Six New Phenylpropanoid Derivatives from Chemically Converted Extract of Alpinia galanga (L.) and Their Antiparasitic Activities.

Chemical conversion of the extract of natural resources is a very attractive way to expand the chemical space to discover bioactive compounds. In order to search for new medicines to treat parasitic diseases that cause high morbidity and mortality in affected countries in the world, the ethyl acetate extract from the rhizome of Alpinia galanga (L.) has been chemically converted by epoxidation using dioxirane generated in situ. The biological activity of chemically converted extract (CCE) of A. galanga (L.) significantly increased the activity against Leishmania major up to 82.6 ± 6.2 % at 25 µg/mL (whereas 2.7 ± 0.8% for the original extract). By bioassay-guided fractionation, new phenylpropanoids (1-6) and four known compounds, hydroquinone (7), 4-hydroxy(4-hydroxyphenyl)methoxy)benzaldehyde (8), isocoumarin cis 4-hydroxymelein (9), and (2S,3S,6R,7R,9S,10S)-humulene triepoxide (10) were isolated from CCE. The structures of isolated compounds were determined by spectroscopic analyses of 1D and 2D NMR, IR, and MS spectra. The most active compound was hydroquinone (7) with IC50 = 0.37 ± 1.37 µg/mL as a substantial active principle of CCE. In addition, the new phenylpropanoid 2 (IC50 = 27.8 ± 0.34 µg/mL) also showed significant activity against L. major compared to the positive control miltefosine (IC50 = 7.47 ± 0.3 µg/mL). The activities of the isolated compounds were also evaluated against Plasmodium falciparum, Trypanosoma brucei gambisense and Trypanosoma brucei rhodeisense. Interestingly, compound 2 was selectively active against trypanosomes with potent activity. To the best of our knowledge, this is the first report on the bioactive "unnatural" natural products from the crude extract of A. galanga (L.) by chemical conversion and on its activities against causal pathogens of leishmaniasis, trypanosomiasis, and malaria.

Phenylpropanoid-conjugated pentacyclic triterpenoids from the whole plants of Leptopus lolonum induced cell apoptosis via MAPK and Akt pathways in human hepatocellular carcinoma cells.

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC50 value of 11.87 µM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs.

Two new phenylpropanoid glycosides from Lagotis brachystachya Maxim and their Xanthione Oxidase inhibitions.

Two new phenylpropanoid glycosides lagotiside C and D, along with 11 known compounds were isolated from the whole plant of Lagotis brachystachya Maxim. The structures of lagotiside C and D was elucidated on the basis of spectroscopic data analysis. Moreover, all isolated components were evalued for the inhibition on Xanthione Oxidase (XOD) activity in vitro. Results indicated that all the compounds exhibited inhibitory effects on XOD with inhibition ratio in the range of 6.35%-83.69%, which suggested that Lagotis brachystachya could be served as an XOD inhibitor.

Isolation and Characterization of Phenylpropanoid and Lignan Compounds from Peperomia pellucida [L.] Kunth with Estrogenic Activities.

Extracts of Peperomia pellucida [L.] Kunth have previously been demonstrated to have in vivo estrogenic-like effects, thereby functioning as an anti-osteoporotic agent. However, the compounds responsible for these effects have not yet been determined. Therefore, the aim of this study is to isolate and elucidate potential compounds with estrogenic activity. The structures of the isolated compounds were identified using 1D 1H and 13C-NMR and confirmed by 2D FT-NMR. The estrogenic activity was evaluated using the E-SCREEN assay, and a molecular docking study was performed to predict the binding affinity of the isolated compounds to estrogen receptors. In this experiment, we successfully isolated three phenylpropanoids and two lignan derivatives, namely, 6-allyl-5-methoxy-1,3-benzodioxol-4-ol (1), pachypostaudin B (2), pellucidin A (3), dillapiole (4), and apiol (5). Among these compounds, the isolation of 1 and 2 from P. pellucida is reported for the first time in this study. Activity assays clearly showed that the ethyl acetate extract and its fractions, subfractions, and isolated compounds exerted estrogenic activity. Methanol fraction of the ethyl acetate extract produced the highest estrogenic activity, while 1 and 2 had partial agonist activity. Some compounds (derivates of dillapiole and pellucidin A) also had, in addition, anti-estrogenic activity. In the docking study, the estrogenic activities of 1-5 appeared to be mediated by a classical ligand-dependent mechanism as suggested by the binding interaction between the compounds and estrogen receptors; binding occurred on Arg 394 and His 524 of the alpha receptor and Arg 346 and His 475 of the beta receptor. In summary, we reveal that P. pellucida is a promising anti-osteoporotic agent due to its estrogenic activity, and the compounds responsible for this activity were found to be lignan and phenylpropanoid derivatives. The presence of other compounds in either the extract or fraction may contribute to a synergistic effect, as suggested by the higher estrogenic activity of the methanol fraction. Hence, we suggest further research on the osteoporotic activity and safety of the identified compounds, especially regarding their effects on estrogen-responsive organs.

Chrysanthemum indicum L.: A Comprehensive Review of its Botany, Phytochemistry and Pharmacology.

Chrysanthemum indicum L. (C. indicum L.), a member of the Compositae family, is a perennial plant that has been used as a traditional medicine for more than 2000 years in China and is widely used for the treatment of Pemphigus, swelling, pain, and scrofula. To date, more than 190 chemical constituents have been isolated and identified from this plant, including flavonoids, terpenoids, phenylpropanoids, and phenolic acids. Numerous modern studies have shown that extracts or monomeric compounds from C. indicum L. have several pharmacological activities, such as anti-inflammatory anti-oxidation, antipathogenic microorganism, anticancer, immune regulation, and hepatoprotective effects. However, resource availability, the research on the mechanism, and quality control are still insufficient, which deserves further efforts. In this paper, the advances in botany, phytochemistry, and pharmacology of C. indicum L were reviewed. We hope that this review can provide important information for traditional Chinese medicine, phytochemistry, synthetic and medicinal chemistry researchers for making full use of C. indicum L. resource.

Structure Elucidation of Two New Norlignans from Anemone vitifolia and Their Anti-Inflammatory Activities.

Two new norlignans together with two known phenylpropanoids were isolated from the whole herb of Anemone vitifolia. All compounds were reported from this plant for the first time. The structures of these compounds were identified by comprehensive HR-ESI-MS, 1D and 2D NMR spectroscopic data analysis and comparison with literature data. Additionally, bioactivity study results showed that two new compounds have potential anti-inflammatory activity. The plausible biosynthetic pathway for these compounds were also speculated in this article.

Natural Deep Eutectic Solvents for the Extraction of Phenyletanes and Phenylpropanoids of Rhodiola rosea L.

The extraction of Rhodiola rosea rhizomes using natural deep eutectic solvent (NADES) consisting of lactic acid, glucose, fructose, and water was investigated. A two-level Plackett-Burman design with five variables, followed by the steepest ascent method, was undertaken to determine the optimal extraction conditions. Among the five parameters tested, particle size, extraction modulus, and water content were found to have the highest impact on the extrability of phenyletanes and phenylpropanoids. The concentration of active compounds was analyzed by HPLC. The predicted results showed that the extraction yield of the total phenyletanes and phenylpropanoids (25.62 mg/g) could be obtained under the following conditions: extraction time of 154 min, extraction temperature of 22 °C, extraction modulus of 40, molar water content of 5:1:11 (L-lactic acid:fructose:water, mol/mol), and a particle size of rhizomes of 0.5-1 mm. These predicted values were further verified by validation experiments in predicted conditions. The experimental yields of salidroside, tyrosol, rosavin, rosin, cinnamyl alcohol and total markers (sum of phenyletanes and phenylpropanoids in mg/g) were 11.90 ± 0.02, 0.36 ± 0.02, 12.23 ± 0.21, 1.41 ± 0.01, 0.20 ± 0.01, and 26.10 ± 0.27 mg/g, respectively, which corresponded well with the predicted values from the models.

Phenylpropanoids from the fruit of Crataegus pinnatifida exhibit cytotoxicity on hepatic carcinoma cells through apoptosis induction.

Eight new phenylpropanoids (1a/1b, 2-4, 5a/5b and 6) including two pairs of enantiomers (1a/1b and 5a/5b), along with a known analogue (7) were isolated from the fruit of Crataegus pinnatifida. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1a/1b and 5a/5b were separated successfully by chiral chromatographic column. The absolute configurations of enantiomers were determined by comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro antitumor activities of the isolates were evaluated against two human hepatocellular carcinoma HepG2 and Hep3B cells. Five compounds (1a/1b, 2-4) exhibited more potent cytotoxicity and their structure-activity relationships were also discussed. Annexin V-FITC/PI staining using flow cytometry was carried out to examine cell apoptosis, and the results showed that compounds 3-4 with the presence of two methoxy groups substituted at C-3' significantly induced apoptosis in HepG2 cells.

Phenylpropanoid profiling reveals a class of hydroxycinnamoyl glucaric acid conjugates in Isatis tinctoria leaves.

The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with 13C6-glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts.

Cinnamyl Alcohol, the Bioactive Component of Chestnut Flower Absolute, Inhibits Adipocyte Differentiation in 3T3-L1 Cells by Downregulating Adipogenic Transcription Factors.

The extract of chestnut (Castanea crenata var. dulcis) flower (CCDF) has antioxidant and antimelanogenic properties, but its anti-obesity properties have not been previously examined. In this study, we tested the effect of CCDF absolute on adipocyte differentiation by using 3T3-L1 cells and determining the bioactive component of CCDF absolute in 3T3-L1 cell differentiation. CCDF absolute (0.1-100[Formula: see text][Formula: see text]g/mL) did not change 3T3-L1 cell viability. At 50[Formula: see text][Formula: see text]g/mL and 100[Formula: see text][Formula: see text]g/mL, the absolute significantly reduced the accumulation of lipid droplets in 3T3-L1 cells that were induced by culture in medium containing 3-isobutyl-1-methylxanthine/dexamethasone/insulin (MDI). GC/MS analysis showed that CCDF absolute contains 10 compounds. Among these compounds, cinnamyl alcohol (3-phenyl-2-propene-1-ol) dose-dependently inhibited the increased accumulation of lipid droplets in MDI-contained medium-cultured 3T3-L1 cells at a concentration range of 0.1[Formula: see text][Formula: see text]g/mL to 10[Formula: see text][Formula: see text]g/mL that did not cause cytotoxicity in 3T3-L1 cells. The inhibitory effect was significant at 5[Formula: see text][Formula: see text]g/mL ([Formula: see text] of response in MDI alone-treated state, [Formula: see text]) and 10[Formula: see text][Formula: see text]g/mL ([Formula: see text] of response in MDI alone-treated state, [Formula: see text]). Moreover, the enhanced expression of obesity-related proteins (PPAR[Formula: see text], C/EBP[Formula: see text], SREBP-1c, and FAS) in MDI medium-cultivated 3T3-L1 cells was significantly attenuated by the addition of cinnamyl alcohol at 5[Formula: see text][Formula: see text]g/mL and 10[Formula: see text][Formula: see text]g/mL. These findings demonstrate that cinnamyl alcohol suppresses 3T3-L1 cell differentiation by inhibiting anti-adipogenesis-related proteins, and it may be a main bioactive component of CCDF absolute, exerting antidifferentiation action in 3T3-L1 cells. Therefore, cinnamyl alcohol, as well as CCDF absolute, may be potential candidates for the prevention or treatment of obesity.

Phenylpropanoids from Juglans mandshurica exhibit cytotoxicities on liver cancer cell lines through apoptosis induction.

Three new phenylpropanoids (1-3) together with six known congeners (4-9) were isolated from the bark of Juglans mandshurica Maxim using anti-hepatoma activity as a guide. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. All the isolated compounds were evaluated for their growth inhibitory activities against two kinds of liver cancer cell lines (HepG2 and Hep3B). Among them, compound 4 showed moderate cytotoxic activities against HepG2 and Hep3B cell lines with IC50 values of 58.58 and 69.87µM. Compound 5 exhibited 50% cell death rate in HepG2 and Hep3B cell lines at 63.70 and 46.45µM, respectively. Further observation of morphological changes and Western blot demonstrated that compounds 4 and 5 exhibited their cytotoxic activities through the induction of apoptosis. A structure-activity relationship study suggested that an α, ß-unsaturated aldehyde might be the most important functional group.

[A new phenylpropanoid glycoside compound isolated from Karelinia caspia].

To study the constituents of Karelinia caspia(Pall.) Less, three phenylpropanoid derivatives and other compounds were isolated by silica gel, RP-18 chromatographic methods. Compound 1 was a new phenylpropanoid glycoside named as kareline A. Their structures were determined by spectroscopic analysis, including 1D- and 2D-NMR and mass spectrometry.

Phytochemical progress made in investigations of Angelica sinensis (Oliv.) Diels.

The phytochemical progress on Angelica sinensis (Oliv.) Diels over the past decades is summarized. Since 1970s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum vulgare on selected human cell lines.

This study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds - syringin and 4-methoxycinnamyl alcohol - on cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was found to exhibit the most significant toxicity with an IC50 value of 19.97 µg/mL on HeLa cells. Bioassay-guided fractionation led to the isolation of two compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that compound 2 showed high toxicity against all the cancer cell lines with IC50 values of 14.24, 7.82 and 22.10 µg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 h at a concentration of 10 µg/mL. However, DNA fragmentation study revealed that necrosis took place at a concentration of 10 µg/mL after 48 h exposure.

Phytochemistry and pharmacology of the genus pedicularis used in traditional Chinese medicine.

In the present review, the literature data on the chemical constituents and biological investigations of the genus Pedicularis are summarized. Some species of Pedicularis have been widely applied in traditional Chinese medicine. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides (PhGs), lignans glycosides, flavonoids, alkaloids and other compounds have been isolated and identified from the genus Pedicularis. In vitro and in vivo studies indicated some monomer compounds and extracts from the genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscle, nootropic effect and other activities.

Horsfiequinones A-F, dimeric diarylpropanoids from Horsfieldia tetratepala.

A new diarylpropanoid, horsfiequinone A (1), and five new dimeric diarylpropanoids with 1,4-p-benzoquinone residue, horsfiequinones B-F (2-6), along with a known compound, combrequinone B (7), were isolated from Horsfieldia tetratepala. Their structures were elucidated by means of spectroscopic analysis. Horsfiequinones B-F (2-6), isolated as enantiomer mixtures with unequal proportions, were verified by analysis on a chiral OD-H HPLC column. Cytotoxicity evaluation against five human tumor lines showed selective inhibitory effects on HL-60 for several compounds tested with IC50 values ranging from 3.18 ± 0.67 to 6.61 ± 0.08 µM.

Three alkaloids from Reineckia carnea herba and their antitussive and expectorant activities.

Three alkaloids, (3-chloro-2-hydroxypropyl) trimethylammonium chloride (1), p-(acetylamino)-phenol (2) and 4,4'-diacetamidodiphenyl ether (3), were isolated from Reineckia carnea herba. Their structures were determined by detailed analysis of their 1D and 2D NMR spectra and MS. Compounds 1 and 3 were new natural products. Compound 2 was isolated for the first time from the Reineckia genus. Compound 1 displayed significant in vivo antitussive and expectorant activities.

Monoterpene glycosides, phenylpropanoids, and acacetin glycosides from Dracocephalum foetidum.

Chemical investigation of the acetone extract from the aerial parts of the Mongolian medicinal plant Dracocephalum foetidum resulted in the isolation of three limonene glycosides, a caffeic acid trimer, four rosmarinic acid glucosides, and five acacetin acyl glycosides, together with 13 known natural products. The chemical structures of all of the compounds were determined by spectroscopic analyses. Among these compounds three showed hyaluronidase inhibitory activity. In addition, one other compound showed stronger 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity than the positive control Trolox, whereas three other compounds demonstrated a similar activity to that of Trolox.

New phenylpropanoid and other compounds from Illicium lanceolatum with inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages.

Illicium lanceolatum is a traditional Chinese medicine (TCM) for treating inflammatory diseases. Anti-inflammatory activities of I. lanceolatum stems and leaves were tested using ear edema models induced by dimethyl benzene in mice. Bioassay-guided fractionation of the ethanol extract of I. lanceolatum leaves and stems revealed that the ethyl acetate fraction exhibited inhibitory potency to dimethyl benzene-induced edema in the mouse ear. Phytochemical investigation on the active fraction led to the isolation of a new phenylpropanoid (1), together with fifteen known compounds. This is the first report of the isolation of 2-16 from I. lanceolatum. Of these compounds, compounds 1, 2 and 3 showed inhibitory activity on LPS-stimulated NO production in RAW 264.7 macrophages with IC50 values of 27.58, 26.59 and 34.35 µg/mL, respectively. I. lanceolatum stems and leaves can be exploited to alleviate inflammatory diseases, which makes the rare medicinal plant resources sustainable.

Caffeoylated phenylpropanoid glycosides from Brandisia hancei inhibit advanced glycation end product formation and aldose reductase in vitro and vessel dilation in larval zebrafish in vivo.

In our continuing efforts to identify effective naturally sourced agents for diabetic complications, five caffeoylated phenylpropanoid glycosides, acteoside (1), isoacteoside (2), poliumoside (3), brandioside (4), and pheliposide (5) were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-5) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end product formation and rat lens aldose reductase activity. All tested compounds exhibited significant inhibition of advanced glycation end product formation with IC50 values of 4.6-25.7 µM, compared with those of aminoguanidine (IC50=1,056 µM) and quercetin (IC50=28.4 µM) as positive controls. In the rat lens aldose reductase assay, acteoside, isoacteoside, and poliumoside exhibited greater inhibitory effects on rat lens aldose reductase with IC50 values of 0.83, 0.83, and 0.85 µM, respectively, than those of the positive controls, 3,3-tetramethyleneglutaric acid (IC50=4.03 µM) and quercetin (IC50=7.2 µM). In addition, the effect of acteoside on the dilation of hyaloid-retinal vessels induced by high glucose in larval zebrafish was investigated. Acteoside reduced the diameters of high glucose-induced hyaloid-retinal vessels by 69% at 10 µM and 81% at 20 µM, compared to the high glucose-treated control group. These results suggest that B. hancei and its active components might be beneficial in the treatment and prevention of diabetic vascular complications.