Valorization and protection of anthocyanins from strawberries (Fragaria×ananassa Duch.) by acidified natural deep eutectic solvent based on intermolecular interaction.

This study introduces an innovative approach for the valorization and protection of anthocyanins from 'Benihoppe' strawberry (Fragaria × ananassa Duch.) based on acidified natural deep eutectic solvent (NADES). Choline chloride-citric acid (ChCl-CA, 1:1) was selected and acidified to enhance the valorization and protection of anthocyanins through hydrogen bond. The optimal conditions (ultrasonic power of 318 W, extraction temperature of 61 °C, liquid-to-solid ratio of 33 mL/g, ultrasonic time of 19 min), yielded the highest anthocyanins of 1428.34 µg CGE/g DW. UPLC-Triple-TOF/MS identified six anthocyanins in acidified ChCl-CA extract. Stability tests indicated that acidified ChCl-CA significantly increased storage stability of anthocyanins in high temperature and light treatments. Molecular dynamics results showed that acidified ChCl-CA system possessed a larger diffusion coefficient (0.05 m2/s), hydrogen bond number (145) and hydrogen bond lifetime (4.38 ps) with a reduced intermolecular interaction energy (-1329.74 kcal/mol), thereby efficiently valorizing and protecting anthocyanins from strawberries.

Insights into the Superrosids phylogeny and flavonoid synthesis from the telomere-to-telomere gap-free genome assembly of Penthorum chinense Pursh.

The completion of the first telomere-to-telomere (T2T) genome assembly of Penthorum chinense Pursh (PC), a prominent medicinal plant in China, represents a significant achievement. This assembly spans a length of 257.5 Mb and consists of nine chromosomes. PC's notably smaller genome size in Saxifragales, compared to that of Paeonia ostii, can be attributed to the low abundance of transposable elements. By utilizing single-copy genes from 30 species, including 28 other Superrosids species, we successfully resolved a previously debated Superrosids phylogeny. Our findings unveiled Saxifragales as the sister group to the core rosids, with both being the sister group to Vitales. Utilizing previously characterized cytochrome P450 (CYP) genes, we predicted the compound classes that most CYP genes of PC are involved in synthesizing, providing insight into PC's potential metabolic diversity. Metabolomic and transcriptomic data revealed that the richest sources of the three most noteworthy medicinal components in PC are young leaves and flowers. We also observed higher activity of upstream genes in the flavonoid synthesis pathway in these plant parts. Additionally, through weighted gene co-expression network analysis, we identified gene regulatory networks associated with the three medicinal components. Overall, these findings deepen our understanding of PC, opening new avenues for further research and exploration.

Tetrastigma hemsleyanum leaf extracts ameliorate NAFLD in mice with low-grade colitis via the gut-liver axis.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder, manifested as oxidative stress, lipid accumulation, and inflammation of the liver. Tetrastigma hemsleyanum leaves (THL), which are rich in flavonoids and phenolic acids, have good anti-inflammatory, antioxidant, and hepatoprotective effects. However, it is unknown whether THL extracts can improve NAFLD and the underlying mechanisms are unknown. Hence, this study was designed to investigate the effects of THL extracts on NAFLD and perform a preliminary inquiry into the underlying mechanism based on the gut-liver axis. The results showed that THL extracts could reverse NAFLD-related oxidative stress, lipid accumulation, and inflammation. Additionally, the protective effect of THL extracts on the gut includes the maintenance of the intestinal barrier and the regulation of gut microbiota, which may be one of the mechanisms by which THL improves NAFLD. To be specific, in our study, THL extracts alleviated hepatic lipid accumulation and oxidative stress by regulating the expression of lipid synthesis/catabolism and the oxidative stress genes (SREBP-1c/ACC-1/PPAR-α/PPAR-γ/Keap1/Nrf2). In addition, THL extracts reduced damage to the intestinal barrier (ZO-1/Mucin2/occludin) and increased the relative abundance of Lactobacillales, Ruminococcaceae, and Bifidobacteriales in NAFLD mice. In short, THL extracts alleviated NAFLD-related oxidative stress, lipid accumulation, and inflammation in NAFLD mice which may be via the gut-liver axis (gut barrier integrity and gut microbiota).

Identification of a novel α-glucosidase inhibitor from Melastoma dodecandrum Lour. fruits and its effect on regulating postprandial blood glucose.

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.

Proteomics and metabolomics reveal the mechanism underlying differential antioxidant activity among the organs of two base plants of Shiliang tea (Chimonanthus salicifolius and Chimonanthus zhejiangensis).

The leaves and branches of Chimonanthus salicifolius and Chimonanthus zhejiangensis are the base ingredients of Shiliang tea. In this study, proteomics and metabolomics were performed to understand the molecular mechanisms underlying antioxidant activity (AA) in the leaves and branches of the two species. Stress and redox related proteins are differentially expressed among organs. The abundance of isoprenoid pathway-related proteins is higher in leaves while the abundance of phenylpropanoid and flavonoid pathway-related proteins is higher in branches in both species. Metabolomics revealed the flavonoid composition and demonstrated that procyanidins are more abundant in branches. Superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and AA are stronger in branches than leaves. Overall, branches might contribute to redox homeostasis through SOD/GSH-PX and flavonoids. Furthermore, the high level of AA of branches might be largely due to their increased accumulation of procyanidins.

Omics Analyses of Intestinal Microbiota and Hypothalamus Clock Genes in Circadian Disturbance Model Mice Fed with Green Tea Polyphenols.

Green tea polyphenols (GTP) have similar activities as prebiotics, which effectively regulate the structure of intestinal flora and affect their metabolic pathways. The intestinal flora is closely related to the host's circadian rhythm, and the supplementation with GTP may be an effective way to improve circadian rhythm disorders. In this study, we established a mouse model of circadian rhythm disturbance of anthropogenic flora to investigate the regulation mechanism of GTP on the host circadian rhythms. After 4 weeks of GTP administration, the results showed that GTP significantly alleviated the structural disorder of intestinal microbiota, thus effectively regulating related metabolites associated with brain nerves and circadian rhythms. Moreover, single-cell transcription of the mouse hypothalamus suggested that GTP up-regulated the number of astrocytes and oligodendrocytes and adjusted the expression of core clock genes Csnk1d, Clock, Per3, Cry2, and BhIhe41 caused by circadian disruption. Therefore, this study provided evidence that GTP can improve the physiological health of hosts with the circadian disorder by positively affecting intestinal flora and related metabolites and regulating circadian gene expression.

Bioactive constituents of Mosla chinensis-cv. Jiangxiangru ameliorate inflammation through MAPK signaling pathways and modify intestinal microbiota in DSS-induced colitis mice.

BACKGROUND: Mosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency. PURPOSE: This study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms. METHODS: The bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored. RESULTS: Totally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE2) and cytokines (TNF-α, IL-6, IL-1ß). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model. CONCLUSIONS: This study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.

The Chimonanthus salicifolius genome provides insight into magnoliid evolution and flavonoid biosynthesis.

Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome-level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein-coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole-genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole-genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius.

A metagenomic analysis of the modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiome in a high-fat diet-induced obesity mouse model.

BACKGROUND: As a result of a low bioavailability, the majority of Cyclocarya paliurus flavonoids (CPF) remain in the large intestine where they accumulate to exert a modulatory effect on the intestinal micro-ecology. Therefore, the present study investigated the modulatory effect of CPF on intestinal microbiota. RESULTS: CPF dramatically ameliorated the obesity-induced gut dysbiosis. A significant decrease (P < 0.05) was observed in the ratio of Firmicutes/Bacteroidetes after CPF treatment for 8 weeks. Moreover, Kyoto Encyclopedia of Genes and Genomes pathways of biosynthesis of amino acids, the two-component system and ATP-binding cassette transporters enriched the most differentially expressed genes after CPF intervention. CONCLUSION: The results of the present study indicate that CPF might have prebiotic-like activity and could be used as a functional food component with potential therapeutic utility to prevent obesity-related metabolic disorders by manipulating the gut flora and affecting certain metabolic pathways, thus contributing to the improvement of human health. © 2019 Society of Chemical Industry.

[Research advances on chemical constituents from Calycanthaceae plants and their pharmacological activities].

Calycanthaceae family comprises of four genera including Chimonanthus, Sinocalycanthus, Calycanthus, and Idiospermum. The plants of Calycanthaceae are popular ornamental shrubs and used as foods and medicines, which are mainly distributed in China, North America, and Australia. The plants of Calycanthaceae are rich in volatile components, alkaloids, sesquiterpenes and coumarins. Dimeric piperidinoquinoline and dimeric pyrrolidinoindoline alkaloids, dimeric and/or trimeric coumarins are characteristic compositions in these plants. In order to provide timely reference for further investigation and development of Calycanthaceae plants, we made a systemic review on chemical constituents, i.e. alkaloids, terpenoids, flavonoids, coumarins, and steroids, from Calycanthaceae plants, focusing on their chemical structures and pharmacological activities.

Isolation and chatacterization of homoisoflavonoids from Dracaena cochinchinensis and their osteogenic activities in mouse mesenchymal stem cells.

Two new homoisoflavonoids, dracaeconolide A (1) and dracaeconolide B (2), together with ten known compounds, namely (3R)-7,4'-dihydroxy-8-methoxyhomoisoflavane (3), (3R)-7-hydroxy-3-(4-hydroxybenzyl)chromane (4), (3R)-7,4'-dihydroxy-5-methoxy-homoisoflavane (5), (3R)-6,4'-dihydroxy-8-methoxyhomoisoflavan (6), 7,4'-dihydroxy-8-methylflavan (7), (2R)-7,4'-dihydroxy-5-methoxy-8-methylflavan (8), 5,4'-dihydroxy-7-methoxy-6-methylflavane (9), 7,4'-dihydroxy-3'-methoxyflavan (10), 7,4'-dihydroxyflavan (11), 4,4'-dihydroxy-2,6-dimethoxydihydrochlcone (12), were isolated from the red resin of Dracaena cochinchinensis (dragon's blood, DB). All the compounds were then evaluated for their effects on mouse bone marrow-derived mesenchymal stem cells (MSCs) proliferation using CCK8 assay and their abilities in promoting MSCs differentiating into osteoblast through the assay of alkaline phosphatase (ALP) activity in vitro. Compounds 2, 3, 4, 7, 9, and 11, at a concentration of 10µM with no cytotoxicity, significantly promoted MSC osteogenic differentiation by increasing the levels of ALP activity to percents of 159.6±5.9, 167.6±10.9, 162.0±1.4, 151.3±4.0, 171.0±8.2, and 169.9±7.3 in relative to the control, respectively. The results of ALP staining were in accordance to that of ALP activity.

Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.

Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.

Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.

Chemical constituents from Melastoma dodecandrum and their inhibitory activity on interleukin-8 production in HT-29 cells.

In search of anti-inflammatory lead compounds from traditional Chinese medicines, a bioassay-guided phytochemical study on Melastoma dodecandrum was carried out. As a result, 18 compounds have been isolated. Their chemical structures were determined on the basis of their physicochemical properties and spectral data. Among the isolates, three pentacyclic triterpenoids, ursolic acid (1), asiatic acid (3) and terminolic acid (6), together with one tannin casuarinin (17), were found to significantly decrease interleukin-8 (IL-8) production in human colon cancer cells. The results imply, at least in part, that the anti-inflammatory effect of M. dodecandrum could be due to inhibition of IL-8 production, demonstrated by these naturally occurring compounds described above.

[Chemical constituents of chloroform fraction from leaves of Chimonanthus salicifolius].

To explore anti-tumor active components of Chimonanthus salicifolius, the phytochemistry of the chloroform fraction from leaves extract was investigated by repeated silica gel column chromatography. Twelve compounds were isolated and their structures were identified by physicochemical properties and spectroscopic data analysis as 9-epi-blumenol C(1), blumenol C(2), (+)-dehydrovomifoliol (3), (+)-vomifoliol (4), robinlin (5), (-)-loliolide (6), isofraxidin (7), scopoletin (8), 6,7-dimethoxycoumarin (9), 6, 7, 8-trimethoxycoumarin (10), beta-sitostenone (11), and beta-stigmasterol(12). Compounds 1-6 belonging to nor-sesquiterpenoids were isolated from the family Calycanthaceae for the first time. Compound 1 was a new natural product. Compounds 7, 11 and 12 were obtained from this plant for the first time.

[Study on chemical constituents of Drosera peltata var. multisepala].

Chemical investigatation of Drosera peltata var. multisepala led to the isolation of eleven compounds using various chromatographic techniques. The structures of these compounds were elucidated as isoshinanolone-4-O-beta-D-glucoside (1), isoshinanolone (2), epi-isoshinanolone (3), plumbagin (4), droserone (5), droserone-5-O-glucoside (6), quercetin (7), kaempferol (8) , gossypetin-8-O-glucoside (9), 3,3'-dimethoxy ellagic acid (10), and ellagic acid (11) by their physicochemical properties and spectral data analysis. Compound 1 was a new compound. Compounds 3, 8, 10, and 11 were isolated from this plant for the first time.

[Anti-HIV chemical constituents of aerial parts of Caragana rosea].

This study was intended to look for anti-HIV chemical constituents of aerial parts of Caragana rosea Turcz. Column chromatographic technique was used for the isolation and purification of constituents of Caragana rosea under the guide of anti-HIV assay. The structures were established on the basis of physical and chemical properties and spectroscopic data. Five compounds were obtained from the EtOAc fraction of aerial parts of Caragana rosea and identified as myricetin (1), mearnsetin (2), p-hydroxy cinnamic acid (3), cararosinol A (4) and cararosinol B (5). At the same time, one possible transformation route between cararosinol B and kobophenol A, another resveratrol tetramer isolated from this plant previously, was proposed. Compounds 4, 5 are new resveratrol tetramers, compounds 1 -3 were isolated from this plant for the first time. All compounds showed no activities in an in vitro assay against HIV-1.

Koboquinone A and B, new metabolites of kobophenol a in rats.

Two new phase I metabolites of phytoestrogen kobophenol A (1), called koboquinone A (2) and B (3), have been isolated from the feces of rats orally administered 1. Their structures were determined by spectroscopic methods. 2 also showed activity of stimulating the proliferation of cultured osteoblasts.