmed that the NCC nanoparticles stabilized the inner W 1 /O phase, whereas the excess concentration of non-adsorbing NCC nanoparticles was suspended in the continuous aqueous phase. The rheological results showed that robust emulsion networks were formed when the NCC concentration increased. A network structure between the droplets and the development of the NCC network during the continuous phase were attributed to a gel-like behavior. Over the course of seven days, the emulsions with a higher proportion of NCC remained stable, as in samples 3%P-%N, 5%P-2%N, and 5%P@1%N, the total anthocyanin content decreased from 89.83% to 76.49%, 89.40% to 79.65, and 86.63% to 71.40%, respectively. These findings have significant implications for the accurate formulation of particle-stabilized double emulsions for anthocyanin delivery with higher stability.
... The perennial leguminous herb Clitoria ternatea (CT) (or butterfly pea) is widely cultivated in tropical regions, and its flower can be utilized in the food industry as a natural pigment [6]. Since CT flowers and extracts are rich in bioactive substances, they have antioxidation, anti-inflammation, antibacterial, antidiabetic, and antitumor activities [7][8][9] Anthocyanin is a water-soluble natural pigment that mainly occurs in the flowers, leaves, fruits, and seeds of plants. The structure of anthocyanins consists of an anthocyanidin (aglycon), sugars, and/or organic acids [7,10]. ...
... The CT flower is rich in blue polyacylated anthocyanins, which are known as ternatins and are derivatives of delphinidin 3, 3 , 5 -triglucoside [6,11]. Currently, researchers have identified about eighteen delphinidin and cyanidin derivatives from CT flower [9,12,13]. Anthocyanins can be used in intelligent films to monitor the freshness of food [14] and offer many health-promoting benefits such as anticancer, antidiabetic, and vascular protective effects [15]. ...
Clitoria ternatea (CT) flowers are rich in phytochemicals. An innovative approach was taken to utilize CT flower extract (CTFE) as a functional ingredient with natural pigment by incorporating it into noodles. The aim of this study was to examine the effect of the CTFE amount (0–30%) on the color, texture, phytochemicals, and sensory quality of both dried and cooked noodles. Dried noodles with 30% CTFE had the highest total anthocyanins (9.48 μg/g), polyphenols (612 μg/g), DPPH radical scavenging capacity (165 μg TE/g), and reducing power (2203 μg TE/g). Cooking resulted in a significant decrease in the anthocyanin levels and blue color, while also increasing the greenness of the noodle. Both dried and cooked noodles with 20–30% CTFE showed a significantly higher color preference compared to the control sample. Despite a significant reduction in the cutting force, tensile strength, and extensibility of cooked noodles with 20–30% CTFE, the sensory attributes such as flavor, texture, and overall preferences were similar to those of noodles with 0–30% CTFE. Blue noodles with high phytochemicals, antioxidant activities, and desirable sensory qualities can be produced by the incorporation of 20–30% CTFE.
... Another plant extract that could potentially enrich the yoghurt nutritional value is flower extract. One of the flowers that has gained popularity due to its potential nutritional value is Clitoria ternatea, a flowering plant belongs to the Fabaceae family, and native to equatorial South and Southeast Asia (Nair et al., 2015). The flower extract of C. ternatea has been used in many purposes, ranging from medicines to foods (Oguis et al., 2019). ...
... The prediction and the actual colours were not so different (Table 1 and Figure 4B). One of the substances in the CTF extract that is quite sensitive to pH changes is anthocyanin (Nair et al., 2015;Chusak et al., 2018;Anuyahong et al., 2020). The presence of lactic acid (as the donor of H + ions) in the fermentation medium may change the stability of conjugated systems in the anthocyanin chemical structure, thus changing the anthocyanin colour (Juhadi and Marpaung, 2021). ...
The aim of the present work was to analyse 24 h yoghurt fermentation supplemented with Clitoria ternatea flower (CTF) extracts (0-10%); especially elucidating the relationship between antioxidant activity, carbohydrate constituent, and microbial growth which has never been reported. Carbohydrate constituent in the CTF was also investigated for the first time. Colour changes was also assessed during yoghurt production. Furthermore, the stability of yoghurt was studied during the 7 d storage under low temperature (4°C). The supplementation of CTF extracts (0-10%) into yoghurt increased the antioxidant activity (up to 46.65 ± 0.29%) and carbohydrate concentration (glucose, up to 9.63 ± 0.3%; sucrose, up to 7.8 ± 0.5%; inulin, up to 5.7 ± 0.8%; and pectin, up to 7.5 ± 0.3%), but decreased dissolved oxygen (DO) down to 0.65 ± 0.023 mg/L in the medium during fermentation. Surprisingly, prebiotic sugars of inulin and pectin were discovered in CTF. The presence of higher carbohydrate concentration and more anaerobic condition enabled Lactobacillus delbrueckii subsp. bulgaricus to grow up to 7.74 ± 0.1 log CFU/mL. In contrast, the final cell concentration of Streptococcus thermophillus decreased up to 8.12 times as the extract concentrations increased. However, the viability of both bacteria still met the international standards (≥ 7 log CFU/mL). The yoghurt colour turned from light turquoise to purple (L* = 69.47 ± 0.2; a* = 14.78 ± 0.15; b* =-21.77 ± 0.2) as the pH decreased to 4.5 ± 0.11, and the lactic acid concentration increased up to 1.74 ± 0.37%. Furthermore, the quality of yoghurt in all parameters was relatively stable during storage for antioxidant activity, microbial growth, carbohydrate constituent, DO, lactic acid concentration, anthocyanin content, and pH; meanwhile colour changes only decreased 0-0.39 times.
... The study utilising the Amberlite XAD7HP resin characterised ternatins B2 or B3, B4, D2 and some delphinidin derivatives while the ternatin B2, B3, B4, C2, D1, D3 and some delphinidin derivatives were characterised in the study utilising C-18 Sep-Pak cartridges. However, it is not known which method is superior or more effective for the purification of C. ternatea flower anthocyanins [21][22][23] . The volume of sample which can be loaded onto the C-18 Sep-Pak cartridges is rather small and would not be convenient thus exploring a larger scale method for anthocyanin purification would be beneficial. ...
... Liquid chromatography-mass spectrometry (LC-MS) analysis. LC-MS analysis was done for the characterisation of anthocyanins with minor modifications 21 . Individual compounds were identified based on retention time, and mass-to-charge ratio using LC-MS. ...
Clitoria ternatea flower is a traditional medicinal herb that has been used as a natural food colourant. As there are limited studies on investigating the bioactivities of the anthocyanin-rich fraction of Clitoria ternatea flower, this study aimed to determine an efficient column chromatography method to obtain the anthocyanin-rich fraction from this flower and characterise its composition, antioxidant, antibacterial, and cytotoxic activities. Amberlite XAD-16 column chromatography was more efficient in enriching the total anthocyanin content (TAC) of the fraction with the highest TAC to total phenolic content (TPC) ratio of 1:6 than that using C18-OPN. A total of 11 ternatin anthocyanins were characterised in the anthocyanin-rich fraction by LC–MS analysis. The antioxidant activity of the anthocyanin-rich fraction was more potent in the chemical-based assay with an IC 50 value of 0.86 ± 0.07 mg/mL using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay than cellular antioxidant assay using RAW 264.7 macrophages. In vitro cytotoxicity assay using human embryonic kidney HEK-293 cell line showed the anthocyanin-rich fraction to be more toxic than the crude extracts. The anthocyanin-rich fraction had more potent antibacterial activity than the crude extracts against Bacillus cereus , Bacillus subtilis , and Escherichia coli . The anthocyanin-rich fraction of C. ternatea has the potential to be used and developed as a functional food ingredient or nutraceutical agent.
... COX-2(Cyclooxygenase-2) enzyme activity was powerfully inhibited by flavonols, with a small reduction in ROS The ternatin anthocyanins inhibited nuclear NF-B (nuclear factor that enhance the activity of B cells) translocation, iNOS(Nitric Oxide Synthase) protein expression, and NO production via a non-ROS suppression technique. As a way, quercetin glycosides and ternatin anthocyanins found in the blue flower petals of Clitoria ternatea could be used to make pharmaceuticals or nutraceuticals that protect against chronic inflammatory diseases by lowering macrophage cells' excessive production of pro-inflammatory mediators (Nair et al., 2015) [77] . (Sharma et al., 1990) [23] . ...
... COX-2(Cyclooxygenase-2) enzyme activity was powerfully inhibited by flavonols, with a small reduction in ROS The ternatin anthocyanins inhibited nuclear NF-B (nuclear factor that enhance the activity of B cells) translocation, iNOS(Nitric Oxide Synthase) protein expression, and NO production via a non-ROS suppression technique. As a way, quercetin glycosides and ternatin anthocyanins found in the blue flower petals of Clitoria ternatea could be used to make pharmaceuticals or nutraceuticals that protect against chronic inflammatory diseases by lowering macrophage cells' excessive production of pro-inflammatory mediators (Nair et al., 2015) [77] . (Sharma et al., 1990) [23] . ...
Dyes and Food Colorings play an important role in the Food Industry. A trend was seen at that time for using natural dyes instead of artificial dyes. A natural dye can be extracted from Clitoria ternatea (CT/Blue pea) flower because of its vivid blue color. The reason for this deep blue color is because of the Anthocyanin compounds contained in the flower. Clitoria ternatea extraction was obtained through different methods and they vary with their manufacturing process. This plant was widely used in traditional medicine because it is rich in bioactive compounds. In treating diabetics, blood pressure, retinal damage, edema, and indigestion both the aerial and underground parts of this plant are being used. Researchers proved this plant's medicinal activities such as nootropic activity, antioxidant activity, analgesic activity, anti-inflammatory and antibacterial activity. Currently, this plant's uses are widely spread in the nanotechnology field as well.
... In polymer-based drug delivery with stealth characteristics, PEG is the most extensively utilised non-ionic hydrophilic and biocompatible polymer [14]. PEG possess an excellent solubility in water as well as in organic solvents making it suitable for the conjugation of polymer-biomolecule. ...
... PEG possess an excellent solubility in water as well as in organic solvents making it suitable for the conjugation of polymer-biomolecule. Moreover, the biological inert characteristic of PEG with low toxicity makes PEG perfect for biological applications [14,15]. Previously, Bayard et al. ...
Ternatin, a highly N-methylated cyclic heptapeptide has promising potential for cancer treatment. However, its efficiency in biological treatment is limited due to its poor solubility and high degradation in aqueous solution. In this present study, methoxy polyethylene glycol (mPEG)-ternatin conjugate abbreviated as mPEG-ternatin was synthesised by direct esterification between a carboxyl end group of methoxy polyethylene glycol, mPEG-COOH and a hydroxyl group in the β-position of ternatin biomolecule which enhanced its solubility and decreased the degradation of ternatin biomolecule in aqueous solution while retaining its inherent anticancer properties. To this end, mPEG-ternatin linked through ester bond was further confirmed using various analytical techniques including FTIR, UV-Vis spectroscopy and HPLC. Importantly, in the solubility and stability studies, the solubility of mPEG-ternatin conjugate was found to be 8% higher than unconjugated ternatin. Furthermore, mPEG- ternatin conjugate exhibited a decreasing percentage of degradation of ternatin biomolecule by 1.9-fold lower than unconjugated ternatin after incubation in 10 mM HEPES pH 7.4 buffer solution at 37 °C for 6 hours. Ultimately, the enhanced properties of ternatin biomolecule by conjugating with a mPEG segment is expected to become new fundamental study in related fields as well as provide new insight into cancer treatments.
... All ternatins carry the basic structure of delphinidin-3, 3 , 5 -triglucoside. A series of 15 ternatins A1-A3, B1-B4, C1-C5 and D1-D3 have been discovered so far (Nair et al., 2015;Jeyaraj et al., 2020). This review focus on the biosynthesis, extraction, stability, antioxidant activity and applications of anthocyanins from blue pea flower. ...
... Several studies have been done on the application of blue pea flower anthocyanins in many areas such as developing dyesensitised solar cells, pharmaceuticals etc. (Gokilamani et al., 2013;Nair et al., 2015). This review focuses on the current research on the application of anthocyanins from blue pea flowers in the food industry. ...
Clitoria ternatea plant is commonly grown as an ornamental plant and possesses great medicinal value. Its flower is edible and also known as blue pea or butterfly pea flower. The unique feature of anthocyanins present in blue pea flowers is the high abundance of polyacylated anthocyanins known as ternatins. Ternatins are polyacylated derivatives of delphinidin 3,3′,5′-triglucoside. This review covers the biosynthesis, extraction, stability, antioxidant activity, and applications of anthocyanins from Clitoria ternatea flower. Hot water extraction of dried or fresh petals of blue pea flower could be employed successfully to extract anthocyanins from blue pea flower for food application. Blue pea flower anthocyanins showed good thermal and storage stability, but less photostability. Blue pea flower anthocyanins also showed an intense blue colour in acidic pH between pH 3.2 to pH 5.2. Blue pea flower anthocyanin extracts demonstrate significant in vitro and cellular antioxidant activities. Blue pea flower anthocyanins could be used as a blue food colourant in acidic and neutral foods. The incorporation of blue pea flower anthocyanins in food increased the functional properties of food such as antioxidant and antimicrobial properties. Blue pea flower anthocyanins have also been used in intelligent packaging. A comparison of blue pea flower anthocyanins with two other natural blue colouring agents used in the food industry, spirulina or phycocyanin and genipin-derived pigments is also covered. Anthocyanins from blue pea flowers are promising natural blue food colouring agent.
... HPLC analysis revealed the presence of 3.80 ± 0.09 (mg/g extract) of glycosylated quercetin, while 80% methanol attained 7.96 ± 0.08. According to Nair et al. [9], quercetin glycosides from butterfly pea flower extract were quantified via HPLC analysis coupled with mass spectrometry (MS) at 365 nm. HPLC-MS chromatogram obtained disclosed that quercetin glycosides accounted for 46.96 percent area, which is the highest amongst all the compounds extracted. ...
... Clitoria ternatea L. from the Fabaceae family [9] was collected from Kampar, Perak, in August 2018. Upon removing flowers, they were sun-dried for three days. ...
The study is focused on incorporating Clitoria ternatea extracts (isolated using water (WE) and ethanol (EE) solvents) into the sol-gel coating for the corrosion mitigation of mild steel. Clitoria ternatea extracts were characterized through Fourier transform infrared spectroscopy (FTIR) and phytochemical analysis. Based on the results obtained, it was remarked that the ethanol extract contained more substantial antioxidant properties compared to the water extract. Corrosion mitigation capability of sol-gel coatings doped with extracts of Clitoria ternatea (0, 25, 50, 75 and 100 ppm) on mild steel was assessed using electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. According to the electrochemical impedance spectroscopy (EIS) data, ethanol extract (EE) doped sol-gel coating at 75 ppm offered higher inhibition efficiency (89.6%) in comparison to the water extract. Scanning electron microscopy (SEM) images affirmed improved surface morphology of mild steel substrates in the presence of both inhibitors. It was revealed that the coated mild steel with Clitoria ternatea extracts provide a smooth surface compared to the untreated mild steel substrate.
... C. tinctorius L. contains as a major dye carthamin (red-orange dye) [28][29][30], G. globosa L. contains betacyanins which are pink-violet in color (gomphrenin, isogomphrenin II, and isogomphrenin III) [31][32][33]. The major dye of K. terantea L. flowers are anthocyanins called ternathins [34][35][36]. The color of P. rhoeas L. is due to the presence of red in color anthocyanins, whose cyanidol is the main component [37,38]. ...
... Polyphenols and flavonoids are responsible for the antioxidant activity, including the ability to reduce the oxidative stress generated by ROS in cells. Numerous studies have demonstrated strong antioxidant potential of the main coloring compounds contained in plant flowers [28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Slezak et al. have shown that aqueous pomegranate peel extract at low concentrations were characterized by the ability to decrease intracellular (V79 cells) oxidative stress after 24h incubation. ...
Nowadays, natural dyes are expected by the cosmetic and food industries. In contrast to synthetic dyes, colorants derived from natural sources are more environmentally friendly and safer for human health. In this work, plant extracts from Gomphrena globasa L., Clitoria ternatea L., Carthamus tinctorius L., Punica granatum L. and Papaver rhoeas L. as the natural and functional dyes for the cosmetics industry were assessed. Cytotoxicity on keratinocyte and fibroblast cell lines was determined as well as antioxidant and anti-aging properties by determining their ability to inhibit the activity of collagenase and elastase enzymes. In addition, the composition of the extracts was determined. The obtained extracts were also applied in face cream formulation and color analyses were performed. It has been shown that the obtained extracts were characterized by no cytotoxicity and a high antioxidant potential. The extracts also show strong ability to inhibit the activity of collagenase and moderate ability to inhibit elastase and provide effective and long-lasting hydration after their application on the skin. Application analyses showed that the extracts of P. rhoeas L., C. ternatea L. and C. tinctorius L. can be used as effective cosmetic dyes that allow for attainment of an intense and stable color during the storage of the product. The extracts of P. granatum L. and G. globasa L., despite their beneficial effects as active ingredients, did not work effectively as cosmetic dyes, because cosmetic emulsions with these extracts did not differ significantly in color from emulsions without the extract.
... A decoction made from C. ternatea flower petals, or the flower itself, is used to make the widely consumed herbal tea 14 , or tisane, known as butterfly pea flower tea in Saudi Arabia. Clinical studies addressing the impact of C. ternatea flower extract (CTE) on insulin response and antioxidant ability are lacking 15 , despite the fact that C. ternatea flower extract (CTE) has a high concentration of phytochemicals that have excellent antioxidant, anti-inflammatory, antidiabetic, and antiproliferative/anticancer aspects 13,[16][17][18][19] . ...
Type 2 diabetes mellitus (T2DM) is one of the expanding global health problems and is the most common metabolic disorder characterized by hyperglycemia, which significantly contributes to producing reactive oxygen species (ROS). More than 400 plant species with hypoglycemic activity have been mentioned in the literature. Clitoria ternatea (C. ternatea), often called Butterfly pea or Asian pigeonwing, is a plant species member of the Fabaceae family. The main goal of this study was to evaluate the methanolic extract of C. ternatea (CT-Mx)'s and/or chitosan-loaded nanoparticles (CHNPs) antihyperglycemic and antioxidant effects in normal and diabetic rats produced by streptozotocin (STZ). A total of 20 male albino rats had been divided into 4 groups, control non-diabetic (NC), STZ/diabetic control, STZ/diabetic + CT-Mx, and STZ/diabetic + CT-CHNPs groups. After 28 days, levels of insulin, fasting blood glucose (FBG), aspartate transaminase (AST), alanine transaminase (ALT), superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation, and mRNA gene expression were assessed. Histopathological and immunohistochemical studies were performed for pancreatic tissues. In the STZ/diabetic (Gp2) rats, levels of FBG, AST, ALT, and both CDKN1A and TP53 gene expression were significantly increased. Moreover, the hyperglycemia-induced hepatic oxidative state is evidenced by a significant increment of lipid peroxidation and deterioration in SOD and GSH levels. On the contrary, both the STZ/diabetic + CT-Mx and STZ/diabetic + CT-CHNPs showed discernible improvement in diabetes-associated complications; however, STZ/diabetic + CT-CHNPs (Gp4) rats significantly suppressed the generated oxidative stress and improved antioxidant activity, liver function, and insulin secretion. Also, their pancreatic section exhibited architecture with normal regenerative pancreatic endocrine islets with normal distribution and number of beta cells and suppressing inflammatory and apoptotic gene expression compared to Gp2. Nanocarrier agents showed excellent antihyperglycemic and effects after antioxidative, making it a promising technology for diabetics.
... The presence of the bioactive compound taraxerol in the extract and ethyl acetate fraction is believed to contribute to its wound healing potential. Overall, Clitoria ternatea extracts hold promise as natural agents for promoting effective wound healing [41][42][43][44][45]. ...
The plant Clitoria ternatea, commonly known as 'Butterfly pea,' has a rich history of traditional use in Ayurvedic medicine, where different parts of the plant are utilized to used health concerns like indigestion, constipation, arthritis, skin diseases, liver, and intestinal problems. Beyond its medicinal uses, the flowers of C. ternatea have gained popularity worldwide as ornamental flowers and have been traditionally employed as a natural food colorant. This review paper aims to explore recent advancements in the medicinal uses and study of phytochemicals from C. ternatea flowers, focusing on their potential biological activities. By examining these developments, the paper seeks to provide valuable insights into the therapeutic potential and diverse applications of C. ternatea flowers, opening new avenues for further research in this promising area of study. of phytochemicals from C. ternatea flowers. Clitoria ternatea flower is a promising candidate for functional food applications owing to its wide range of pharmacotherapeutic properties as well as its safety and effectiveness.
... Previous studies showed that the terpenoid fraction in oregano [41] and jatropha [42] had anti-inflammatory properties. Furthermore, additional studies would be needed to determine which phenolic fractions in whole cardamom exerts higher bioactivity as shown previously in clitorea ternata, where flavonoid and anthocyanin fractions were reported to exert anti-inflammatory properties [43]. In addition, studies involving the microbiota metabolites of cardamom extracts are encouraged since recent studies with urolithins, which are microbial metabolites of ellagic acid, have shown they reduce lipid accumulation in adipocytes and reduce LPS-induced inflammation [44]. ...
The chemical profiling of phenolic and terpenoid compounds in whole cardamom, skin, and seeds (Elettaria cardamomum (L.) Maton) showed 11 phenolics and 16 terpenoids, many of which are reported for the first time. Herein, we report the anti-inflammatory properties of a methanolic extract of whole cardamom in colon and macrophage cells stimulated with an inflammatory bacteria lipopolysaccharide (LPS). The results show that cardamom extracts lowered the expression of pro-inflammatory genes NFkβ, TNFα, IL-6, and COX2 in colon cells by reducing reactive oxygen species (ROS) while not affecting LXRα. In macrophages, cardamom extracts lowered the expression of pro-inflammatory genes NFkβ, TNFα, IL-6, and COX2 and decreased NO levels through a reduction in ROS and enhanced gene expression of nuclear receptors LXRα and PPARγ. The cardamom extracts in a range of 200-800 μg/mL did not show toxicity effects in colon or macrophage cells. The whole-cardamom methanolic extracts contained high levels of phenolics compounds (e.g., protocatechuic acid, caffeic acid, syringic acid, and 5-O-caffeoylquinic acid, among others) and are likely responsible for the anti-inflammatory and multifunctional effects observed in this study. The generated information suggests that cardamom may play a protective role against low-grade inflammation that can be the basis of future in vivo studies using mice models of inflammation and associated chronic diseases.
... Researchers Thilavech et al. (2021) found that 2 g/day of Clitoria ternatea extract lowered levels of proinflammatory cytokines (IL-6 and Tumor Necrosis Factor) in obese male patients who had consumed a high-fat diet. In another study, Nair et al. (2015) reported that Clitoria ternatea is beneficial in nutraceutical protection against chronic inflammatory illnesses by inhibiting macrophage cells overproduction of pro-inflammatory mediators. Swathi et al. (2021) found that the ethanolic extract of Clitoria ternatea inhibited the release of histamine and prostaglandins, hence exerting an anti-inflammatory action. ...
... Tác dụng kháng viêm trên hoa Đậu biếc chủ yếu là do thành phần flavonoid là anthocyanin và flavonol. Điều này được thể hiện trong thí nghiệm của Bang và cộng sự [8] khi thực hiện trên mô hình gây viêm do lipopolysaccarid gây ra ở các tế bào đại thực bào RAW 264.7. Kết quả chỉ ra quercetin glycosid và ternatin anthocyanin từ cánh hoa Clitoria ternatea L. có khả năng ngăn chặn sản xuất quá mức các chất gây viêm từ các đại thực bào, điều này giúp hạn chế các triệu chứng viêm và hạn chế được các tổn thương mô trong các bệnh viêm mãn tính. ...
Hoa Đậu biếc với tên khoa học Clitoria ternatea L. chứa anthocyanin được biết đến như là nguồn hợp chất có hoạt tính sinh học đầy hứa hẹn vì chúng được sử dụng theo truyền thống để điều trị các bệnh khác nhau. Nghiên cứu nhằm đánh giá hoạt tính chống oxy hóa và chống viêm in vitro của dịch chiết etanol toàn phần và các phân đoạn của Clitoria ternatea L. Kết quả cho thấy dịch chiết etanol toàn phần và tất cả các phân đoạn của chloroform, ethyl acetat, buthanol, nước có hiệu quả in vitro về hoạt động chống oxy hóa và chống viêm. Trong đó dịch chiết ethyl acetat có tác dụng cao nhất với IC50 là 19,51 ± 1,14µg/mL trong thử nghiệm chống oxy hóa (cao hơn của acid ascorbic 7,98 ± 0,46µg/mL) và IC50 là 3, 02 ± 0,09mg/mL trong việc chống viêm (cao hơn so với diclofenac natri 1,28 ± 0,02mg/mL).
... The identification and determination of chemical constituents of A. quinata and C. ternatea by various analytical methods have been reported, including HPLC [38][39][40], NMR [41][42][43][44], ...
Two herbal plants, Akebia quinata D. leaf/fruit and Clitoria ternatea L. flower, well-known in traditional medicine systems, were investigated using a non-target effect-directed profiling. High-performance thin-layer chromatography (HPTLC) was combined with 11 different effect-directed assays, including two multiplex bioassays, for assessing their bioactivity. Individual active zones were heart-cut eluted for separation via an orthogonal high-performance liquid chromatography column to heated electrospray ionization high-resolution mass spectrometry (HPLC–HESI-HRMS) for tentative assignment of molecular formulas according to literature data. The obtained effect-directed profiles provided information on 2,2-diphenyl-1-picrylhydrazyl scavenging, antibacterial (against Bacillus subtilis and Aliivibrio fischeri), enzyme inhibition (tyrosinase, α-amylase, β-glucuronidase, butyrylcholinesterase, and acetylcholinesterase), endocrine (agonists and antagonists), and genotoxic (SOS-Umu-C) activities. The main bioactive compound zones in A. quinata leaf were tentatively assigned to be syringin, vanilloloside, salidroside, α-hederin, cuneataside E, botulin, and oleanolic acid, while salidroside and quinatic acids were tentatively identified in the fruit. Taraxerol, kaempherol-3-rutinoside, kaempferol-3-glucoside, quercetin-3-rutinoside, and octadecenoic acid were tentatively found in the C. ternatea flower. This straightforward hyphenated technique made it possible to correlate the biological properties of the herbs with possible compounds. The meaningful bioactivity profiles contribute to a better understanding of the effects and to more efficient food control and food safety.
... A wide variety of polyphenols are found in the flower petals; however, the main polyphenol constituents contained within are anthocyanins [31]. The anthocyanins are blue in the petals and acylated based on delphinidin, known as ternatins isolated from C. ternatea, which are ternatin A1-A3, B1-B4, C1-C4, and D1-D3 [21,23,[32][33][34][35]. Another study reported that minor delphinidin glycosides and the preternatins A3 and C4 were isolated from the young C. ternatea [34]. ...
Due to the beneficial health effects of polyphenolics and their limited stability during inadequate processing conditions, there is an increasing interest in their microencapsulation in order to improve the stability. As previous publications do not include a substantive review focusing on these topics, in the present work, we focused on recent reports on the topic of Clitoria ternatea flower bioactive components and the conditions under which they are microencapsulated for subsequent use in food and nutraceuticals. Our findings highlighted the importance of optimizing the variables of the microencapsulation process for optimal application.
... Efek lain dari ekstrak bunga telang dapat meningkatkan insulin serum dan glikogen otot hati dan tulang (Daisy et al., 2009). Penelitian lain oleh Nair et al menunjukkan bahwa ekstrak bunga telang memiliki aktifitas antiinflamasi pada cell line makrofag RAW 264.7 (Nair et al. 2015). Menurut Shen et al kandungan bioaktif bunga segar Bunga Telang yang bersifat lipofilik (kelompok fitosterol dan asam lemak )lebih banyak dibanding kandungan hidrofilik (antosianin dan flavonol glikosida) yaitu sebesar 27,67 dan 11,08 mg/100 g bunga segar (Shen et al., 2016). ...
Inhibition of atherogenesis can be done through several mechanisms, one of which is inhibiting intestinal cholesterol absorption through inhibition of NPC1L1. The activity of Telang flower extract in overcoming various problems of degenerative diseases, especially cardiovascular disease, has been proven by many scientific studies. Likewise, related to the activity of Rosella flowers. Previous research conducted by researchers showed the potential of Rosella flower extract as an LXR agonist, one of the pathways that play a role in NPC1L1 inhibition. The combination of the two extracts is expected to increase its activity as a candidate for NPC1L1 inhibitor. The purpose of this study was based on the results of the determination of total phenolic levels and the characterization of the active compounds with LC MS/MS extracts of telang flower and rosella, which are expected to be developed into further research in vivo to strengthen scientific evidence so that they can be developed into phytopharmaca preparations. Instrumentation analysis method with LC-MS/MS to identify the content of active compounds and determination of total phenolic content with Folin ciocalteu in order to obtain standardized extracts of telang flower and roselle. The results of this study showed that the total phenolic content based on the largest order was purple rosella flower extract (114.129.35 ± 266.20 g GAE), a combination of purple rosella and telang flower extract (101.760.58 ± 116.09 g GAE), telang flower extract (90.477.41 ± 107.38 g GAE) and extract red rosella flowers (84,601.00 ± 266.91 g GAE). The combination of extracts showed reduced total phenolic content compared to the single extract. The phenolic content in each extract affected the total phenolic in the combination of extracts. 8 anthocinin compounds were identified in both the telang flower extract and the rosella flower extract.
Keywords: NPC1L1 inhibitor, telang, extract, Roselle, total phenolics, LC-MS/MS, atherogenesis
... Ternatins give the flowers their vibrant blue color and were discovered in 1985 ( Saito et al., 1985 ). Its flowers also contain high levels of phytochemicals which have antidiabetic ( Chusak et al., 2018), antioxidant ( López Prado et al., 2019, anti-microbial ( Mahmad et al., 2018 ), anti-inflammatory ( Nair et al., 2015 ) and anti-proliferative/anti-cancer properties ( Shen et al., 2016 ). Together with these unique anthocyanins in abundance and other secondary metabolites, the plant proves to be the ideal source of natural blue anthocyanin pigment with bioactive properties that enhance the appearance and nutritive values of the food products upon addition ( Azima et al., 2017 ;Pasukamonset et al., 2018 ;Escher et al., 2020 ). ...
Among natural colours, blue is probably the most difficult natural colour to work with since the sources are scarce; the pigment colour is dependent on pH and it is the least stable. Clitoria ternatea L. produces edible flowers that are rich sources of brilliant blue-coloured anthocyanins called "ternatins". The present study was conducted with the objective of coming up with an efficient, low-cost, and eco-friendly method of anthocyanin pigment extraction from Butterfly pea flowers with the perspective of food application. Among different extraction methods used, aqueous method gave significantly higher TMAC (7925.29±36.07 mg/L) and per cent polymeric colour (25.28±1.14 %), whereas higher recovery (73.17±1.76 %), antioxidant activity viz., DPPH (3.49±0.59 µl/ml), FRAP (3.99±1.10 µl/ml) and ABTS ((2.42±0.01 µl/ml), total phenolics (29.78±1.79 mgGAE/100g), total flavonoids (20.13±0.40 mgQE/100g), instrumental colour values indicating brilliant-blue colour viz., L* (27.74±0.73), a* (46.90±0.77), b* (-63.25±0.13) and chroma (78.74±0.38) hue angle (306.56±0.50) were observed in microwave assisted extraction (MAE) method. LC-MS/MS analysis of the pigment concentrate resulted in the detection of myristyl sulphate and DL-malic acid, having pharmacological significance. The proposed extraction method is the safest, economic, convenient, and eco-friendly solution for commercial anthocyanin extraction that can be up-scaled as a green-extraction technique at the industrial level.
... Berbagai penelitian telah membuktikan potensi antioksidan yang signifikan dari senyawa bioaktif dari kelompok flavonoid. Penelitian yang dilakukan oleh Nair et al. (2015), ...
... These molecules have shown strong inhibition of COX-2 activity and partial ROS suppression. In general, polyphenols present in CTE showed anti-inflammatory properties in LPS-induced inflammation in RAW 264.7 macrophage cells[68]. ...
Flowers are a natural source of bioactive compounds that not only have antioxidant, anti-inflammatory, and anti-aging properties, but can also be used as natural dyes. For this reason, nowadays plants are widely used to produce natural cosmetics and foods. In these studies, the properties of the water extracts of Papaver rhoeas L., Punica granatum L., Clitoria ternatea L., Carthamus tinctorius L., and Gomphrena globosa L., as bioactive, natural dyes, were investigated. Plant flower extracts were tested for their antioxidant (ABTS and DPPH radical methods) and anti-inflammatory effects by determining the ability to inhibit the activity of lipoxygenase and proteinase. The extracts were tested for their cytotoxic effect on skin cells, using Alamar Blue and Neutral Red tests. The ability to inhibit the activity of enzymes responsible for the destruction of elastin and collagen was also studied. Research has shown that extracts have no toxic effect on skin cells, are a rich source of antioxidants and show the ability to inhibit the activity of elastase and collagenase enzymes. P. rhoeas extract showed the strongest antioxidant properties with IC50 value of 24.8 ± 0.42 µg/mL and 47.5 ± 1.01 µg/mL in ABTS and DPPH tests, respectively. The tested plants are also characterized by an anti-inflammatory property, for which the ability to inhibit lipoxygenase at a level above 80% and proteinase at the level of about 55% was noted. Extracts from P. rhoeas, C. ternatea, and C. tinctorius show the strongest coloring ability and can permanently dye cosmetic products, without significant color changes during the storage of the product.
... The extract yield of C. ternatea flowers in this study was found to be lower than the 72% extract yield in a study that used a 5:4:1 methanol/acetone/water mixture for 24 h but was higher than findings reported in another study with a 6.5% extract yield using 100% methanol at 30°C for 12 h. 14,20 The differences obtained in the extract yield could be strongly influenced by the solvent system used as well as the extraction time, temperature, and source of flowers that may differ in their phytochemical content. The TAC of pure methanol, ethanol, and acetone extract was extremely low or absent compared to those extracted using aqueous methanol/ethanol/acetone mixtures (Table 1), and the TAC was also not significantly different from that of the distilled water extract. ...
... The main compound that gives antioxidant activity is anthocyanin. Nair et al. (2015) identified 12 phenolic metabolites consisting of nine ternatin anthocyanins and three glycosylated quercetins from the butterfly pea flower. The phenolic compound is also contributed to its antioxidant activity. ...
An antioxidant compound is the main compound that is used to prevent cell damage from free radicals. These unstable molecules can be produced in the environmental condition such as pollution or lifestyle. One of the antioxidant molecules are anthocyanins, which can be found in the butterfly pea flower. This compound could be obtained from the extraction process. However, extraction conditions such as sample/solvent ratio, extraction time, and pH are the main factors in maximizing the yield. In this research, various factors on anthocyanins and phenolic content in butterfly pea extract were studied to get the optimum extraction condition. Extraction of the butterfly pea flower was done using the agitation method with heating and water solvent at 60 °C and various parameters. The sample was a dried butterfly pea flower. Various factors in extraction were: sample/solvent ratio, 1 : 20 and 1 : 50 (g.mL-1), extraction time of 90 and 150 min, and pH 1.0 and 7.0. Yield is calculated by comparing the extract weight before and after drying. Total anthocyanins content and total phenolic content are determined spectrophotometrically. Based on the results, the extraction of anthocyanins was affected by the stability of structures at different pH values. The highest total anthocyanins content was 1,206.77 mg.L-1 at sample/solvent ratio 1 : 20, 90 min and pH 1.0 conditions. Then, the maximum total phenolic content was 94.04 GAE mg.mg-1 sample at the sample/solvent ratio 1 : 50, 90 min and pH 7.0.
... Nitric oxide is regarded as a proinflammatory mediator when excessively produced in abnormal conditions [38]. The observed increase in cardiac and hepatic nitrite level of LPG-exposed animals implies the occurrence of damaging inflammatory events in these organs, whereas the decrease in the concentration of nitrite in polyphenoltreated groups can be attributed to the anti-inflammatory effects of the polyphenols [39][40][41]. LDH, which is present in high concentrations in cardiac muscle and liver, is an important diagnostic enzyme. It is released into the bloodstream upon the destruction of cells by lipid peroxidation. ...
Objective
This study was designed to investigate the effects of liquefied petroleum gas (LPG) on hematotoxic, cardiotoxic, and hepatotoxic indices and the modifying influence of selected polyphenols.
Methods
Adult male Wistar rats were exposed to1000 ppm LPG for 10 min at 12-h interval for 30 days with or without cotreatment with 50 mg/kg rutin, quercetin, tannic acid, or gallic acid followed by hematological, biochemical, and histopathological evaluations in animal tissues.
Results
Exposure to LPG induced hematotoxicity, cardiotoxicity, and hepatotoxicity. This is reflected in alterations to levels or activities of blood parameters (hemoglobin, packed cell volume, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, and platelets), enzymatic and nonenzymatic oxidative stress markers, nitrite, lactate dehydrogenase, creatine kinase-MB, transaminases, γ-glutamyl transpeptidase, bilirubin, and plasma albumin. LPG exposure also caused dyslipidemia and histoarchitectural changes. Treatment with the selected polyphenols effectively attenuated LPG-induced toxicity in rat tissues.
Conclusion
The results indicate that continuous exposure to LPG could lead to blood-, heart-, and liver-related diseases and dietary polyphenols could provide benefits in diseases associated with LPG inhalation toxicity.
... The concentration of anthocyanin is higher in fresh flower extract than the processed powder. The boiling of the flowers causes anthocyanin degradation (Purwaniati and Yuliantini 2020) ternatin B4, ternatin C2, and ternatin D1 (Nair et al. 2015). Seeds: The ethanol extract of seeds contain sterols, alkaloids, glycosides, saponins, tannins, carbohydrates, proteins, phenolic compound, and flavonoids (Kalyan et al. 2011). ...
... A study by Silva et al. [35] showed that ferric reducing antioxidant power of different lipid-soluble fractions derived from brown seaweed Bifurcaria bifurcata were ranging from According to Pearson's correlation analysis (Table 2), there is a positive correlation between antioxidant activity (DPPH and FRAP assay) and anti-inflammatory activity (both pre-incubated and co-incubated cell culture model). The antioxidant capacity of the bioactive compounds in Sargassum extract might contribute to suppressing oxidative stress status in the inflamed cells [36], so the positive reciprocal feedback loop between inflammation and oxidative stress could be interrupted. UGB was found to show the strongest NO-inhibition capacity in the two indicated models. ...
Sargassum brown seaweed is reported to exhibit several biological activities which promote human health, such as anticancer, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant activity. This study aimed to investigate the anti-inflammatory and antioxidant activity of crude lipid extracts of Sargassum ilicifolium obtained from four different coastal areas in Indonesia, namely Awur Bay–Jepara (AB), Pari Island–Seribu Islands (PI), Sayang Heulang Beach–Garut (SHB), and Ujung Genteng Beach–Sukabumi (UGB). Results showed that treatment of RAW 264.7 macrophage cells with UGB and AB crude lipid extracts (12.5–50 µg/mL) significantly suppressed the nitric oxide production after lipopolysaccharide stimulation, both in pre-incubated and co-incubated cell culture model. The anti-inflammatory effect was most marked in the pre-incubated cell culture model. Both two crude lipid extracts showed 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and high ferric reducing antioxidant power, which were amounted to 36.93–37.87 µmol Trolox equivalent/g lipid extract and 681.58–969.81 µmol FeSO4/g lipid extract, respectively. From this study, we can conclude that crude lipid extract of tropical S. ilicifolium can be further developed as a source of anti-inflammatory and antioxidant agent.
... The antioxidant activity of the color indicator films is mainly due to the bioactive compounds of anthocyanin and shikonin [11,13,22,49]. It is well known that various biologically active phenolic components such as ferulic acid, tannic acid, gallic acid, rutin, etc., are the main components found in butterfly pea flowers and have potent antioxidant properties [11,50]. It is known that the antioxidant activity of shikonin is primarily determined by the ability of the phenoxy group to donate or accept electrons to fight free radicals [23,51]. ...
Natural colorants (anthocyanin and shikonin) were blended in different ratios (3:1 and 1:3) and used for the preparation of carboxymethyl cellulose (CMC)/agar-based functional halochromic films. The colorants were compatible with the polymer matrix and evenly spread over the polymer matrix. The addition of colorants slightly improved the mechanical strength and significantly improved the water vapor barrier properties of CMC/agar-based films without altering the thermal stability. The color indicator film exhibited excellent UV- barrier properties without substantially reducing the transparency. It also showed distinct pH-responsive color-changing properties in the pH range of 2–12, showing excellent acid and base gas sensing properties. The shikonin-added film showed potent antimicrobial activity against food-borne pathogenic bacteria, and the color indicator films exhibited intense antioxidant activities. The CMC/agar-based color indicator films with improved physical and functional properties are likely to be used in active and intelligent food packaging applications.
... Ang II-induced ROS production leading to the activation of NF-κB and inflammation has been well-described [16]. Furthermore, the preventive effects of CT extract on lipopolysaccharide-induced inflammation in macrophage cells have been shown [56]. ...
In this study, we examine whether Clitoria ternatea Linn. (CT) can prevent Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin–angiotensin system activation due to L-NAME in rats.
... Thus, the suppression of mRNA production of pro-inflammatory cytokines could not be attributed to one specific phytochemicals. Nevertheless, as other authors have pointed out, the examination of the whole extract is the first step of investigation and additional tests are needed in order to elucidate the mechanism of action each component (Leyva-López et al., 2016b;Nair et al., 2015). ...
Ethnopharmacological relevance
Nectandra angustifolia belongs to the Lauraceae family and it is widely known in phytomedicine by local inhabitants of South America against various maladies. It is popularly used for the treatment of different types of inflammatory processes, like rheumatism, arthritis and its associated pain.
Aim of the study
To characterize the phytochemicals in an ethanolic extract of Nectandra angustifolia and to evaluate the total antioxidant content and its anti-inflammatory effect with multiparametric analyses through in vitro assays and an in vivo model.
Methods
Leaves and stems of Nectandra angustifolia were air-dried and an ethanolic extract (NaE) was further obtained. Total phenolic, flavonoid and tannin content were determined and the antioxidant activity was addressed by DPPH and FRAP assays. NaE was first analyzed by HPLC and then two tests were carried out as screening assays for anti-inflammatory activities: red blood cell membrane stabilization and protein denaturation. The non-cytotoxic concentration of NaE was determined for in vitro biological assays using RAW 264.7 (murine macrophages) cell cultures through cell counting with Trypan-blue and XTT assay. Subsequently, the cell cycle of RAW 264.7 cells exposed for 24 h to NaE was analyzed. Additionally, the anti-inflammatory capacity of NaE was evaluated by RT-qPCR of pro-inflammatory cytokines. Furthermore, NF-κB translocation was observed by confocal microscopy at different times. Finally, formalin-induced mice paw inflammation was used as an in vivo model.
Results
The chromatographic profile of NaE showed peaks compatible with flavonoids content. NaE exhibited better membrane stabilization effect on HRBC and protection of BSA denaturation than the standard drug (diclofenac). NaE diminished mRNA levels of pro-inflammatory cytokines when added 1-hour prior LPS stimulation. Moreover, NaE prevented the translocation of NF-κB to the nucleus and in formalin-induced mice paw inflammation, reduced the edema and the stimulus of inflammatory phase.
Conclusion
This study shows for the first time, that Nectandra angustifolia ethanolic extract has a high content of flavonoids and that possess antioxidant and anti-inflammatory biological properties as demonstrated by multiparametric analyses from in vitro assays and an in vivo model of inflammation.
... A nutrient mixture made with the germinated seeds of green gram and horse gram with herbs such as turmeric and fenugreek ameliorated CCl 4 -induced liver cirrhosis due to their antiinflammatory and antioxidant activities [82]. The herb Clitoria ternatea L., commonly known as the butterfly pea, showed its antiinflammatory action in RAW 264.7 macrophage cells by suppressing LPS-induced inflammation due to the presence of polyphenols [83]. Emblica officinalis treatment attenuated aluminuminduced proinflammatory responses and endoplasmic reticulum stress through its antiinflammatory, antioxidant, and antiapoptotic activities, which suggest that E. officinalis could be a good therapeutic lead to manage Alzheimer's disease due to its neuroprotective efficacy [84]. ...
Inflammation is a biological function that is caused after a mechanical tissue disorder or from the reactions by the occurrence of a physical, chemical, or biological mediator in the body. It is also an essential act provided by the immune system during infection and tissue injury to preserve normal tissue homeostasis. Numerous health problems are associated with prolonged inflammation, which effects nearly all minor to major diseases. Current antiinflammatory drugs are expensive and have a high risk of side effects. Hence, the natural product-based formulations have received extensive recognition by medical experts and the public to treat inflammation, and this has provided extensive value for pharmaceutical discoveries over the last century. This chapter provides an update on inflammation and its associated diseases, molecular targets, inflammatory mediators, and the function of natural products. Accordingly, the current studies in identifying new molecules from natural products can lead to future antiinflammatory pharmaceutical and nutraceutical discoveries.
Eye shadow is one of the decorative cosmetic that contains color that is applied to the eyelids. Eye shadows were generally blue, pink, dark red, silver, green, and brown. Natural dyes are derived from plants, animals, and microorganisms. Butterfly pea flower (Clitoria ternatea L.) and secang wood (Caesalpinia sappan L.) are plants that contain natural dyes that can be used as dyes. The two plants were removed by maceration in 70% ethanol. Eye shadow preparation using a combination of extract spissum of butterfly pea flower and secang wood produces eye shadow with a purple color in 3 formulations, namely F3 extract spissum butterfly pea flower and secang wood (3:2), F4 extract spissum butterfly pea flower and secang wood (2:3), F5 extract spissum butterfly pea flower and secang wood (1:4). In the hedonic test, there was no significant difference >0.05% among F3, F4, and F5. Thus, the results of the irritation test showed that the eye shadow cream preparation produced an irritation index of 1.00, namely, mild irritation. Keywords: Eye shadow, butterfly pea flower, Secang wood.
Colorectal cancer is a malignancy with high incidence and mortality worldwide, and ulcerative colitis (UC) is strongly associated with colorectal cancer. Purple yam, also known as Dioscorea alata, has been reported to be rich in plant polyphenols that have possessed anti-inflammatory, antioxidant, and antitumor properties. However, it is not clear whether purple yam polyphenol extracts (PYPE) can improve colitis and inhibit colitis-related colorectal tumorigenesis. Therefore, we used dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer (CAC) models in mice to evaluate the preventive value and possible mechanisms of PYPE. It was found that PYPE effectively alleviated DSS-induced colitis, inhibited macrophage infiltration, and reduced the production of the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, IL-17A, CXCL1, and MCP-1, and the higher the concentration of PYPE, the better the inhibitory effect. In addition, PYPE dramatically prevented the development of CAC and tumor proliferation in mice. Furthermore, PYPE inactivated NF-κB and STAT3 signaling to exert anti-inflammatory and anticancer effects. Taken together, these findings indicate that PYPE may be used as a promising preventive strategy against UC and CAC.
This study aimed to explore the enhancive effects of butterfly pea flower (BF) extracts on metabolic and immune homeostasis in a low-grade inflammation mouse model. The BF extract was found to contain mainly anthocyanins among other flavonoids. BF supplementation alleviated metabolic endotoxemia by lowering the plasma glucose, lipopolysaccharide (LPS), and tumor necrosis factor-α (TNF-α) levels and restored lipid metabolism and the balance between Treg and Th17 cells, thereby inhibiting the dysfunctional liver and abdominal white adipose tissues. BF extract increased the tight junction protein expression and reduced the expression of proinflammatory cytokines, therefore sustaining the colonic mucosa structure. Furthermore, BF extracts reshaped the gut microbiota structure characterized by significantly promoted SCFA-producing gut microbiota such as Akkermansia and Butyricicoccaceae. Additionally, BF extracts enhanced fecal primary bile acid (BA) levels and modulated bile acid signaling in the liver and ileum to facilitate BA synthesis for the restoration of lipid metabolism. In summary, anthocyanin-enriched BF extracts alleviated the profound negative dietary alterations and helped maintain the metabolic health by modulating the various aspects of the gut microenvironment and enhancing hepatic bile acid synthesis.
A biologically inspired anthocyanin-graphene hybrid heterojunction has been designed and demonstrated to serve as a highly pH-value sensitive and self-powered photodetector. The photosensor shows a photo responsivity as high as...
This study examined the chemical compounds and bioactivity of the aqueous extract of Clitoria ternatea blue petals and investigated its beneficial effects in vivo on a mouse model of obesity and metabolic syndrome. The extract mainly contained flavonoids, and nine compounds were tentatively identified. Male C57BL/6J mice were either fed a standard diet (SD) or a high-fat, high-fructose diet (HFFD) for 16 weeks, and HFFD-fed animals were treated with 0.25%, 0.5%, and 2% (w/w) of the aqueous extract in drinking water. The aqueous extract ameliorated oxidative stress and inflammation mediators. Furthermore, the aqueous extract reduced plasma leptin, free fatty acid, low-density lipoprotein cholesterol levels and hepatic malondialdehyde content. The aqueous extract significantly reduced total cholesterol and ameliorated insulin resistance. The results demonstrated that the aqueous extract of C. ternatea blue petals contains bioactive anthocyanins that exert substantial hypolipidemic and anti-inflammatory effects by promoting reverse cholesterol transport in HFFD-fed mice.
Background
The number of COVID-19 cases continues to grow in Indonesia. This phenomenon motivates researchers to find alternative drugs that function for prevention or treatment. Due to the rich biodiversity of Indonesian medicinal plants, one alternative is to examine the potential of herbal medicines to support COVID therapy. This study aims to identify potential compound candidates in Indonesian herbal using a machine learning and pharmacophore modeling approaches.
Methods
We used three classification methods that had different decision-making processes: support vector machine (SVM), multilayer perceptron (MLP), and random forest (RF). For the pharmacophore modeling approach, we performed a structure-based analysis on the 3D structure of the main protease SARS-CoV-2 (3CLPro) and repurposed SARS, MERS, and SARS-CoV-2 drugs identified from the literature as datasets in the ligand-based method. Lastly, we used molecular docking to analyze the interactions between the 3CLpro and 14 hit compounds from the Indonesian Herbal Database (HerbalDB), with lopinavir as a positive control.
Results
From the molecular docking analysis, we found six potential compounds that may act as the main proteases of the SARS-CoV-2 inhibitor: hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4’-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside.
Conclusions
Our layered virtual screening with machine learning and pharmacophore modeling approaches provided a more objective and optimal virtual screening and avoided subjective decision making of the results. Herbal compounds from the screening, i.e. hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4’-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside are potential antiviral candidates for SARS-CoV-2. Moringa oleifera and Psidium guajava that consist of those compounds, could be an alternative option as COVID-19 herbal preventions.
Butterfly pea flower contains many bioactive substances. To make more use of it, an approach of adding butterfly pea flower extract (BPFE) to Chinese steamed bread (CSB) as a natural colorant and functional ingredient was applied. The objective of this study was to investigate the effect of BPFE level (0‐30%) on phytochemical, textural and sensory properties of CSB. Total anthocyanins, free polyphenols, DPPH radical scavenging capacity and reducing power of CSB were enhanced by increasing BPFE level. BPFE‐fortified CSB appeared blue in color. However, steaming process caused obvious decrease in anthocyanin content and blueness of CSB. Although addition of 30% BPFE significantly reduced the springiness, cohesiveness and elasticity of CSB, CSB with 0‐30% BPFE had similar sensory scores in flavor, texture and overall preferences. Blue healthy CSB having high phytochemicals and antioxidant activities as well as acceptable sensory attributes can be manufactured by the addition of 20‐30% BPFE.
Colorimetric films are emerging as a facile and effective indicator for freshness monitoring. To meet the versatile demands of consumers, multifunctionality is desirable for the colorimetric films. Here, an antibacterial-antioxidant colorimetric film was developed by incorporating nisin and anthocyanins of pomegranate/Clitoria ternatea (PGA/CTA) into ethylene vinyl alcohol (EVOH) matrix. The precursor of EVOH/nisin10 was determined for the incorporation of PGA/CTA of 1:2. The pH-sensing nature and antioxidant activity were originated from the mixture of PGA/CTA, while the antibacterial activity was from nisin. The components of and PGA/CTA in the matrix were well-dispersed and hydrogen-bonded. The color changes of the target film of EVOH/nisin-(PGA/CTA)3 were distinguishable at pH 2–12 and film was sensitive to the pH-stimuli of volatile ammonia and acetic acid. In addition, the film exhibited good antioxidant activity (DPPH·scavenging activity of ~80 %) and antibacterial activity against S. aureus (approximating bactericidal effectiveness). The film can not only monitor shrimp freshness effectively but extend the shelf-life of the packaged shrimp by 100 % at storage of 4 °C, revealing its potential in active intelligent food packaging. The combination of two different sourced anthocyanins along with nisin provides a strategy for achieving an efficacy of freshness retaining plus monitoring.
Morbiditas nifas semakin meningkat dengan adanya luka jalan lahir. Salah satunya adalah ruptur perineum pada persalinan normal yang mencapai 88.9%. Akibat penatalaksanaan yang tidak sesuai akan berdampak pada timbulnya keterbatasan mobilitas dan juga infeksi, oleh sebab itu upaya pendampingan bagi ibu nifas khususnya dengan riwayat luka perineum perlu mendapatkan perhatian. Agar tercapainya penyembuhan tanpa komplikasi pada ibu. Ekstrak clitoria ternatea atau bunga telang memiliki kandungan antiimflamasi yang memiliki kemampuan analgesi yang mempengaruhi sistem syaraf untuk menghambat sinyal nyeri ke otak dan memberikan efek penyembuhan luka. Bunga berwarna cantik yang memiliki beragam manfaat kesehatan ini sudah sangat populer namun demikian pemanfaatannya dalam ranah asuhan kebidanan khususnya masa nifas masih belum banyak diterapkan. Penelitian ini bertujuan untuk mengetahui efektivitas pemberian ekstrak bunga telang terhadap penyembuhan luka perienum, adapun ekstrak bunga telang yang digunakan dalam dua bentuk sediaan yaitu infus water untuk di konsumsi dan larutan yang akan dipergunakan saat melakukan pulva hygien (cebok). Metode kuasi ekperimen pada 2 kelompok ibu nifas dengan riwayat luka perineum grade II. Hasil penelitian diperoleh skala nyeri pada ibu nifas kedua kelompok sebelum dilakukan intervensi yaitu skala nyeri ringan, sedang dan berat, sedangkan waktu penyembuhan luka perineum pada kedua kelompok bervariasi antara 5-10 hari. Penyembuhan luka pada kelompok kontrol 7-10 hari dan pada kelompok intervensi 5-7 hari, artinya pemberian bunga telang secara dikonsumsi dan juga dijadikan larutan pulva hygiene lebih efektif dalam perawatan luka perineum ibu nifas. Hasil analisis dengan uji mann withney diperoleh nilai p 0,000 dengan kesimpulannya terdapat pengaruh pemberian bunga telang terhadap penyembuhan luka perineum. Saran diperlukan bentuk sediaan lain dari bunga telang utuk dimanfaatkan pada penelitian selanjutnya Kata Kunci: Perwatan perieneum, nifas, bunga telang
This study aimed to evaluate the effect of Moringa-Albumin (MA) combination on pro-inflammatory cytokine expressions, especially IFN-γ and TNF-α, in a diabetic mouse model. Streptozotocin with a 145 mg/kg BW dose was used to induce diabetes condition in BALB/c mice. Mice with positive DM (blood glucose levels ≥ 200 mg/dL) were orally administered with MA for 14 days at dose 1, dose 2, and dose 3. On day 15th, spleen cells were isolated to analyze IFN-γ and TNF-α expressions by flow cytometry. The data were statistically analyzed with one-way ANOVA (ρ≤ 0.05) and Tukey test using SPSS version 16 for Windows. The results showed that the MA combination had anti-inflammatory activity in inhibiting IFN-γ and TNF-α. Furthermore, dose 1 affected to decrease in the IFN-γ expression while dose 3 decreased the expression of TNF-α. Thus, it can be concluded that the MA combination has a role in inhibiting IFN-γ and TNF-α in a dosage-dependent manner. Based on the results, we assumed that MA might be one of the biological materials with efficacy to treat DM patients.
Treatment of chronic wounds requires good monitoring for the wound infection. One of the indicators for the infected wound is the change of pH values around the wound area. In this study, the visual pH sensor from Clitoria ternatea (CT) flower was used to indicate the pH value and evaluate the wound status. The CT extract contains anthocyanins which are pigments that appear in different colors depending on the pH values. The color of CT extract at pH values ranges from 2.0 to 12.0 was investigated by the UV-vis spectrophotometer and the naked eye. The antioxidant activity, antibacterial activity, and cytotoxicity of CT extract were evaluated for their biological activities. The concentration of CT extract that can scavenge 50% of DPPH free radicals was 0.80 mg/mL. Besides, the CT extract showed non-toxic to NCTC 929 cells. However, the CT extract demonstrated low inhibition of S. aureus, E. coli, P. aeruginosa, and S. epidermidis bacteria. Also, the CT extract was loaded on the paper to observe the color changes in bacterial solutions. The color changed from blue-purple to blue-green color in bacterial solutions indicating the wound infection. Therefore, the natural dyes extracted from the CT flower had the potential to apply for colorimetric pH sensor in wound dressing application.
Clitoria ternatea (CT) or butterfly pea was one herbs used for Ayurvedic and other traditional medicines. Utilization of its roots, flowers, and leaves proposed several medical adventages with anthelmintic was one of it. Among current anthelmintic burden of resistance, this study aimed to examine the anthelmintic profile from CT flower aqueous extract on Tubifex tubifex . The study was done by conducting a pilot experimental study by extracting CT flowers to water and piping the extracts of different level of dilution to several group of pots containing Tubifex tubifex . Anthelmintic activity was determined with its paralyzing effect and was compared to negative and positive controls with levamisole. Phytochemicals substances were detected with alkaloids, flavonoids, glycosides, saponins, tannins, and triterpenoids detected. The extract exerts anthelmintic activity it 1:4, 1:40, and 1:400 dilutions and was comparable to 1mg/mL and 0.1mg/mL levamisole. Time to paralysis observed suggested a dose-response relationship of the extract on its anthelmintic activities. It was understood the phytochemicals influents the anthelmintic activity by paralysis worms and leads to death. It was concluded that CT flower aqueous extract presents anthelmintic activity, with further experimental study will needed to be conducted.
Inflammation and Natural Products brings together research in the area of the natural products and their anti-inflammatory action in medical, nutraceutical and food products, addressing specific chronic inflammatory diseases like cancer and the mechanistic aspects of the mode of action of some key natural products. Inflammation is a complicated process, driven by infection or injury or genetic changes, which results in triggering signalling cascades, activation of transcription factors, gene expression, increased levels of inflammatory enzymes, and release of various oxidants and pro-inflammatory molecules in inflammatory cells. Excessive oxidants and inflammatory mediators have a harmful effect on normal tissue, including toxicity, loss of barrier function, abnormal cell proliferation, inhibiting normal function of tissues and organs and finally leading to systemic disorders. The emerging development of natural product formulations utilizing the unique anti-inflammatory compounds such as polyphenols, polysaccharides, terpenes, fatty acids, proteins and several other bioactive components has shown notable successes. Inflammation and Natural Products: Recent Development and Current Status provides a comprehensive resource, ranging from detailed explanation on inflammation to molecular docking strategies for naturally occurring compounds with anti-inflammatory activity. It is useful for graduate students, academic and professionals in the fields of pharmaceutical and medical sciences and specialists from natural product-related industries.
Background
Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages.Methodology/Principal FindingsNon-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages.Conclusions/SignificanceThese results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.
Flavonoids are a widely distributed group of natural products with a variety of pharmacological activities including antioxidant, anticancer and anti-inflammatory activities. There are a variety of mechanisms reported to explain the anti-inflammatory activity of flavonoids. The present work involves use of in silico methods to study the binding of flavonoids to COX-2. The flavonoids involved in the present work were members of flavonol,flavone, flavanone or isoflavone class. Docking studies were carried out to determine whether flavonoids can act as COX-2 inhibitors. The results indicated that some flavonols and flavones containing a 2,3-double bond may act as preferential inhibitors of COX-2.
Reactive oxygen species (ROS) have an established role in inflammation and host defense, as they kill intracellular bacteria and have been shown to activate the NLRP3 inflammasome. Here, we find that ROS generated by mitochondrial respiration are important for normal lipopolysaccharide (LPS)-driven production of several proinflammatory cytokines and for the enhanced responsiveness to LPS seen in cells from patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder caused by missense mutations in the type 1 TNF receptor (TNFR1). We find elevated baseline ROS in both mouse embryonic fibroblasts and human immune cells harboring TRAPS-associated TNFR1 mutations. A variety of antioxidants dampen LPS-induced MAPK phosphorylation and inflammatory cytokine production. However, gp91(phox) and p22(phox) reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits are dispensable for inflammatory cytokine production, indicating that NADPH oxidases are not the source of proinflammatory ROS. TNFR1 mutant cells exhibit altered mitochondrial function with enhanced oxidative capacity and mitochondrial ROS generation, and pharmacological blockade of mitochondrial ROS efficiently reduces inflammatory cytokine production after LPS stimulation in cells from TRAPS patients and healthy controls. These findings suggest that mitochondrial ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases.
STAT1 is an essential transcription factor for macrophage activation by IFN-γ and requires phosphorylation of the C-terminal Ser727 for transcriptional activity. In macrophages, Ser727 phosphorylation in response to bacterial lipopolysaccharide (LPS), UV irradiation, or TNF-α occurred through a signaling path sensitive to the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 whereas IFN-γ-mediated Ser727 phosphorylation was not inhibited by the drug. Consistently, SB203580 did not affect IFN-γ-mediated, Stat1-dependent transcription but inhibited its enhancement by LPS. Furthermore, LPS, UV irradiation, and TNF-α caused activation of p38 MAPK whereas IFN-γ did not. An essential role for p38 MAPK activity in STAT1 Ser727 phosphorylation was confirmed by using cells expressing an SB203580-resistant p38 MAPK. In such cells, STAT1 Ser727 phosphorylation in response to UV irradiation was found to be SB203580 insensitive. Targeted disruption of the mapkap-k2 gene, encoding a kinase downstream of p38 MAPK with a key role in LPS-stimulated TNF-α production and stress-induced heat shock protein 25 phosphorylation, was without a significant effect on UV-mediated Ser727 phosphorylation. The recombinant Stat1 C terminus was phosphorylated in vitro by p38MAPKα and β but not by MAPK-activated protein kinase 2. Janus kinase 2 activity, previously reported to be required for IFN-γ-mediated Ser727 phosphorylation, was not needed for LPS-mediated Ser727 phosphorylation, and activation of Janus kinase 2 did not cause the appearance of STAT1 Ser727 kinase activity. Our data suggest that STAT1 is phosphorylated at Ser727 by a stress-activated signaling pathway either through p38 MAPK directly or through an unidentified kinase downstream of p38MAPK.
The production of nitric oxide by macrophages has been implicated as a host defense mechanism against microbial pathogens and tumor cells. Recent reports have implicated interferon-alpha/beta (IFN-alpha/beta) as an autocrine/paracrine signal critical for the induction of murine iNOS. In this report we have systematically investigated the role of IFN-beta in the induction of iNOS in the murine macrophage cell line, RAW 264.7. First, we demonstrate that IFN-beta expression is highly up-regulated, and is secreted in response to lipopolysaccharide (LPS). Treatment of RAW macrophages with LPS results in a time-dependent phosphorylation of STAT-1 on both tyrosine residue 701 (Tyr-701) and serine residue 727 (Ser-727) that is consistent with the timing of endogenous IFN-beta expression. LPS also induces interferon regulatory factor-1 expression with similar kinetics. We further demonstrate that exogenous IFN-beta accelerates the induction of iNOS by LPS. The acceleration of iNOS induction is observed at the levels of transcription, protein expression, and NO formation. Accordingly, we propose that the cytokine environment of macrophages may determine the rate and magnitude of nitric oxide production, thereby regulating the cytotoxic response to pathogen challenge.
Lipopolysaccharide (LPS) stimulates macrophages to release inflammatory cytokines, interleukin-1 beta (IL-1), and tumor necrosis factor (TNF). LPS-induced TNF suppresses scavenger receptor functions in macrophages (van Lenten, B. J., and Fogelman, A. M. (1992) J. Immunol. 148, 112-116), which is regulated by TNF-mediated protein kinases (Hsu, H. Y., and Twu, Y. C. (2000) J. Biol. Chem. 275, 41035-41048). To examine the molecular mechanism for LPS induction of IL-1 in macrophages, we demonstrated that LPS quickly stimulated reactive oxygen species (ROS), and 3 h later induced prointerleukin-1 beta (pro-IL-1, precursor of IL-1) production and IL-1 secretion. LPS stimulated pro-IL-1 message/protein between 3 and 10 h; however, there was a 40% reduction of pro-IL-1 in preincubation of the antioxidant, N-acetylcysteine (NAC). Moreover, NAC moderated LPS-induced IL-1 secretion partially via interleukin 1-converting enzyme. The maximal activity of LPS-induced ERK, JNK, and p38 was 12- (30 min), 5- (30 min), and 16-fold (15 min), respectively. In contrast, NAC reduced ERK activity to 60% and decreased p38 activity to the basal level, but JNK activity was induced 2-fold. Furthermore, the pharmacological antagonists LY294002, SB203580, curcumin, calphostin C, and PD98059 revealed the diverse roles of LPS-mediated protein kinases in pro-IL-1. On the other hand, NAC and diphenyleneiodonium chloride partially inhibited LPS-induced Rac activity and protein-tyrosine kinase (PTK), indicating that LPS-mediated ROS and NADPH oxidase correspond to Rac activation and IL-1 expression. Our findings establish for the first time that LPS-mediated PTK/phosphatidylinositol 3-kinase/Rac/p38 pathways play a more important role than pathways of PTK/PKC/MEK/ERK and of PTK/phosphatidylinositol 3-kinase/Rac/JNK in the regulation of pro-IL-1/IL-1. The findings also further elucidate the critical role of LPS-mediated ROS in signal transduction pathways. Our results suggest that understanding LPS-transduced signals in IL-1 induction upon the antibacterial action of macrophages should provide a therapeutic strategy for aberrant inflammatory responses leading to severe cellular injury or concurrent multiorgan septic damage.
The present investigation was aimed at determining the spectrum of activity of the methanolic extract of Clitoria ternatea (CT) on the CNS. The CT was studied for its effect on cognitive behavior, anxiety, depression, stress and convulsions induced by pentylenetetrazol (PTZ) and maximum electroshock (MES). To explain these effects, the effect of CT was also studied on behavior mediated by dopamine (DA), noradrenaline, serotonin and acetylcholine. The extract decreased time required to occupy the central platform (transfer latency, TL) in the elevated plus maze (EPM) and increased discrimination index in the object recognition test, indicating nootropic activity. The extract was more active in the object recognition test than in the EPM. The extract increased occupancy in the open arm of EPM by 160% and in the lit box of the light/dark exploration test by 157%, indicating its anxiolytic activity. It decreased the duration of immobility in tail suspension test (suggesting its antidepressant activity), reduced stress-induced ulcers and reduced the convulsing action of PTZ and MES. The extract exhibited tendency to reduce the intensity of behavior mediated via serotonin and acetylcholine. The effect on DA- and noradrenaline-mediated behavior was not significant. In conclusion, the extract was found to possess nootropic, anxiolytic, antidepressant, anticonvulsant and antistress activity. Further studies are necessary to isolate the active principle responsible for the activities and to understand its mode of action.
An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the stem bark of Populus davidiana showed considerable inhibitory activity against cyclooxygenase (COX-1, COX-2). Continuous phytochemical study of the MeOH extract of this plant led to the isolation of ten flavonoids; sakuranetin (1), rhamnocitrin (2), 7-O-methylaromadendrin (3), naringenin (4), eriodictyol (5), aromadendrin (6), kaempferol (7), neosakuranin (8), sakuranin (9) and sakurenetin-5,4'-di-beta-D-glucopyranoside (10). Their structures were identified on the basis of their physicochemical and spectroscopic analyses. The isolated compounds, 1-10, were tested for their inhibitory activities against COX-1 and COX-2. Compound 7 was found to have potent inhibitory effect on COX-1 and a moderate effect on COX-2, meanwhile, compounds 1-6 showed moderate inhibition against COX-1 only. Moreover, compounds 5-8 exhibited suppressive effects on xanthine oxidase (XO). These results may explain, in part, the traditional uses of P. davidiana in ethnomedicine.
Flavonoids may play an important role for adjunct nutritional therapy of chronic intestinal inflammation. In this study, we characterized the molecular mechanisms by which quercetin and its enteric bacterial metabolites, taxifolin, alphitonin, and 3, 4-dihydroxy-phenylacetic acid, inhibit tumor necrosis factor α (TNF)-induced proinflammatory gene expression in the murine small intestinal epithelial cell (IEC) line Mode-K as well as in heterozygous TNFΔARE/WT mice, a murine model of experimental ileitis. Quercetin inhibited TNF-induced interferon-γ-inducible protein 10 (IP-10) and macrophage inflammatory protein 2 (MIP-2) gene expression in Mode-K cells with effective inhibitory concentration of 40 and 44 μmol/L, respectively. Interestingly, taxifolin, alphitonin, and 3,4-dihydroxy-phenylacetic acid did not inhibit TNF responses in IEC, suggesting that microbial transformation of quercetin completely abolished its anti-inflammatory effect. At the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit TNF-induced RelA/I-κB phosphorylation and IκB degradation or TNF-α-induced nuclear factor-κB transcriptional activity. Most important for understanding the mechanism involved, chromatin immunoprecipitation analysis revealed inhibitory effects of quercetin on phospho-RelA recruitment to the IP-10 and MIP-2 gene promoters. In addition, and consistent with the lack of cAMP response element binding protein (CBP)/p300 recruitment and phosphorylation/acetylation of histone 3 at the promoter binding site, quercetin inhibited histone acetyl transferase activity. The oral application of quercetin to heterozygous TNFΔARE/WT mice [10 mg/(d x kg body wt)] significantly inhibited IP-10 and MIP-2 gene expression in primary ileal epithelial cells but did not affect tissue pathology. These studies support an anti-inflammatory effect of quercetin in epithelial cells through mechanisms that inhibit cofactor recruitment at the chromatin of proinflammatory genes.
The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by oxidative stress and pro-inflammatory stimuli and controls the expression of numerous genes involved in the inflammatory response. Dampening NF-kappaB activation and thereby limiting the inflammatory response have been suggested as a potential strategy to prevent chronic inflammatory diseases. In cultured monocytes, anthocyanins isolated from bilberries and black currants (Medox) efficiently suppressed LPS-induced activation of NF-kappaB. Furthermore, we studied the effect of anthocyanin supplementation (Medox, 300 mg/d for 3 wk) in a parallel-designed, placebo-controlled clinical trial (n = 120 men and women aged 40-74 y). Differences were observed in several NF-kappaB related inflammatory mediators in the Medox group compared to placebo. The changes in the NF-kappaB-controlled pro-inflammatory chemokines IL-8, "regulated upon activation, normal T cell expressed and secreted," (RANTES) and IFNalpha (an inducer of NF-kappaB activation) in the Medox group (45, 15, and 40% decreases from baseline, respectively) differed from those in the placebo group (20, 0, and 15% decreases from baseline, respectively) (P < 0.050). Similarly, changes in IL-4 and IL-13, 2 cytokines that mediate pro-inflammatory responses and induce NF-kappaB activation, in the Medox group (60 and 38% decreases from baseline, respectively) tended to differ from those in the placebo group (4 and 6% decreases) (P = 0.056 and, P = 0.089, respectively). These data suggest that anthocyanin supplementation may have a role in the prevention or treatment of chronic inflammatory diseases by inhibition of NF-kappaB transactivation and deceased plasma concentrations of pro-inflammatory chemokines, cytokines, and inflammatory mediators.
We investigated the effects of the flavonols kaempferol and quercetin on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), endothelial cell selectin (E-selectin), inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), and on the activation of the signalling molecules NF-kappaB and activator protein-1 (AP-1), induced by a cytokine mixture in cultured human umbilical vein endothelial cells. Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin. The present study indicates that differences exist in the modulation of pro-inflammatory genes and in the blockade of NF-kappaB and AP-1 by kaempferol and quercetin. The minor structural differences between both flavonols determine differences in their anti-inflammatory properties and in their efficiency in inhibiting signalling molecules.
Dietary flavonoids are a large family of polyphenols ubiquitously expressed in plants. Recent evidence show that flavonoids possess several anti-inflammatory activities due to their ability to scavenge reactive oxygen and nitrogen species (ROS and RNS), to inhibit the pro-inflammatory activity of ROS-generating enzymes including cyclooxygenase (COX), lipoxygenase (LOX) and inducible nitric oxide synthase (iNOS) and to modulate different intracellular signaling pathways from NF-kB to mitogen-activated protein kinases (MAPKs) through perturbation of redox-sensible networks in immune cells. This report will review current knowledge on the anti-inflammatory effects of flavonoids on immune cells focusing on their ability to modulate multiple redox-sensible pathways involved in inflammation.
The present study was aimed to establish a protocol for multiple shoot induction via the culture of nodes of Clitoria ternatea L., through callogenesis and organogenesis. Explants were cultured on Murashige and Skoog's medium supplemented with different concentrations and combinations of BAP, 24-D and NAA for shoot and root induction. The sub-cultured of callus on MS basal medium supplemented with BAP (2.5 mg/l) and NAA (0.5mg/l) showed highest rate of shoot multiplication. In vitro shoots were rooted on to the MS basal medium supplemented with NAA (0.5mg/l). The preliminary phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, carbohydrates, steroids and phenol in in vitro grown products of Clitoria ternatea L. DPPH free radical scavenging assay was studied for evaluation of antioxidant potential. The ethanolic extract of in vitro grown Clitoria ternatea significantly inhibited the DPPH free radicals at the concentration ranging from 25-600μg mL-1. It showed highest inhibition 67% at 600μg mL,-1 equal to in vivo grown plant 70% at 600μg mL,-1. The in vitro multiplication ensures germplasm conservation of rare, endangered, aromatic medicinal plant while intrinsic natural antioxidants level could be harnessed for cure of diseases.
Following pathogen infection or tissue damage, the stimulation of pattern recognition receptors on the cell surface and in the cytoplasm of innate immune cells activates members of each of the major mitogen-activated protein kinase (MAPK) subfamilies - the extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK) subfamilies. In conjunction with the activation of nuclear factor-κB and interferon-regulatory factor transcription factors, MAPK activation induces the expression of multiple genes that together regulate the inflammatory response. In this Review, we discuss our current knowledge about the regulation and the function of MAPKs in innate immunity, as well as the importance of negative feedback loops in limiting MAPK activity to prevent host tissue damage. We also examine how pathogens have evolved complex mechanisms to manipulate MAPK activation to increase their virulence. Finally, we consider the potential of the pharmacological targeting of MAPK pathways to treat autoimmune and inflammatory diseases.
Flavonoids in the petals of several C. ternatea lines with different petal colors were investigated with LC/MS/MS. Delphinidin 3-O-(2"-O-alpha-rhamnosyl-6"-O-malonyl)-beta-glucoside was newly isolated from the petals of a mauve line (wm) together with three known anthocyanins. They were identified structurally using UV, MS, and NMR spectroscopy. Although ternatins, a group of 15 (poly)acylated delphinidin glucosides, were identified in all the blue petal lines (WB, BM-1, 'Double Blue' and 'Albiflora'), WM accumulated delphinidin 3-O-(6"-O-malonyl)-beta-glucoside instead. The white petal line (WW) did not contain anthocyanins. Quantitative data showed that the total anthocyanin contents in WB and 'Double Blue' were ca. 8- and 10-fold higher than that in BM-1, a bud mutant of 'Double Blue', respectively. The total anthocyanin content in 'Albiflora' was less than 2 x 10(-3) times those in WB or 'Double Blue'. While all the lines contained the same set of 15 flavonol glycosides in similar relative ratios, the relative ratio of myricetin glycosides in ww and 'Albiflora' was ca. 30-70 times greater than those in the other lines. The change in flower color from blue to mauve was not due to a change in the structure of an anthocyanidin from delphinidin, but to the lack of (polyacylated) glucosyl group substitutions at both the 3'- and 5'-positions of ternatins. This implies that glucosylation at the 3'- and 5'-positions of anthocyanin is a critical step in producing blue petals in C. ternatea.
Measurement of total serum cholesterol is a valuable test in the study of lipide metabolism. It requires a stable reagent for cholesterol color development and a simple procedure for the routine determination. A reagent for the Liebermann-Burchard reaction is described, which is stable for 2 weeks at room temperature and 4 weeks or longer under refrigeration, in contrast to 24 hours' stability of the ordinary acetic anhydride-sulfuric acid reagent. This reagent is also useful for rapid serum cholesterol determination. Only one reagent and one step are required.
Methods for the quantitative analysis of anthocyanins, leuco-anthocyanins, flavanols and total phenols in plant tissue extracts are critically examined and suitable modifications of existing methods are described.
Nitrite level in cell supernatants is cm index of nitric oxide (NO) produced by lipopolysaccharide/interferon-γ (LPS/IFN-y) activated RAW 264.7 macrophages. The Griess assay has been widely used to quantify nitrite in biological fluids including cell supernatants. The assay is based on the reaction of nitrite under acidic conditions with Griess reagent to form a purple azo dye with a maximum wavelength (λmax) at 540 nm. In acidic media anthocyanins also have intense absorbance at the same visible absorption range as the azo dye. A modified Griess assay is described to quantify nitrite in cell supernatants in the presence of anthocyanin pigments. Gas chromatography mass spectrometry (GC/MS) with electron impact ioniziation (EI) was also used to quantify nitrite but suffered from poor repeatability. Results obtained by the modified Griess and the GC/MS assay were significantly correlated and served to demonstrate the effects of anthocyanins on NO production in RAW 264.7 macrophages.
Butterfly pea, Clitoria ternatea is used in Africa as a companion crop and in the United States as an ornamental. The USDA, ARS, PGRCU curates 28 butterfly
pea accessions. Butterfly pea accessions were transplanted from about 30-day-old seedlings to the field in Griffin, GA around
01 June 1999, 2003, 2006–2007 or directly sown in 2001. At 50% maturity, 19 accessions were characterized for morphology,
phenology, and evaluated for regeneration. High quality plants regenerated from all accessions produced 6 to more than 3,400
total seeds. Butterfly pea can be successfully grown and regenerated in Griffin, GA. Coefficients of variation and principal
component analysis revealed considerable variability among accessions for morphological and reproductive traits. Butterfly
pea has potential to be used as a nutraceutical, pharmaceutical, or food. The flavonoid quercetin has been shown to reduce
upper respiratory infections in humans while delphinidin and malvidin identified in butterfly pea flowers may inhibit various
forms of cancer.
Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity, and inflammation. Macrophage products also impact metabolism, as illustrated by obesity-associated pathologies. Defining the mechanisms regulating macrophage metabolic activity and orchestration of metabolism by macrophages is crucial to pathology and therapeutic intervention.
Six pecan cultivars were analyzed for their antioxidant capacity (AC), total phenolics (TP), condensed tannin (CT), HPLC phenolic profile, tocopherol and fatty acid composition. Kernels which included the outer brown testa or pellicle, and shells which is the hard cover that surrounds the kernel, were evaluated for each cultivar. Strong correlations were found in kernels between AC and TP for both DPPH (r2 = 0.98) and ACORAC (r2 = 0.75) antioxidant assays. ACORAC values ranged from 372 to 817 μmol trolox equivalents/g defatted kernel, corresponding to Desirable and Kanza cultivars, respectively. CT ranged from 23 to 47 mg catechin equivalents/g defatted kernel and TP from 62 to 106 mg of chlorogenic acid equivalents/g defatted kernel. After a consecutive basic-acid hydrolysis, gallic acid, ellagic acid, catechin and epicatechin were identified by HPLC. The TP, AC and CT were 6, 4.5 and 18 times higher, respectively, for shells compared to kernels. The presence of phenolic compounds with high antioxidant capacity in kernels and shells indicates pecans can be considered an important dietary source of antioxidants.
Metabolism and immunity are two fundamental systems of metazoans. The presence of immune cells, such as macrophages, in metabolic tissues suggests dynamic, ongoing crosstalk between these two regulatory systems. Here, we discuss how changes in the recruitment and activation of macrophages contribute to metabolic homeostasis. In particular, we focus our discussion on the pathogenic and protective functions of classically and alternatively activated macrophages, respectively, in experimental models of obesity and metabolic disease.
Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-kappaB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.
The USDA, ARS, Plant Genetic Resources Conservation Unit curates several important nutraceutical and medicinal plant species. Anthocyanins are responsible for flower, leaf and seed coat color in plants, and are antioxidants as well. However, little is known about anthocyanin content in Clitoria ternatea, Desmodium adscendens, Corchorus olitorius, Catharanthus roseus, Hibiscus sabdariffa and Acer saccharum. This study was conducted to identify anthocyanin indexes and additional health enhancing components in these species. An anthocyanin meter with an LED diode of 520 nm was used to measure the anthocyanin index of leaves and flowers from plants growing in the field during July, September and October 2006. We found anthocyanin indexes ranging from 4.1 to 52.4 for leaves and 0.8 to 26.8 for flowers in all five species. The highest leaf anthocyanin index average of 14.6 was found in D. adscendens (PI 316623) followed by sugar maple (A. saccharum) with a leaf anthocyanin average index of 13.0. Catharanthus roseus (PI 608581) also had the highest flower anthocyanin index average of 17.3. These data were recorded at or prior to 50% maturity. In addition, potential health uses for these species are discussed. Phytochemicals identified include but are not limited to an antimicrobial protein from C. ternatea, anthocyanin rich extracts from H. sabdariffa for potential use as a chemopreventive agent, and antitumor promoters in C. olitorius leaves. These anthocyanins and phytochemicals have potential value in the nutraceutical and medical industries. These variable anthocyanin indexes among these species will assist breeders and other scientists with valuable germplasm for development of anthocyanin enriched cultivars.
Yerba mate tea ( Ilex paraguariensis ) is growing in popularity around the world. The objective of this study was to investigate the potential anti-inflammatory effect of yerba mate tea (MT) extracts as well as some of its phytochemicals and their interactions. MT and decaffeinated MT extracts [1-300 microM chlorogenic acid (CHA) equiv]; CHA, caffeine from MT (matein), and mate saponins (1-300 microM); quercetin (1-200 microM); and ursolic and oleanolic acids (1-100 microM) were tested by measuring their ability to inhibit COX-2/PGE(2) and iNOS/NO pathways in LPS-induced RAW 264.7 macrophages. Mate saponins (IC(50) = 20 microM) and oleanolic acid (IC(50) = 80 microM) significantly inhibited iNOS/NO pathways, whereas ursolic acid showed low or no inhibition at 100 microM. Quercetin was the most potent inhibitor of pro-inflammatory responses at a concentration 10 times lower than the concentrations used of other compounds (IC(50) = 11.6 microM for NO, 7.9 microM for iNOS, and 6.5 microM for PGE(2)). Combination of quercetin/mate saponins (0.001:0.004, molar ratio) resulted in synergistic interaction inhibiting both NO and PGE(2) production. It also suppressed IL-6 and IL-1beta production and resulted in reduction of LPS-induced nuclear translocation of nuclear factor-kappaB subunits. MT extract did not have a potent anti-inflammatory effect perhaps due to the antagonistic effect of some of its compounds. However, whole MT consumption still has a promising anti-inflammatory outcome mainly through the PGE(2)/COX-2 pathway. To the authors' knowledge, this is the first study demonstrating the efficacy, interactions, and mechanisms of some MT phytochemicals in inhibiting pro-inflammatory responses.
Our objective was to evaluate the cancer suppression activity of extracts from a commercial variety of yellow-fleshed peach 'Rich Lady' (RL) and a red-fleshed plum 'Black Splendor' (BS) and identify the phenolic fractions that may possess potential as chemopreventive and/or chemotherapeutic natural compounds. The peach RL extract effectively inhibited the proliferation of the estrogen-independent MDA-MB-435 breast cancer cell line. The concentration to inhibit 50% of cell proliferation (IC(50)) was approximately 42 mg/L for this cell line compared to an IC(50) of approximately 130 and approximately 515 mg/L for the noncancerous breast cell line MCF-10A and the estrogen-dependent breast cancer cell line MCF-7, respectively. Similarly, BS extracts showed greater effects on MDA-MB-435 cells as compared to the other breast cancer or the normal breast cell lines. In general, BS extracts were less effective than RL extracts. Within all RL and BS fractions, fraction 3 (F3, flavonoids) and fraction 4 (F4, procyanidins) were more potent than fraction 1 (F1, phenolic acids) and fraction 2 (F2, anthocyanins) against the three cell lines. The order of potency of RL fractions against MDA-MB-435 was F(3) approximately F(4) > F(1) > F(2). The antiproliferative activity of pure compounds identified in F(3) and F(1) confirmed that quercetin 3beta-glucoside is the bioactive compound in F(3), with the same level of toxicity on the estrogen-independent MDA-MB-435 breast cancer and breast epithelial MCF-10A cells (IC(50) = 1.9 +/- 0.2 and 1.8 +/- 0.3, respectively). However, we confirmed that phenolic acids present in F(1): chlorogenic and neo-chlorogenic acids have potential as chemopreventive dietary compounds because of the relatively high growth inhibition exerted on the estrogen-independent MDA-MB-435 breast cancer cell line and low toxicity exerted in the normal MCF-10A cells.
Five new ternatins 1-5 have been isolated from Clitoria ternatea flowers, and the structures have been determined by chemical and spectroscopic methods as delphinidin 3-malonylG having 3'-GCG-5'-GCG, 3'-GCG-5'-GC, 3'-GCGCG-5'-GC, 3'-GCGC-5'-GCG, and 3'-GCGC-5'-GC side chains, respectively, in which G is D-glucose and C is p-coumaric acid. Pigment 1 had symmetric 3',5'-side chains. Compounds 3 and 4 are structural isomers. These ternatins were shown to form an intramolecular stacking between the aglycon ring and the 3',5'-side chains in solution.
Eight new anthocyanins 1-8 (ternatins C1, C2, C3, C4, C5, and D3 and preternatins A3 and C4) were isolated from Clitoria ternatea flowers. By the application of chemical, UV-vis, and FABMS methods, the structures of 1-6 were postulated as delphinidin 3-malonylglucoside having 3'-GCGC-5'-G, 3'-GCGCG-5'-G, 3'-GC-5'-G, 3'-GCG-5'-G, 3'-G-5'-G, and 3'-GC-5'-GC, and compounds 7 and 8 as delphinidin 3-glucoside having 3'-GCG-5'-GCG and 3'-GCG-5'-G as side chains, respectively, in which Dp is delphinidin, G is D-glucose, and C is p-coumaric acid. The structures of the compounds 1, 3-5, and 7 were established completely by additional NMR methods.
The transcription factor NF-kappa B stimulates the transcription of proinflammatory cytokines including TNF-alpha. LPS (endotoxin) and hypoxia both induce NF-kappa B activation and TNF-alpha gene transcription. Furthermore, hypoxia augments LPS induction of TNF-alpha mRNA. Previous reports have indicated that antioxidants abolish NF-kappa B activation in response to LPS or hypoxia, which suggests that reactive oxygen species (ROS) are involved in NF-kappa B activation. This study tested whether mitochondrial ROS are required for both NF-kappaB activation and the increase in TNF-alpha mRNA levels during hypoxia and LPS. Our results indicate that hypoxia (1.5% O2) stimulates NF-kappa B and TNF-alpha gene transcription and increases ROS generation as measured by the oxidant sensitive dye 2',7'-dichlorofluorescein diacetate in murine macrophage J774.1 cells. The antioxidants N-acetylcysteine and pyrrolidinedithiocarbamic acid abolished the hypoxic activation of NF-kappa B, TNF-alpha gene transcription, and increases in ROS levels. Rotenone, an inhibitor of mitochondrial complex I, abolished the increase in ROS signal, the activation of NF-kappa B, and TNF-alpha gene transcription during hypoxia. LPS stimulated NF-kappa B and TNF-alpha gene transcription but not ROS generation in J774.1 cells. Rotenone, pyrrolidinedithiocarbamic acid, and N-acetylcysteine had no effect on the LPS stimulation of NF-kappa B and TNF-alpha gene transcription, indicating that LPS activates NF-kappa B and TNF-alpha gene transcription through a ROS-independent mechanism. These results indicate that mitochondrial ROS are required for the hypoxic activation of NF-kappa B and TNF-alpha gene transcription, but not for the LPS activation of NF-kappa B.
Nitric oxide (NO.) produced by inducible nitric oxide synthase (iNOS) mediates a number of important physiological and pathophysiological processes. The objective of this investigation was to examine the role of mitogen-activated protein kinases (MAPKs) in the regulation of iNOS and NO. by interferon-gamma (IFN-gamma) + lipopolysaccharide (LPS) in macrophages using specific inhibitors and dominant inhibitory mutant proteins of the MAPK pathways. The signaling pathway utilized by IFN-gamma in iNOS induction is well elucidated. To study signaling pathways that are restricted to the LPS-signaling arm, we used a subclone of the parental RAW 264.7 cell line that is unresponsive to IFN-gamma alone with respect to iNOS induction. In this RAW 264.7gammaNO(-) subclone, IFN-gamma and LPS are nevertheless required for synergistic activation of the iNOS promoter. We found that extracellular signal-regulated kinase (ERK) augmented and p38(mapk) inhibited IFN-gamma + LPS induction of iNOS. Dominant-negative MAPK kinase-4 inhibited iNOS promoter activation by IFN-gamma + LPS, also implicating the c-Jun NH(2)-terminal kinase (JNK) pathway in mediating iNOS induction. Inhibition of the ERK pathway markedly reduced IFN-gamma + LPS-induced tumor necrosis factor-alpha protein expression, providing a possible mechanism by which ERK augments iNOS expression. The inhibitory effect of p38(mapk) appears more complex and may be due to the ability of p38(mapk) to inhibit LPS-induced JNK activation. These results indicate that the MAPKs are important regulators of iNOS-NO. expression by IFN-gamma + LPS.
Both lipophilic and hydrophilic antioxidant capacities were determined using the oxygen radical absorbance capacity (ORAC(FL)) assay with fluorescein as the fluorescent probe and 2,2'-azobis(2-amidinopropane) dihydrochloride as a peroxyl radical generator on over 100 different kinds of foods, including fruits, vegetables, nuts, dried fruits, spices, cereals, infant, and other foods. Most of the foods were collected from four different regions and during two different seasons in U.S. markets. Total phenolics of each sample were also measured using the Folin-Ciocalteu reagent. Hydrophilic ORAC(FL) values (H-ORAC(FL)) ranged from 0.87 to 2641 micromol of Trolox equivalents (TE)/g among all of the foods, whereas lipophilic ORAC(FL) values (L-ORAC(FL)) ranged from 0.07 to 1611 micromol of TE/g. Generally, L-ORAC(FL) values were <10% of the H-ORAC(FL) values except for a very few samples. Total antioxidant capacity was calculated by combining L-ORAC(FL) and H-ORAC(FL). Differences of ORAC(FL) values in fruits and vegetables from different seasons and regions were relatively large for some foods but could not be analyzed in detail because of the sampling scheme. Two different processing methods, cooking and peeling, were used on selected foods to evaluate the impact of processing on ORAC(FL). The data demonstrated that processing can have significant effects on ORAC(FL). Considering all of the foods analyzed, the relationship between TP and H-ORAC(FL) showed a very weak correlation. Total hydrophilic and lipophilic antioxidant capacity intakes were calculated to be 5558 and 166 micromol of TE/day, respectively, on the basis of data from the USDA Continuing Survey of Food Intakes by Individuals (1994-1996).
Reduction/oxidation (redox) regulation mediates numerous cellular responses and contributes to several physiological diseases. The transcription factor nuclear factor kappaB (NF-kappaB) is known to be a redox-sensitive factor. NF-kappaB plays a central role in immune responses and inflammation, through regulation of the gene expression of a large number of cytokines and other immune response genes. NF-kappaB is trapped in the cytoplasm in stimulated cells and translocates into the nucleus in response to several stimuli, including oxidative stress. Reactive oxygen species enhance the signal transduction pathways for NF-kappaB activation in the cytoplasm and translocation into the nucleus. In contrast, the DNA binding activity of oxidized NF-kappaB is significantly diminished, and that activity is restored by reducing enzymes, such as thioredoxin or redox factor 1. This review describes the signal transduction pathways for NF-kappaB activation and redox regulation of NF-kB activation in the cytoplasm and nucleus.
We examined the ability of the flavonoids quercetin and kaempferol to modulate inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reactive C-protein (CRP) expression, and to induce changes in the nuclear factor kappa B (NF-kappaB) pathway in the human hepatocyte-derived cell line Chang Liver. Cells were incubated with a cytokine mixture supplemented with quercetin or kaempferol (5 to 200 micromol/l). Kaempferol produced a significant concentration-dependent decrease of iNOS, COX-2 and CRP protein level at all concentrations, but the percentage of inhibition induced by quercetin was reduced at high concentrations. Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP. Inhibitory effects by quercetin and kaempferol were also observed on NF-kappaB activation and on protein concentration of the phosphorylated form of the inhibitor IkappaB alpha and of IKK (IkappaB kinase)alpha. The present study suggests that the modulation of iNOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in Chang Liver cells, via mechanisms likely to involve blockade of NF-kappaB activation and the resultant up-regulation of the pro-inflammatory genes. Our data also indicate that the minor structural differences between both compounds determine differences in their inhibitory capacity.
Monocyte chemoattractant protein-1(MCP-1) is secreted by activated macrophages and endothelial cells, and is involved in the pathogenesis of cardiovascular and neurodegenerative disorders. There is need to develop drugs that inhibit excessive infiltration of monocytes and lymphocytes to the arterial wall and central nervous system. The aim of this study was to evaluate the effect of apigenin on the synthesis and release of MCP-1 by J774.2 macrophages in vitro. Apigenin studied at higher doses (10 and 30 microM) diminished MCP-1 release in lipopolysaccharide activated J774.2 macrophages. Apigenin administered at lower doses (3.1 and 0.3 microM) did not change secretion of MCP-1 in LPS-stimulated macrophages. Apigenin treated at a dose of 30 microM strongly reduced the number of MCP