Lignanamides: A comprehensive review of chemical constituents, biological activities, extraction methods and synthetic pathway.

Lignanamides are a class of compounds containing amide functional groups in lignans. These compounds have excellent anti-inflammatory and neuroprotective, which have shown great potential in terms of food additives, medicine and health supplement. We summarized the recent progress of lignanamides, including chemical constituents, extraction methods, biological activities, and synthetic pathways. The structures were classified according to an updated nomenclature system, can be classified into sixteen types and have certain roles in many respects such as anti-inflammatory, anti-cancer, and antioxidative, which may be important source of materials for functional food. The potential and limitations of different extraction method, chromatographic packing, and synthetic pathway are analyzed. Notably, this review provides an overview of synthesis pathways and applications of lignanamides, further research is needed to improve extraction efficiency and synthesis method, especially in a greener way for better application.

Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus.

In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the 'golden chamber' medical text, Huangdi Neijing, diabetes mellitus falls under the category 'collateral disease'. TCM, with its wealth of experience, has been treating diabetes for over two millennia. Different antidiabetic Chinese herbal medicines reduce blood sugar, with their effective ingredients exerting unique advantages. As well as a glucose lowering effect, TCM also regulates bodily functions to prevent diabetes associated complications, with reduced side effects compared to western synthetic drugs. Chinese herbal medicine is usually composed of polysaccharides, saponins, alkaloids, flavonoids, and terpenoids. These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion, enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals. These actions regulate glycolipid metabolism in the body, eventually achieving the goal of normalizing blood glucose. Using different animal models, a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer. Nonetheless, there is a dearth of scientific data about the pharmacology, dose-effect relationship, and structure-activity relationship of TCM and its constituents. Further research into the efficacy, toxicity and mode of action of TCM, using different metabolic and molecular markers, is key to developing novel TCM antidiabetic formulations.

Neuroprotective effects of dendrobium endophytes metabolites in SH-SY5Y cells via the Nrf2/Keap1 pathway.

Recent studies have revealed that endophytes in plants can produce metabolites with activity that is comparable to or identical to the host. Dendrobine has attracted much attention in the field of neurodegenerative diseases by exhibiting anti-oxidative stress and neuroprotective effects. This study aimed to investigate the protective effects and mechanisms of metabolites of dendrobium endophytes Pseudomonas protegens CM-YJ44 and Priestia megaterium D-HT207 against H2O2-induced oxidative stress injury in SH-SY5Y cells. Results showed that there were 50 neuroprotective compounds in CM-YJ44 and 72 neuroprotective compounds in D-HT207. Those both increased significantly cell viability, decreased contents of ROS in H2O2-induced SH-SY5Y cells. It was confirmed that metabolites of CM-YJ44 and D-HT207 inhibited the H2O2-induced oxidative stress injury in SH-SY5Y cells, which mechanism is related to inhibition of ROS production, alteration of MMP, and inhibition of apoptosis and inflammatory factors expression via the Nrf2/Keap1 pathway.

Antimicrobial activity and comparative metabolomic analysis of Priestia megaterium strains derived from potato and dendrobium.

The growth of endophytic bacteria is influenced by the host plants and their secondary metabolites and activities. In this study, P. megaterium P-NA14 and P. megaterium D-HT207 were isolated from potato tuber and dendrobium stem respectively. They were both identified as Priestia megaterium. The antimicrobial activities and metabolites of both strains were explored. For antimicrobial activities, results showed that P. megaterium P-NA14 exhibited a stronger inhibition effect on the pathogen of dendrobium, while P. megaterium D-HT207 exhibited a stronger inhibition effect on the pathogen of potato. The supernatant of P. megaterium P-NA14 showed an inhibition effect only on Staphylococcus aureus, while the sediment of P. megaterium D-HT207 showed an inhibition effect only on Escherichia coli. For metabolomic analysis, the content of L-phenylalanine in P. megaterium P-NA14 was higher than that of P. megaterium D-HT207, and several key downstream metabolites of L-phenylalanine were associated with inhibition of S. aureus including tyrosine, capsaicin, etc. Therefore, we speculated that the different antimicrobial activities between P. megaterium P-NA14 and P. megaterium D-HT207 were possibly related to the content of L-phenylalanine and its metabolites. This study preliminarily explored why the same strains isolated from different hosts exhibit different activities from the perspective of metabolomics.

Combined metabolomics and proteomics to reveal beneficial mechanisms of Dendrobium fimbriatum against gastric mucosal injury.

As a dietary and medicinal plant, Dendrobium fimbriatum (DF) is widely utilized in China for improving stomach disease for centuries. However, the underlying mechanisms against gastric mucosal injury have not been fully disclosed. Here, metabolomics and proteomics were integrated to clarify the in-depth molecular mechanisms using cyclophosphamide-induced gastric mucosal injury model in mice. As a result, three metabolic pathways, such as creatine metabolism, arginine and proline metabolism, and pyrimidine metabolism were hit contributing to DF protective benefits. Additionally, γ-L-glutamyl-putrescine, cytosine, and thymine might be the eligible biomarkers to reflect gastric mucosal injury tatus, and DF anti-gastric mucosal injury effects were mediated by the so-called target proteins such as Ckm, Arg1, Ctps2, Pycr3, and Cmpk2. This finding provided meaningful information for the molecular mechanisms of DF and also offered a promising strategy to clarify the therapeutic mechanisms of functional foods.

Effect of pearling on composition, microstructure, water migration and cooking quality of highland barley (Hordeum vulgare var. Coeleste Linnaeus).

Highland barley (HB) has become popular due to its nutritional benefits, and pearling as a necessary process that could broaden its applications. The influence of pearling on the composition, microstructure, water migration and cooking characteristics of HB was investigated. With different degrees of pearling (DOPs), the levels of nutritious components except for starch and ß-glucan, decreased, and the ß-glucan content gradually increased and reached a plateau when the DOP was over 15%. Pearling can significantly shorten the cooking time by removing different tissues, and removal of the pericarp layer had significant influence by reducing the cooking time by 17 min (i.e., HB with DOP 5%). From the result of Peleg model fitting and low-field nuclear magnetic resonance spectroscopy, the saturated water absorption of HB did not differ for a DOP 5% and above, and cooking mainly increased the amount of moderately bound water and added small amount of bound water.

Effect of freezing treatment of soybean on soymilk nutritional components, protein digestibility, and functional components.

Soymilk is a popular beverage in many countries owing to its nutrition and health effects. To increase household consumption of soymilk, instant soybeans were developed by freezing and subsequent drying pretreatment, which overcome the time-consuming need of soaking during soymilk preparation for home making. However, compared with the traditional soymilk making, the nutritional quality and functional properties of this soymilk made from the soybean by direct grinding in water without soaking are not clear yet. Soymilk made from untreated soybeans, soaked soybeans, and soaking, freezing, and air-drying soybeans (FADTS) were compared on their properties including nutritional components, in vitro protein digestibility, and functional components. It was found that FADTS was the best at extracting lipid and Ca, good at extracting of protein, carbohydrate, oligosaccharides, Fe, phytic acids, and tannins, and in producing soymilks with highest in vitro protein digestibility. The soluble protein and protein digestibility of FADTS (4 day) increased significantly from 44.4% and 78.5% of control to 56.2% and 85.0%, respectively. Soymilk from 4 days FADTS contained similar protein content and higher Fe content (4.40 mg/kg) compared to soaked sample (3.82 mg/kg). The results revealed that FADTS performed better at producing soymilk than untreated and soaked soybeans.

[Identification of active components of Dendrobium inhibit growth of gastric cancer cells based on component-activity relationship].

Three cancer cell lines including gastric cancer SGC-7901, HGC-27, and MGC-803 cells were employed to evaluate the bioactivity of seven Dendrobium species. Simultaneously, these Dendrobium species were assessed with UPLC-Q-TOF-MS, and 504 common peaks were found. Based on the hypothesis that biological effects varied with differences in components, multivariate relevance analysis for chemical component-activity relationship of Dendrobium, including grey relation(GRA) and partial least squares(PLS) analysis were performed to evaluate the contribution of each identified component. The target peaks were identified by standards toge-ther with databases of Dendrobium, Nature Chemistry, MassBank, etc. Finally, four active components, including 3,5,9-trihydroxy-23-methylergosta-7,22-dien-6-one, diacylglycerol(14∶1/22∶6/0∶0), pipercitine, and 22-tricosenoic acid, might have negative effect on the growth of gastric cancer cells.

Analysis of Endophytic Bacterial Diversity From Different Dendrobium Stems and Discovery of an Endophyte Produced Dendrobine-Type Sesquiterpenoid Alkaloids.

As the unique component of Dendrobium, dendrobine-type sesquiterpenoid alkaloids (DSAs) possess a variety of medicinal properties. It has been well documented that plant endophytes can in vitro synthesize secondary metabolites identical or similar to metabolites produced by their host plants. This study aimed to investigate the composition and distribution of endophytic bacteria of Dendrobium stems by Illumina MiSeq platform sequencing and cultivation-dependent methods and then to assess the potential for endophytic bacteria to produce DSAs. Results indicated that it was necessary to combine both cultivation-dependent and cultivation-independent methods to analyze the community structure of endophytic bacterial in plants comprehensively. The length of the Dendrobium stems influenced the endophytic bacterial community. The diversity and richness of endophytic bacteria in group J10_15cm of stems were the highest, which showed a significant difference from the other stem groups. However, there was no certain connection between the diversity and richness of endophytic bacteria and the content of dendrobine. It was most likely due to the influence of several specific endophytic bacteria genera, such as Sphingomonas and Rhodococcus. Athelia rolfsii, Myrothecium roridum, as pathogenic fungi, and Pectobacterium carotovorum subsp. actinidiae, as pathogenic bacteria of Dendrobium, were used to determine the antimicrobial activities. In these assays, six strains belonging to five genera showed antimicrobial activity against at least two phytopathogens. The strain BL-YJ10_15-29 (Paracoccus pueri THG-N2.35, 98.98%) showed the best antimicrobial activity against the three phytopathogens. In addition, 2 DSAs (6-hydroxydendrobine and nobilonine) were identified in the fermentation supernatant of the strain CM-YJ10_15-44 (Pseudomonas protegens CHA0, 99.24%), whereas the whole-genome analysis results further demonstrated that the precursors of the two DSAs [geranyl-PP and (E, E)-famesyl-PP] were synthesized mainly through the methyl-D-erythritol 4-phosphate pathway in this strain. This study provides new insight into the studies on the biosynthesis of DSAs and provides potential biocontrol bacteria.

Antimicrobial Activity Against Phytopathogens and Inhibitory Activity on Solanine in Potatoes of the Endophytic Bacteria Isolated From Potato Tubers.

As an important global crop, the potato (Solanum tuberosum L.) contains the endotoxin solanine that leads to human poisoning and major economic losses. Poisoning symptoms and even acute poisoning may occur when the content of solanine in potatoes exceeds 200 mg/kg. In addition, potatoes are susceptible to some pathogenic bacteria, including Streptomyces scabies and Erwinia carotovora subsp. atroseptica (Van Hall) dye, which can cause potato scab and potato blackleg disease, respectively. In this study, 37 culturable endophytic bacteria strains were obtained from potato tubers based on the culture-dependent method. Results indicated that nine strains showed antimicrobial activity against at least one pathogen by antimicrobial activity screening and 23 strains showed inhibitory activity on solanine in potato tubers. Among them, strain P-NA2-14 (Bacillus megaterium NBRC 15308T, 99.31%) showed not only better antimicrobial activity against both the two indicator pathogens, but also the best inhibitory activity on solanine, which was proved to be a potential biocontrol bacterium. Meanwhile, the relationship between the distribution of the endophytic bacterial community and the content of solanine in potato tubers was studied by Illumina-based analysis, indicating that the distribution of the endophytic bacterial community was obviously influenced by the content of solanine. The results showed a new insight into the relationship between plant secondary metabolites and endophytic bacteria in potato tubers and provided potential new technical support for the biological control of potato storage.

1H NMR-based chemometric metabolomics characterization of soymilk fermented by Bacillus subtilis BSNK-5.

Microbial fermentation can endow food with unique flavors, increase its nutritional value and enhance functional characteristics. Our previous research has shown that liquid fermentation of soymilk by Bacillus subtilis BSNK-5 imparted new functional properties of to the fermented product via production of nattokinase. In this study, in order to further investigate the changes in the flavor, nutritional quality and functional characteristics of soymilk during fermentation using proton nuclear magnetic resonance (1H NMR) metabolomics to monitor the metabolite profile of BSNK-5-fermented soymilk. A total of 44 differential metabolites were identified between BSNK-5-fermented soymilk and uninoculated/unfermented soymilk, among which the levels of flavor-related substances (acetate, isovalerate and 2-methylbutyrate), nutrient-related substances (12 free amino acids), and functional substances (taurine, GABA and genistein) significantly increased after fermentation. These metabolites were closely associated with eight potential metabolic pathways. This work highlighted the significance of BSNK-5 strain in improving the nutritional quality and functional characteristics of fermented soymilk; however, the use of the strain also caused flavor deterioration. This study lays a theoretical foundation for the improvement and development of fermented soy products via liquid fermentation with B. subtilis.

Extraction of Proanthocyanidins from Chinese Wild Rice (Zizania latifolia) and Analyses of Structural Composition and Potential Bioactivities of Different Fractions.

Due to the importance of proanthocyanidin bioactivity and its relationship with chemical structure, ultrasound-assisted extraction and purification schemes were proposed to evaluate the proanthocyanidin content and analyze the structural composition and potential bioactivities of different proanthocyanidin fractions from Chinese wild rice (Zizania latifolia). Following an optimized extraction procedure, the crude wild rice proanthocyanidins (WRPs) were purified using n-butanol extraction, chromatography on macroporous resins, and further fractionation on Sephadex LH-20 to yield six specific fractions (WRPs-1-WRPs-6) containing proanthocyanidin levels exceeding 524.19 ± 3.56 mg/g extract. Structurally, (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin were present as both terminal and extension units, and (-)-epicatechin was the major extension unit, in each fraction. This is the first preparation of WRP fractions with a different mean degree of polymerization (mDP), ranging from 2.66 ± 0.04 to 10.30 ± 0.46. A comparison of the bioactivities of these fractions revealed that fractions WRPs-1-WRPs-5 had significant DPPH radical scavenging activities, whereas fraction WRPs-6 with a high mDP showed better α-glucosidase and pancreatic lipase inhibitory effects. These findings should help define possible applications of WRPs to functional foods or nutraceuticals.

Liquid chromatography-mass spectrometry-based urinary metabolomics study on a rat model of simulated microgravity-induced depression.

The pathophysiological mechanism of depression is complex and its etiology remains unclear. Metabolomics can be used to monitor multiple metabolic pathways simultaneously, thereby investigating the mechanisms of depression onset and its regulation. Therefore, we studied the metabolic profile of urine samples from a rat model of depression for identifying potential metabolic biomarkers associated with depression. The depression model of rats was induced by 14-d simulated microgravity (SMG) treatment. Principal component analysis and orthogonal partial least squares discriminate analysis were performed to classify and identify the differences of endogenous metabolites in urine between the normal and depressed rats. Multivariate statistical analysis revealed distinct separation between the urinary metabolic profiles of SMG-treated and control rats. Citric acid, oxalosuccinic acid, creatine, proline, cyclic AMP, L-dihydroxyphenylalanine (DOPA), phenylacetylglycine, 5-hydroxyindole acetaldehyde, succinylcholine, deoxyuridine, 3-hydroxyhippuric acid, glutamine, and 5-hydroxytryptophan levels were significantly reduced, whereas indole-3-acetaldehyde, xanthurenic acid, taurine, kynurenic acid, hippuric acid, 5-hydroxyindoleacetic acid, 2-phenylethanol glucuronide, 2-isopropyl-3-oxosuccinate, and adrenaline levels were elevated significantly in model group. These biochemical changes were related to tryptophan, arginine, proline, and phenylalanine metabolism, and perturbations in energy metabolism. These details of depression will be helpful to the clinical diagnosis of depression caused by space and gravity.

Partial Purification, Identification, and Quantitation of Antioxidants from Wild Rice (Zizania latifolia).

To provide further insights into the potential health-promoting antioxidants from wild rice (Zizania latifolia), which is an abundant but underutilized whole grain resource in East Asia, a partial purification based on D101 macroporous resin was carried out for the purification and enrichment of the antioxidants from the bioactive ethanol extracts of wild rice. On that basis, 34 phenolic compounds in the antioxidant fractions were identified by a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MSn). The results suggested that phenolic acids could be enriched in the 10% ethanol-eluted fraction whereas flavonoids (including procyanidins and flavonoid glycosides) could be enriched in 20⁻30% ethanol-eluted fractions. A quantitative analysis determined by the multiple reaction monitoring mode of the ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UPLC-QqQ-MS/MS) revealed a high content of procyanidins in wild rice. Compared with phenolic acids, flavonoids may contribute more to the potent antioxidant activity of wild rice. This is the first study on the antioxidants from wild rice Z. latifolia. These findings provide novel information on the functional components of wild rice, and will be of value to further research and development on Z. latifolia.

[Protective effect and underlying mechanism of cordycepin on non-alcoholic fatty liver in ob/ob mice].

This study is designed to investigate the protective effect and mechanism of cordycepin on non- alcoholic fatty liver in ob/ob mice. Twelve-week-old male ob/ob mice were divided into 5 groups according to their body weight and blood glucose, and C57BL/6J mice were used in the control group. The animals were orally administered with cordycepin for 7 weeks. Body weight and food intake were measured once a week. Blood were collected from ophthalmic venous and biochemical indexes were determined at the 2nd and 4th week. Insulin tolerance test was performed at the 5th week. After 7 weeks of administration, liver tissues were collected to determine the contents of triglycerides and total cholesterol, and pro-inflammatory cytokines. Liver histology was performed by hematoxylin-eosin and oil-red O staining. Total RNA were extracted from liver tissues and the levels of lipid metabolism-related and inflammation-related genes were detected by real time PCR. Cordycepin effectively reduced the blood lipids level and improved liver function. Nevertheless, it did not improve insulin resistance in ob/ob mice. Cordycepin significantly reduced the contents of triglycerides and cholesterol, and the levels of pro-inflammatory cytokines in liver tissues. Moreover, cordycepin remarkably suppressed the expression of genes related to lipids synthesis and inflammation. These results indicate that cordycepin may improve non-alcoholic fatty liver in ob/ob mice, and the underlying mechanism may be associated with decreased expression of genes related to lipids synthesis and inflammation.